Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375-3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3’-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

[Five-year survival analysis of gastric cancer from population-based cancer registration data in Zhejiang province, China].

Objective: To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration. Methods: The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed. Results: 51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively. Conclusion: The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.

[Cancer incidence and mortality in China, 2022].

Objective: The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods: According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results: The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions: The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

[The effects and mechanisms of Gefitinib on airway inflammation and airway remodeling in C57BL/6 mice with asthma].

Objective: To investigate the effects of the epidermal growth factor receptor(EGFR) inhibitor Gefitinib on airway inflammation and airway remodelling in asthmatic C57BL/6 mice, and to analyze its possible mechanisms. Methods: Male C57BL/6 mice, aged 6-8 weeks, were randomly assigned into five groups: Group A (control group), Group B (asthma group), Group C (asthma+20 mg/kg gefitinib group), Group D (asthma+40 mg/kg gefitinib group), and Group E (40 mg/kg gefitinib group), with seven mice per group. Mice were sensitized by intraperitoneal injection of a mixture of 0.2 ml solution containing OVA and Al(OH)3 [20 µg OVA+2 mg Al(OH)3 dissolved in 0.2 ml of physiological saline] at Day 0 and 14. Starting from Day 25 to 31, Group B, C, and D were challenged with nebulization of 1% OVA solution (8 ml) to induce asthma, once a day for approximately 40 minutes, with continuous aerosolization for 7 days. Group C and D were given 0.2 ml of Gefitinib dissolved in 0.5% carboxymethylcellulose sodium (CMCNa) by gavage half an hour before challenging, and Group E was simultaneously given with 0.2 ml of Gefitinib dissolved in 0.5% CMCNa only. Group A and B were given an equivalent volume of 0.5% CMCNa by gavage. After 24 h of final challenge, the bronchoalveolar lavage fluid (BALF) was prepared for the determination of total cell count and eosinophil count. The levels of total immune globulin E (IgE) in serum and interleukin (IL)-4, IL-5 and IL-13 in BALF and lung tissue homogenates were measured by ELISA. The mRNA expression levels of IL-4, IL-5, IL-13 in lung were measured. Immunohistochemistry and Western blot experiments were used to detect the expression levels of EGFR in lung tissues. Results: In Group B, the level of total IgE in serum, total cell count, eosinophil count, the levels of IL-4, IL-5, IL-13 in BALF and the phosphorylation of EGFR and its downstream activation in lung were higher than those in Group A (all P<0.05). The levels of total IgE in serum [(261.32±44.38) ng/ml, (194.09±52.39) ng/ml vs (1 023.70±105.51) ng/ml], total cell count [(23.70±4.08)×105/ml, (14.92±4.06)×105/ml vs (35.36±6.30)×105/ml], eosinophil count [(108.00±13.69)×104/ml, (67.00±17.28)×104/ml vs (147.86±20.06)×104/ml], IL-4 [(36.42±4.48) pg/ml, (30.45±8.12) pg/ml vs (58.72±7.17) pg/ml], IL-5 [(16.20±4.62) pg/ml, (13.38±5.14) pg/ml vs (23.46±5.38) pg/ml], IL-13 [(18.45±7.28) pg/ml, (14.33±7.70) pg/ml vs (104.12±24.66) pg/ml] in BALF of Group C and D were lower than those in Group B (all P<0.05). The levels of IL-4, IL-5, and IL-13 as well as their mRNA levels in the lung tissue of Group C and D were lower than those in Group B (all P<0.05). In Group C and D, the positive expression rate of phosphorylated epidermal growth factor receptor (p-EGFR) in lung tissue [(40.53±6.80)%, (23.60±4.42)% vs (70.78±5.36)%], p-EGFR/EGFR (61.68±7.48, 51.13±5.19 vs 105.90±11.66), phosphorylated extracellular regulated protein kinase (p-Erk)/extracellular regulated protein kinase (Erk) (75.28±7.11, 47.54±4.83 vs 98.76±4.71), and phosphorylated protein kinase B (p-Akt)/protein kinase B (Akt) (96.24±5.40, 68.52±2.73 vs 103.30±4.52) was lower than those of Group B (all P<0.05). There was no statistically significant difference in the relevant indicators between Group A and E (all P>0.05). Conclusion: Gefitinib may alleviate airway inflammation and airway remodeling in asthmatic mice by inhibiting EGFR phosphorylation and affecting the activation of downstream Erk and Akt.

[Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients].

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

[Analysis of clinical characteristics and risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia].

Objective: To analyze and explore the clinical characteristics and risk factors related to nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia. Methods: 252 hospitalized patients with liver cirrhosis combined with atrial arrhythmia from January 2014 to December 2021 were enrolled, and their clinical characteristics were analyzed. The above-mentioned patients were divided into groups according to their nosocomial mortality rate. Among them, 45 nosocomial mortality cases were classified as the mortality group, and 207 survival cases were classified as the survival group. The differences in clinical data and laboratory data between the two groups were compared. The risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia were analyzed. The t-test, or rank-sum test, was used to compare measurement data. The chi-square test, or Fisher's exact probability method, was used to compare enumeration data. Multivariate analysis was performed by the logistic regression method. Results: Among the 252 cases, the male-to-female ratio was the same (male/female ratio: 126/126). The age range was 26 to 89 (66.77±10.46) years. Han ethnicity accounted for 79.5%. The main type of atrial arrhythmia was atrial fibrillation (P < 0.001). The main cause of liver cirrhosis was post-hepatitis B cirrhosis (56.3%). There were 57/72/123 cases of CTP grade A/B/C. The CTP and Model for End-Stage Liver Disease (MELD) scores were 10.30±1.77 and 18.0(11.0, 29.0), respectively. The nosocomial mortality rate was 17.9% (45/252). The overall incidence rate of complications in all patients was 89.28%, with complications occurring in the following order: 71.4% ascites, 71.0% hypersplenism, 64.7% spontaneous peritonitis, 64.3% esophageal gastric varices, 32.5% hepatorenal syndrome, 32.1% hepatic encephalopathy, and 26.2% esophageal gastric variceal bleeding. The incidence rate of new-onset atrial fibrillation in the nosocomial mortality group was 73.3%, which was much higher than the 44.0% rate in the survival group (P < 0.05). Multivariate logistic regression analysis showed that new-onset atrial fibrillation (OR=2.707, 95%CI 1.119 ~ 6.549), esophageal-gastric varices (OR=3.287, 95%CI 1.189 ~ 9.085), serum potassium (OR=3.820, 95%CI 1.532 ~ 9.526), and MELD score (OR=1.108, 95%CI 1.061~1.157) were independent risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia. Conclusion: Patients with cirrhosis combined with atrial arrhythmias have more severe liver function damage and are more likely to develop complications such as ascites, hypersplenism, and hepatorenal syndrome. New-onset atrial fibrillation, esophageal-gastric varices, hyperkalemia, and a high MELD score are risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia, so more attention should be paid to corresponding patients for timely symptomatic treatment.

Bacterial dormancy: A subpopulation of viable but non-culturable cells demonstrates better fitness for revival.

The viable but non culturable (VBNC) state is a condition in which bacterial cells are viable and metabolically active, but resistant to cultivation using a routine growth medium. We investigated the ability of V. parahaemolyticus to form VBNC cells, and to subsequently become resuscitated. The ability to control VBNC cell formation in the laboratory allowed us to selectively isolate VBNC cells using fluorescence activated cell sorting, and to differentiate subpopulations based on their metabolic activity, cell shape and the ability to cause disease in Galleria mellonella. Our results showed that two subpopulations (P1 and P2) of V. parahaemolyticus VBNC cells exist and can remain dormant in the VBNC state for long periods. VBNC subpopulation P2, had a better fitness for survival under stressful conditions and showed 100% revival under favourable conditions. Proteomic analysis of these subpopulations (at two different time points: 12 days (T12) and 50 days (T50) post VBNC) revealed that the proteome of P2 was more similar to that of the starting microcosm culture (T0) than the proteome of P1. Proteins that were significantly up or down-regulated between the different VBNC populations were identified and differentially regulated proteins were assigned into 23 functional groups, the majority being assigned to metabolism functional categories. A lactate dehydrogenase (lldD) protein, responsible for converting lactate to pyruvate, was significantly upregulated in all subpopulations of VBNC cells. Deletion of the lactate dehydrogenase (RIMD2210633:ΔlldD) gene caused cells to enter the VBNC state significantly more quickly compared to the wild-type, and adding lactate to VBNC cells aided their resuscitation and extended the resuscitation window. Addition of pyruvate to the RIMD2210633:ΔlldD strain restored the wild-type VBNC formation profile. This study suggests that lactate dehydrogenase may play a role in regulating the VBNC state.

