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BACKGROUND:The basic principle of the design of the robot system used for total knee arthroplasty is to combine three-dimensional surgical planning,early warning of danger areas during surgery,real-time data feedback,robot arm assisted osteotomy and other technologies to achieve precision and personalization of total knee arthroplasty,which is exactly its biggest advantage.Therefore,it has become a hot topic in the field of joint surgery in recent years and attracted much attention. OBJECTIVE:To summarize the development status of robotic-assisted total knee arthroplasty in the field of joint surgery and the comparison of advantages and disadvantages with conventional total knee arthroplasty and to prospect the future development of robotic-assisted total knee arthroplasty. METHODS:Relevant articles were searched from PubMed,CNKI,Wanfang and VIP databases by computer.English key words were"robot OR robotic OR robotics OR robotically OR computer,total knee arthroplasty OR total knee replacement,TKA OR TKR".Chinese key words were"robotic-assisted,computer navigation,total knee arthroplasty".Finally,64 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The robot system used to assist total knee arthroplasty is divided into active,semi-active and passive according to its degree of freedom.The semi-active system,currently widely used in robotic systems,effectively enhances the accuracy and personalization of total knee arthroplasty.However,its high implementation cost and relatively steep learning curve remain key factors to be balanced when promoting its adoption in joint surgery field.(2)Robotic-assisted total knee arthroplasty can achieve precise osteotomy and correct placement of prosthesis in local three-dimensional space of the knee joint.It has been widely proven that it can provide better accuracy of prosthesis implantation,reduce imaging abnormalities,obtain good soft tissue balance during the operation,and ultimately improve the motion and functional status of the knee joint after the operation.(3)However,the current robotic-assisted system still has objective shortcomings,including the problem of learning curve between different robot devices and operators,additional installation and maintenance costs,and potential complications related to robot surgery.Therefore,whether it can truly benefit the medical system and patients still needs to be proven by long-term research,and the robotic-assisted system also needs to be further improved substantially.(4)Robotic-assisted total knee arthroplasty technique is still in the preliminary research stage in clinical practice and has not been widely applied.To better define the usage of robotic-assisted total knee arthroplasty and enhance its clinical procedural standards and safety,refining these aspects will become a focal point of future research on robotic-assisted total knee arthroplasty.
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Objective:To evaluate the clinical curative effect of self-made Lishi Qufeng Juanbi Decoction combined with Febuxostat tablet on uric acid nephropathy (UAN).Methods:Randomized controlled trial. A total of 150 patients with UAN in Yixing Hospital of Traditional Chinese Medicine were enrolled as the observation objects between October 2019 to October 2021. According to random number table method, they were divided into two groups, 75 in each group. The control group was treated with Febuxostat tablets on basis of routine diet intervention, while the observation group was treated with self-made Lishi Qufeng Juanbi Decoction on basis of control group. All were continuously treated for 6 months. TCM syndromes were scored before and after treatment. The levels of serum uric acid (SUA) and creatinine (SCr) were detected by full-automatic biochemical analyzer, and levels of serum CRP, IL-6 and IL-8 were detected by ELISA. The 24h urine was collected to detect 24 h urine protein quantitation. The adverse events were recorded, and clinical curative effect was evaluated.Results:There were significant differences in total response rate between observation group and control group [93.33% (70/75) vs. 80.00% (60/75); χ2=5.77, P=0.016]. After treatment, scores of waist soreness-fatigue and frequent nocturia in observation group were significantly lower than those in the control group ( t=9.17, 2.67, P<0.01), and frequency of joint swelling pain was significantly lower than that of the control group ( t=9.49, P<0.01). The levels of serum SUA and SCr, and 24 h urine protein quantitation in observation group were significantly lower than those in the control group ( t=3.38, 2.49, 12.55, P<0.01 or P<0.05), and levels of CRP, IL-6 and IL-8 were significantly lower than those in the control group ( t=5.44, 4.15, 9.61, P<0.01). There was no significant difference in incidence of adverse reactions between observation group and control group [4.00% (3/75) vs. 10.67% (8/75); χ2=2.45, P=0.117]. Conclusion:The self-made Lishi Qufeng Juanbi Decoction combined with Febuxostat tablets can promote uric acid metabolism, improve high uric acid environment, protect renal function, inhibit the release of inflammatory factors, improve curative effect and reduce adverse reactions in UAN patients.
