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Objective:To investigate the prognostic value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma (HCC) receiving immunotherapy combined with targeted therapy.Methods:The clinical data of a total of 120 patients with advanced HCC who received immunotherapy combined with targeted therapy at Cancer Center of Renmin Hospital of Wuhan University from December 2019 to March 2022 were analyzed retrospectively. Receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII) and prognostic nutritional index (PNI). According to the optimal cut-off values, the study objects were divided into high value group and low value group. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the factors associated with prognosis.Results:By the end of follow-up, 74 patients died and 46 survived. The median follow-up time was 23.0 months, the median overall survival (mOS) was 15.6 months, and the median progression-free survival (mPFS) was 13.1 months. ROC curve analysis showed that the optimal cut-off values of NLR, PLR, SII, LMR and PNI were 3.45, 131.87, 626.21, 2.12 and 43.30, respectively. The mPFS (18.3 months vs. 8.7 months) and mOS (26.6 months vs. 10.9 months) of patients in the low-NLR group ( n=75) were longer than those of the high-NLR group ( n=45), and there were statistically significant differences ( χ2=55.64, P<0.001; χ2=64.14, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (24.5 months vs. 13.5 months) of patients in the low-PLR group ( n=55) were longer than those of the high-PLR group ( n=65), and there were statistically significant differences ( χ2=5.27, P=0.023; χ2=11.84, P<0.001). The mPFS (18.0 months vs. 10.7 months) and mOS (25.7 months vs. 12.8 months) of patients in the low-SII group ( n=75) were longer than those of the high-SII group ( n=45), and there were statistically significant differences ( χ2=24.46, P<0.001; χ2=25.42, P<0.001). The mPFS (18.2 months vs. 10.9 months) and mOS (26.6 months vs. 13.2 months) of patients in the high-LMR group ( n=56) were longer than those of the low-LMR group ( n=64), and there were statistically significant differences ( χ2=19.25, P<0.001; χ2=19.92, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (25.4 months vs. 13.4 months) of patients in the high-PNI group ( n=62) were longer than those of the low-PNI group ( n=58), and there were statistically significant differences ( χ2=13.69, P<0.001; χ2=19.07, P<0.001). Univariate analysis showed that Barcelona clinic liver cancer (BCLC) stage ( HR=1.83, 95% CI: 1.17-2.87, P=0.008), Child-Pugh grade ( HR=2.21, 95% CI: 1.47-3.34, P<0.001), modified albumin-bilirubin (mALBI) grade ( HR=1.35, 95% CI: 1.01-1.81, P=0.045), extrahepatic metastases ( HR=2.18, 95% CI: 1.47-3.25, P<0.001), NLR ( HR=1.40, 95% CI: 1.28-1.54, P<0.001), PLR ( HR=1.00, 95% CI: 1.00-1.01, P=0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P<0.001), LMR ( HR=0.64, 95% CI: 0.51-0.79, P<0.001) and PNI ( HR=0.95, 95% CI: 0.93-0.98, P=0.001) were correlated with PFS; BCLC stage ( HR=2.18, 95% CI: 1.21-3.91, P=0.009), Child-Pugh grade ( HR=2.57, 95% CI: 1.61-4.09, P<0.001), Eastern Cooperative Oncology Group performance status score ( HR=1.59, 95% CI: 1.01-2.51, P=0.044), mALBI grade ( HR=1.60, 95% CI: 1.17-2.17, P=0.003), extrahepatic metastasis ( HR=2.51, 95% CI: 1.59-3.96, P<0.001), NLR ( HR=1.45, 95% CI: 1.32-1.60, P<0.001), PLR ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), SII ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), LMR ( HR=0.57, 95% CI: 0.40-0.72, P<0.001) and PNI ( HR=0.92, 95% CI: 0.89-0.96, P<0.001) were correlated with OS. Multivariate analysis showed that extrahepatic metastasis ( HR=1.78, 95% CI: 1.10-2.87, P=0.018) and NLR ( HR=1.46, 95% CI: 1.24-1.73, P<0.001) were independent influencing factors for PFS; extrahepatic metastasis ( HR=2.09, 95% CI: 1.21-3.61, P=0.009), NLR ( HR=1.56, 95% CI: 1.29-1.88, P<0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P=0.025), LMR ( HR=0.59, 95% CI: 0.45-0.78, P=0.008) and PNI ( HR=0.93, 95% CI: 0.88-0.99, P=0.013) were independent influencing factors for OS. Conclusion:NLR and extrahepatic metastasis can be regarded as important indicators to predict PFS in patients with advanced HCC receiving immunotherapy combined with targeted therapy, and NLR, SII, LMR, PNI and extrahepatic metastasis can be regarded as important indicators to predict OS in patients with advanced HCC receiving immunotherapy combined with targeted therapy. High NLR, high SII, low LMR, low PNI and extrahepatic metastasis indicate poor prognosis of HCC patients.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with a high incidence and fatality rate in China. Since sorafenib opened up a new era of targeted therapy for HCC, drug developers around the world have made a lot of efforts and contributions to the exploration of systematic therapy for HCC. In recent years, novel molecular targeted agents, immune checkpoint inhibitors and their combined treatment regimens in advanced HCC have been implemented for many large samples, international multi-center clinical trials. The results show that the therapeutic effect of immunotherapy combined with targeted therapy and dual immunotherapy have significant advantages compared with that of targeted or immune monotherapy, and have satisfactory safety while prolonging survival and improving the quality of life of patients.