Blood eosinophils to direct oral corticosteroid treatment for patients with nasal polyps â€" an open label, non-inferiority, randomized control trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disorder. We aimed to evaluate the value of blood eosinophil count (BEC) for guiding oral corticosteroid therapy for CRSwNP. METHODS: Subjects with CRSwNP were entered into a 2:1 randomized biomarker-directed corticosteroid versus standard therapy study base on the principle of potential benefits to patients. Subjects in the standard arm received oral prednisone (30mg/day) alone for 7 days, whereas in the biomarker-directed arm, prednisone (30mg/day), or nasal steroid spray (budesonide 256ug/day) was given according to the BEC which was measured to define eosinophil-high and -low CRSwNP (BEC > and < 0.37x109/L, respectively). The primary outcome was the total nasal symptom scores (TNSS) of the two arms with the non-inferiority margin of 1.8. Secondary outcomes included nasal polyp size scores (NPSS) and SNOT-22. Patients were followed up the day after last dose of treatment. RESULTS: A total of 105 subjects with CRSwNP were randomized into the biomarker-directed therapy group or the standard care group. The biomarker therapy demonstrated non-inferiority compared to standard care. There were no between-group differences for TNSS, NPSS and SNOT-22 improvements after treatment. Comparisons of TNSS, SNOT-22 and NPSS revealed no significant difference in terms of the effectiveness ratios of the biomarker-directed therapy and the standard care. CONCLUSION: A biomarker-directed strategy using the BEC can be used to direct corticosteroid therapy without increasing treatment failure or worsening of symptoms in patients with CRSwNP.

[Analysis on the trends of incidence and age change for global female breast cancer].

Objective: To analyze the trends of incidence and age change for global female breast cancer in different regions of the world according to the database from Cancer Incidence in Five Continents Time Trends (CI5plus) published by the International Association of Cancer Registries (IACR). Methods: The recorded annual female breast cancer (ICD-10: C50) incidence data and corresponding population at-risk data (1998-2012) were extracted from CI5plus published by IACR. The annual change percentage and average annual change percentage (AAPC) were calculated to examine the trends of incidence. The age-standardized mean age at diagnosis and proportion of incidence cases by age were calculated to analyze the relationship between incidence and age. Results: For crude incidence, except in Northern America, all other regions showed an upward trend, with Asia showing the most obvious upward trend (AAPC: 4.1%, 95% CI: 3.9%, 4.3%). For age-standardized incidence, in Asia, Latin America and Europe, the rising trends had slowed down, in Oceania and Africa, the trends began to be stable, and in Northern America, the trend showed a downward trend (APPC: -0.6%; 95% CI: -1.0%, -0.1%). The mean age at diagnosis were increased from 1998 to 2012 in Asia, Latin America, Oceania and Europe, with an annual increase of 0.12 years, 0.09 years, 0.04 years and 0.03 years, respectively. But after age-standardized, only Europe still kept increasing year by year, with an annual increase of 0.02 years, while Northern America showed a decreasing trend, with an annual decrease of about 0.03 years. Conclusions: From 1998 to 2012, the trends of incidence and age change for global female breast cancer vary in different regions of the world, and the global population aging is widespread, which affects the trend of the actual age change. Prevention and control strategies should be targeted at different age groups in different regions.

[Cancer statistics in China, 2016].