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Objective:This study was conducted using scientometric methods and visualization technology to review the research status and demonstrate the hotspots, evolutionary paths, and frontiers of community nursing in stroke patients at home and abroad.Methods:This study employed the CiteSpace software to analyze the literature on community care for stroke patients published from January 1, 2012 to June 1, 2022 in the core databases of CNKI and Web of Science Core Collection (WOSCC) database.Results:A total of 1 535 articles were included in this study. The trend of CNKI publications numbers had been first increasing and then decreasing. The number of WOSCC publications had experienced an annual increase over the past 10 years, albeit with certain inverted S-shaped fluctuations. The hot topics at home and abroad could be summarized in three points: rehabilitation nursing for community stroke patients, social support for community stroke patients, and community aged care for stroke patients. Domestic research in this field had been continuously refined, and there had been a significant shift in the development of this field abroad from focusing on the disease itself and public health issues to evidence-based nursing practices. The new research frontiers mainly included experiments and guidelines.Conclusions:There are differences in the level of emphasis placed on community care for stroke in the academic community both domestically and internationally. Conducting clinical trials and developing relevant guidelines will be an international research frontier. Moreover, relevant papers might provide Chinese research theory and methodology.
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Objective To analyze the short-and long-term efficacy and influencing factors of 125I seed implantation for relapsed primary lung cancer.Methods Forty patients who received 125I seed implantation for relapsed primary lung cancer were retrospectively included.CT examination was performed 3 months after surgery to evaluate the short-term efficacy.Patients were divided into the effective group(complete remission and partial remission)or the ineffective group(stable disease and progressive disease).Patient deaths and survival times were documented through telephone or electronic case inquiry.Factors influencing short-term efficacy and long-term survival were evaluated using logistic and Cox regression analysis,respectively.Results Among the 40 patients,16 cases were effective and 24 were ineffective.Multivariate logistic regression analysis indicated that postoperative dose delivered to 100%gross tumor volume(D100)(OR= 0.944,95%CI:0.898-0.992,P= 0.023)was an independent factor for short-term efficacy.The median duration of follow-up was 12 months.Twenty-five patients died,ten survived,and five were lost to follow-up.Multivariate Cox regression analysis suggested that the longest tumor diameter(HR= 1.310,95%CI:1.010-1.698,P= 0.042)was an independent factor for long-term survival.Conclusion 125I seed implantation has improved the short-and long-term efficacy of treatment for relapsed primary lung cancer.Postoperative D100 is an independent factor influencing short-term efficacy,and longest tumor diameter is an independent factor for long-term survival,in patients receiving 125I seed implantation for relapsed primary lung cancer.
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Constraint-based genome-scale metabolic network models (genome-scale metabolic models, GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric constraints, other constraints such as enzyme availability and thermodynamic feasibility may also limit the cellular phenotype solution space. Recently, extended GEM models considering either enzymatic or thermodynamic constraints have been developed to improve model prediction accuracy. This review summarizes the recent progresses on metabolic models with multiple constraints (MCGEMs). We presented the construction methods and various applications of MCGEMs including the simulation of gene knockout, prediction of biologically feasible pathways and identification of bottleneck steps. By integrating multiple constraints in a consistent modeling framework, MCGEMs can predict the metabolic bottlenecks and key controlling and modification targets for pathway optimization more precisely, and thus may provide more reliable design results to guide metabolic engineering of industrially important microorganisms.