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Objective:To investigate the effects and mechanisms of Wnt pathway inhibitor IWR-1-endo on the biological behaviors of human hepatocarcinoma cell Huh7.Methods:Human hepatocellular carcinoma cell Huh7 was cultured in vitro, and Huh7 cells were treated with IWR-1-endo at different concentrations (0, 20, 40, 80, 160, 320 μmol/L). Scratch test was used to detect changes in cell migration ability at diffe-rent drug concentrations, plate cloning was used to detect changes in cell proliferation, Western blotting was used to detect changes in the expression of Wnt pathway related protein β-catenin, and immunofluorescence staining was used to detect the expression of β-catenin in cytoplasm and nucleus. Results:The results of the scratch test showed that the 24 h scratch healing rates of Huh7 cells treated with 0, 20, 40, 80, 160, 320 μmol/L IWR-1-endo were (20.55±0.05)%, (12.10±0.08)%, (9.36±0.10)%, (3.62±0.09)%, (0.62±0.04)% and (0.23±0.02)%, respectively, and there was a statistically significant difference ( F=230.87, P<0.001). Further pair comparison showed that there were statistically significant differences in 24 h scratch healing rates among different concentrations (all P<0.001). The 48 h scratch healing rates were (34.77±0.08)%, (17.69±0.05)%, (11.60±0.04)%, (5.68±0.07)%, (2.66±0.04)% and (1.75±0.02)%, respectively, and there was a statistically significant difference ( F=589.68, P<0.001). Further pair comparison showed that there were statistically significant differences in 48 h scratch healing rates among different concentrations (all P<0.001). After treatment with IWR-1-endo at the concentration of 0, 20, 40, 80, 160, 320 μmol/L, the clone formation rates of Huh7 cells were (61.67±0.21)%, (57.33±0.11)%, (50.00±0.25)%, (36.67±0.28)%, (23.33±0.12)% and (15.00±0.08)%, respectively, and there was a statistically significant difference ( F=403.56, P<0.001). Further pair comparison showed that there were statistically significant differences in clone formation rates among different concentrations (all P<0.001). After treatment with 0, 20, 40, 80, and 160 μmol/L IWR-1-endo for 24 h, the relative expression levels of β-catenin in Huh7 cells were 0.30±0.08, 0.25±0.07, 0.22±0.05, 0.15±0.01 and 0.06±0.02, respectively, and there was a statistically significant difference ( F=247.00, P<0.001). Compared with 0 μmol/L, the relative expression levels of β-catenin treated with 80 and 160 μmol/L had statistical significance ( P=0.014; P=0.008). Compared with 0 mol/L, immunofluorescence showed that the expressions of β-catenin in cytoplasm and nucleus were reduced after 80 μmol/L IWR-1-endo treatment. Conclusion:Wnt pathway inhibitor IWR-1-endo can inhibit the migration and proliferation of hepatocarcinoma cells Huh7 by inhibiting the activity of Wnt pathway. The above inhibitory effects are dose-dependent.
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Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and, thus, repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a new virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a new restraint energy distribution (RED) function designed to accelerate the FEP-ABFE calculations and make the practical FEP-ABFE-based virtual screening of the existing drug library possible for the first time. As a result, out of twenty-five drugs predicted, fifteen were confirmed as potent inhibitors of SARS-CoV-2 Mpro. The most potent one is dipyridamole (Ki=0.04 M) which has showed promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki=0.36 M) and chloroquine (Ki=0.56 M) were also found to potently inhibit SARS-CoV-2 Mpro for the first time. We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts. Significance StatementDrug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. It has been demonstrated that a new virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions can reach an unprecedently high hit rate, leading to successful identification of 16 potent inhibitors of SARS-CoV-2 main protease (Mpro) from computationally selected 25 drugs under a threshold of Ki = 4 M. The outcomes of this study are valuable for not only drug repurposing to treat COVID-19, but also demonstrating the promising potential of the FEP-ABFE prediction-based virtual screening approach.