Objective: Data for 2016 from cancer registries were used to estimate cancer incidence and mortality in China in 2016. Methods: According to the quality control process of the National Central Cancer Registry, the data from 683 cancer registries submitted by each province were evaluated, and the data of 487 cancer registries were qualified and included in the final analysis. Age-specific incidence and mortality rates were calculated by area (urban/rural), sex, age and cancer site, combined with national population data to estimate cancer incidence and mortality in China in 2016. Chinese population census in 2000 and Segi's population were used for age-standardized incidence and mortality rates. Results: Total population covered by 487 cancer registries was 381 565 422 (192 628 370 in urban and 188 937 052 in rural areas). The percentages of morphologically verified (MV%) and death certificate-only cases (DCO%) accounted for 68.31% and 1.40%, respectively, and the mortality to incidence ratio was 0.61. It was estimated about 4 064 000 new cases occurred in China in 2016, with the crude incidence rate being 293.91/100 000 (the rates of males and females were 315.52/100 000 and 271.23/100 000), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.76/100 000 and 186.46/100 000, with the cumulative incidence rate (0-74 years old) being 21.42%. The crude incidence and ASIRC were 314.74/100 000 and 196.38/100 000 in urban areas, whereas in rural areas, they were 265.90/100 000 and 182.21/100 000, respectively. It was estimated about 2 413 500 cancer deaths occurred in China in 2016, the crude mortality rate was 174.55/100 000 (216.16/100 000 in males and 130.88/100 000 in females), the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 106.00/100 000 and 105.19/100 000, and the cumulative mortality rate (0-74 years old) was 11.85%. The crude mortality and ASMRC were 180.31/100 000 and 104.44/100 000 in urban areas, whereas in rural areas, they were 166.81/100 000 and 108.01/100 000, respectively. The most common cancer cases include lung, colorectal, stomach, liver and female breast cancers. The top five cancers accounted for about 57.27% of all cancer cases. The most common cancer deaths included lung, liver, stomach, colorectal and esophageal cancers. The top five cancers accounted for about 69.25% of all cancer deaths. Conclusions: The burden of cancer shows a continuous increasing trend in China. Regional and gender differences in cancer burden are obvious. The cancer patterns still show the coexistence of cancer patterns in developed countries and developing countries. The situation of cancer prevention and control is still serious in China.

[Effects of caspase recruitment domain protein 9 gene knockout on airway inflammation in C57BL/6 mice with steroid resistant asthma].

Objective: To investigate the role of caspase recruitment domain protein 9 (CARD9) in airway injury and inflammation of steroid resistant asthma in C57BL/6 mice. Methods: C57BL/6 mice were divided into A group (control group), B group (model group) and C group (dexamethasone treatment group), with 6 mouse in each group using random number table. The mouse asthma model was established in B and C group by subcutaneous injection of ovalbumin (OVA)/complete Freund adjuvant (CFA) in the abdomen and OVA aerosol challenge, the pathological change and cell count in broncho alveolar lavage fluid (BALF) were detected in order to confirm the model as steroid resistant asthma, and the lung tissue inflammatory infiltration was scored. Western blot was used to detect the changes of CARD9 protein between the group A and B; then wild-type and CARD9 knockout mice were divided into D group (wild-type control group), E group (wild-type model group), F group (CARD9 knockout control group) and G group (CARD9 knockout model group), the following indicators were observed and compared after establishing steroid resistant asthma model separately: HE staining was used to observe the pathological changes of lung tissue, ELISA was used to detect the protein levels of interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17(IL-17) in BALF, and RT-PCR was used to detect the mRNA levels of CXC motif chemokine ligand-10 (CXCL-10) and IL-17 in lung. Results: The inflammatory score (3.33±0.82 vs 0.67±0.52) and BALF total cell count [(10.13±4.83) ×105/ml vs (3.76±0.84) ×105/ml] in B group were higher than those in the A group with statistical significance (P<0.05). There was no significant difference between group C and group B in inflammatory infiltration score (2.83±0.75 vs 3.33±0.82) and BALF total cell count [(9.80±3.19) ×105/ml vs (10.13±4.83) ×105/ml] (P>0.05). Moreover the protein level of CARD9 was increased in the B group than A group (0.245±0.090 vs 0.047±0.014, P=0.004). Compared to E group and F group, more obviously inflammatory cells, neutrophils, eosinophils infiltration and tissue injury were observed in G group (P<0.05), so did the expression of IL-4 (P<0.05), IL-5 and IL-17. Meanwhile the mRNA expression levels of IL-17 and CXCL-10 also increased in lung tissue (P<0.05) of G group. Conclusion: CARD9 gene deletion may aggravate the steroid resistant of asthma by increasing neutrophil chemokines, such as IL-17 and CXCL-10, therefore increasing infiltration of neutrophils in C57BL/6 mice asthma model.

[Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms].

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

[Preliminary insights into the practice of hypoallergenic home visiting program].

