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 establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

Objectives: Lack of physical activity has a critical effect on the physical and mental health of adolescents. This study examined the influence of family adversities on the longitudinal changes in physical inactivity among adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: The study used multi-wave data from the Korean Children and Youth Panel Survey, including 2590 Korean adolescents aged 12-14 years. The longitudinal trajectory of physical inactivity among adolescents and the effects of related factors were estimated using a latent growth modeling method. Results: Our results revealed a significant increase in physical inactivity among adolescents over time. At the onset of the pandemic, approximately one-seventh of Korean middle schoolers reported a lack of physical activity. However, 3 years later, during the quarantine, nearly one-fifth of these adolescents reported a significant increase in their physical inactivity. Initially, low level parental education was predictive of adolescents’ physical inactivity, but this effect diminished over time, becoming statistically insignificant by the end of the 3-year period. Moreover, the increase in physical inactivity over the 3 years was significantly influenced by parental rejection. Conclusions These findings suggest that adolescents who experience parental rejection are more likely to report an increase in sedentary behaviors in contexts such as the COVID-19 pandemic.

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Lung cancer has the highest incidence rate and mortality in China, even in the world, and non-small cell lung cancer (NSCLC) accounts for about 85%. The growth and metastasis of tumor depend on the generation of blood vessels, and anti-angiogenic therapy is playing an increasingly important role, however, no significant improvement was observed in the underwent anti-angiogenic agents used for patients alone. In recent years, the application of immune checkpoint inhibitor (ICI) has significantly improved the prognosis of some lung cancer patients, however, the objective response rate of patients receiving ICI alone is low. While anti-angiogenic agents and ICI both regulate the tumor immune microenvironment and have a potential synergistic mechanism, showing a bright prospect in the combined application of anti-tumor therapy. In this review, we focused on the research and application of anti-angiogenic agents in combination with ICI in advanced non-small cell lung cancer.

Objective To investigate the application of Critical Care Chest Ultrasonic Examination (CCUE)-plus (CCUE-plus) in the etiological diagnosis in patieuts with dyspnea and/or hemodynamic instability caused by abdominal abnormalities.Methods Patients who suffered from dyspnea and/or hemodynamic instability in the Department of Critical Care Medicine,Xiangya Hospital,Central South University from September 2013 to September 2016 were recruited in this study.A total of 255 consecutive patients completed CCUE within 2hrs of admission.If the diaphragm could not be seen in the routine phrenic points according to Bedside Lung Ultrasound Evaluation (BLUE) protocol,it would be found along midaxillary line and defined m-point.The 59 patients with altered diaphragmatic position (m-point was more than 2 cm higher than phrenic point) received sequential abdominal ultrasonography.The latter ultrasonographic findings were compared with CT results.Results There were 42 (71.19％) cases with positive findings of abdominal ultrasonography,including 18 cases of seroperitoneum,16 cases of intestinal obstruction and 8 cases combined.Compared with 56 patients who applied with CT exam,the abdominal ultrasonography revealed a sensitivity of 76.7％ and a specificity of 100.0％ to diagnose seroperitoneum (AUCRoc 0.917);whereas the sensitivity was 75.0％ and the specificity was 90.9％ (AUCRoc 0.778) to diagnose intestinal obstruction.Moreover,there were 44 (74.58％) patients with normal left ventricular systolic function;more than three quarters (46/59,77.97％) patients had pulmonary consolidation.Conclusion In patients with dyspnea and/or hemodynamic instability caused by abdominal abnormalities and altered diaphragmatic position in BLUE protocol,CCUE-plus protocol has a high positive predictive value of more than 90％ in abdominal abnormality.The findings of abdominal ultrasonography may change therapeutic target from cardio-pulmonary optimization to relief of intestinal obstruction or drainage of seroperitoneum.

BACKGROUND:Lumbar spinal stenosis can result in lumbar nerve root pain and other symptoms or even disability, which seriously impacts people’s quality of life. Interbody fusion is the main clinical treatment. Studies have shown that an interspinous fusion cage is prone to have hairline fractures and loss of implant; therefore, biomechanical properties and biocompatibility of the interbody fusion cage at L4/5need to be studied.
OBJECTIVE:To analyze the stability of the interspinous fusion cage at L4/5, and to explore the biomechanical properties and biocompatibility of adjacent segments.
METHODS: Ten adult fresh frozen spine specimens were selected and divided into normal group and model group, with five specimens in each group. The specimens were numbered and placed in a special fixture. The interspinous fusion cage, made in Zhengzhou Cast Medical Instrument Co., Ltd., China, was implantedin vivo and fixed using a cage fixator made of Ti6AL-4V ELI.
RESULTS AND CONCLUSION:Artificial vertebral bodies had less strain changes than the normal vertebrae in different implantation positions in terms of central compression, anteflexion, rear protraction, lateroflexion (P < 0.05). During vertebral displacement under the maximum load of 500 N, the linear displacement and angular displacement in anteflexion, rear protraction, left lateral flexion, levorotation were decreased significantly in the model group than the normal group (P < 0.05). These findings indicate that the interspinous fusion cage can maximaly preserve the range of motion of the injured vertebral body, maintain the stability of the segment, and reduce the stress of the intervertebral disc.

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.