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Objective:To investigate the effect of high mobility group box-1 protein (HMGB1)-nuclear factor-κB (NF-κB) signaling pathway on autophagy and chemosensitivity of human hepatocellular carcinoma cells and its possible mechanism.Methods:Human hepatocellular carcinoma BEL-7402 cells were cultured in vitro and divided into control group (BEL-7402 cells without any treatment), doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine + doxorubicin group. The methyl thiazolyl tetrazolium (MTT) method was used to detect cell proliferation inhibition rate. Western blot method was used to detect the expressions of HMGB1 and NF-κB subunit p-p65 protein, the autophagy-related proteins Beclin-1, LC3Ⅰ, LC3Ⅱ and apoptosis-related protein bcl-2. Enzyme labeling method was used to detect Caspase-9 and Caspase-3 activity.Results:The cell proliferation inhibition rates in the control group, doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine+doxorubicin group were (1.31±0.16)%, (47.80±6.30)%, (31.60±5.68)%, (67.20±6.83)%, (66.60±6.27)%, and (68.60±11.19)%, respectively, and the difference was statistically significant ( F = 75.91, P < 0.01), suggesting that doxorubicin had a proliferation inhibitory effect on BEL-7402 cells; the expression levels of HMGB1 were 1.17±0.11, 1.37±0.15, 1.43±0.15, 0.70±0.09, 1.27±0.12, 1.29±0.18, and the difference was statistically significant ( F = 18.70, P < 0.01), suggesting that doxorubicin could increase the expression of HMGB1 in BEL-7402 cells, and the anti-HMGB1 neutralizing antibody could block or attenuate this effect; after pretreatment with recombinant human HMGB1, the proliferation inhibitory effect of doxorubicin on BEL-7402 cells was weakened; after pretreatment with anti-HMGB1 neutralizing antibody, pyrrolidine dithiocarbamate and 3-methyladenine, the proliferation inhibitory effect of doxorubicin on BEL-7402 cells was enhanced. Compared with the control group, the expression of p-p65 protein in the doxorubicin group, recombinant human HMGB1+doxorubicin group and 3-methyladenine+doxorubicin group increased (all P < 0.05). The expression of p-p65 protein in the recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group and pyrrolidine dithiocarbamate+doxorubicin group was lower than that in the doxorubicin group (all P < 0.05). Compared with the control group, the expression of bcl-2 protein in doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine+ doxorubicin group decreased (all P < 0.05), and the activity of Caspase-9 and Caspase-3 was enhanced (all P < 0.05); after adding recombinant human HMGB1 pretreatment, the expression of bcl-2 protein in the cells increased compared with doxorubicin alone, and the activity of Caspase-9 and Caspase-3 was weakened (all P < 0.05). The expression levels of autophagy-related protein Beclin-1 in the control group, doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group, and 3-methyl adenine+doxorubicin group were 0.77±0.12, 0.92±0.07, 1.29±0.10, 0.51±0.03, 0.49±0.06, and 0.42±0.05, and the difference was statistically significant ( F = 97.01, P < 0.01). The expression levels of LC3Ⅱ were 0.24±0.04, 0.39±0.04, 0.49±0.07, 0.23±0.05, 0.20±0.06, and 0.20±0.05, and the difference was statistically significant ( F = 26.98, P < 0.01). Conclusion:The activation of HMGB1-NF-κB signaling pathway can reduce the chemosensitivity of hepatocellular carcinoma cells to doxorubicin, and its mechanism may be related to the regulation of autophagy and down-regulation of doxorubicin inducing apoptosis of hepatocellular carcinoma cells.