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

[Analysis of curative effect and short-term survival rate of plasma exchange and double plasma molecular adsorption combined with half-volume plasma exchange in the treatment of liver failure].

Objective: To investigate how plasma exchange (PE) and double plasma molecular adsorption combined with half-volume plasma exchange (DPMAS + half-volume PE) affect the curative effect and short-term survival rate in liver failure. Methods: Data from 181 cases of liver failure caused by different etiologies from January 1, 2017 to September 31, 2020, were selected. Patients were divided into a PE treatment alone group and a DPMAS + half-dose PE treatment group. The laboratory indicators with different models of artificial liver before and after treatment and the survival rates of 7, 14, 28, and 90 days after discharge were observed in the two groups. Measurement data were analyzed by t-tests and rank sum tests. Categorical data were analyzed by χ (2) test. Results: Non-biological artificial liver therapy with different models improved the liver and coagulation function in the two groups of patients with liver failure (P < 0.05 in PTA% intra-group). The coagulation function was significantly improved in the PE treatment alone group compared with that in the DPMAS + half-dose PE group [PT after treatment: (20.15 ± 0.88) s in the PE treatment alone group, (23.43 ± 1.02) s, t = -2.44, P = 0.016 in the DPMAS+half-dose PE group; PTA: 44.72% ± 1.75% in the PE treatment alone group, 35.62% ± 2.25%, t = 3.215 P = 0.002 in the DPMAS + half-dose PE group]. Bilirubin levels were significantly decreased in the DPMAS+half-dose PE group compared to the PE treatment alone group [total bilirubin after treatment: (255.30 ± 15.64) µmol/L in the PE treatment alone group, (205.46 ± 9.03) µmol/L, t = 2.74, P = 0.07 in the DPMAS + half-dose PE group; direct bilirubin after treatment: (114.74 ± 7.11) µmol/L in the PE treatment alone group, (55.33 ± 3.18) µmol/L, t = 7.54, P < 0.001) in the DPMAS + half-dose PE group]. However, there was no significant effect on leukocytes and neutrophils after treatment with different models of artificial liver (P > 0.05) in the two groups, and platelets decreased after treatment, with no statistically significant difference between the groups (t = -0.15, P = 0.882). The inflammatory indexes of the two groups improved after treatment with different models of artificial liver (P < 0.05], and the 28 and 90 d survival rates were higher in the DPMAS+half-dose PE group than those of the PE treatment alone group (28 d: 60.3% vs. 75.0%, χ (2) = 4.315, P = 0.038; 90 d: 56.2% vs. 72.5%. χ (2) = 10.355 P < 0.001). DPMAS + half-dose PE group plasma saving was 1385 ml compared with PE treatment alone group (Z = -7.608, P < 0.05). Conclusion: Both DPMAS+half-dose PE and PE treatment alone have a certain curative effect on patients with liver failure. In DPMAS+half-dose PE, the 28-day survival rate is superior to PE treatment alone, and it saves plasma consumption and minimizes blood use in clinic.

[Advances in anticoagulant therapy for cirrhosis combined with atrial fibrillation].

Relevant research in recent years has demonstrated that the atrial fibrillation occurrence rate is significantly higher in patients with cirrhosis. The most common indication for long-term anticoagulant therapy is chronic atrial fibrillation. The use of anticoagulant therapy greatly reduces the incidence rate of ischemic stroke. Patients with cirrhosis combined with atrial fibrillation have an elevated risk of bleeding and embolism during anticoagulant therapy due to cirrhotic coagulopathy. At the same time, the liver of such patients will go through varying levels of metabolism and elimination while consuming currently approved anticoagulant drugs, thereby increasing the complexity of anticoagulant therapy. This article summarizes the clinical studies on the risks and benefits of anticoagulant therapy in order to provide a reference for patients with cirrhosis combined with atrial fibrillation.

[Effect of RBP2 gene silencing on proliferation, migration and invasion of ovarian epithelial cancer SKOV3/DDP cells and its mechanism].

