Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Rectal carcinoma is one of the most common gastrointestinal malignancies in China.Surgical resection is its preferred treatment.The scope of lymph node dissection influences the postoperative recurrence and metastasis.There are many studies The significance of lateral lymph node dissection in rectal carcinoma is extensively discussed,here we make a review of lateral lymph node dissection in rectal carcinoma,which may provide assistance for the treatment of rectal carcinoma.

Objective:To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit,bleeding risk and platelet aggregation in very elderly patients. Methods:Arachidonic acid induced platelet aggregation(AA-Ag)was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d).In the study,100 patients with low on-treatment platelet ag-gregation and at high risk of bleeding and low risk of cardiovascular events,were switched to aspirin (40 mg/d)and their platelet aggregation was measured again 7 days later.Their bleeding and upper gastroin-testinal symptoms were also recorded in following 3 months.Results:The study observed a heterogeneous distributed aspirin 100 mg/d AA-Ag (range:0.42% to 28.78%)in the 537 very elderly patients.Aspi-rin 100 mg/d AA-Ag before the switch in aspirin 40 mg/d group was 5.00% ±2.32% and the rate of the patients with low on-treatment platelet aggregation was 71.00%.The rates of melena or occult blood positive,other minimal bleeding,upper gastrointestinal symptoms and a history of gastrointestinal bleeding in 40 mg/d group were higher than those in 100 mg/d group.On a regimen of aspirin 40 mg/d,AA-Ag increased to 11.21% ±4.95%(range:2.12% to 28.84%)with 95.00%of the patients with AA-Ag<20%and the rate of the patients with low on-treatment platelet aggregation was 15.00%.Multiple vari-able analysis revealed that aspirin 40 mg/d AA-Ag was significantly influenced by aspirin 100 mg/d AA-Ag,BMI and platelet counts.The rate of gastrointestinal bleeding decreased from 12.00% to 5.00%, and upper gastrointestinal symptoms decreased from 59.00% to 21.00% after the switch in 40 mg/d group.Conclusion:Switching aspirin dosage from 100 mg/d to 40 mg/d reduces the bleeding events and improves upper gastrointestinal symptoms,thus inhibiting platelet aggregation effectively in very elderly patients.

Objective To compare the efficacy and safety of atorvastatin,rosuvastatin and xuezhikang capsule in elderly.Methods A total of 314 60-to-94-year-old (average (73.6 ± 7.9) years old) patients who were given different doses and types of statins were divided into three groups:the atorvastatin group (108 patients),the rosuvastatin group (104 patients) and the xuezhikang capsule group (102 patients).The serum TG,TC,LDL-C,HDL-C,ALT and CK were examined before and after the treatment which lasted for at least 4 weeks.All patients were divided into moderate risk group (13,12 and 21 patients respectively in 3 groups) ; high risk group (40,44 and 48 patients respectively in 3 groups) and very high risk group (55,48 and 33 patients respectively in 3 groups) according to guidelines on prevention and treatment of dyslipidemia in chinese adults (2007 version).The rate of reaching target goal and the dose when reaching target levels in different risk stratification groups were calculated and compared.Results Serum TC,LDL-C and non-HDL-C were significantly reduced after the 4-week-treatment in all the three groups (P ＜ 0.01).Serum LDL-C level before and after treatment were (3.14 ± 0.78) mmol/L vs.(2.14 ±0.65) mmol/L in atorvastatin group (the arevage dose was (16.4 ± 4.8) mg/d),(2.92 ± 0.77)mmol/L vs.(1.96 ±0.55) mmol/L in rosuvastatin group (the arevage dose was (8.7 ±3.0) mg/d),and (2.70 ±0.62) mmol/L vs.(2.16 ±0.61) mmol/L in xuezhikang capsule group (the arevage dose was (0.9 ± 0.3) g/d).Among all the three groups of patients,the cases of reaching target levels of LDL-C were 13,11 and 20 in patients at moderate risk,were 38(95.0％),38(86.4％) and 40 (83.3％) in patients at high risk,and were 22(40.0％),30(62.5％) and 17(51.5％) in patients at very high risk.There were no statistical differences in the rate of reaching target levels of LDL-C,non-HDL-C and TC in the three groups and at different risks (P ＞ 0.05).One patient in the atorvastatin group showed ALT level elevation ＞ 3 times of the upper limit of normal value,there was no patient with CK level elevation ＞ 5 times of the upper limit of normal value.Conclusion Atorvastatin,rosuvastatin and xuezhikang capsule at low dose and/or standard dose are effective and safety in elderly patients.