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Objective:To investigate the clinical features, treatment methods and prognostic factors of extranodal nasal type NK/T lymphoma (ENKTL).Methods:The clinical data of 45 patients treated in Renmin Hospital of Wuhan University from January 2013 to June 2019 were retrospectively analyzed. Short-term efficacy was compared among low-risk, medium-risk and high-risk three groups according to PINK score. According to the treatment methods, the patients of stage Ⅰ-Ⅲ were divided into radiotherapy group and radiotherapy+ chemotherapy group. Chi-square test was used to compare the treatment outcomes. The effects of diagnosis time, clinical staging, symptom B, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), Ki-67, prognostic index of NK lymphoma (PINK) and treatment methods on overall survival (OS) and progression-free survival (PFS) were analyzed by using Kaplan-Meier method, log-rank test was used for univariate analysis, and Cox proportional hazard model was used for multivariate prognostic analysis.Results:The median age of 45 patients was 51 years old. There were 39 cases (86.7%) of stage Ⅰ-Ⅱ, 4 cases (8.9%) of stage Ⅲ, 2 cases(4.4%) of stage Ⅳ. The median time from first onset to diagnosis was 3.0 months (1.0-36.0 months), and serum EBV-DNA positive rate was 95.6% (43/45). The complete remission (CR) rate and progression of the disease (PD) rate were statistically different of different risk groups ( χ2 = 10.952, P < 0.01; χ2 = 12.217, P = 0.002). Among 43 patients of stage Ⅰ-Ⅲ, there were 11 patients in the radiotherapy alone group, including 4 cases (36.3%) of CR, 3 cases (27.3%) of partial remission (PR), 4 cases (36.4%) of PD; and 32 patients in the chemotherapy combined with radiotherapy group, including 23 cases (71.9%) of CR, 4 cases (12.5%) of PR, 5 cases (15.6%) of PD. The difference in CR rate of both groups was statistically significant ( χ2 = 4.418, P = 0.036). Univariate analysis suggested that PINK score and B symptom were related to OS ( χ2 = 8.140, P = 0.017; χ2 = 5.545, P = 0.019). PINK score and clinical staging were associated with PFS ( χ2 = 12.517, P = 0.002; χ2 = 10.016, P = 0.002); Cox multivariate analysis indicated that clinical staging was an independent influencing factor of PFS ( HR = 4.104, 95% CI 1.571-10.725, P = 0.004). Conclusions:ENKTL with specific location has longer clinical diagnosis time, and the positive rate of EBV-DNA is high. The patients with B symptom and high PINK score have poor OS, and patients with late clinical staging and high PINK score have short PFS. Clinical staging is considered as an independent factor affecting PFS. The PINK score risk stratification has a guiding significance in the short-term efficacy evaluation, and the chemotherapy combined with radiotherapy can increase CR rate for patients less than stage Ⅳ.
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AIM: The expression of microRNA143HG (miR143HG) was significantly downregulated in hepatocellular carcinoma (HCC) tissues by bioinformatics analysis. This study aimed to determine the role of miR143HG in HCC cell proliferation and metastasis. METHODS: Fifty patients with HCC were divided into two groups based on median miR143HG expression levels. The correlation between miR143HG expression and prognosis, and the correlations between miR143HG expression and the patients' clinicopathological characteristics were evaluated based on the two groups. Gain-of-function and loss-of-function measurements of miR143HG were carried out to verify the biological function of miR143HG by Cell Counting Kit-8, EdU, Transwell, and western blotting assays and flow cytometric analysis. The underlying mechanism was explored by quantitative real-time polymerase chain reaction of miRNA (miR-155-5p and miR-26b-5p), luciferase reporter assay, western blotting of Wnt signaling pathway-related proteins (ß-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3ß (GSK3ß), ZEB1, and E-cadherin), mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (extracellular signal-regulated kinase [ERK]1/2, p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, P38, and p-P38), and immunofluorescence staining of ß-catenin. RESULTS: miR143HG expression was markedly downregulated in HCC tissues and cells. Its expression was associated with the presence or absence of portal vein tumor thrombus, hepatitis B virus infection, relapse and metastasis, and Barcelona Clinic Liver Cancer stage. Additionally, miR143HG expression predicted a good prognosis and acted as an independent prognostic factor in HCC for overall survival. Overexpression of miR143HG suppressed HCC cell proliferation and metastasis, and induced cell cycle arrest and apoptosis. Consistently, the depletion of miR143HG resulted in the opposite phenomenon of the aforementioned results. miR143HG inhibits miR-155 expression; miR-155 directly targets APC, which is a negative regulator of the Wnt/ß-catenin pathway, so miR143HG can act on the Wnt pathway. miR143HG was further found to reduce the expression of ß-catenin and block the nuclear accumulation of ß-catenin, ultimately inhibiting the activation of the Wnt pathway. It inhibits the expression of Wnt downstream target gene ZEB1, and then E-cadherin expression is increased and cell motility is inhibited. Furthermore, miR143HG exerts its antiproliferative function by influencing the MAPK signaling pathway and then inducing G2 /M arrest in cells. CONCLUSION: This study showed that miR143HG plays critical roles in the development and progression of HCC by suppressing the MAPK and Wnt signaling pathways.
