The activation of the P2X7 receptor as an ATP-gated ion channel,triggers the release of pro-inflammato-ry cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons,thereby exacerbating the transmission of pain.In preclinical cancer pain models,it has the potential to serve as a new therapeutic target for cancer pain management.

AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.

Objective To statistically analyze the allergen-specific IgE test results for allergic patients and observe the distribution of allergens and their prevalence trends.Methods Allergen-specific IgE test results were collected from 12 486 patients with suspected allergic diseases who attended the outpatient clinic of the Department of Dermatology of the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2023,and the distribution of the positivity rate of various allergens and their differences among different age,gender and seasonal subgroups were statistically analyzed.Results Allergen-specific IgE positive results were found in 5 109 cases out of 12 486 patients with suspected allergic diseases,with a positive rate of 40.92%.Between different gender groups,the allergen positivity rate were 45.41%(2 371/5 221)in males and 37.69%(2 738/7 265)in females,respectively,and the difference in positivity rate between males and females was statistically significant(x2=74.99,P<0.001).The allergen positivity rate among different age groups was highest in the 3～<6 years group(60.00%),followed by the 6～<18 years group(54.92%),and lowest in the≥60 years group(29.18%),with statistically significant differences in allergen positivity rates among different age groups(x2=344.97,P<0.001).The top three overall allergen positivity rates were milk(11.73%),dwarf ragweed/artemisia/rudolfia/quinoa(11.43%)and house dust mite(10.82%),and the positivity rates of milk and house dust mite had a tendency to increase year by year.The highest allergen positivity rate among groups in different seasons was in summer(42.28%),followed by fall(41.32%)and lowest in winter(38.31%),and the difference in allergen positivity rates among the four seasons was statistically significant(x2=9.09,P=0.028).Dwarf ragweed/artemisia/rutabaga/quinoa had the highest positivity rate in the fall(15.75%),while milk(14.59%)and egg white(2.58%)had the highest positivity rates in the summer,and the differences in the positivity rates of dwarf ragweed/artemisia/rutabaga/quinoa,milk and egg white between the four seasons were statistically significant(x2=92.50,70.45,8.10,all P<0.05).Multiple positives were present for allergen-specific IgE,with 22.18%single positives and 18.92%double and more than double positives.Positive test results for ingestion were mainly distributed in the lower levels,while positive test results for inhalation were more distributed in the higher levels,especially for dwarf ragweed/artemisia/rutabaga/quinoa,which were most distributed in level 6.Conclusion Different types of allergens have different distribution characteristics among different genders,ages and seasons,the distribution levels of positive results are different,and there are multiple positive results.Based on the distribution characteristics of allergens in the region,rational arrangement of the dietary and living shoule be mode to avoid the risks and to reduce the probability of the occurrence of allergic diseases.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective To investigate the relationship between spicy diet and uremic pruritus(UP)in the patients with maintenance haemodialysis(MHD).Methods A total of 403 patients receiving the treat-ment in the blood purification center of this hospital from December 2023 to February 2024 were selected as the study subjects and grouped by the sum of the scores of frequency and degree of pepper intake.The visual analogue rating scale(VAS)was used to conduct the preliminary pruritus score in all patients,and the pa-tients with the score＞0 point conducted the multidimensional evaluation by the 14-item uremic skin pruritus scale.The blood routine and itch-related blood biochemical indexes levels of all patients were measured.Results There were 65 cases in the bland diet group,119 cases in the mild spicy diet group and 219 cases in the spicy diet group,and there was no significant difference in the number of genders between the groups(P＞0.05).There were statistically significant differences in age,dialysis age and lymphocyte count among the groups(P＜0.05).There was no statistically significant difference in the degree of pruritus among the groups(Z=9.301,P=0.157),but it was seen that the proportion of moderate and severe pruritus in the mild spicy diet group and the spicy diet group was decreased,and the proportions of no pruritus and mild pruritus showed the increasing trend.The itching score of the bland diet group was higher than that of the mildly spicy diet group and spicy diet group,and the difference was statistically significant(P＜0.05),but there was no statistically significant difference between the mild spicy diet group and spicy diet group(P＞0.05).There was a statistically significant difference in the itch score of the patients aged 40-60 years in each group(P＜0.05),and there was no statistically significant difference in the itch score between the patients aged＞60 years old and＜40 years old in each group(P＞0.05).There was no statistically significant difference in the itch-related blood biochemical indexes among the groups(P＞0.05).Conclusion The spicy diet may reduce the degree of pruritus in patients with MHD,moreover which is not affected by the age and other factors,and may be associated with lymphocyte level decrease in the patients.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective To explore the predictive value of heart rate variability(HRV)for long-term prognosis in elderly patients with stable coronary heart disease(CHD)based on dynamic electro-cardiogram(ECG).Methods A retrospective trial was conducted on 402 elderly patients with sta-ble CHD admitted to our hospital from January 2015 to December 2018,and all of them were fol-lowed up for 5 years.According to occurrence of major adverse cardiovascular events(MACE)or not,they were divided into a MACE group(n=102)and a control group(n=300).The main clin-ical characteristics and differences in HRV were compared between the two groups.Multivariate logistic regression analysis and ROC curve analysis were used.Results Advanced age,larger ratio of diabetes,more severe coronary artery stenosis,and higher low-frequency power and ratio of low-frequency power/high-frequency power,but lower left ventricular ejection fraction(LVEF)and high-frequency power were observed in the MACE group than the control group(P＜0.01).There was also statistical difference in use of hypoglycemic drugs between the two groups during the follow-up period(P＜0.01).Multivariate logistic regression analysis showed that diabetes,age ≥80 years,LVEF＜50％,coronary artery stenosis ≥70％and ratio of low-frequency power/high-frequency power＞1.16 were independent influencing factors for MACE in elderly patients with stable CHD within 5 years(P＜0.05,P＜0.01).ROC curve analysis indicated that the AUC value for low-frequency power and ratio of low-frequency power/high-frequency power in predic-ting MACE occurrence within 5 years was 0.801(95％CI:0.749-0.854,P=0.000)and 0.798(95％CI:0.752-0.844,P=0.000),respectively,and the value of high-frequency power in predic-ting the absence of MACE was 0.629(95％CI:0.566-0.692,P=0.000).Conclusion HRV is an independent influencing factor for MACE occurrence within 5 years in elderly patients with stable CHD,and it shows certain predictive value for MACE occurrence within 5 years in these patients.