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Genoma , Engenharia Metabólica , Redes e Vias Metabólicas/genética , Modelos Biológicos , TermodinâmicaRESUMO
Objective:To construct breast cancer organoid culture system and conduct histological characterization and preliminary radiobiological characteristics study.Methods:Different molecular types of breast cancer cell lines and patient-derived tumor cells were cultured in vitro to form breast cancer organoids and characterize their tissue structure. In addition, Ki-67, ER, PR and Her2 markers were evaluated by immunohistochemical staining. Breast cancer organoids were irradiated with 4 Gy and 8 Gy. The numbe and diameter changes of breast cancer organoids at 0, 24, 48 and 96 h after irradiation were observed to evaluate the irradiation-induced damage to the organoids. Results:Breast cancer cell lines and patient-derived tissues formed organoid structures at 6 d. HE staining showed the microstructures, and the expression profile of markers was spatially heterogeneous. The expression patterns of markers were similar between patient-derived organoids and original tumor tissues. Irradiation of MCF-7 breast cancer organoids led to growth arrested, and some of the formed organoids collapsed and the proliferating trend gradually recovered from 48 h to 96 h. MDA-MB-231 breast tumor organoids showed radioresistance, growth arrested, but the structures remained intact, the recovery trend was still not observed at 96 h. The tissue-derived organoids from triple-negative patients also showed radiation tolerance. After irradiation, the organoids continued to grow without significant structural changes, whereas the growth trend was significantly smaller than that in the non-irradiated group.Conclusions:Breast cancer organoids formed by in vitro culture of breast cancer cells from different sources and different molecular types have microstructure and heterogeneity, which can reflect the expression of source tissue markers and show different radioresistance. Organoids derived from triple-negative breast cancer are more resistant to irradiation.
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Background Studies on the association between greenness exposure and allergic rhinitis (AR) in children are mostly conducted in developed countries, and the conclusion is not consistent. Objective Using street view data to explore the association between greenness exposure and allergic rhinitis (AR) prevalence in Chinese children. Methods A cross-sectional study was conducted among 40868 children aged 2-17 years in three cities of Northeast China from 2012 to 2013, which consisted of 20886 (51.1%) boys and 19982 (48.9%) girls. The information of AR prevalence was obtained through questionnaire. Based on downloaded street view images from Tencent Maps, a green view index (GVI) of green vegetation (trees and grass) within 800 m and 1000 m buffer of the participants' schools was calculated by using artificial intelligence, and it was used as a surrogate of the greenness exposure. A mixed-effect logistic regression model was used to estimate the odds ratio (OR) of AR prevalence in children for per increase of inter-quartile range (IQR) of GVI. In addition, according to ambient PM2.5 concentration, the participants were divided into a low PM2.5 exposure group (≤56.23 μg·m−3) and a high exposure group (>56.23 μg·m−3) to investigate whether PM2.5 was a modifier on the association between GVI and AR. Results The average age of the subjects was (10.40±3.68) years and 3 963 (9.7%) subjects reported diagnosed AR. Within 800 m buffer, an IQR increase in GVI for trees (IQR=0.031, OR=0.85, 95%CI: 0.81-0.90) and overall greenness (IQR=0.029, OR=0.86, 95%CI: 0.81-0.90) was associated with lower adjusted odds ratio of AR. The interaction between PM2.5 and GVI was statistically significant (P< 0.1), that is, the negative associations of trees and overall greenness with AR were observed only at low PM2.5 exposure levels. The sensitivity analysis results of GVI within 1000 m buffer was consistent with that within 800 m buffer. Conclusion Exposure to green vegetation, especially trees, may be associated with decreased risks of AR in children, and such associations may be more obvious in areas with a low PM2.5 concentration.
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SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin1, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model2 highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.
