Betel nut chewing (BNC) is a prevalent risk factor for oral squamous cell carcinoma (SCC) in South and Southeast Asia, yet its influence on response to neoadjuvant immunochemotherapy remains unexplored. This study aimed to evaluate the association between BNC and pathologic response in oral SCC patients receiving neoadjuvant immunochemotherapy. We retrospectively reviewed 192 patients with primary oral SCC who received neoadjuvant immunochemotherapy (docetaxel, cisplatin, and PD-1 inhibitors) followed by surgery between January 2020 and October 2024. Pathologic complete response (pCR), major pathologic response (mPR), objective response rate (ORR), clinical to pathological downstaging, adverse pathologic features, and disease-free survival (DFS) were compared between BNC (n = 42) and no-BNC (n = 150) groups. BNC patients demonstrated significantly lower pCR (16.7
With the increasing severity of arsenic (As) pollution, quantifying the environmental behavior of pollutant based on numerical model has become an important approach to determine the potential impacts and finalize the precise control strategies. Taking the industrial-intensive Jinsha River Basin as typical area, a two-dimensional hydrodynamic water quality model coupled with Soil and Water Assessment Tool (SWAT) model was developed to accurately simulate the watershed-scale distribution and transport of As in the terrestrial and aquatic environment at high spatial and temporal resolution. The effects of hydro-climate change, hydropower station construction and non-point source emissions on As were quantified based on the coupled model. The result indicated that higher As concentration areas mainly centralized in urban districts and concentration slowly decreased from upstream to downstream. Due to the enhanced rainfall, the As concentration was significantly higher during the rainy season than the dry season. Hydro-climate change and the construction of hydropower station not only affected the dissolved As concentration, but also affected the adsorption and desorption of As in sediment. Furthermore, As concentration increased with the input of non-point source pollution, with the maximum increase about 30%, resulting that non-point sources contributed important pollutant impacts to waterways. The coupled model used in pollutant behavior analysis is general with high potential application to predict and mitigate water pollution.
Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17-2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.
OBJECTIVE:To examine the distribution of non-sentinel lymph nodes (SLNs) and to determine the feasibility of omitting elective neck dissection (END) in cases of cT1/2N0 oral cancer presenting with SLN metastasis. METHODS:A prospective cohort of patients with cT1/2N0 oral cancer underwent SLN biopsy using a γ-probe alongside methylene blue staining, followed by subsequent END. The primary outcome variable was non-SLN metastasis, with its predictors evaluated through logistic regression analysis. RESULTS:A total of 200 patients with detectable SLNs were analyzed. Logistic regression revealed a significant odds ratio of 4.28 [95 % confidence interval: 2.11-14.56] for predicting non-SLN metastasis when comparing a depth of invasion greater than 4.0 mm to a DOI of 4.0 mm or less. Among the six cases of non-SLN metastasis, three patients with negative SLN biopsy results exhibited metastasis; one was found in ipsilateral level V and two in contralateral level Ib. In contrast, all three patients with positive SLN biopsy results had a DOI surpassing 4.0 mm, presenting with at least two positive SLNs. Non-SLN metastasis was detected in ipsilateral level III for one patient and at level IV for two others. CONCLUSION:END may be judiciously omitted in cases where only one positive SLN is identified in early-stage oral cancer with a depth of invasion of ≤ 4.0 mm.
