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.

OBJECTIVE: To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP). METHODS: The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining. RESULTS: The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01). CONCLUSIONS BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.
Male ; Humans ; Rats ; Animals ; Reactive Oxygen Species ; Tandem Mass Spectrometry ; bcl-2-Associated X Protein ; Rats, Sprague-Dawley ; Erectile Dysfunction/drug therapy* ; Collagen ; Fibrosis ; Disease Models, Animal

Objective:To determine the epidemiology of hyperkalemia and influencing factors in a general population in Pinggu district of Beijing city.Methods:This study was a cross-sectional survey. The subjects were from the epidemiological survey population of chronic diseases in Pinggu district of Beijing city from March to May 2014. All participants completed a questionnaire, anthropological measurement, and venous blood samples collection to detect serum creatinine and potassium and so on. First void morning urine was collected to detect the albumin-creatinine ratio. Hyperkalemia and hypokalemia were defined as serum potassium level>5.0 mmol/L and≤3.5 mmol/L, respectively. Logistic regression analysis method was used to analyze the influencing factors of hyperkalemia.Results:Of the 10 252 people in this study, the prevalence of hyperkalemia was 6.17%(95% CI 5.70%-6.67%), the prevalence of hypokalemia was 0.61%(95% CI 0.47%-0.79%), and the prevalence of participants with serum potassium>5.5 mmol/L was 0.53%(95% CI 0.40%-0.69%). Multivariate logistic regression analysis results showed that males ( OR=1.269, 95% CI 1.074-1.498, P=0.005), diabetes ( OR=1.226, 95% CI 1.008-1.490, P=0.041), increased total cholesterol ( OR=1.219, 95% CI 1.119-1.329, P<0.001), and decreased estimated glomerular filtration rate ( OR=0.971, 95% CI 0.965-0.977, P<0.001) were significantly correlated with the increased risk of hyperkalemia. Usage of renin-angiotensin-aldosterone system inhibitors and diuretics were not found to be significantly associated with the risk of hyperkalemia ( OR=1.018, 95% CI 0.751-1.380, P=0.908; OR=0.638, 95% CI 0.229-1.781, P=0.391). Conclusions:The prevalence of HK in the general population is 6.17%. The male, decreased estimated glomerular filtration rate, diabetes, and increased total cholesterol are influencing factors of hyperkalemia.

Objective:To explore the association between urinary stone disease (USD) and peripheral arterial disease (PAD).Methods:The study was based on the cross-sectional chronic diseases survey performed in Pinggu district, Beijing from March to May, 2014. All subjects completed a questionnaire, physical examination, renal ultrasound examination to detect USD, ankle-brachial index (ABI) examination to detect PAD (defined as ABI<0.9 on either side of the body), and brachial-ankle pulse wave velocity (baPWV) measurement to estimate arterial stiffness. Blood and first morning urine sample were detected for serum creatinine, blood glucose and so on.Results:There were 10 281 participants included in this study. Among these participants, the prevalences of USD and PAD were 5.66% and 3.95%, respectively. Compared with non-stone participants, the persistent USD formers had a higher prevalence of PAD (8.26% vs 3.90%, P<0.001) and baPWV [(16.3±3.5) m/s vs (15.5±3.2) m/s, P<0.001]. Even after adjusting the confounding factors, the persistent USD formers also had a 2.066-fold increased risk of PAD ( OR=2.066, 95% CI 1.276-3.343, P=0.003). In the subgroup analysis, persistent USD patients in older participants who were≥60 years old, women, chronic kidney disease, and central obesity had a significantly increased risk of PAD. Conclusions:In the present population, persistent USD is positively associated with a high risk of PAD and increased arterial stiffness. Patients with persistent USD should be screened for vascular diseases.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective: To observe the effect of metoprolol combined with trimetazidine on coronary heart disease with chronic congestive heart failure, and its effects on myocardial structure, plasma brain natriuretic peptide (BNP) and matrix metalloproteinase-9 (MMP-9). Methods: From January 2016 to November 2017, 160 coronary heart disease patients with chronic congestive heart failure in the First People's Hospital of Wenling were randomly divided into treatment group (78 cases)and control group (77 cases)through random number table method.The control group was given conventional anti-heart failure treatment.The treatment group was treated with metoprolol and trimetazidine.After 3 months of treatment, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume(LVESV), LVEF, BNP and changes in MMP-9 were compared. Results: The total effective rate of the treatment group was 90.36%, which was significantly higher than 77.92% of the control group (χ²=5.024, P<0.05). There were no statistically significant differences in LVESV and LVEDV between the two groups before and after treatment (t=0.07, P=0.47; t=0.75, P=0.22; t=0.90, P=0.18; t=1.24, P=0.10). Compared with before treatment, the LVEF change in the control group had no statistically significant difference(P>0.05), the LVEF of the treatment group was increased[(41.38±9.26)% vs.(46.31±10.8)%] (t=-3.15, P=0.001). After treatment, the LVESV between the treatment group and control group had statistically significant difference[(124.54±16.57)mL vs.(106.36±16.44)mL](t=7.16, P<0.05). The BNP level was decreased in the treatment group after treatment[(4 036.39±696.24)ng/L vs.(3 621.78±732.57)ng/L] (t=3.73, P<0.05), while the BNP level had no statistically significant change in the control group (t=1.47, P=0.07). the MMP-9 level in the treatment group was lower than that before treatment[(396.21±97.56)ng/mL vs.(345.11±86.25)ng/mL](t=3.57, P<0.05), while the MMP-9 level in the control group had no statistically significant change (t=1.06, P=0.15). The MMP-9 and BNP levels decreased more significantly in the treatment group than those in the control group (t=3.73, 3.57, all P<0.05). Conclusion Metoprolol combined with trimetazidine in the treatment of patients with chronic heart failure can significantly alleviate clinical symptoms, reduce the expression level of MMP-9, and is safe for clinical use.Therefore, it is recommended use in clinical.

