Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Objective To investigate the in vitro antibacterial effect of Radix Sophorae Flavescentis on tigecycline-resistant carbapenem-resistant Klebsiella pneumonia(CRKP)and elucidate how Radix Sophorae Flavescentis restores the sensitivity of CRKP to tigecycline through the efflux pump pathway.Methods The CRKP standard strain BAA1705 was induced to be tigecycline-resistant using the microdilution broth method,and the expression of efflux pumps was verified by efflux pump inhibitors.The fractional inhibitory concentration index(FIC)was calculated using the microdilution checkerboard method to determine the minimum inhibitory concertration(MIC)of the two drugs in combination.Fluorescent real-time quantitative PCR(qRT-PCR)was used to analyze the expression of the AcrB gene before and after Radix Sophorae Flavescentis treatment,and the e?ux pump activity was validated by the Rhodamine 6G e?ux assay.Results The e?ux pump inhibition experiment on the artificially induced T-BAA1705 strain showed overexpression of e?ux pumps.The combined antibacterial test results indicated synergy between Radix Sophorae Flavescentis and tigecycline(FIC=0.375 2).The qRT-PCR results showed that the AcrB levels in the Radix Sophorae Flavescentis monotherapy group were lower than in the untreated group(0.018±0.002 vs 0.040±0.001),and the AcrB levels(0.009±0.001),RamA levels(0.184±0.003)and MarA(0.013±0.001)levels in the combination therapy group were all lower than in the untreated group(0.040±0.001,0.387±0.016,0.125±0.007),while the AcrR level was higher than in the untreated group(0.388±0.001 vs 0.288±0.001),and the differences were statistical significance(t=12.28～47.12,all P<0.05);the e?ux pump activity in the Radix Sophorae Flavescentis monotherapy group and the combination therapy group was lower than in the untreated T-BAA1705(60.667±0.448,60.267±0.376,65.133±0.296),and the differences were statistical significance(t=8.31,10.17,all P<0.05).Conclusion Radix Sophorae Flavescentis can restore the sensitivity of tigecycline-resistant CRKP to tigecycline and effectively inhibit bacterial growth when used in combination with tigecycline.The mechanism may involve Radix Sophorae Flavescentis inhibiting the expression of the AcrAB-TolC e?ux pump.

Objective To investigate the in vitro antibacterial effect of Radix Sophorae Flavescentis on tigecycline-resistant carbapenem-resistant Klebsiella pneumonia(CRKP)and elucidate how Radix Sophorae Flavescentis restores the sensitivity of CRKP to tigecycline through the efflux pump pathway.Methods The CRKP standard strain BAA1705 was induced to be tigecycline-resistant using the microdilution broth method,and the expression of efflux pumps was verified by efflux pump inhibitors.The fractional inhibitory concentration index(FIC)was calculated using the microdilution checkerboard method to determine the minimum inhibitory concertration(MIC)of the two drugs in combination.Fluorescent real-time quantitative PCR(qRT-PCR)was used to analyze the expression of the AcrB gene before and after Radix Sophorae Flavescentis treatment,and the e?ux pump activity was validated by the Rhodamine 6G e?ux assay.Results The e?ux pump inhibition experiment on the artificially induced T-BAA1705 strain showed overexpression of e?ux pumps.The combined antibacterial test results indicated synergy between Radix Sophorae Flavescentis and tigecycline(FIC=0.375 2).The qRT-PCR results showed that the AcrB levels in the Radix Sophorae Flavescentis monotherapy group were lower than in the untreated group(0.018±0.002 vs 0.040±0.001),and the AcrB levels(0.009±0.001),RamA levels(0.184±0.003)and MarA(0.013±0.001)levels in the combination therapy group were all lower than in the untreated group(0.040±0.001,0.387±0.016,0.125±0.007),while the AcrR level was higher than in the untreated group(0.388±0.001 vs 0.288±0.001),and the differences were statistical significance(t=12.28～47.12,all P<0.05);the e?ux pump activity in the Radix Sophorae Flavescentis monotherapy group and the combination therapy group was lower than in the untreated T-BAA1705(60.667±0.448,60.267±0.376,65.133±0.296),and the differences were statistical significance(t=8.31,10.17,all P<0.05).Conclusion Radix Sophorae Flavescentis can restore the sensitivity of tigecycline-resistant CRKP to tigecycline and effectively inhibit bacterial growth when used in combination with tigecycline.The mechanism may involve Radix Sophorae Flavescentis inhibiting the expression of the AcrAB-TolC e?ux pump.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD)mouse,investigating the activation of neurons in different brain regions,and identifying differentially expressed genes(DEGs)and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD.Methods Randomly assign 32 male C57BL/6J mice,aged two months,to an OCD group and a control group(n=16).Administering quinpirole(0.75 mg/kg)via subcutaneous injection to the OCD group mice every other day for a total of 19 injections,while the control group mice received an equivalent volume of saline solution.Following the completion of the model construction,open field testing,elevated plus maze testing,and marble burying tests were conducted.After the completion of behavioral studies,tissue samples were collected.Neuronal damage was assessed using Nissl staining,while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining.Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways.The expression of inflammatory cytokines,including TNF-α,NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),and IL-6,was detected using Western Blot analysis.Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors.Neurons in the hippocampal and hypothalamic regions exhibit signs of damage.The expression of c-Fos and Iba1 proteins is increased in the cortex,striatum,hypothalamus,and other brain regions.Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α,p-NF-κB p65,and IL-6.Conclusions In OCD mouse,neurons in multiple brain regions are abnormally activated,microglia exhibit dysfunction,and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.

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.

Under the background of the Healthy China Strategy, public hospitals urgently need to break through the limitations of the traditional medical mode, build a precise and continuous medical service system to meet the growing personalized health needs of the people. In 2022, a tertiary public hospital launched a multidisciplinary whole course management service practice. By integrating multidisciplinary medical and health resources, clarifying service targets and contents, forming a whole course management service team, constructing a supporting information platform, linking full process services, creating standardized service processes, and providing patients with comprehensive, full process, professional, and accurate full cycle intervention management and care. The hospital covered diseases in stages, ensuring continuous medical for patients after leaving the hospital, improving their medical experience, and supporting the high-quality development of the hospital. As of June 2024, the hospital′s multidisciplinary whole course management services had covered 25 departments and 41 disease, and 43 management teams have been established. A total of 7 453 patients signed up for the whole course service. This practice achieved good results, could provide references for the implementation of whole course management services led by public hospitals.