目的 探讨微小RNA-33b-5p(miR-33b-5p)靶向E26转录因子-1(E26 transformation specific-1,ETS1)在胰腺导管腺癌(PDAC)吉西他滨耐药中的作用.方法 通过实时荧光定量聚合酶链反应(RT-qPCR)和蛋白质印迹法(Western blot)检测胰腺癌细胞ASPC-1和胰腺癌耐药细胞ASPC-1/GEM中miR-33b-5p和ETS1的表达水平,双荧光素酶报告实验验证miR-33b-5p与ETS1之间的靶向关系;免疫组织化学染色检测PDAC患者敏感组与抵抗组ETS1的表达;转染ASPC-1/GEM细胞,分为 NC mimic 组、miR-33b-5p mimic 组、ETS1 小干扰 RNA(siRNA)NC 组及 ETS1 siRNA 组,RT-qPCR检测转染后miR-33b-5p,ETS1 mRNA的表达水平,Western blot检测ETS1的表达水平,细胞计数试剂盒(CCK-8)检测细胞活性并计算吉西他滨半数抑制浓度(IC50),流式细胞术检测细胞凋亡水平.结果 与ASPC-1细胞比较,ASPC-1/GEM细胞株中miR-33b-5p表达下降(t=-11.011,P<0.05)、ETS1表达升高(P<0.05);双荧光素酶报告实验表明miR-33b-5p可明显降低野生型ETS1-33b-5p-WT载体荧光素酶活性(t=-4.453,P<0.05);免疫组织化学结果显示ETS1在抵抗组中表达量明显高于敏感组(8.11±2.80比2.78±0.83,P<0.05);miR-33b-5p mimic组IC5n明显低于 NC mimic 组[(25.10±1.77)μmol/L 比(43.63±3.04)μmol/L,t=-9.110,P<0.05],miR-33b-5p表达量明显高于NC mimic组(t=19.444,P<0.05),ETS1的表达量明显低于NC mimic组(P<0.05),凋亡率明显高于 NC mimic 组[(18.8±1.9)%比(5.3±0.4)%,t=12.239,P<0.05];ETS1 siRNA 组吉西他滨 IC50 明显低于 ETS1 siRNA NC 组[(20.39±0.89)μmol/L 比(37.38±2.62)μmol/L,t=-10.628,P<0.05].结论 miR-33b-5p 可能通过抑制 ETS1 表达促进 PDAC 对吉西他滨化疗的敏感性.
目的 利用轧塞酸二钠(Gd-EOB-DTPA)增强核磁共振成像(MRI)肝胆期的结节强化程度预测肝细胞癌(HCC)靶向联合免疫治疗的效果.方法 回顾性收集2020年1月至2022年1月河南省人民医院诊断为HCC,且在靶向联合免疫治疗前行钆塞酸二钠增强MRI检查的53例患者信息,利用影像处理软件测量107个肝内结节的信号强度,计算肝胆期相对强化比(RER),并比较高强化和低强化HCC结节间的每个结节体积增加20%的时间(TTNP).根据实体肿瘤免疫疗效评价标准(iRECIST),比较肝胆期高强化的HCC结节患者和低强化的HCC结节患者的无进展生存期(PFS)和客观缓解率(ORR)与疾病控制率(DCR)等.结果 高强化HCC结节患者的中位PFS为3.4 个月[95%置信区间(CI):2.5-4.3,n=21),ORR 为 14.3%(3/21),DCR 为 47.5%(10/21).低强化 HCC 结节患者的中位 PFS 为 6.8 个月(95%CI:6.2-7.3,n=32),ORR 为 37.5%(12/32),DCR为75.0%(24/32);进展型高强化HCC结节(n=23)的中位TTNP为2.3个月(95%CI:2.0-2.6),低强化 HCC 结节(n=62)的中位 TTNP 为 6.1 个月(95%CI:5.0~7.2).结论 Gd-EOB-DTPA增强MRI肝胆期肝内HCC结节的强化程度与结节TTNP、PFS、DCR明显相关.
目的 探讨长链非编码RNA HOTAIR在肝细胞癌(HCC)组织中的表达及对HCC细胞奥沙利铂耐药的影响.方法 实时荧光定量反转录聚合酶链反应(RT-qPCR)检测HOTAIR在47例HCC肿瘤组织和2株细胞系的表达水平,分析HOTAIR对HCC患者的总生存期(OS)的影响.应用小干扰RNA(si-HOTAIR)对HOTAIR进行敲低,对照组转染空白质粒(si-NC),流式细胞技术、细胞活力检测试剂盒检测细胞的凋亡比例和奥沙利铂(OxP)的半数抑制浓度(1Cs0)值.结果 HOTAIR在HCC肿瘤组织的表达水平高于癌旁组织,差异有统计学意义(t=5.976,P<0.001),HOTAIR高表达的患者OS较低表达的患者缩短(P<0.01).OxP干预HepG2和Huh7细胞,si-HOTAIR 组凋亡率分别为(40.83±0.89)%和(41.30±1.50)%,高于 si-NC 组[(13.40±0.36)%、(15.50±0.80)%],差异有统计学意义(t=28.64,P<0.001;t=15.46,P<0.001).HOTAIR 敲低后,OxP 对 HepG2 和 Huh7 细胞的 IC50 分别从(31.64±1.07)μmol/L 和(28.36±0.45)μmol/L下降至(15.09±0.83)μmol/L 和(14.13±1.36)μmol/L,差异有统计学意义(t=12.25,P<0.01;t=9.97,P<0.05).结论 HOTAIR在HCC组织中高表达,HOTAIR表达高的患者预后较差,敲低HOTAIR可以提高HCC细胞对OxP的敏感性.