Objective To prevent and treat of ceramic membrane purification of membrane fouling process of TCM extracts; To explore new methods of forecasting membrane fouling degree.Methods BP neural network model was improved. Methods to fast determine the optimal number of neurons in the hidden layer and fast algorithm for optimizing the weight and threshold of BP neural network were studied. Data of 207 groups of TCM extracts were under network training and prediction.ResultsCompared with the models of multiple regression analysis, basic BP neural network and RBF neural network, the error of the improved BP neural network model was less than that of the BP neural network model, and the mean square error was only 0.0057. In addition, the improved BP neural network model performance was more stable. In the 20 random running experiments, the goal of the success rate achieved up to 95%.Conclusion The improved model has a good network performance, the fitting effect and prediction ability, and can forecast the fouling degree of membrane stably and accurately.

Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study.Methods All participants were investigated by questionnaires,physical examinations and laboratory tests including liver and renal function,lipid profile,serum fasting glucose,glycosylated hemoglobin.Nephrolithiasis was diagnosed by kidney Bultrasonography.Subjects with estimated glomerular filtration rate (eGFR) ＜ 60 ml · min-1 · (1.73 m2)-1were excluded.Results 10 316 individuals were enrolled with an average age of (54.88 ± 10.27) years (range 17-88 years) and the ratio of male to female 1:1.12.The prevalence of nephrolithiasis was 5.6％,3.7％ and 7.8％ for whole population,women and men,respectively.In women,only eGFR in stone group was significantly lower than that in non-stone group (P ＜ 0.05).However,participants in stone group were significantly older (P ＜ 0.05),of higher blood pressure (P ＜ 0.01),higher serum uric acid (P ＜ 0.01),worse renal function (serum creatinine,P ＜ 0.05;eGFR,P ＜ 0.01),and higher low-density lipoprotein (LDL) (P ＜ 0.05),compared with those in non-stone group in men.Logistic regression analysis showed that only eGFR (P ＜ 0.05) was the independent influential factor for kidney stones in women;In men,LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95％CI 1.003-1.317,P ＜ 0.05),except for mean blood pressure and eGFR.After being divided into normal group,borderline high group and high LDL group according to the LDL level,with the increase of LDL,the prevalence of nephrolithiasis was significantly increased by 7.3％,8.3％ and 10.6％ in men respectively.There was no significant relationship between total cholesterol,triglyceride,high-density lipoprotein and nephrolithiasis.Conclusions Dyslipidemia is associated with nephrolithiasis in men,and high LDL cholesterol is an independent risk factor for nephrolithiasis.Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease,but also reduces the risk of kidney stones.