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Objective To investigate the application of the flipped classroom based on micro-class versus traditional class in animal surgery teaching, and to provide new thinkings for animal surgery teaching. Methods A total of 120 undergraduates from Navy Medical University were randomly divided into control group (class A) and experimental group (class B). The students in class A received traditional teaching, and those in class B received flipped classroom teaching . Questionnaire survey and course assessment were performed after teaching, and a comparative analysis was also performed. Results The self-assessment survey showed that 88.3％, 73.3％, 71.6％, 48.3％, and 73.3％ of the students in class A (traditional teaching) filled in the questionnaire with "Very Helpful and Helpful", while 91.7％, 85.0％, 83.3％, 78.3％, and 75.0％of the students in class B (flipped classroom teaching) filled in with"Very Helpful and Helpful"; class B gave better overall evaluation of teaching model than that of class A. The mean total score of class B was 0.91, higher than that of class A (8.43 vs. 7.52, P<0.05), and the mean total score of examination papers in class B was 10.92, higher than that in class A (101.13 vs. 90.21, P<0.05). Conclusion Flipped classroom based on micro-class could improve the teaching effect of debridement course on animal surgery and increase students' self-learning ability.
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Objective@#To investigate the application of the flipped classroom based on micro-class versus traditional class in animal surgery teaching, and to provide new thinkings for animal surgery teaching.@*Methods@#A total of 120 undergraduates from Navy Medical University were randomly divided into control group (class A) and experimental group (class B). The students in class A received traditional teaching, and those in class B received flipped classroom teaching. Questionnaire survey and course assessment were performed after teaching, and a comparative analysis was also performed.@*Results@#The self-assessment survey showed that 88.3%, 73.3%, 71.6%, 48.3%, and 73.3% of the students in class A (traditional teaching) filled in the questionnaire with "Very Helpful and Helpful", while 91.7%, 85.0%, 83.3%, 78.3%, and 75.0% of the students in class B (flipped classroom teaching) filled in with "Very Helpful and Helpful"; class B gave better overall evaluation of teaching model than that of class A. The mean total score of class B was 0.91, higher than that of class A (8.43 vs. 7.52, P<0.05), and the mean total score of examination papers in class B was 10.92, higher than that in class A (101.13 vs. 90.21, P<0.05).@*Conclusion@#Flipped classroom based on micro-class could improve the teaching effect of debridement course on animal surgery and increase students' self-learning ability.
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Objective@#To compare the dosimetric differences among Target-Segmented Plan (TSP), Non-TSP, and conventional static 8-field intensity modulated radiation therapy (8F-IMRT) plan for post-mastectomy irradiation of left-sided breast cancer patients.@*Methods@#This study enrolled thirty consecutive breast cancer patients who underwent radical mastectomy and treated with post-op radiation in Department of Radiation Oncology, Renmin Hospital of Wuhan University from June 2017 to November 2018.The clinical target volume (CTV) included the ipsilateral chest wall, supra/infra-clavicular, high-risk partial axillary in high risk, and internal mammary nodes (IMN). The organs at risk (OARs) near the targets, including ipsilateral lung, heart, contralateral breast, ipsilateral humeral head and spinal cord, were contoured as well. The maximum distance of PTV′s tangent to the outermost side of the affected lung was more than 2 cm. Depending on the maximum distance, the patients were classified into three groups: A(<3 cm), B(3~4 cm) and C(>4 cm), respectively. Three types of treatment plans (TSP, Non-TSP and 8F-IMRT) were created for each patient using the Eclipse treatment planning system with the same dose optimization objective . The dose-volume histograms were compared for the PTVs and OARs.@*Results@#All plans achieved the intended dose criteria.The D98% of TSP was lower than that of Non-TSP and 8F-IMRT (Z=-3.294, -3.266, P<0.05). However, the homogeneity index (HI) and conformal index (CI) of the three plans had no statistically significant difference among the three plans (P>0.05). Non-TSP required more Monitor Units (MUs)than the other two plans (Z=-3.04, -2.669, P<0.05). The Dmean of TSP was higher than that of 8F-IMRT (Z=-3.181, P<0.05). Compared with Non-TSP and 8F-IMRT plans, TSP significantly reduced V5 Gy, V10 Gy, V20 Gy and Dmeanof ipsilateral lung and heart in all patients (lung: V5 Gy: Z=-3.408, -3.408; V10 Gy: Z=-3.408, -3.408; V20 Gy: Z=-3.408, -3.124; Dmean: Z=-3.408, -3.408, P<0.05; heart: V5 Gy: Z=-3.408, -3.408; V10 Gy: Z=-3.408, -3.408; V20 Gy: Z=-2.499, -3.067; Dmean: Z=-3.408, -3.408, P<0.05). The Dmean of contralateral breast in Non-TSP was higher than that in TSP and 8F-IMRT (Z=-2.954, -2.215, P<0.05), and the Dmaxhas no significant difference in (P>0.05). There was no significant difference in spinal cord Dmax among the three plans, but the Dmean of humeral head in 8F-IMRT was higher than that in TSP and Non-TSP (Z=-3.01, -2.442, P<0.05). In the three groups, the mean amplitude of difference comparing Non-TSP and 8F-IMRT with TSP in ipsilateral lung(V5 Gy, V10 Gy, V20 Gy) and heart(V5 Gy, V10 Gy, Dmean) satisfied the relation: D(N-T, A)<D(N-T, B) <D(N-T, C)和D(8F-T, A)<D(8F-T, B) <D(8F-T, C).@*Conclusions@#For post-mastectomy left-sided breast cancer patients, TSP is not only dosimetrically feasible as Non-TSP and 8F-IMRT treatment techniques, but also could effectively reduce the irradiation volume of the ipsilateral lung and heart in the low dose area with minimum adverse dosimetric impact on the treatment targets and other OARs.The advantage of TSP is more prominent with increasing curvature of the clinic target volume.