Objective The aim of this study is to identify the risk factors associated with orocutaneous fistula (OCF) formation after free flap reconstruction for oral squamous cell carcinoma (SCC). Methods Patients undergoing free flap reconstruction for oral SCC were retrospectively enrolled. The relationship between clinicopathologic variables and OCF formation was analyzed by univariate and multivariate analyses. Results A total of 87 OCFs occurred in 856 patients. Univariate analysis revealed cachexia, tumor at the tongue/floor of the mouth (TFOM), T4 stage, preoperative hemoglobin level, pull-through procedure, preoperative albumin level, and surgical site infection were associated with the formation of OCF. Multivariate analysis confirmed the independence of cachexia, TFOM, T4 stage, and surgical site infection in predicting OCF development. Conventional wound care could achieve successful fistula closure in 82.4% of the patients with a median time of 28 days. Conclusions OCF formation was common after free flap reconstruction. The presence of cachexia, TFOM tumor site, T4 stage, and surgical site infection significantly increased the risk of OCF formation. Although it required a long period, conventional wound care can obtain satisfactory outcomes in OCF management.
In this work, we first prove the existence of the classic solutions to the dimensionless bipolar Vlasov–Poisson–Boltzmann equations by employing hypocoercive properties of the linear Boltzmann operators. Based on the uniform estimates and employing the Ohm’s law, two fluids Navier–Stokes–Poisson system is derived from the dimensionless Vlasov–Poisson–Boltzmann equations.
The Budyko framework is an effective and widely used method for describing long-term water balance in large catchments. However, it only considers the limits of water and energy in evaporation (E), and ignores the impacts of climate seasonality and water storage capacity (Sc), resulting in errors for Mediterranean climate and catchments with small Sc. Here we combined the Ponce-Shetty model with Budyko hypothesis, and analytically generalized Budyko framework with physical accounts of climate seasonality and Sc. Precipitation (P), potential evaporation (PE), and Sc are used to represent the limits of water, energy, and space for E, respectively. Our results show that previous Budyko-type equations can be treated as special cases of generalized Budyko-type equations with uniform P and PE and infinite Sc. The new generalized equations capture the observed decrease in E due to asynchronous P and PE and small Sc, and perform better than the Budyko-type equations with varying parameters in the contiguous United States with fewer parameters. Overall, our generalization of Budyko framework improves the robustness and accuracy for estimating mean annual E with the aid of physical interpretation, and will facilitate water balance assessment at regional to global scales.
