Objective:To investigate the effects and underlying mechanisms of silent information regulator 1(SIRT1)on the dysfunction of umbilical vein endothelial cells(HUVECs)induced by oxidized low-density lipoprotein(ox-LDL).Methods:The impact of ox-LDL on the viability of HUVEC was assessed using the Cell Counting Kit-8(CCK-8)assay, which also facilitated the determination of the optimal ox-LDL concentration.Subsequent to ox-LDL treatment, several parameters were evaluated, including reactive oxygen species(ROS)production, apoptosis, migration, and angiogenesis, utilizing a ROS detection kit, flow cytometry, a Transwell migration assay, and an angiogenesis assay, respectively.The expression levels of apoptosis-related proteins, namely cleaved caspase-3(c-caspase-3), Bcl-2-associated X protein(Bax), B-cell lymphoma-2(Bcl-2), SIRT1, and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α), were quantified using Western blot analysis.Adenoviral vectors were employed to either overexpress or silence SIRT1, while the ROS inhibitor N-acetylcysteine(NAC)was applied to assess its effects on cell function.Additionally, PGC-1α acetylation(Ac-Lys)was investigated through co-immunoprecipitation.Results:In the oxidative model of ox-LDL-stimulated HUVECs, compared to controls, we observed a significant increase in ROS-positive cells(35.9±3.1 vs.5.4±0.9), heightened apoptosis(16.3±0.9 vs.7.6±0.7), diminished endothelial cell migration capacity, and reduced angiogenic capacity.Additionally, there was an elevation in the pro-apoptotic protein c-caspase3 and Bax, alongside a decrease in the anti-apoptotic protein bcl-2.Furthermore, SIRT1 expression was increased, as was the expression of PGC-1α.In comparison to the GFP group(28.5±1.9), the reduction in SIRT1 expression resulted in an increase in apoptosis(37.0±1.9).Conversely, overexpression of SIRT1 mitigated ox-LDL-induced apoptosis(25.2±1.6)(all P<0.05).Notably, the expression levels of PGC-1α and SIRT1 exhibited consistent changes: PGC-1α expression increased with SIRT1 overexpression and decreased when SIRT1 expression was reduced(both P<0.05).The administration of NAC to the ox-LDL-treated group led to a reduction in ROS production( t=11.18, P<0.01)and a significant enhancement in cell function.Immunoprecipitation results indicated that SIRT1 overexpression decreased ox-LDL-induced PGC-1α acetylation( t=18.18, P<0.01), whereas silencing of SIRT1 further increased PGC-1α acetylation levels( t=-19.09, P<0.01). Conclusions:SIRT1 is shown to protect against ox-LDL-induced apoptosis and dysfunction in HUVECs by deacetylating and activating PGC-1α, thereby highlighting its therapeutic potential in the context of endothelial cell injury.

Objective:To investigate the effects and underlying mechanisms of silent information regulator 1(SIRT1)on the dysfunction of umbilical vein endothelial cells(HUVECs)induced by oxidized low-density lipoprotein(ox-LDL).Methods:The impact of ox-LDL on the viability of HUVEC was assessed using the Cell Counting Kit-8(CCK-8)assay, which also facilitated the determination of the optimal ox-LDL concentration.Subsequent to ox-LDL treatment, several parameters were evaluated, including reactive oxygen species(ROS)production, apoptosis, migration, and angiogenesis, utilizing a ROS detection kit, flow cytometry, a Transwell migration assay, and an angiogenesis assay, respectively.The expression levels of apoptosis-related proteins, namely cleaved caspase-3(c-caspase-3), Bcl-2-associated X protein(Bax), B-cell lymphoma-2(Bcl-2), SIRT1, and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α), were quantified using Western blot analysis.Adenoviral vectors were employed to either overexpress or silence SIRT1, while the ROS inhibitor N-acetylcysteine(NAC)was applied to assess its effects on cell function.Additionally, PGC-1α acetylation(Ac-Lys)was investigated through co-immunoprecipitation.Results:In the oxidative model of ox-LDL-stimulated HUVECs, compared to controls, we observed a significant increase in ROS-positive cells(35.9±3.1 vs.5.4±0.9), heightened apoptosis(16.3±0.9 vs.7.6±0.7), diminished endothelial cell migration capacity, and reduced angiogenic capacity.Additionally, there was an elevation in the pro-apoptotic protein c-caspase3 and Bax, alongside a decrease in the anti-apoptotic protein bcl-2.Furthermore, SIRT1 expression was increased, as was the expression of PGC-1α.In comparison to the GFP group(28.5±1.9), the reduction in SIRT1 expression resulted in an increase in apoptosis(37.0±1.9).Conversely, overexpression of SIRT1 mitigated ox-LDL-induced apoptosis(25.2±1.6)(all P<0.05).Notably, the expression levels of PGC-1α and SIRT1 exhibited consistent changes: PGC-1α expression increased with SIRT1 overexpression and decreased when SIRT1 expression was reduced(both P<0.05).The administration of NAC to the ox-LDL-treated group led to a reduction in ROS production( t=11.18, P<0.01)and a significant enhancement in cell function.Immunoprecipitation results indicated that SIRT1 overexpression decreased ox-LDL-induced PGC-1α acetylation( t=18.18, P<0.01), whereas silencing of SIRT1 further increased PGC-1α acetylation levels( t=-19.09, P<0.01). Conclusions:SIRT1 is shown to protect against ox-LDL-induced apoptosis and dysfunction in HUVECs by deacetylating and activating PGC-1α, thereby highlighting its therapeutic potential in the context of endothelial cell injury.

