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Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
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OBJECTIVE@#To explore the mechanism of ursolic acid in treating sepsis using myeloid differentiation protein-2 (MD-2) as the research carrier.@*METHODS@#The affinity of ursolic acid and MD-2 was determined by biofilm interferometry technique, and the bonding mode between ursolic acid and MD-2 was tested with the aid of molecular docking technique. Raw 264.7 cells were cultured in RPMI 1640 medium and subcultured was conducted when the cell density reached 80%-90%. The second-generation cells were used for in the experiment. The effects of 8, 40 and 100 mg/L ursolic acid on cell viability were assessed by methyl thiazolyl tetrazolium (MTT) method. Cells were divided into blank group, lipopolysaccharide (LPS) group (LPS 100 μg/L) and ursolic acid group (100 μg/L LPS treatment after addition of 8, 40 or 100 mg/L ursolic acid). The effect of ursolic acid on the release of cytokines nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) were evaluated by enzyme-linked immunosorbent assay (ELISA). The influence of ursolic acid on the mRNA expressions of TNF-α, IL-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). The implication of ursolic acid on the protein expressions of LPS-Toll-like receptor 4 (TLR4)/MD-2-nuclear factor-κB (NF-κB) pathway were tested by Western blotting.@*RESULTS@#Ursolic acid could bind to the hydrophobic cavity of MD-2 through hydrophobic bond with the amino acid residues of the protein. Therefore, ursolic acid showed high affinity with MD-2 [dissociation constant (KD) = 1.43×10-4]. The cell viability were decreased slightly, with the concentration of ursolic acid increasing, and the cell viability of 8, 40 and 100 mg/L ursolic acid were 96.01%, 94.32% and 92.12%, respectively, and there was no significant difference compared with the blank group (100%). Compared with the blank group, the cytokine level of the LPS group was significantly increased. The level of cytokines were significantly reduced by the treatment of 8, 40 and 100 mg/L ursolic acid, and the higher the concentration, the more obvious effect [compared between 100 mg/L ursolic acid group and LPS group: IL-1β (μmol/L): 38.018±0.675 vs. 111.324±1.262, IL-6 (μmol/L): 35.052±1.664 vs. 115.255±5.392, TNF-α (μmol/L): 39.078±2.741 vs. 119.035±4.269, NO (μmol/L): 40.885±2.372 vs. 123.405±1.291, all P < 0.01]. Compared with the blank group, the mRNA expressions of TNF-α, IL-6, IL-1β, iNOS and COX-2 in the LPS group were significantly increased, and the protein expressions of MD-2, myeloid differentiation factor 88 (MyD88), phosphorylation NF-κB p65 (p-NF-κB p65) and iNOS in the LPS-TLR4/MD-2-NF-κB pathway were significantly up-regulated. Compared with the LPS group, the mRNA expressions of TNF-α, IL-6, IL-1β, iNOS and COX-2 were significantly reduced by the treatment of 100 mg/L ursolic acid bound with MD-2 protein [TNF-α (2-ΔΔCt): 4.659±0.821 vs. 8.652±0.787, IL-6 (2-ΔΔCt): 4.296±0.802 vs. 11.132±1.615, IL-1β (2-ΔΔCt): 4.482±1.224 vs. 11.758±1.324, iNOS (2-ΔΔCt): 1.785±0.529 vs. 4.249±0.811, COX-2 (2-ΔΔCt): 5.591±1.586 vs. 16.953±1.651, all P < 0.01], and the proteins expressions of MD-2, MyD88, p-NF-κB p65 and iNOS in the LPS-TLR4/MD-2-NF-κB pathway were significantly down-regulated (MD-2/β-actin: 0.191±0.038 vs. 0.704±0.049, MyD88/β-actin: 0.470±0.042 vs. 0.875±0.058, p-NF-κB p65/β-actin: 0.178±0.012 vs. 0.571±0.012, iNOS/β-actin: 0.247±0.035 vs. 0.549±0.033, all P < 0.01). However, there was no difference in protein expression of NF-κB p65 among the three groups.@*CONCLUSIONS@#Ursolic acid inhibits the release and expression of cytokines and mediators and regulates LPS-TLR4/MD-2-NF-κB signaling pathway by blocking MD-2 protein, and thus plays an anti-sepsis role.