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Objective:To observed the effects of electroacupuncture frequency on the nerve function and postsynaptic destination-95 (PSD-95), growth associated protein-43 (GAP-43) in brain tissue of rats with cerebral ischemia were observed.Methods:Healthy adult male SD rats were randomly divided into the blank group, sham operation group, model group and 2 Hz, 50 Hz, 100 Hz electroacupuncture groups. MCAO models were prepared in each group, except blank group and sham operation group. After modeling, Qiansanli and Waiguan acupoints were given stimulation with 2 Hz, 50 Hz and 100 Hz respectively in 2 Hz electroacupuncture group, 50 Hz electroacupuncture group and 100 Hz electroacupuncture group, 1 time/d and 20 min/time for 21 consecutive days. All groups were scored by Bederson score on the 1st, 3rd, 7th, 14th and 21th day after operation. The ultrastructure of synapses was observed by transmission electron microscope, and the positive expression of PSD-95 and GAP-43 was detected by immunohistochemistry. Results:After modeling 7, 14 and 21 days, compared with the model group, the Bederson behavioral score (1.70 ± 0.52 vs. 2.40 ± 0.56, 1.20 ± 0.65 vs. 2.30 ± 0.46, 0.70 ± 0.72 vs. 2.00 ± 0.86) in 50 Hz electroacupuncture group significantly decreased ( P<0.01 or P<0.05). The expression of PSD-95 (58.67 ± 1.72, 55.22 ± 2.45, 60.10 ± 2.49 vs. 70.87 ± 2.34) intergral optical density of rats’ cortex in 2 Hz, 50 Hz, 100 Hz electroacupuncture groups significantly decreased ( P<0.01), the expression of GAP-43 in 2 Hz and 50 Hz electroacupuncture groups (58.89 ± 1.28, 64.76 ± 3.94 vs. 53.24 ± 2.58) significantly increased ( P<0.01). Conclusions:Electroacupuncture with different frequency can improve motor nerve disfunction of cerebral ischemia rats, and 50 Hz electroacupuncture group showed the most obvious effect. It can regulate PSD-95 and GAP-43 expressions of ischemic area, lower neural excitatory toxicity, increase neuronal axon regeneration and exert the neural protect function.
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Objective:To analyze the efficacy and safety of radioactive 125I seed implantation in the treatment of unresectable early-stage non-small cell lung cancer (NSCLC), in order to provide data for clinical practice and relevant research. Methods:A retrospective study was conducted on the data of 39 patients with early-stage NSCLC who received CT-guided radioactive 125I seed implantation from Dec 2010 to Dec 2018 in multiple hospitals.The seed implantation process consisted of preoperative planning and design, CT-guided puncture, seed implantation, and postoperative evaluation and dose verification.The efficacy and complications of the treatment were analyzed.The clinical efficacy was evaluated by adopting the Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) and the adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Results:All the patients were 70 years old on average (51-85). The median lesion diameter was 2.7 cm (1.1-6.0 cm), the median seed activity was 0.7 mCi (0.6-0.8 mCi), while the median follow-up duration was 29 months (3-97 months). Meanwhile, the 1-, 3-, and 5-year overall local control rates were 89.5%, 79%, and 79%, respectively, and the 1-, 3-, and 5-year overall survival rates were 100%, 74.8%, and 49.9%, respectively.Local recurrence and distant metastasis were the main causes of failure, accounting for 17.9% (7 cases) each.The incidence of pneumothorax was 56.4% (22 cases), among which nine cases (23.1%) required invasive closed thoracic drainage.Only 1 case of grade-2 radiation pneumonia (2.6%) was observed, with no other adverse reactions such as dermatoses, esophagitis, or myelitis being discovered.As indicated by univariate analysis, the patients with KPS scores of 80-90, pathological type of adenocarcinoma, T stage of T 1-2, and D90>180 Gy exhibited better local control ( χ2=6.202, P<0.05). Meanwhile, high D90 was also associated with a higher survival rate ( χ2=6.907, P<0.05). Conclusions:Radioactive 125I seed implantation is a safe and effective treatment for unresectable early-stage NSCLC.In cases where external beam radiotherapy is not available, radioactive 125I seed implantation can be considered as one of the treatment options.Pneumothorax is the most common complication of radioactive 125I seed implantation, and adenocarcinoma (pathological type) and higher values of D90 are predictors of better local control.