Objective:To observe the expression of plakophilin 3 (PKP3) in pancreatic cancer, and to discuss the effect of PKP3 on the proliferation and migration of pancreatic cancer cells.Methods:The online biometric analysis network database gene expression profiling interactive analysis (GEPIA) was used to observe the expression level of PKP3 in pancreatic cancer. A total of 25 cases of pancreatic cancer tissues and their corresponding normal tissues that were treated in our hospital from April 2019 to April 2021 were collected. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of PKP3 in tissues. Western blotting was used to detect the expression of PKP3 in SW1990, BXPC3 human pancreatic cancer cell lines, and human normal pancreatic ductal epithelial cells (HPDE). The small interfering RNA was used to construct PKP3 low-expressing cell lines, which were divided into siPKP3-1, siPKP3-2 and negative control (NC-PKP3) groups. The cell counting kit-8 (CCK-8) assay was used to detect the proliferation ability of pancreatic cancer cells, and the scratch healing experiment and the Transwell experiment was used to detect the migration ability. The t test was used for comparison between groups. Results:The expression level of PKP3 in pancreatic cancer tissues was (2.32±0.93), which was significantly higher than that in normal pancreatic tissues (1.57±0.42, t=9.246, P<0.01). Western blotting results showed that the expression of PKP3 in pancreatic cancer cells BXPC3 was higher than in HPDE [(1.74±0.15) times], and the expression in SW1990 cells was higher than in pancreatic cell HPDE [(1.34±0.08) times]. The CCK-8 assay indicated that at 72 h after transfection, the absorbance values of siPKP3-1 and siPKP3-2 groups in BXPC3 cells were 2.09±0.37 and 1.67±0.42, respectively, which were significantly lower than in the NC-PKP3 group (3.66±0.67, t=10.683, 11.361, P<0.01). The absorbance values of the siPKP3-1 and siPKP3-2 groups in SW1990 cells were 2.36±0.45 and 1.68±0.39, respectively, which were significantly lower than in the NC-PKP3 group (3.54±0.98, t=7.664, 8.727, P<0.01). At24 h after transfection, the scratch healing experiment showed that the percentage of scratch healing in the siPKP3-1 and siPKP3-2 groups in BXPC3 cells was (36.14±4.77)% and (22.56±5.15)% respectively, which was significantly lower than in NC-PKP3 group [(78.61±5.03)%, t=9.375, 9.716, P<0.01]. In siPKP3-1 and siPKP3-2 groups in SW1990 cells, the percentages of scratch healing were (18.03±3.85)% and (23.12±5.02)% respectively, which were significantly lower than the NC-PKP3 group [(68.33±6.98)%, t=9.772, 9.913, P<0.01]. Transwell Experiments showed that the number of cells penetrating the membrane in the siPKP3-1 and siPKP3-2 groups in SW1990 cells was (33.23±4.26) and (35.93±5.76) cells/field respectively, which was less than in NC-PKP3 group [(67.33±5.98)/field, t=8.551, 9.132, P<0.01). The number of cells penetrating the membrane in the siPKP3-1 and siPKP3-2 groups in BXPC3 cells was (40.61±5.17)/field and (37.08±4.19)/field respectively, which was less than in NC-PKP3 group [(70.84±6.23)/field, t=9.834, 9.019, P<0.01). Conclusion:PKP3 is up-regulated in pancreatic cancer tissues and cells. Knockdown of PKP3 expression can significantly inhibit the proliferation and migration of pancreatic cancer cells.
In this work, the Poisson-Nernst-Planck-Fourier system in three dimensions is considered. For when the initial data regards a small perturbation around the constant equilibrium state in a H 3 ∩ Ḣ − s (0 ≤ s ≤ 1/2) norm, we obtain the time convergence rate of the global solution by a regularity interpolation trick and an energy method.
Objective The association between metastasis to the lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) and cN0 papillary thyroid carcinoma (PTC) located in the thyroid isthmus remains unknown; therefore, our goal was to analyze the characteristics of LN-prRLN metastasis of cN0 PTCs of the thyroid isthmus and determine its potential predictors. Patients and methods This retrospective study included patients who underwent bilateral central neck dissection between January 2018 and January 2021. The specimen was divided into five groups of prelaryngeal lymph node (LN), pretracheal LN, left paratracheal LN, lymph node anterior to the right recurrent laryngeal nerve (LN-arRLN), and LN-prRLN. Univariate and multivariate analyses were used to assess the association between the clinical pathologic variables and LN-prRLN metastases. Surgical complications were presented descriptively. Results A total of 357 patients were included, LN-prRLN metastasis occurred in 23 (6.4%) patients, and LN-prRLN was positive only when there were other LN metastases, especially LN-arRLN metastases. Other independent risk factors for LN-prRLN included foci numbers ≥2, tumor size ≥5.0 mm, and extrathyroidal extensions. The rates of permanent hypoparathyroidism and vocal cord paralysis were 1.1% and 2.0%, respectively. Conclusion LN-prRLN metastases should not be ignored in cN0 PTC located in the thyroid isthmus; however, its dissection is a safe procedure, and the status of LN-arRLN can be a reliable predictor for LN-prRLN metastases.