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Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) ,glucose trans-porter-1 (GLUT-1) and lactate dehydrogenase-5 (LDH-5) in gastric cancer tissues and their correlation with pathological features.Methods From June 2015 to June 2017 ,93 cases of gastric cancer resection were select-ed as the observation group ,and the cancer adjacent tissues were taken as the control group.Immunohisto-chemical staining was used to detect the expression of HIF-1α ,GLUT-1 and LDH-5.The gastric cancer tissues from 93 patients with gastric cancer who underwent gastrectomy in the hospital were taken as the observation group ,and the adjacent tissues were taken as the control group.The expressions of HIF-1α ,GLUT-1 and LDH-5 in two groups were determined by Immunohistochemical MaxVision Ⅲ method.The positive expres-sions of HIF-1α ,GLUT-1 and LDH-5 in two groups were compared ,and the correlation between HIF-1α , GLUT-1 and LDH-5 in gastric cancer tissues ,and the expressions of HIF-1α ,GLUT-1 and LDH-5 in different sex ,age ,clinical stage and differentiation degree were compared.Results The positive expression rates of HIF-1α ,GLUT-1 and LDH-5 in the observation group were higher than those in the control group ,and the differences were statistically significant (P＜ 0.05) ;HIF-1α ,GLUT-1 and LDH-5 were positively correlated with each other ;there were no significant differences of HIF-1α ,GLU T-1 and LDH-5 levels in different gender group and different age group (P＞0.05) ;the positive expression rates of HIF-1α ,GLU T-1 and LDH-5 at Ⅲ and Ⅳ stages were higher than those at Ⅰ and Ⅱ stages ,the positive expression rates of HIF-1α ,GLUT-1 and LDH-5 of low differentiation were higher than those of high and middle differentiation and the differences were statistically significant (P＜ 0.05).Conclusion The high expressions of HIF-1α ,GLUT-1 and LDH-5 were observed in gastric cancer tissue.HIF-1α ,GLUT-1 and LDH-5 were linearly and positively correlated with each other ,and had a significant correlation with the clinicopathological features.With the increase of clinical stage and the degree of differentiation ,the expression of HIF-1 a ,GLUT-1 and LDH-5 were higher.
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Objective To investigate the clinical effect of anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine.Methods The data of 45 cases with cervical posterior longitudinal ligament ossification treated by ACAF from March 2017 to October 2017 were retrospectively analyzed,including 25 males and 20 females,age 45-68 years,average 57.5 years.There were 18 cases involving C3 vertebral body,30 cases involving C4 vertebral body,40 cases involving C5 vertebral body,34 cases involving C6 vertebral body,and 7 cases involving C7 vertebral body.The function of the neural function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system at preoperation and latest follow-up.The curvature of the cervical spine was measured on the lateral X-ray film of the cervical spine,the maximum occupying ratio of the spinal canal was measured on the cross section of the CT scan,and compression of the cervical spinal cord was evaluated by the cervical MRI.Results Patients were followed up for 3 to 6 months (average,3.9 months).The improvement of neurological function was obtained in all the patients.The JOA score improvement rate at the latest follow-up was 71.3％±9.6％.The cervical lordosis was improved from preoperative 4.5°±3.8° to 10.3°±4.8° at the latest follow-up.The canal stenosis ratio was decreased from preoperative 54.3％±8.2％ to 12.5％±5.3％ at the latest follow-up.MRI showed that the cervical spinal cord was adequately decompressed in situ.No specific complications were identified that were associated with this technique.Conclusion The present study elaborates the surgical tips and demonstrates the satisfactory outcome of ACAF for the treatment of OPLL.This novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL.