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OBJECTIVE:To establish the method for content determination of 6 components in Fuzheng guben granules ,such as 2,3,5,4′-tetrahydroxystilbene glucoside ,baicalin,icariin,scutellarin,baicalein and wogonin. METHODS :HPLC method was adopted. The determination was performed on Dikma Diamonsil C 18 column with mobile phase consisted of acetonitrile- 0.1% phosphoric acid aqueous solution (gradient elution )at the flow rate of 1.0 mL/min. The detection wavelengths were set at 275 nm (0-8 min),320 nm(8-9 min)and 275 nm(9-33 min). The column temperature was set at 25 ℃,and sample size was 10 μL. With baicalin as reference material ,the relative corr ection factors (fk/s) of other five components were calculated by multi-point correction method and slope correction method ;the retention time difference method was used to locate the chromatographic peaks ; the calculation values obtained by above 2 QAMS were compared with measured values of external standard method. RESULTS : The linear range of 2,3,5,4′-tetrahydroxystilbene glucoside ,baicalin,icariin,scutellarin,baicalein and wogonin were 0.053-2.12, 0.163-6.52,0.059-2.36,0.021 6-0.864,0.03-1.2,0.021-0.84 μg(r>0.999),respectively. RSDs of precision ,stability(12 h)and reproducibility tests were all lower than 3%. Average recoveries were 98.72%-99.82%(RSDs were 0.89%-1.24%,n=9). Using baicalin as reference material ,fk/s of multi-point correction method for 2,3,5,4′-tetrahydroxystilbene glucoside ,icariin,scutellarin, baicalein and wogonin were 1.172,0.528,1.479,1.820 and 2.534,respectively;fk/s of slope correction method were 1.234, 0.550,1.559,1.939,2.664. RSDs of 6 components in 10 batches of Fuzheng guben granules by 3 methods were 0.29%-2.77% (n=10),respectively. Pearson correlation coefficient was not lower than 0.999 9(P<0.001)in measured values between QAMS and external standard method. CONCLUSIONS :QAMS method is established successfully for simultaneous determination of 6 components in Fuzheng guben granules.
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BackgroundAs increasing cases of COVID-19 around world, urgent need for effective COVID-19-specific therapeutic drugs is necessary; therefore, we conducted a pilot randomized-controlled study to evaluate the efficacy of 99mTc-MDP for COVID-19 therapeutic treatment. MethodsA total of 21 mild patients with COVID-19 were enrolled in this pilot RCT from February 2020 through March 2020, and then were assigned, in a 1:1 ratio, into control (11 patients) and 99mTc-MDP group (10 patients). Patients in the control group received routine treatment and patients assigned to the 99mTc-MDP group received a combination of routine treatment and an administration of 99mTc-MDP injection of 5ml/day. Both of the patients in the control and 99mTc-MDP groups were treated for 7 days with the primary end point of CT-based radiological pulmonary changes during 7-day follow-up. FindingsFrom baseline to the day 7, 8 (80%) of 10 mild patients in the 99mTc-MDP group had a significant radiological improvement in lung and a decline in inflammatory infiltration, whereas only 1 (9.1%) of 11 patients in the control group had a radiological improvement in lung. None of the patients in the 99mTc-MDP group had disease progression from mild to severe, as well as an inflammatory cytokine storm, and 2 mild patients (18.2%) in the control group developed severe. During days 7 through 14, the number of patients with radiological improvement in the 99mTc-MDP group remained consistent, and only 1 additional case (22%) in the control group were reported. ConclusionIn this randomized pilot study, 99mTc-MDP had an effective inhibitory effect on the inflammatory disease progression for the therapy of COVID-19, and it can accelerate the absorption of pulmonary inflammation in a short period of time during the process of treatment.