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Humans , Tumor Necrosis Factor-alpha , Actins , Cyclooxygenase 2 , Interleukin-6 , Lipopolysaccharides , Lymphocyte Antigen 96 , Molecular Docking Simulation , Myeloid Differentiation Factor 88 , NF-kappa B , Toll-Like Receptor 4 , Sepsis , Cytokines , Cell Differentiation , RNA, MessengerABSTRACT
Objective:To explore the diagnostic value of quantitative 99Tc m-hydrazinonicotinamide(HYNIC)-prostate specific membrane antigen (PSMA) SPECT/CT in patients with prostate cancer. Methods:From November 2018 to March 2021, the data of 56 patients ((69.8±8.0) years) with clinically suspected prostate cancer, who had elevated radioactive uptake in prostate on 99Tc m-HYNIC-PSMA SPECT/CT images in Henan Provincial People′s Hospital, were retrospectively analyzed. According to the pathological results, patients were divided into prostate cancer group ( n=45) and non-prostate cancer group ( n=11). The xSPECT-QUANT software was used to quantitatively analyze the high uptake area of the prostate, and SUV max was measured. The independent-sample t test, Mann-Whitney U test, ROC curve and Spearman correlation analysis were used for data analysis. Results:The prostate cancer group had higher SUV max than non-prostate cancer group (10.79±5.96 vs 3.60±1.27; t=7.43, P<0.001). When SUV max≥6.46, the AUC of prostate cancer was 0.887, with the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 73.3%(33/45), 11/11, 100%(33/33), 47.8%(11/23), 78.6%(44/56), respectively. The SUV max of prostate cancer group was positively correlated with Gleason score ( rs=0.632, P<0.001). The SUV max of 29 patients with Gleason score≥8 was higher than that of 16 patients with Gleason score≤7 ( z=-3.89, P<0.001). There was no statistical difference in PSA level between patients with Gleason score≤ 7 and patients with non-prostate cancer ( z=-1.63, P=0.110), but the SUV max was significantly different ( z=-2.22, P=0.026). The SUV max of 23 patients with metastases was higher than that of 22 patients without metastasis (12.99±5.85 vs 8.50±5.28; t=2.69, P=0.010). ROC analysis showed that the AUC was 0.709; with SUV max≥13.02 as the threshold, the sensitivity for diagnosing prostate cancer metastases was 56.5%(13/23), the specificity was 86.4%(19/22), and the accuracy was 71.1%(32/45). Conclusions:The 99Tc m-HYNIC-PSMA SPECT/CT quantitative analysis is feasible in patients with prostate cancer. SUV max of 99Tc m-HYNIC-PSMA can be used in the diagnosis of prostate cancer, assessment of the malignancy and prediction of metastasis.
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Objective:To evaluate the clinical application value of MR amide proton transfer weighted imaging (APTWI) in predicting the pathological grade of brainstem glioma (BSG).Methods:The data of 41 BSG patients in Beijing Tiantan Hospital, Capital Medical University from August 2019 to June 2020 who underwent both MRI and APTWI 2 weeks before surgery and had pathological grading results were retrospectively analyzed. According to the pathological results, 41 patients were classified into high-grade BSG (20 patients) and low-grade BSG (21 patients). Combined with conventional MR images, the signal intensity (%) of amide proton transfer (APT) in the parenchymal area of the tumor was obtained on APTWI images. χ 2 test or independent sample t-test was used to analyze the differences in gender distribution, age and APT signal intensity between patients with high and low grade BSG. Receiver operating characteristic (ROC) curve was drawn to predict the efficacy of APT signal intensity in the differential diagnosis of high and low grade BSG, and Youden index was calculated to obtain the optimal diagnostic threshold; the predictive ability of APT signal intensity was analyzed in combination with Hosmer-Lemeshow goodness of fit test. Results:There was no significant difference in age [(23±18) years, (20±17) years, t=0.97, P=0.340] and gender distribution (9/11, 9/12 for males/females, χ 2=0.02, P=0.890) between high-grade and low-grade BSG patients. The APT signal intensity of high-grade BSG [(3.9±0.9)%] was significantly higher than that of low-grade BSG [(2.8±0.9)%], and the difference had statistical significance ( t=4.16, P<0.001). The area under the ROC curve of APT signal intensity to distinguish high-grade and low grade BSG was 0.836, and with 2.85% as the optimal diagnostic threshold of APT signal intensity, its sensitivity for the diagnosis of high-grade BSG was 90.0% and specificity was 71.4%. The Hosmer-Lemeshow test showed that APTWI had a good predictive ability for BSG grade (χ 2=13.33, P=0.101). Conclusion:APTWI can be applied in distinguishing high grade BSG from low grade BSG, and has clinical value in predicting glioma grading.
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Objective:To explore the clinicopathological characteristics and prognosis of pancreatic gastrointestinal interstitial tumors(pGISTs).Methods:Three cases of pGISTs diagnosed in the Affiliated Tumor Hospital of Guangxi Medical University from August 2015 to October 2019 were analyzed retrospectively. Relevant literatures at home and abroad were searched and reviewed through PubMed, China knowledge Network, Wanfang and VIP databases. The sex, age, tumor size, tumor location, cystic or solid tumor, mode of treatment, mitosis, gene mutation, survival status and survival time were recorded, and the correlation between tumor cystic-solid characteristics and clinicopathological parameters was analyzed. Kaplan-Meier′s method was used to calculate the overall survival (OS) rate and disease-free survival (DFS) rate. Univariate and multivariate Cox regression models were used to analyze the independent risk factors affecting the prognosis of pGISTs.Results:In this group, 3 cases were combined with 71 cases reported in the literature, and a total of 74 cases of pGISTs were included. Among them, 36 cases were male and 38 were female, the age of onset was 55(19-84) years, and the diameter of the tumor was 8 cm(2-35 cm). The tumor location of 71 patients was recorded by literature; 30 cases (42.3%) were located in the head of the pancreas. The solid-cystic characteristics of tumor in 63 patients were recorded by literature, and 33 cases (52.4%) were solid. The mode of treatment of 74 patients was recorded, and 60 cases (81.1%) underwent radical resection. The mitosis figures of 59 patients were recorded, and 33 cases (55.9%) were <5/50 high power field of vision (HPF). The gene mutation of 14 patients was recorded, and 11 cases (78.6%) were c-kit exon gene mutation. Correlation analysis showed that the cystic-solid characteristics of the tumor were significantly correlated with tumor location, tumor diameter and mitosis figures, but not with age, sex, histological type, Ki-67 index and modification National Institutes of Health(mNIH) classification. The 5-year OS rate of 51 patients after radical resection was 88.8%, and the 5-year DFS rate was 60.3%. The 1-year OS rate of patients receiving palliative treatment was 51.9%, and the 1-year fatality rate was 33.3%. Univariate Cox regression analysis showed that male ( P=0.083), mitosis figures >5/50 HPF ( P=0.008)and CD 34 negative ( P=0.055)were risk factors for postoperative recurrence of pGISTs, while multivariate Cox regression analysis showed that mitosis figures >5/50 HPF ( P=0.023)was an independent risk factor for the prognosis of pGISTs. Kaplan-Meier survival analysis showed that patients with mitosis figures ≤5/50 HPF had a higher survival rate ( P=0.0003), but there was no significant difference on prognosis between patients with 10/50 HPF and >10/50 HPF( P=0.3075). Conclusions:pGISTs usually occured in the head of pancreas, and the tumor volume was usually found to be large. The main treatment was radical operation, and the main mutation type was exon mutation of c-kit gene. Nuclear fission image figures >5/50HPF was an independent risk factor for postoperative recurrence.