Objective: To explore the effect of down-regulation of retinol binding protein 2 (RBP2) expression on the biological characteristics of ovarian cancer cells and its mechanism. Methods: Knockdown of RBP2 and cisplatin (DDP)-resistant ovarian cancer cell line SKOV3/DDP-RBP2i was established, the negative control group and blank control group were also set. Cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, flow cytometry was used to detect cell apoptosis, scratch test and Transwell invasion test were used to detect cell migration and invasion ability, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of molecular markers related to epithelial-mesenchymal transition (EMT). The effect of RBP2 on the growth of ovarian cancer was verified through experiment of transplanted tumors in nude mice, and the relationships between RBP2 expression and tumor metastasis and patient prognosis were analyzed using the clinical data of ovarian cancer in TCGA database. Results: After down-regulating the expression of RBP2, the proliferation ability of SKOV3/DDP cell was significantly reduced. On the fifth day, the proliferation activities of SKOV3/DDP-RBP2i group, negative control group and blank control group were (56.67±4.16)%, (84.67±3.51) and (87.00±4.00)% respectively, with statistically significant difference (P<0.001). The apoptosis rate of SKOV3/DDP-RBP2i group was (14.19±1.50)%, higher than (8.77±0.75)% of the negative control group and (7.48±0.52)% of the blank control group (P<0.001). The number of invasive cells of SKOV3/DDP-RBP2i group was (55.20±2.39), lower than (82.60±5.18) and (80.80±7.26) of the negative control group and the blank control group, respectively (P<0.001). The scratch healing rate of SKOV3/DDP-RBP2i group was (28.47±2.72)%, lower than (50.58±4.06)% and (48.92±4.63)% of the negative control group and the blank control group, respectively (P<0.001). The mRNA and protein expressions of E-cadherin in the SKOV3/DDP-RBP2i group were higher than those in the negative control group (P=0.015, P<0.001) and the blank control group (P=0.006, P<0.001). The mRNA and protein expression of N-cadherin in SKOV3/DDP-RBP2i group were lower than those in the negative control group (P=0.012, P<0.001) and the blank control group (P=0.005, P<0.001). The mRNA and protein expressions of vimentin in SKOV3/DDP-RBP2i group were also lower than those in the negative control group (P=0.016, P=0.001) and the blank control group (P=0.011, P=0.001). Five weeks after the cells inoculated into the nude mice, the tumor volume of SKOV3/DDP-RBP2i group, negative control group and blank control group were statistically significant different. The tumor volume of SKOV3/DDP-RBP2i group was smaller than those of negative control group and blank control group (P=0.001). Bioinformatics analysis showed that the expression of RBP2 in patients with metastatic ovarian cancer was higher than that without metastasis (P=0.043), and the median overall survival of ovarian cancer patients with high RBP2 expression was 41 months, shorter than 69 months of low RBP2 expression patients (P<0.001). Conclusion: Downregulation of the expression of RBP2 in SKOV3/DDP cells can inhibit cell migration and invasion, and the mechanism may be related to the inhibition of EMT.

[Analysis of PROKR2 gene mutation in patients with hypogonadotropic hypogonadism].

To investigate the clinical and genetic characteristics of patients with idiopathic hypogonadotropic hypogonadism (IHH), the clinical data of 23 patients with IHH were retrospectively analyzed. Gene analyses were accomplished with whole-exome sequencing (WES) and Sanger sequencing. Functional prediction of mutation sites was conducted using two bioinformatics platforms, SIFT and Polyphen. Among the 23 patients with IHH, 9 patients carried prokinin 2 (PROKR2) gene mutations including 4 missense mutations (p.W178S, p.Y113H, p.A103V, p.R164Q), and 1 frameshift mutation (p.D42delinsDED), the remaining 14 cases were found negative in gene sequencing. Functional prediction showed that the above mutations may affect protein function suggestive of a pathogenic role of PROKR2 mutation in the patients. There were no significant differences in the levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol between the IHH patients with PROKR2 gene mutation and those without. PROKR2 gene mutation might associated with IHH, and the mutations reported in the present study could enrich the pathogenic spectrum of genes.

[The incidence and mortality of endometrial cancer in China, 2015].