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The main treatment options for cervical cancer include surgery and/or radiotherapy combined with chemotherapy. Radiotherapy consists of external beam radiotherapy and brachytherapy (BT). BT contains high-dose-rate (HDR-BT) and low-dose-rate brachytherapy (LDR-BT). The prognosis of cervical cancer is relatively good. However, some patients experience substantial treatment failures, such as intra-pelvic and/or extra-pelvic recurrences. Recurrent cervical cancer (RCC) has poor prognosis due to lack of effective and safe approach. In 2002, Professor Wang Junjie introduced CT-guidance into the field of LDR-BT, and fully applied 3D printing technology in BT in 2015, which met the requirement of preoperative LDR-BT planning, and significantly improving the precision, quality and efficiency of BT. In 2018, Professor Wang Junjie proposed the concept of stereotactic ablation brachytherapy (SABT). Chinese experts have attempted to treat RCC with BT for nearly two decades and accumulated certain clinical experience. Based on the 3D-printing template (3D-PT) assisted CT-guidance, the standard and consensus of BT for RCC were established, including the indications, dosimetric requirements, technological procedures and radiation protection, etc. At present, there is still a lack of phage Ⅲ clinical and evidence-based medicine for the treatment of RCC with 3D-PT guidance, which requires prospective multi-center, randomized studies to improve the evidence-based level of BT.
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OBJECTIVE: The objective of the study was to evaluate computed tomography (CT)-guided 125I implantation for the treatment of recurrent and malignant pelvic tumors. MATERIALS AND METHODS: Fifteen cases of pelvic malignant tumors were studied. Tumor length/diameter was 4-10 cm (average: 6.8 ± 2.3 cm). In patients with pelvic recurrence or metastasis of malignant tumors, comprehensive treatment, including surgery, chemotherapy, or radiotherapy, was performed alongside CT-guided 125I implantation. The follow-up clinical benefit rate, rate of pain relief, quality of life score, and status of any complications were analyzed. RESULTS: The patients were followed up for 6 months after the operation, and evaluation of lesions revealed complete response (CR) in 3/15 cases, partial response (PR) in 8/15 cases, stable disease in 3/15 cases, and progressive disease in 1/15 cases. The total effective rate (CR + PR) was 73.3% (11/15), and the pain relief rate was 86.6% (13/15). No bleeding, pelvic abscesses, intestinal fistulas, intestinal perforations, or other complications were reported. CONCLUSIONS: When using CT-guided 125I implantation, patients with malignant abdominal tumors undergo a convenient operation, sustain little trauma, and have an improved quality of life.
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Braquiterapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/radioterapia , Radioterapia Guiada por Imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Feminino , Humanos , Aumento da Imagem , Radioisótopos do Iodo/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor/etiologia , Manejo da Dor , Qualidade de Vida , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem/métodos , Recidiva , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Three-dimensional cell culture is a novel type of in vitro culture method.This system can mimic the microenvironment of cell growth in vivo,where cells exhibit similar state and function to that in the in vivo environment.Currently,three-dimensional culture system has been widely applied in tissue engineering and tumor cell biology fields,etc.Radiotherapy is an important treatment of cancer.Radioresistance of tumor cells is the main cause of treatment failure,tumor recurrence and metastasis.Tumor cells can exhibit the resistant characteristics in the three-dimensional culture system,similar to those of tumor cells in vivo.Therefore,three-dimensional culture system can be adopted to investigate the radioresistance and underlying mechanism of tumor cells and identify the key factors regulating the radioresistance of tumor cells,which plays a pivotal role in enhancing the radioresistance and improving the effect of radiotherapy.This article will review recent research progress in the radioresistance and sensitization of tumor cells under three-dimensional culture system,aiming to provide reference for relevant investigations.