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ObjectiveTo determine the risk factors associated with colorectal adenoma among the residents in Nanchang city， and provide scientific evidence for primary preventive measures against colorectal cancer. MethodsA matched case-control study was conducted. A total of 155 patients newly diagnosed with colorectal adenomas during 2018‒2019 were selected as cases， and 155 healthy persons attending the screening as controls. Both the case group and control group completed the questionnaires on the risk factors. Conditional logistic regression analysis was performed using SPSS 25.0. ResultsAge， gender， and educational level were used for match between case group and control group. Conditional multivariate logistic regression analysis showed that salted and dried food intake（OR=5.634， 95%CI：1.308‒24.256）， smoking（OR=3.266， 95%CI：1.419‒7.518）， passive smoking（OR=3.125，95%CI：1.415‒6.898）， and hyperlipidemia（OR=3.975， 95%CI：1.643‒9.618）were associated with higher risk of colorectal adenoma. In contrast， coarse grain intake ≥500 g/week（OR=0.377， 95%CI：0.177‒0.805） was a protective factor. ConclusionColorectal adenoma may be caused by multiple risk factors， particularly salted and dried food intake， smoking， passive smoking and hyperlipidemia. It warrants specific intervention to reduce the risk of colorectal adenoma.
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OBJECTIVE To study in vitro inhibitory effects of realgar nanoparticles on breast cancer stem cells. METHODS Human breast cancer MCF- 7 parent cells were selected as subjects and cultured by serum-free culture to obtain breast cancer stem cells. Using adriamycin （1 mg/L）as positive control ，same concentration of water-processed realgar as reference ，the effects of realgar nanoparticles on the proliferation of MCF- 7 parent cells and stem cells were detected by CCK- 8 method. The effects of realgar nanoparticles on the formation of mammosphere ，the ability of differentiation ，migration and invasion ，the proportion of CD44+/CD24－ subgroup in breast cancer stem cells were detected by mammosphere formation and differentiation experiment ， scratch experiment ，Transwell invasion experiment and flow cytometry. Western blot assay was used to detect the expression of proteins related to epithelial mesenchymal transformation pathway （E-cadherin and vimentin ） in breast cancer stem cells. RESULTS The survival rates of MCF- 7 parent cells and stem cells （except for breast cancer stem cells in both 1 mg/mL groups ）in 1，5，10，40，60，80 mg/L groups of water-processed realgar and realgar nanoparticles were significantly lower than blank control group（P＜0.01）. The number of mammosphere （＞20 stem cells ）in 1，2.5，5，10 mg/L groups of water-processed realgar and realgar nanoparticles was significantly lower than blank control group （P＜0.01）；the volume of mammosphere decreased and the differentiated adherent cells decreased ；the healing rate of wound ，relative invasion rate （except for water-processed realgar 1 mg/L group）and the proportion of CD 44+/CD24－ subgroup were significantly lower than blank control group （P＜0.01）. The expressions of E-cadherin in 2.5，10 mg/L groups of water-processed realgar and realgar nanoparticles was significantly higher than blank control group ，and the expressions of vimentin was significantly lower than those in blank control group （P＜0.01）. The above effects of realgar nanoparticles were generally better than those of water-processed realgar with the same mass concentration （P＜ 0.01）. CONCLUSIONS Compared with water-processed realgar with the same mass concentration ，realgar nanoparti cles can significantly inhibit the proliferation of breast cancer stem cells， the formulation and differential ability of mammo- sphere，and reduce the proportion of CD 44+/CD24－ subgroup. The effect may be associated with the inhibition of migration and invasion of breast cancer stem cells by inhibiting the expression of proteins related to epithelial mesenchymal transformation pathway.