OBJECTIVETo study the relationship between endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism and chronic periodontitis (CP) with type 2 diabetes mellitus (T2DM).

METHODSDNA from patients' buccal swabs of CP, CP with T2DM, T2DM and health was isolated and extracted. The eNOS Glu298Asp gene polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively.

RESULTSThe distribution of eNOS Glu298Asp genotype in CP group, T2DM group, CP with T2DM group and health group showed statistical differences (chi2 = 18.503, P = 0.005), and the gene frequency showed statistical differences (chi2 = 8.243, P = 0.041). Compared health group to CP with T2DM group, OR value of the genetype T was 0.962, 95% confidence interval lay in between 0.737 to 1.256, which showed T maybe a protective factor. While OR value of the genetype G was 1.043, 95% confidence interval lay in between 0.781 to 1.391, which showed G maybe a risk factor. However, neither T nor G was statistically significant.

CONCLUSIONBased on these findings, there are some association between eNOS Glu298Asp polymorphism and the risk of CP group, T2DM group, CP with T2DM group.

Chronic Periodontitis ; Diabetes Mellitus, Type 2 ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Nitric Oxide Synthase Type III ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors

Objective To estimate the patterns and frequency of anomalous coronary origin with angiography in the Chinese elderly population and evaluate the correlation between anomalous coronary origin and development of coronary atherosclerotic stenosis. Methods A retrospective analysis was performed on the basis of angiographic data among elderly patients who underwent coronary arteriography in Beijing University First Hospital. Those with anomalous origin of coronary arteries were selected for further assessment and significant stenosis in coronary arteries was recorded.Results Among 2031 patients, 46 patients were found to have anomalous origin of coronary artery,with an incidence rate of 2.3%. Right coronary artery was the most common anomalous vessel, being involved in 26 patients (56.5%). The anomalous origin was more frequent in right coronary artery than in left coronary artery (41.3%). The most common anomaly was right coronary artery arising from left coronary sinus in 13 patients (28.3%). Significant atherosclerotic lesions in the anomalous arteries were seen in 37 patients (80.4%). Conclusions In Chinese elderly population, the anomalous origin of coronary artery is more frequent in right coronary artery, the most common anomaly resides in right coronary artery arising from left coronary sinus. The anomalous coronary artery increases risk for development of coronary atherosclerotic stenosis.

Objective: To study the relationship between C-reactive protein (CRP) gene polymorphisms and the risk of chronic peri-odontitis and severe chronic periodontitis (CP) with type2 diabetes to confirm the effect of genetic factor in chronic periodontitis and chronic periodontitis with type2 diabetes. Methods; DNA was extracted by Chelex-100 from buccal swabs of patients who suffered from chronic periodontitis or chronic periodontitis with type2 diabetes and patients with healthy periodontium. PCR-RFLP was used to test the CRP genotype distribution. The correlationship between the incidence of chronic periodontitis and chronic periodontitis with type2 diabetes and CRP gene polymorphism was analyzed statistically. Results; There was no statistical difference in the distribution of CPR +1059 genotype and allele frequency between experiment group and control group (X~2 = 0. 223, P=0.994). The genotype and allele frequency distribution were in line with Hardy-Weinberg equilibrium. Conclusion; There is no correlation between CRP + 1059G/C single nucleotide polymorphisms and the susceptibility of chronic periodontitis as well as chronic periodontitis with type2 diabetes.