Objective:Observation of the effect of centromere protein U (CENPU) on the proliferation, migration and invasion of hepatocellular carcinoma cells.Methods:Short hairpin RNA (shRNA) was used to construct low-expressing HepG2 cell lines, divide it into an experimental group (sh-HepG2) and a control group (NC); Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and protein immunoblotting (Western blotting) were used to detect the expression of CENPU in the experimental and control groups; cell counting kit (CCK-8) was used to detect its effect on The effect of HepG2 on the proliferation ability of HepG2 was detected by using the CCK-8 kit; the effect of HepG2 migration ability was detected by using the scratch assay; the effect of HepG2 invasion ability was detected by using the Transwell assay; the experimental data were analyzed by using SPSS 26.0 statistical analysis software.Results:The results of RT-qPCR showed that the expression in the experimental group was lower than that in the control group (1.49±0.14 vs. 6.72±0.21, t=8.593, P<0.01), and the difference was statistically significant; the relative expression of CENPU protein in the experimental group was lower than that in the control group (1.01±0.13 vs. 2.12±0.04, t=11.572, P<0.05), and the difference was statistically significant; CCK-8 results showed that the absorbance (A) values of the experimental group at 0, 24, 48 and 72 h were lower than those of the control group (0.40±0.01, 0.46±0.02, 0.73±0.01, 1.29±0.02 vs. 0.39±0.01, 0.63±0.01, 0.99±0.02, 1.73±0.01, t=8.735, 9.774, 7.682, 4.482, P<0.01), all differences were statistically significant; Transwell results showed that the number of invaded cells in the experimental group at 24 h was lower than the number of invaded cells in the control group (63±3.57 vs. 143±2.49, t=14.758, P<0.05), the difference was statistically significant; the scratch test showed that the number of migrated cells in the experimental group at 24 h was lower than that in the control group (29.51±7.26 vs. 61.31±3.71, t=11.385, P<0.05), and the difference was statistically significant. Conclusion:CENPU promotes the proliferation, invasion, and migration of hepatocellular carcinoma cells.
Objective:To detect the expression of GINS complex subunit 4 (GINS4) protein in hepatocellular carcinoma tissues and observe its effect on the invasion and proliferation of hepatocellular carcinoma cells.Methods:From September 2019 to December 2020 in our hospital, 60 patients with hepatocellular carcinoma were collected during surgery and hepatocellular carcinoma tissues and corresponding para-cancerous tissue specimens were selected as the observation group and the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting was used to detect the expression of GINS4 in hepatocellular carcinoma tissues, use specific short hairpin RNA (shRNA) to construct low-expressing stable hepatocellular carcinoma cell lines, and divide them into experimental groups (shRNA group) and the control group (NC group); Transwell tested its ability to invade HepG2 cells; colony formation test and cell counting kit (CCK-8) test tested its proliferation ability on HepG2 cells. Comparison between groups is by paired sample t test. Results:RT-qPCR showed that the expression of GINS4 in hepatocellular carcinoma tissues (2.89±0.11) was higher than that in adjacent tissues (1.34±0.15), and the difference was statistically significant ( t=8.56, P<0.01). Western blot showed that the expression of GINS4 in hepatocellular carcinoma tissue was (1.54±0.76) times higher than that in adjacent tissues, and the difference was statistically significant ( t=2.67, P<0.05). After shRNA transfection of HepG2 cells, GINS4 in the experimental group The expression level was (1.88±0.34) times lower than that of the control group, and the difference was statistically significant ( t=7.43, P<0.05); the Transwell experiment showed that the number of perforated cells in the experimental group was (56.33±3.51) compared with the control group (90.42±1.53) cells were significantly reduced, and the difference was statistically significant ( t=3.34, P<0.01); the colony formation experiment showed that the number of cell clusters in the experimental group (83.33±7.37) was significantly less than that in the control group (345.00±16.64). The difference was statistically significant ( t=15.28, P<0.01); CCK-8 experiment showed that the 3 d absorbance of the experimental group was (1.43±0.11) lower than that of the control group (2.15±0.15), and the difference was statistically significant ( t=6.52, P<0.001). Conclusion:The expression of GINS4 in hepatocellular carcinoma tissues is higher than that in adjacent tissues. Reducing the expression of GINS4 can significantly inhibit the invasion and proliferation of hepatocellular carcinoma cells.