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Primary liver cancer is one of the most common malignant tumors in the world, and hepatocellular carcinoma accounts for the majority of liver cancer. Hepatectomy is one of the most important treatment methods, but the high postoperative recurrence rate is the leading cause of treatment failure, which seriously reduces the long-term survival rate and reduces quality of life. Therefore, preventing the recurrence of liver cancer is an important part of treatment. At present, there is no standard program for the treatment of hepatocellular carcinoma to prevent recurrence after surgery, most of the treatment programs include transarterial chemoembolization, antiviral therapy, traditional Chinese medicine treatment, targeted therapy, immunity therapy, etc., which has certain clinical significance in preventing recurrence. This paper reviewed the research progress on preventing recurrence of hepatocellular carcinoma after surgery, which may provide guidance for the clinical study.
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Objective:To assess the value of the ROX index in evaluating the efficacy of high-flow nasal cannula oxygen therapy (HFNC) in patients with coronavirus infected disease (COVID-19).Methods:This is a retrospective study. The included patients were diagnosed as COVID-19 in the intensive care unit (ICU) of the Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from February 15, 2020 to March 15, 2020. All the patients were treated by HFNC. According to whether the patient subsequently received non-invasive positive pressure ventilation or invasive positive pressure ventilation, patients were divided into the HFNC success group and the HFNC failure group. Parameters in the two groups such as basic characteristics, lactic acid, number of chest radiographs, APACHE II, lymphocyte count, baseline respiratory rate, baseline percutaneous oxygen saturation, baseline PaO 2/FiO 2, baseline ROX index, and ROX index after 2, 6 and 12 h HFNC treatment were analyzed with t test, Chi-square test or rank sum test. Results:A total of 57 cases were included in this study. There were no significant differences in sex, age, comorbidities, lactic acid, quadrants of chest radiograph lung infection, APACHE II, lymphocyte count, and baseline respiratory frequency, transcutaneous oxygen saturation, oxygenation index, and ROX index between the HFNC success group and the HFNC faliure group ( P>0.05). Logistic regression analysis showed that ROX index after 2 h HFNC treatment ( OR=0.069), ROX index after 6 h HFNC treatment ( OR=0.194) and ROX index after 12 h HFNC treatment ( OR=0.036) were all protective factors for the therapeutic effect of HFNC treatment in COVID-19 patients. ROC curve showed that there were significant differences in ROX index after 2 h HFNC treatment, ROX index after 6 h HFNC treatment, and ROX index after 12 h HFNC treatment ( P<0.05). In the evaluation index, the area under the ROC curve of the ROX index after 2 h HFNC treatment was 0.838, the sensitivity was 64.5%, and the specificity was 100%. After 6 h HFNC treatment, the area under the ROX index ROC curve was 0.762, the sensitivity was 64.5%, and the specificity was 92.3%. After 12 h HFNC treatment, the ROX index ROC curve area was 0.866, the sensitivity was 67.7%, and the specificity was 100%. Conclusions:The ROX index can be used to evaluate the efficacy of HFNC in COVID-19 patients in a timely, simple and real-time manner.
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Objective:To construct a comprehensive, systematic and quantifiable quality evaluation index system for blood purification care in ICU.Methods:The contents of the evaluation index system for blood purification care in ICU were determined by reviewing the literature, discussion of the research group and two rounds of Delphi expert consultation.Results:The response rate of the two rounds of experts was 100%. The authoritative coefficients of the two rounds of experts were 0.908 and 0.965 respectively. The coordination coefficient of the indicators of the second round of consultation results was 0.210-0.292, P<0.05 or 0.01. The quality evaluation index system for blood purification care included 3 first-class indicators, 16 second-class indicators, and 56 third-class indicators. Conclusions:The enthusiasm, authority, concentration of opinions and degree of coordination of the consulting experts are relatively high. The constructed evaluation system for the quality of blood purification care indicators can be used for reference in the implementation, training and quality control.
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OBJECTIVE：To prepare cell penetrating peptide PFV-modified paclitaxel （PTX）/artesunate（ART）co-loaded targeting micelles ，and to investigate in vitro anti-tumor activity. METHODS ：According to optimal technology ，PFV-modified PTX/ ART co-loaded targeting micelles were prepared by membrane hydration method ，and were characterized. Using blank micelle as blank control ，sulforhodamine B （SRB）method was used to evaluate the toxicity of PTX micelles ，ART micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to human gastric cancer BGC- 823 cells. The coumarin was used as fluorescent probe replacing PTX to prepare corresponding micelles. Then ，the uptake of BGC- 823 cells to corresponding micelles and targeting effect were observed and determined by flow cytometry and fluorescence microscope. The effects of PTX micelles ， ART micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles on the invasion of BGC- 823 cells were investigated by Transwell chamber method. RESULTS ：Average particle size of PFV-modified PTX/ART co-loaded targeting micelles was （51.30±3.95）nm；PDI was 0.19±0.01，and Zeta potential was （0.21±0.02）mV. The encapsulation efficiency of PTX and ART were higher than 90％. The shape of micelles were spherical. The blank micelles had no obvious toxicity to BGC-823 cells. The IC 50 value of PTX micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to BGC-823 cells were （3.09±0.22），（1.93±0.24），（1.11±0.15）μmol/L，respectively. The distribution amount of different micelles in BGC- 823 cell nucleus in the descending order were PFV-modified coumarin/ART micelles ＞coumarin/ART micelles ＞coumarin micelles＞blank control. The order of inhibitory effect was PFV-modified PTX/ART co-loaded targeting micelles ＞PTX/ART micelles＞ART micelles ＞PTX micelles ＞blank control. CONCLUSIONS： Prepared PFV-modified PTX/ART No.81874347） co-loaded targeting micelles are in line with the quality of 1915286446@qq.com Chinese Pharmacopoeia . It shows strong cytotoxicity to BGC-823 cells，can improve the drug targeting and the cell uptake，and inhibit the inv asion and metastasis of BGC- 823 cells.