Objective: To estimate endometrial cancer (EC) incidence and mortality in China in 2015. Methods: Qualified cancer registry data collected in 2011-2015 were pooled for analysis, from which EC cases and deaths were extracted. EC cases were classified into endometrioid, nonendometrioid and other & unspecified according to their histologic types. Incidence and mortality rates stratified by region and age group were calculated. Population data of 2015 was used to estimate cancer cases and deaths in China. Segi's population was used for the calculation of age-standardized rates by world standard population (ASW). Results: Data from 158, 176, 239, 235, 231 qualified cancer registries of 2011 to 2015 were pooled together. These registries covered about 488 million population, including about 255 million population in urban area and 233 million population in rural area. In 2015, a total of 53 600 EC cases were estimated, with a crude incidence rate of 7.74/100 000 and an ASW of 5.13/100 000. Incidence rates were higher in urban areas (9.15/100 000) than in rural areas (6.20/100 000). A total of 10 700 deaths were estimated, with a crude mortality rate of 1.60/100 000 and an ASW of 0.98/100 000. Mortality rate was higher in urban areas (1.78/100 000) than in rural areas (1.40/100 000). Among reported EC cases during 2011-2015, 70.92% (23 641 cases) were endometrioid, 5.13% (1 709 cases) were nonendometrioid and 23.95% (7 982 cases) were other & unspecified. The mean age at onset of all EC cases was 55.9±10.6. The mean age at onset of endometrioid cases (55.7±10.0) was younger than that of nonendometrioid cases (57.7±10.8) (P<0.001). The mean age at onset of all histologic types in urban areas was higher than that in rural areas (P<0.001). The mean age at death for EC deaths was 63.9±12.5. The mean age at death in urban areas (65.3±12.5) was higher than that in rural areas (61.4±12.2) (P<0.001). Conclusion: EC disease burden differs between urban and rural areas. Targeted cancer prevention and control strategies should be made for each region.

[Sero-epidemiological characteristics of the hepatitis D virus infection among hepatitis B virus infected-patients at a single center in Xinjiang region].

Objective: To investigate the sero-epidemiological characteristics of the hepatitis D virus (HDV) infection among hepatitis B virus (HBV)-infected patients in Xinjiang region. Methods: A single-center cross-sectional analysis method was used to select 264 cases of hepatitis B virus infection who were hospitalized in the Center for Infectious Diseases and Liver Diseases of the First Affiliated Hospital of Xinjiang Medical University from August 2021 to January 2022. All patients were tested for HDV Ag, HDV IgM, HDV IgG, and HDV RNA. The infection status of hepatitis D virus was analyzed by grouping according to their clinical type, HBV viral load, and HBsAg level. A paired t-test was used for data with measurement data conforming to normal distribution. A paired rank sum test was used for data that did not conform to normal distribution before and after treatment. Results: A total of 36 cases (13.64%) and 26 cases (9.85%) were positive for HDV serological markers and HDV RNA. According to clinical type grouping, the positive rates of HDV serum markers in patients with chronic hepatitis B, hepatitis B-related cirrhosis, liver cancer, and liver failure were 13.46%, 12.43%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=0.86, P=0.649). The positive rates of HDV RNA were 11.54%, 8.11%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=4.015, P=0.134). According to HBV viral load grouping, the positive rates of HDV serum markers among patients with viral loads <20, 20-2 000, and >2 000 IU/ml were 17.15%, 7.81%, and 6.67%, respectively, and the difference was not statistically significant among the three groups (χ2=4.846, P=0.089). The positive rates of HDV RNA were 9.47%, 10.94%, and 10%, respectively, and the difference was not statistically significant among the three groups (χ2=0.113, P=0.945). According to HBsAg level grouping, the positive rates of HDV serum markers in HBsAg<0.05, 0.05~250, and >250 IU/ml were 14.29%, 16.67%, and 10.85%, respectively, and there was no statistically significance between the three groups (χ2=1.745, P=0.418). The positive rates of HDV RNA were 4.76%, 8.77%, and 11.63%, respectively, and there was no statistically significant difference among the three groups (χ2=1.221, P=0.543). Clinical outcome, disease course, HBV DNA, serological markers of viral hepatitis, routine blood test, biochemical indicators, coagulation function, and other laboratory indicators were compared between HDV serum marker and/or nucleic acid positive and negative patients, and there was no statistically significant difference (P>0.05). Conclusion: The positive rate of HDV serological markers and HDV RNA is 13.64% and 9.85%, respectively, at a single center in the Xinjiang region, and there is still a high HDV infection rate among the HBV-infected patients with low levels of viral load and HBsAg.