Objective PD-L1 is one of the predictors of immunotherapy efficacy. Our goal was to analyze its expression and prognostic significance in high-grade salivary gland carcinoma (SGC). Methods PD-L1 expression was evaluated using paraffin-embedded specimens from patients with surgically treated high-grade SGC, and it was scored by the tumor proportion score (TPS), combined positive score (CPS), and immune cell (IC) score. Associations between clinicopathological variables, disease-free survival (DFS), overall survival (OS) and PD-L1 expression were assessed. Results TPS≥1% occurred in 47 patients with an incidence of 43.1%, and it was significantly related to an advanced tumor stage. In patients with TPS<1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year DFS rates were 36%, 26%, and 13%, respectively, and the difference was significant. In patients with TPS<1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year OS rates were 49%, 24%, and 13%, respectively, and the difference was significant. CPS≥1 occurred in 87 patients with an incidence of 79.8%. IC scores of 0, 1, 2, and 3 were noted in 24 (22.0%), 37 (33.9%), 31 (28.4%), and 17 (15.6%) patients, respectively. Both CPS and IC scores had no impact on DFS or OS. Conclusions The expression of PD-L1 in tumor cells of high-grade SGCs was not uncommon, and it was significantly associated with tumor stage. PD-L1 expression in tumor cells rather than in immune cells indicated a poor prognosis.
Objective: Our objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion. Methods: A total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes. Results: In 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 +/- 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy. Conclusion: RAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue. (C) 2020 AACE. Published by Elsevier Inc. All rights reserved.
目的 探讨siRNA沉默结肠癌转移相关基因1(MACC1)表达对耐药性非小细胞肺癌细胞株A549增殖及侵袭的影响.方法 培养非耐药性和耐药性非小细胞肺癌A549细胞,应用RT-PCR技术检测MACC1 mRNA的表达水平;通过化学合成特异性siRNA,与阳离子脂质体Lipofectamine 2000形成复合体,转染耐药性A549细胞,RT-PCR检测转染效果;继续顺铂药物处理耐药性A549细胞,MTT法检测细胞增殖抑制率;Hoechst33258染色法观察siMACC1后耐药性A549细胞的凋亡形态;Transwell法检测siMACC1后耐药性A549细胞迁移能力;Western blot法检测siMACC1后耐药性A549细胞周期蛋白E-cadherin和N-cadherin的表达水平.结果 与耐药性A549细胞组比较,非耐药性A549细胞组中MACC1 mRNA表达量显著下降(P<0.05).与siRNA NC耐药性A549细胞组比较,siRNA MACC1耐药性A549细胞组中MACC1 mRNA表达量显著降低(P<0.05),细胞增殖抑制率上升(P<0.05);Hoechst 33258细胞染色结果表明siRNA MACC1耐药性A549细胞组发生细胞皱缩,细胞核聚集,细胞形态学呈现细胞凋亡改变;Transwell实验表明MACC1基因沉默后,细胞迁移能力变弱;Western blot结果表明MACC1基因沉默后,与siRNA NC耐药性A549细胞组比较,siRNA MACC1耐药性A549细胞组中E-cadherin蛋白表达显著增加(P<0.05),N-cadherin蛋白表达显著减少(P<0.05),细胞的侵袭转移能力显著减弱.结论 MACC1在耐药性A549细胞中的异常升高,可能是肺癌肿瘤细胞耐药性产生的分子机制之一.siRNA MACC1能够有效转染耐药性A549细胞,能显著地抑制耐药性A549细胞增殖与侵袭.
洪涝灾害往往容易在短期内突然发生,从而造成巨大的人员伤亡和财产损失,但目前有关突发性洪涝现象的甄别与分析并没有达成共识.在利用标准化前期降水指数SAPI(Standardized Antecedent Precipitation Index)评估出逐日洪涝状态的基础上,提出突变性洪涝指数AFI(Abrupt Flood Index)以综合反映水量由前期(当天)到后期(后10天)突变及后期洪涝程度,同时定义并计算AFI阈值AFI,,认为AFI超过AFI,的日期为临界状态,后期将发生突变性洪涝事件.以汉江上游流域为例计算出该流域1972~ 2017年逐日AFI指数,并利用AFIt判别出了处于临界状态的日期.进一步分析表明,AFI指数能够较好地反映突变性洪涝现象,利用AFI指数甄别出的洪涝临界状态有利于识别流域突变性洪涝事件并有助于流域水资源系统应急管理.