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With the rapid development of biomedicine and molecular imaging, multimodal and multiscale imaging have gradually become one of the mainstreams in biomedical imaging. It can provide one or multiple imaging contrast including optical, ultrasonic, photoacoustic, magnetic and radionuclide characteristics, and create multiscale images of living organism ranging from single molecules, cells, tissues and living animals. Therefore, multifunctional contrast agents for multimodal and multiscale imaging have been designed and developed. Lanthanide-doping upconversion nanoparticles (UCNPs) are a novel type of phosphor that can convert low-energy near-infrared photons into a high-energy one, which are located in the ultraviolet, visible or near-infrared region. UCNPs provide a new platform for the development of multimodal contrast agents and have been widely used in the field of multimodal imaging. In this review, recent progress of lanthanide-doping UCNPs in multimodal and multiscale imaging is summarized.
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Objective:To investigate the feasibility and accuracy of inserting two pedicle screws through different trajectories in the same pedicle.Methods:3D image data of 100 adults lumbar spine in the database of radiology department from March 2019 to October 2019 were randomly selected. The cancellous bone width and height of pedicles were measured by using Mimics software. The diameters of pedicle screws and revision screws were chosen according to the width of pedicles. A revision screw was implanted into the same vertebral pedicle after inserting a traditional pedicle screw. The successful rates were analyzed. The head inclination angles and outer inclination angles were measured.Results:1) Pedicle morphology: the height of L 1-L 5 pedicle cancellous bone were 10.94±2.22 mm, 9.76±1.82 mm, 9.47±1.77 mm, 8.71±1.52 mm, and 8.66±1.62 mm respectively, showing a trend of gradually decreasing. The width of L 1-L 5 pedicle cancellous bone were 5.01±1.61 mm, 5.48±1.69 mm, 6.95±1.79 mm, 8.58±1.85 mm, and 11.72±2.25 mm respectively, showing a trend of gradually increasing. 2) The successful rates of dual pedicle screws fixation: 57.2% dual pedicle screws fixation were successfully planned in 500 pedicles of 100 people. The successful rates of L 1-L 5 were 100%, 93.2%, 79.8%, 27.6%, and 11.0% respectively, showing a trend of gradually increasing. As the width of pedicles increased, the successful rates gradually decreased. (3) The angle of revision screws: the head inclination angles of L 1-L 4 revision screws were 9.73°±3.96°, 9.57°±4.58°, 9.13°±4.11°, and 6.10°±3.00° respectively, showing a decreasing trend; the outer inclination angles were 9.57°±3.85°, 8.76°±4.83°, 6.61°±4.93°, and 5.03°±5.80° respectively, showing a decreasing trend. The head inclination angle of L 5 revision screw was 28.42°±6.06° and the outer inclination angle was 150.58°±2.08°. Conclusion:CBW is related to the successful rate of dual trajectory pedicle screws fixation. Measurement of CBW is of great significance for the feasibility and accuracy of double-channel pedicle screws fixation before operation. The digital simulation of pedicle screw fixation provides reference for the clinical application of double-channel pedicle screws fixation.
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OBJECTIVE@#To establish a clinical prediction model of the mid-term fatality risk after radical resection in patients with primary hepatocellular carcinoma (HCC) based on the albumin-bilirubin (ALBI) grade and to assess its prediction value.@*METHODS@#Clinical data of 533 patients who received HCC radical resection in Jinhua Hospital of Zhejiang University, Jinhua People's Hospital, Jinhua Hospital of Traditional Chinese Medicine and Jinhua Guangfu Hospital from January 2010 to August 2016 were retrospectively reviewed. In the training group ( =407), Cox model was used to screen the clinical risk factors of postoperative death, and a predictive model based on ALBI grade was established and then examined in the validation group ( =126). The value of the prediction model was assessed by ROC curve and calibration curve; the prediction results of the model were visualized by the nomogram for the convenience of clinical use.@*RESULTS@#Cox model showed that ALT ≥ 80 U/L, tumor maximum diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 were independent risk factors for the prognosis of patients with HCC radical resection. The prognosis index (PI) was 0.550×ALT+0.512×ALBI grade+0.872×maximum tumor diameter+1.377×portal vein tumor thrombus. The AUCs for predicting the risk of death in 12, 36 and 60 months were 0.872, 0.814 and 0.810, respectively (all < 0.01), and the goodness of fit ( ) of the established model were 0.953, 0.976 and 0.994. AUC of the established model for predicting risk of death in 36 months after resection was 0.814, which was higher than those of ALBI (AUC=0.683), BCLC (AUC=0.713), CLIP (AUC=0.689), Child-Pugh (AUC=0.645), TNM (AUC=0.612) ( < 0.05 or < 0.01).@*CONCLUSIONS@#ALT ≥ 80 U/L, maximum tumor diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 are independent risk factors of patients after HCC resection, and ALBI grade-based prediction model is satisfactory in prediction of mid-term death risk of the patients.