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Objective To investigate the effect of apatinib on the migration ability of nasopharyngeal carcinoma NPC cells after X-ray irradiation and involved protein expressions. Methods The migration abilities of human immortalized nasopharyngeal epithelial cells ( NP69) and nasopharyngeal carcinoma cells ( CNE-1, CNE-2 ) treated with different concentrations of apatinib ( 0, 5, 10 and 15 μmol/L) were compared by wound healing assay. The effect of apatinib on the activity of NPC cells was detected by CCK-8 for determining the suitable intervention concentration of apatinib. Then NPC cells were divided into control group, apatinib group (15 μmol/L), X-ray irradiation group and apatinib combined with X-ray irradiation group, and the migration ability of each group was compared by wound healing assay. The expressions of pVEGFR2, pSTAT3, STAT3, MMP-9 and EMT related proteins were detected by western blot. Results Compared with the NP69, the migration abilities of CNE-1 and CNE-2 were significantly enhanced ( t=-5. 759, -16. 578, P<0. 05) . Compared with the control group ( 0 μmol/L) , the migration ability of NPC cells after treatment with apatinib(5, 10 and 15 μmol/L) was significantly decreased in a concentration dependent manner ( t=2. 804-13. 362, P<0. 05) . Compared with the X-ray irradiation group, the wound healing rate of NPC cells in the apatinib combined with X-ray irradiation group was decreased ( t=5. 932, 2. 791, P<0. 05) , indicating that apatinib can significantly inhibit the migration of NPC cells after X-ray irradiation. Western blot assay showed that the expressions of pVEGFR2 and pSTAT3 were significantly decreased in NPC cells treated with apatinib, meanwhile, the expression of MMP-9 protein was significantly decreased, and the EMT-related protein was changed. Conclusions Apatinib inhibits migration of X-ray irradiated NPC cells by inhibiting EMT through down-regulating VEGFR2/STAT3/MMP-9 signaling pathway.
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In the original publication, the funding information was incorrectly published. The correct funding information is provided in this correction. This work is supported by grants from the Projects of International Cooperation and Exchanges Ministry of Science and Technology of China (2013DFG32390) and the National Natural Science Foundation of China (31472059) to X.S. X.S is a recipient of the Young Thousand Talents program (KJ2070000026).
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Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.
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Animais , Camundongos , Polaridade Celular , Imiquimode , Interleucina-23 , Metabolismo , Macrófagos , Metabolismo , Patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Psoríase , Metabolismo , PatologiaRESUMO
Objective To investigate the relationship between multidrug resistance of X-ray irradiated human nasopharyngeal squanous carcinoma cell line CNE1 and platelet endothelial cell adhesion molecule-1 (PECMA-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/Bcl-2 signaling pathway.Methods ①The CNE1 cells were cultured in incubator.Exponentially growing CNE1 cells were exposed to 50 Gy ionizing radiation administered in 25 fractions,2 Gy per fraction,once every two days,and the CNE1/R cells were collected.②CNE1/R cells were cultured for 24 h,and divided into three groups:the control group,experimental group one (CNE1/R cells were processed through 1 ∶ 600 PECAM-1 antibody for 24 h) and experimental group two (CNE1/R cells were processed through 10 μmol/L PI3K inhibitor LY294002 for 24 h).③The half maximal inhibitory concentration (IC50) values of the control group and two experimental groups of CNE1/R cells were detected by methyl thiazolyl tetrazolium (MTT).④The mRNA expressions of PI3K and Bcl-2 in the control group and experimental group one were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).⑤The mRNA expressions of AKT and Bcl-2 in the control group and experimental group two were measured by semi-quantitative RT-PCR.Results ①The IC50 of the control group,experimental group one and two were (2.99 ± 0.02) μg/ml,(1.50 ± 0.03) μg/ml and (1.60 ±0.05)μg/ml,and the difference among the three groups was statiatically signficant (F =4 381.263,P =0.000).The IC50 of the two experimental groups were obviously lower than that of the control group (t =116.885,P =0.000;t =73.006,P =0.000).②The semi-quantitative values of PI3K in the control group and experimental group one were 1.66 ±0.01 and 0.90 ±0.05 (t =50.394,P =0.000),and the semi-quantitative values of Bcl-2 were 1.66 ±0.02 and 0.71 0.05 (t =183.165,P =0.000),and the differences were statistically significant.③The semi-quantitative values of AKT of control group and experimental group two were 1.53 ± 0.01 and 0.72 ± 0.01 (t =135.281,P =0.000),and the semi-quantitative values of Bel-2 were 1.66 ± 0.02 and 0.63 ± 0.02 (t =128.814,P =0.000),and the differences were statistically significant.Conclusion PECAM-1 induced multidmg resistance of human nasopharyngeal squamous cell carcinoma CNE1 cells may be related to the activity of Bcl-2 through the signal pathway of PI3K/AKT.
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Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.