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Skeleton metabolic diseases such as osteoporosis and fracture have posed an detrimental impact on the elderly, which is a primary cause of paralysis and even death in patients. Osteoblast and osteoclast are the two major parts in the regulation of bone homeostasis and imbalance of these two cells, which may result in dysfunction of bone metabolism. Recent researches indicated that bone homeostasis was primarily regulated by endocrine, paracrine, and local mechanical processes. However, increasing evidences have indicated that the significant role of nerve system may involve in bone metabolism via both central and peripheral pathways. Neuropeptide Y(NPY), a neurotransmitter that belongs to a family of peptides,serves as a critical hinge connecting nerve system and skeleton system. Several studies have suggested that NPY generated by both central and peripheral nerve system could regulate bone homeostasis and that NPY-energic nerve fibers distributed on bone surface and in intramedullary cavity and NPY receptors located at osteoblast, chondrocyte, and osteocytes also provide a basis for nerve-skeleton metabolic pathways. NPY can directly regulate osteoprogenitor, involving in the production and differentiation of osteoblast and osteoclast. In addition, as a pivotal molecular of energy homeostasis, NPY may affect glucose and fat homeostasis. Studies of animal models also have further indicated energy metabolism may directly or indirectly participate in the regulation of bone mass. Therefore, further researches on the relationship between NPY and bone homeostasis may facilitate to unveil the central and peripheral regulatory effect of NPY on bone homeostasis and provide a new sight for the treatment of skeleton metabolism-related diseases in the future.
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Competing endogenous RNAs (ceRNAs) transcripts can communicate with microRNAs (miRNAs) through competitively binding the common miRNA response elements (MREs),which remove or decrease the repression of target genes of miRNAs.The present studies indicate that a large amount of genes,serving as ceRNAs,can promote or inhibit the occurrence of liver cancer by competing the binding site of same genes that can promote or suppress tumorigenesis.
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Objective To investigate up-regulation of lncRNA-AK058003 expression in SK-Hep1 hepatocellular carcinoma cells and its effect on the growth of human hepatocellular carcinoma xenograft tumor in nude mice.Methods The recombinant plasmid of lncRNA-AK058003 and empty plasmid were transferred into SK-Hep1 human hepatocellular carcinoma cell line by the method of slow virus transfection.The overexpression of lncRNA-AK058003 cell line was screened by neomycin.Overexpression of lncRNA-AK058003 in SK-Hep1 hepatocarcinoma cells was detected by quantitative PCR.SK-Hep1 hepatocellular carcinoma cells stably overexpressing lncRNA-AK058003 and SK-Hep1 hepatocellular carcinoma cells containing empty plasmids were injected subcutaneously into armpit of nude mice.The long and short diameters of the transplanted tumor were measured regularly to calculate the volume of the xenograft tumor.After 35 days of feeding we measure the weight of the xenograft tumor.Results The recombinant plasmid of lncRNA-AK058003 was successfully constructed and stably over expressed in hepatocellular carcinoma cells.The experimental results of subcutaneous tumor bearing nude mice showed that the volume(308.4 ± 439.4mm3),weight (0.464 ± 0.518g)and growth rate of the xenograft tumor in the over expression group were lower than that of the empty plasmid group(1410.0 ± 973.0mm3,1.363 ± 0.856g,P ＜ 0.05).Conclusion LncRNA-AK058003 has inhibitory effect on the proliferation of human hepatocellular carcinoma xenograft tumor in nude miee.
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Objective To investigate up-regulation of lncRNA-AK058003 expression in SK-Hep1 hepatocellular carcinoma cells and its effect on the growth of human hepatocellular carcinoma xenograft tumor in nude mice.Methods The recombinant plasmid of lncRNA-AK058003 and empty plasmid were transferred into SK-Hep1 human hepatocellular carcinoma cell line by the method of slow virus transfection.The overexpression of lncRNA-AK058003 cell line was screened by neomycin.Overexpression of lncRNA-AK058003 in SK-Hep1 hepatocarcinoma cells was detected by quantitative PCR.SK-Hep1 hepatocellular carcinoma cells stably overexpressing lncRNA-AK058003 and SK-Hep1 hepatocellular carcinoma cells containing empty plasmids were injected subcutaneously into armpit of nude mice.The long and short diameters of the transplanted tumor were measured regularly to calculate the volume of the xenograft tumor.After 35 days of feeding we measure the weight of the xenograft tumor.Results The recombinant plasmid of lncRNA-AK058003 was successfully constructed and stably over expressed in hepatocellular carcinoma cells.The experimental results of subcutaneous tumor bearing nude mice showed that the volume(308.4 ± 439.4mm3),weight (0.464 ± 0.518g)and growth rate of the xenograft tumor in the over expression group were lower than that of the empty plasmid group(1410.0 ± 973.0mm3,1.363 ± 0.856g,P ＜ 0.05).Conclusion LncRNA-AK058003 has inhibitory effect on the proliferation of human hepatocellular carcinoma xenograft tumor in nude miee.