Subject(s)
Humans , Albumins , Bilirubin , Carcinoma, Hepatocellular , Liver Neoplasms , Prognosis , Retrospective StudiesABSTRACT
Objective@#To assess the effect of viral macrophage inflammatory protein (vMIP) -Ⅱ on the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) , and to explore the mechanisms.@*Methods@#A recombinant plasmid pEGFP-N3-K4 (vMIP-Ⅱ plasmid group) and an empty plasmid pEGFP-N3 (empty plasmid group) were separately transfected into 293T cells, and quantitative PCR and Western blot analysis were performed to evaluate the effect of transfection with vMIP-Ⅱ gene on the APOBEC3G expression in 293T cells. Some 293T cells in the empty plasmid group and vMIP-Ⅱ plasmid group were treated with 1 000 IU/ml interferon (IFN) -α for 36 hours, and then Western blot analysis was conducted to determine the APOBEC3G expression in the empty plasmid group and vMIP-Ⅱ plasmid group with or without IFN-α treatment. Some 293T cells transfected with vMIP-Ⅱ plasmids were treated with 75 μmol/L AG490 (a JAK/STAT signaling pathway inhibitor) and 20 μmol/L U0126 (an ERK signaling pathway inhibitor) separately; after 24 hours, total protein was extracted from 293T cells, and Western blot analysis was conducted to determine the expression of APOBEC3G. A recombinant plasmid containing APOBEC3G promoter was constructed by using a luciferase reporter gene, and the promoter fragment included the full-length promoter sequence (POS) of APOBEC3G, sequences with the lengths of 1 560, 960, 720, 480, 420, 360, 330 and 240 bp, and the regulatory element-free region (NEG) of APOBEC3G, separately. Some 293T cells were co-transfected with the recombinant plasmid carrying luciferase reporter gene and vMIP-Ⅱ plasmid (experimental group), or the recombinant plasmid and empty plasmid (control group). Subsequently, the activity of the APOBEC3G promoter was evaluated, and the key promoter region through which the transcriptional activity of APOBEC3G was regulated by vMIP-Ⅱ was analyzed. Statistical analysis was carried out by using t test, one-way analysis of variance and least significant difference (LSD) -t test.@*Results@#The mRNA and protein expression of APOBEC3G was significantly higher in the vMIP-Ⅱ plasmid group (2.500 ± 0.013, 1.472 ± 0.013 respectively) than in the control group (1, 0.364 ± 0.030 respectively; t = 6.22, 6.54 respectively, both P < 0.05) . The APOBEC3G expression significantly differed among the empty plasmid group, vMIP-Ⅱ plasmid group, empty plasmid + IFN-α group and vMIP-Ⅱ plasmid + IFN-α group (1, 2.030 ± 0.108, 2.700 ± 0.081 and 2.600 ± 0.099 respectively; F = 67.026, P < 0.001) , but there was no significant difference between the vMIP-Ⅱ plasmid group and empty plasmid + IFN-α group (t = 3.46, P > 0.05) . The APOBEC3G expression also significantly differed among the vMIP-Ⅱ plasmid group, vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱ plasmid + U0126 group (0.617 ± 0.025, 0.179 ± 0.061, 0.359 ± 0.012 respectively; F = 70.019, P < 0.001) , and was significantly lower in the vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱ plasmid + U0126 group than in the vMIP-Ⅱ plasmid group (t = 9.66, 11.836 respectively, both P < 0.01) . Luciferase activity assay showed that the promoter activity significantly differed among the vMIP-Ⅱ plasmid groups transfected with POS, 1 560-, 960-, 720-, 480-, 420-, 360-, 330-, 240-bp or NEG sequences (F = 81.092, P < 0.001) , and the APOBEC3G promoter activity decreased greatly from the 720-bp group to 480-bp group.@*Conclusion@#vMIP-Ⅱ upregulates the expression of APOBEC3G, likely through the JAK/STAT signaling pathway or the key promoter region regulating the transcriptional activity of APOBEC3G.