Background Since the outbreak of COVID-19, primary health care workers have been facing unprecedented work pressure, and their occupational stress should be taken seriously. Objective To analyze the occupational stress situation and its influencing factors of primary health care workers in Guangdong Province, and to propose targeted interventions. Methods Using a multi-stage stratified random sampling method, each prefecture-level city in Guangdong Province was classified into "good", "medium", or "poor" category based on its gross domestic product (GDP) in 2019 released by the Guangdong Provincial Bureau of Statistics. In September 2021, four primary health care institutions were randomly selected from each stratum, and a total of 1327 staff members were selected for the study. The Core Occupational Stress Scale (COSS) and a basic information questionnaire designed by the authors were used. Mann-Whitney U test was used to compare the means between two groups, and Kruskal-Walis H test was used to compare the means among multiple groups. The comparison of categorical data was performed by trend χ² test or Pearson χ² test; the analysis of factors influencing occupational stress was performed by dichotomous multiple logistic regression analysis. Results There were 365 health care workers reporting occupational stress in this survey, and the positive rate of occupational stress was 27.5%. The total occupational stress score in M (P₂₅, P₇₅) and the scores of social support, organization and reward, demand and effort, and control were 45.0 (40.0, 50.0), 20.0 (17.0, 21.0), 14.0 (12.0, 17.0), 12.0 (10.0, 15.0), and 5.0 (4.0, 6.0), respectively. The results of dichotomous multiple logistic regression analysis showed that high education, low income, doctor positions, long working hours in a day, and shift work were associated with the occurrence of reporting occupational stress (P<0.05). Conclusion Education, average monthly income, job category, daily working hours, and shifts are factors influencing the occurrence of reporting occupational stress in primary health care workers; targeted interventions should be implemented to reduce their occupational stress levels.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

Objective:To analyze the disease burden of liver cancer in China.Methods:Based on eight data sources, including the series of Chinese Cancer Registry Annual Report, three national death cause surveys in China, China Health Statistical Yearbook, China Death Cause Surveillance Datasets, GLOBOCAN, Cancer Incidence in Five Continents (CI5), WHO Mortality Database and the Global Burden of Disease (GBD), the information on incidence, mortality and disability-adjusted life year (DALY) of liver cancer, were extracted for the analysis on the past, current and future disease burden caused by liver cancer in China.Results:1) Past situation: The long-term data from 1973 to 2012 reported by the CI5 showed that in urban populations in China (taking Shanghai as an example), the incidence rate of liver cancer in males and females decreased by 41.3 % and 36.3 %, respectively, and that in rural areas (taking Qidong as an example) decreased by 32.3 % and 12.2 %, respectively. The Chinese Cancer Registry Annual Reports showed that the national incidence and mortality rates of liver cancer decreased by 8.1 % and 12.8 % respectively from 2005 to 2015. The Joinpoint analysis based on the data from the China Health Statistics Yearbook also showed a declining trend: the average annual percentage change of liver cancer mortality in China from 2002 to 2017 was -3.0 % ( P<0.05), and that in rural areas was -3.1 % ( P<0.05). 2) Current status: GLOBOCAN estimates that the rates of incidence, mortality and prevalence of liver cancer in China in 2018 were 18.3 per 100 000, 17.1 per 100 000 and 10.8 per 100 000, respectively. According to the latest annual report, the incidence and mortality rates of liver cancer in cancer registration areas in 2015 were 17.6 per 100 000 and 15.3 per 100 000, respectively, and both increased with age. The mortality rate was similar to that reported in 2017 (16.7 per 100 000) by the China Death Cause Surveillance Datasets, and the male to female ratio of live cancer deaths was estimated as 3.1. The GBD 2017 reports that the DALYs caused by liver cancer in China reached 11 153.0 thousand in 2017 (accounting for 53.7 % of the global DALYs) and hepatitis B virus infection was always the leading cause. 3) Prediction: The GLOBOCAN 2018 predicts that, by 2040, the number of liver cancer cases and deaths in China would reach 591 000 and 572 000 (with an increase of 50.5 % and 54.9 %, respectively, compared with those in 2018), with a more significant increase in people over 70 years old. 4) Economic burden: According to the literature review of economic burden data on liver cancer, the direct medical expenditure per patient with liver cancer generally showed a rising trend. Conclusions:Multiple data sources indicate that the incidence and mortality rates of liver cancer in populations in China decreased in the past decades, indicating the effect of population interventions. However, the population-level disease burden are still substantial, and comprehensive intervention strategies need to be continually strengthened and optimized, especially the primary and secondary prevention.