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Objective To report a novel technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of severe ossification of the posterior longitudinal ligament of the cervical spine,which allows for direct decompression of the nerve without resection of the ossification,making up for deficiencies in traditional anterior or posterior decompression.Methods The main surgical procedures of the ACAF included treatment of intervertebral space,removal of the anterior part of vertebrae,installation of titanium plate and interbody fusion cages,bilateral osteotomies of the vertebrae,and antedisplacement of the vertebrae ossification complex.The clinical data of two patients undergoing this surgery for severe ossification of the posterior longitudinal ligament of cervical spine were collected and analyzed.Results ACAF enabled direct decompression of spinal cord and nerve root through antedisplacement of the vertebrae ossification complex.The two patients who underwent ACAF gained satisfactory restoration with decompression of spinal cord and good recovery of neurological function,with no specific complications.Conclusion ACAF surgery takes into account the effectiveness of anterior direct decompression and the safety of posterior indirect decompression.Preliminary results shows that it can be used for severe cervical ossification of the posterior longitudinal ligament.
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Semen Ziziphi spinosae ( SZS) , as a commonly used traditional Chinese medicine in clinic for insomnia therapy, is rich in pharmacological active ingredients such as saponins, flavonoids, alkaloids, oil and the other chemical compounds. The recent stud-ies indicated that some active ingredients in SZS exhibited a variety of activities including sedative hypnotics, antianxiety and anti-de-pression by regulating particular neurotransmitters such as 5-hydroxytryptamine (5-HT), gamma-amino butyric acid (GABA), norepi-nephrine, dopamine and glutamate. In accordance with the previous studies on pharmacological activities of SZS, this paper summa-rized and reviewed the applications of SZS in the treatment of central nervous system diseases, myocardial diseases and hepatic disea-ses, which might provide solid evidence for the application development of SZS.
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Objective To evaluate the effect of silencing ACAT1 gene on colon cancer cells proliferation,migration,invasion and colon cancer development by using the small interference RNA (siRNA) in colon cancer cell line HT-29.Methods Acyl coenzyme A cholesterol acyltransferase 1 (ACAT1) gene was silenced in HT-29 cell lines using Hiperfect transfection reagent.The expression level of ACAT1 was detected by real time PCR.CFSE and transwell assays were used to evaluate the effect of ACAT1 gene interfering on cells proliferation,mi gration and invasion.Result ACAT1 mRNA expression decreased obviously after siRNA interference.Compared with pre-transfection,proliferation,migration and invasion of colon cancer cells have been significantly inhibited (P ＜ 0.05).Conclusion ACAT1 gene interference reduced proliferation,migration and of invasion of HT29 cells,which provide a new potential target for colon cancer treatment.
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OBJECTIVE: To evaluate the effect of ShenQi FuZheng Injection (SFI) on cellular immunity and clinical efficacy in patients with advanced non small cell lung cancer(NSCLC) when combined with chemotherapy. METHODS: Electronic databases including EMBASE, PUBMED, the conference proceedings of the American Society of Clinical Oncology (ASCO), Cochrane, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biological Medical disc(CBM) were searched, until July, 2015. The randomized controlled clinical studies reporting results of efficacy and immune function were collected according to the inclusion criteria. Cochrane handbook 5.1.0 was applied to assess the quality of included trials and Revman 5 software was used for data analysis. RESULTS: Fifteen studies including 1006 cases of advanced NSCLC were included based on the inclusion criteria. The results of meta-analysis showed that there were significant differences in percentages of CD3+ cells (SMD = 13.48; 95%CI: 8.11-18.85; p<0.01), CD4+ cells (SMD = 10.78; 95%CI, 6.38-15.18; p<0.01), NK [WMD = 8.59, 95% CI(3.97, 13.21), p = 0.003], and ratio of CD4+/ CD8+ (SMD = 0.32; 95%: 0.28-0.36; p<0.01) between SFI combination group and control group, whereas the difference was not significant in CD8+ (SMD = -1.44; 95%CI, -4.53-1.65; p = 0.36). Funnel plot, Begg's rank correlation test and Egger's linear regression analysis indicated that there was significant publication bias across studies. CONCLUSION: SFI is effective to improve the efficacy of chemotherpay and function of cellular immunity in NSCLC patients, however, high quality RCTs are needed to further confirm the findings.