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Objective@#To investigate the effect of NACHT-LRR-PYD- containing proteins 3 (NLRP3) mediated pyroptosis in myocardial cells undergoing hypoxia/deoxygenation (H/R) injury.@*Methods@#In order to observe whether H/R-treatment could cause pyroptosis, H9c2 cells were divided into 2 groups randomly using the lottery method: control group(without H/R-treatment) and H/R group (in which the H9c2 cells were underwent H/R-treatment). In order to clarify the role of pyroptosis in H/R-injury, H9c2 cells were divided into 4 groups randomly using the lottery method: control group(in which the H9c2 cells were cultivated with normal medium); YVAD group(in which the H9c2 cells were pretreated with z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-YVAD-FMK) 20 μm for 4 hours, then replaced with normal medium); H/R group(H9c2 cells underwent H/R-treatment); YVAD+H/R group (in which the H9c2 cells were pretreated with 20 μm Z-YVAD-FMK for 4 hours before H/R-treatment). To determine whether H/R-induced cell pyroptosis is associated with NLRP3, H9c2 cells were divided into 4 groups randomly using the lottery method: control group (in which cells were transfected with a control nonspecific siRNA); si-NLRP3 group (in which cells were transfected with NLRP3-targeting siRNA); H/R group(in which cells were transfected with a control nonspecific siRNA before H/R-treatment); si-NLRP3+H/R group(in which the H9c2 cells were transfected with NLRP3-targeting siRNA before H/R-treatment). Pore formation on cell membrane was detected by propidium iodide (PI) staining. Cell viability was detected by CCK8 reagent. The protein expression of Caspase-1, interleukin-1β (IL-1β) and NLRP3 was detected by Western blot.@*Results@#(1) The positive rate of PI staining ((26.46±5.15)% vs. (1.69±0.73)%,P<0.01), expression of NLRP3 (0.57±0.16 vs. 0.23±0.06,P<0.01), expression of Caspase-1 (1.07±0.13 vs. 0.37±0.08,P<0.01), and expression of IL-1β (0.38±0.08 vs. 0.16±0.05,P<0.01) were significantly higher in H/R group than in control group. (2)The cell vitality was significantly higher in YVAD+H/R group than in H/R group ((87.31±9.05)% vs. (73.30±7.19)%, P<0.05).The positive rate of PI staining was significantly decreased in YVAD+H/R group than in H/R group ((18.12±4.36)% vs. (26.45±4.60)%, P<0.05). The expression of Caspase-1 (0.72±0.12 vs. 1.07±0.15, P<0.05) and IL-1β(0.29±0.07 vs. 0.39±0.06, P<0.05) were significantly lower in YVAD+H/R group than in H/R group. (3) The cell vitality was significantly increased in si-NLRP3+H/R group than in H/R group ((85.46±7.71)% vs. (72.41±5.53)%, P<0.05). The positive rate of PI staining was significantly lower in si-NLRP3+H/R group than in H/R group ((18.22±4.20)% vs. (26.73±3.26)%, P<0.05). The expression of Caspase-1(0.87±0.07 vs. 1.15±0.15, P<0.05) and IL-1β(0.41±0.07 vs. 0.58±0.10, P<0.05) were significantly decreased in si-NLRP3+H/R group than in H/R group.@*Conclusion@#NLRP3 mediated pyroptosis is involved in H/R injury of myocardial cells.
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OBJECTIVE： To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis， and to provide reference for clinical application and R&D of the decoction. METHODS： Based on TCM integrative pharmacology platform （TCMIP）， chemical component analysis of Xiaochaihu decoction， disease target prediction， gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of “TCM-chemical components-core targets-key pathways” was established， and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS： A total of 224 predicted chemical ingredients of Xiaochaihu decoction （including saikoside， ginsenoside， glycyrrhizin， etc.） interacted with 118 key targets about sepsis， including PF4， MYD88， TLR4， CD14， NOS3， etc. Its anti-sepsis mechanism involved nervous system， endocrine system， immune response and energy metabolism， etc. CONCLUSIONS： Based on “neuronal- endocrine-immune-metabolism”， Xiaochaihu decoction achieved its role in regulating sepsis by multi-level， multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis， and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action．
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Objective To assess the effect of viral macrophage inflammatory protein (vMIP)-Ⅱ on the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G),and to explore the mechanisms.Methods A recombinant plasmid pEGFP-N3-K4 (vMIP-Ⅱ plasmid group) and an empty plasmid pEGFP-N3 (empty plasmid group) were separately transfected into 293T cells,and quantitative PCR and Western blot analysis were performed to evaluate the effect of transfection with vMIP-]Ⅱ gene on the APOBEC3G expression in 293T cells.Some 293T cells in the empty plasmid group and vMIP-Ⅱ plasmid group were treated with 1 000 IU/ml interferon (IFN)-α for 36 hours,and then Western blot analysis was conducted to determine the APOBEC3G expression in the empty plasmid group and vMIP-Ⅱ plasmid group with or without IFN-α treatment.Some 293T cells transfected with vMIP-Ⅱplasmids were treated with 75 μ mol/L AG490 (a JAK/STAT signaling pathway inhibitor) and 20 μ mol/L U0126 (an ERK signaling pathway inhibitor) separately;after 24 hours,total protein was extracted from 293T cells,and Western blot analysis was conducted to determine the expression of APOBEC3G.A recombinant plasmid containing APOBEC3G promoter was constructed by using a luciferase reporter gene,and the promoter fragment included the full-length promoter sequence (POS) of APOBEC3G,sequences with the lengths of 1 560,960,720,480,420,360,330 and 240 bp,and the regulatory element-free region (NEG) of APOBEC3G,separately.Some 293T cells were co-transfected with the recombinant plasmid carrying luciferase reporter gene and vMIP-Ⅱ plasmid (experimental group),or the recombinant plasmid and empty plasmid (control group).Subsequently,the activity of the APOBEC3G promoter was evaluated,and the key promoter region through which the transcriptional