Background: Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment out?comes. We conducted a phase II randomized controlled trial to evaluate the efcacy of intensity?modulated radio?therapy with concomitant weekly cisplatin on locally recurrent NPC. Methods: Between April 2002 and January 2008, 69 patients diagnosed with non?metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group(n= 35). All patients received intensity?modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23–53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m2 by intravenous infusion weekly during radiotherapy. Results: The median follow?up period of all patients was 35 months (range 2–112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3?year and 5?year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showedthat concomitant chemoradiotherapy significantly improved the 5?year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, P = 0.009), stages III–IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%,P= 0.017), and tumor volume >26 cm3 (37.6% vs. 0%, P = 0.006). Conclusion: Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm3.

Objective:To establish a method for the uncertainty evaluation of the determination of benzoic acid. Methods: The content of benzoic acid was determined by acid-base titration. By constructed mathematics model, the source of the measurement uncer-tainty was analyzed, and the uncertainty components were quantized and combined. Results:The expanded uncertainty of benzoic acid was 0. 36% and the results were expressed as(99. 99 ± 0. 36%,k=2). Conclusion:The mathematics model is reasonable and relia-ble,and can be used in the uncertainty evaluation of content measurement of benzoic acid.

Objective To retrospectively analyze the influence of intensity-modulated radiotherapy (IMRT) on tumor regression in primary nasopharyngeal carcinoma (NPC).Methods 272 patients with NPC received radical radiotherapy alone,196 by IMRT with a total treatment time of 6 weeks,and 76 by bilateral field conventional radiotherapy (CRT) with the total treatment timc of 7 weeks.Results By the end of radiotherapy,the primary tumor and neck lymph node residual rates of the IMRT group were 36.7％ and 44.2％,respectively,both significantly higher than those of the GRT group (21.1％ and 26.6％,x2 =6.15,3.99,P ＜ 0.05).Three months after the radiotherapy,residual lesions were observed at the nasopharynx or neck lymph nodes in 12 of the IMRT group,with a residual rate of 6.1％,not significantly different from that of the CRT group (9.2％,7/76).The 12 residual lesions of the IMRT group all vanished completely 4 -9 months after the radiotherapy.Conclusions There is an obvious difference in regressive mode between IMRT and CRT technique in NPC treatment.At the end of IMRT,the tumor residual rate is slightly increased.However,the delivered dose of gross tumor volume (GTV) is sufficient,and the boost dose should not be delivered indiscreetly.

Objective To investigate the tendency of quality of life in patients with nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy. Methods Quality of life in NPC patients was assessed using FACT-H&N and NPC-QOL Patients were divided into nine groups according to the treatment period :before treatment group, 0 -20 Gy group, 20 -50 Gy group, > 50 Gy group, 0 -6 months after treatment group, 6 - 12 mouths group, 1 -2 years group, 2 -3 years group and 3 -5 years group. Scores of FACT-H&N and NPC-QOL were compared between the either two groups. Results 450 NPC patients were assessed. The total score of FACT-H&N decreased during the treatment and then increased six months after the treatment. The tendencies of physical and functional well-being were similar. The social/family and emotional well-being did not change significantly along with the treatment but the scores of head and neck well-being and NPC-QOL decreased obviously. Xerotomia was aggravated from the initiation of treatment and became the most severe at 6 - 12 months after treatment. 50% - 60% of the patients with disease-free reported severe xerotomia at 3 -5 years after radiotherapy. Incidence of severe trismus increased up to 14% at 3 -5 years after treatment. Conclusions Quality of life of NPC patients with conventional radiotherapy deteriorates during the treatment period, but recovers to the normal level six months after the treatment. Xerotomia and trismus can affect the quality of life of NPC patients.