activity of APOBEC3G was regulated by vMIP -Ⅱ was analyzed.Statistical analysis was carried out by using t test,one-way analysis of variance and least significant difference (LSD)-t test.Results The mRNA and protein expression of APOBEC3G was significantly higher in the vMIP-Ⅱ plasmid group (2.500 ± 0.013,1.472 ± 0.013 respectively) than in the control group (1,0.364 ± 0.030 respectively;t =6.22,6.54 respectively,both P ＜ 0.05).The APOBEC3G expression significantly differed among the empty plasmid group,vMIP-Ⅱ plasmid group,empty plasmid + IFN-oα group and vMIP-Ⅱ plasmid + IFN-α group (1,2.030 ± 0.108,2.700 ± 0.081 and 2.600 ± 0.099 respectively;F =67.026,P ＜ 0.001),but there was no significant difference between the vMIP-Ⅱ plasmid group and empty plasmid + IFN-α group (t =3.46,P ＞ 0.05).The APOBEC3G expression also significantly differed among the vMIP-Ⅱ plasmid group,vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱplasmid + U0126 group (0.617 ± 0.025,0.179 ± 0.061,0.359 ± 0.012 respectively;F =70.019,P ＜ 0.001),and was significantly lower in the vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱ plasmid + U0126 group than in the vMIP-Ⅱ plasmid group (t =9.66,11.836 respectively,both P ＜ 0.01).Luciferase activity assay showed that the promoter activity significantly differed among the vMIP-Ⅱ plasmid groups transfected with POS,1 560-,960-,720-,480-,420-,360-,330-,240-bp or NEG sequences (F =81.092,P ＜ 0.001),and the APOBEC3G promoter activity decreased greatly from the 720-bp group to 480-bp group.Conclusion vMIP-Ⅱ upregulates the expression of APOBEC3G,likely through the JAK/STAT signaling pathway or the key promoter region regulating the transcriptional activity of APOBEC3G.
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Objective · To explore the clinical application value of hysteroscopic transcervical resection of endometrium (TCRE) combined with levonorgestrel-releasing intrauterine system (Mirena) in the treatment of adenomyosis. Methods · A total of 112 cases of adenomyosis patients were divided randomly into the combination group and Mirena group. The combination group (56 cases) was treated by TCRE endometrium endometrial resection, assisted Mirena treatment after operation. Mirena group (56 cases) was treated by Mirena only. The follow-up lasted 36 months after treatment, including measures of the volumes of menstrual bleeding, hemoglobin levels, dysmenorrhea scores, uterine volume, serum CA125 levels and incidences of complications.Results · The median follow-up duration was 42 months, and the three-year follow-up rate was 73.21% for the combination group and 50% for the Mirena group. After surgery, the volumes of menstrual bleeding of patients in 3-36 months decreased significantly, with an increase in hemoglobin level and a decrease in serum CA215 level and dysmenorrhea scores. Compared with their situations before surgery, the difference was significant (P<0.05). A comparison of uterine volume before and after surgery showed that there is a significant decrease in the uterine volume in both groups in6-12 months after surgery (P<0.05).Twenty-four months after surgery, it shows thatthe combination group has a much more significant decrease in uterine volume [(171.3±34.8) mm3] than Mirena group [(213.7±38.6) mm3] (P<0.05). The hysterectomy rate in Mirena group was significantly higher than that in the combination group (12.50% vs 5.36%); the ring expulsion rate was 16.07% in Mirena group and 5.36% in the combination group, and the break through bleeding happeningrate was 8.93% in Mirena group and 3.57% in the combination group. After 36 months an irregular small amount of vaginal bleeding rate was 62.25% in Mirena group, while it was only 12.50% in the combination group. There was significant differencewhen comparing above indices between two groups (P<0.05). There was no obvious differences in most common side effects of both groups. Conclusion · HysteroscopicTCRE combined with Mirena reduces significantly the irregular menstrual bleeding caused by merely applying Mirena. It has a prominent clinical efficacy and can be an effective approach in treatment of adenomyosis.
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Objective To investigate the clinical effect of treatment of severe carbon monoxide poisoning with Naoxingjing injection combined with naloxone.Methods Emergency department of affiliated theorem clinical college, hospital 70 patients diagnosed with severe carbon monoxide poisoning from emergency department in June 2014 to December 2016, were randomly divided into observation group and control group 35 cases.In the control group were treated with naloxone treatment, observation group were treated based on the use Naoxingjing injection treatment.The two groups were observed and recorded recovery time, mortality, the incidence of delayed encephalopathy, Glasgow Coma Score(GCS)and serum levels of IL-1β.Results The patients in the observation group total effective rate of 97.14% was significantly higher than 77.14%, and the difference was statistically significant(P<0.05);the recovery time was observed in patients(2.25 ± 0.88)h, significantly shorter than the control group(3.46 ± 1.10)h, and the difference was statistically significant(P<0.05);and follow-up observation group mortality rates were delayed encephalopathy(1.43%, 8.57%)than the control group(17.14%, 25.71%), and the difference was statistically significant(P<0.05);④ observation group were GCS score was (12.77±1.89), significantly better than the control group, and the difference was statistically significant(P<0.05);⑤ observed in patients IL-1β is(65.41±9.93)ng / L was significantly lower than the control group(89.86±10.74)ng / L, and the difference was statistically significant(P<0.05).Conclusion Naoxingjing injection combined with naloxone treatment of severe carbon monoxide poisoning exact clinical effect, can effectively reduce patient recovery time, reduce mortality and morbidity.