[Risk factors for the occurrence of laryngopharyngeal reflux disease in the aged and the clinical characteristics of patients complicated with pneumonia].

Objective: To investigate the risk factors for the occurrence of laryngopharyngeal reflux disease in the aged, and to analyze the characteristics of patients with pneumonia. Methods: Patients who underwent 24-hour laryngopharyngeal pH monitoring from June 2020 to July 2022 and the positive patients of those who underwent 24-hour esophageal pH monitoring from March 2017 to July 2022 at the Second Medical Center of the PLA General Hospital were enrolled retrospectively. Positive results of 24-hour laryngopharyngeal reflux monitoring were in the laryngopharyngeal reflux group, and the negative results were in the non-laryngopharyngeal reflux group. Patients with pneumonia and simple gastroesophageal reflux disease were in the esophageal reflux pneumonia group, and patients with pneumonia and simple laryngopharyngeal reflux disease were in the laryngopharyngeal reflux pneumonia group. Patients' basic data, co-morbidities, drug use and relevant examination and test results were collected. Multivariate logistic regression analysis was used to analyze the risk factors of laryngopharyngeal reflux disease in the aged and its relationship with pneumonia. Results: A total of 80 patients with 24-hour laryngopharyngeal pH monitoring were enrolled finally, including 34 cases, all male, aged (73±12) years, in the laryngopharyngeal reflux group, and 46 cases [44 males, 2 females, aged (78±11) years] in the non-laryngopharyngeal reflux group. Multivariate logistic regression analysis showed that the risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years (OR=13.07, 95%CI: 2.53-67.68), body mass index (BMI) (OR=1.37, each additional 1 kg/m2, 95%CI: 1.03-1.83), use of antipsychotic drugs (OR=8.00, 95%CI: 1.40-45.73) and calcium channel blockers (OR=5.27, 95%CI: 1.13-24.53) (all P<0.05). The protective factors of the laryngopharyngeal reflux disease in the aged included antacids (OR=0.19, 95%CI: 0.04-0.90, P=0.035). The incidence of pneumonia was higher in the laryngopharyngeal reflux group compared with the non-laryngopharyngeal reflux group [44.1% (15/34) vs 21.7% (10/46), P=0.033]. The esophageal reflux pneumonia group included 32 cases [31 males and 1 females, aged (84±12) years]. The laryngopharyngeal reflux pneumonia group included 15 cases [ 15 males, aged (79±11) years]. Compared to the patients in the laryngopharyngeal reflux pneumonia group, the patients in the esophageal reflux pneumonia group had a longer course of antibiotics [(27.7±27.0) vs (14.6±13.9) days, P=0.034], a higher frequency of seizure frequency [(4.3±3.0) vs (1.8±1.5) times/year, P<0.001] and a higher maximal body temperature [(38.2±0.9) vs (37.6±1.1) ℃, P=0.037]. Conclusions: The risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years, higher BMI, use of antipsychotic drugs and calcium channel blockers. The incidence of pneumonia in laryngopharyngeal reflux disease is higher, but the condition of pneumonia is milder.

[Arterial spin labeling in assessment of interstitial fibrosis in renal allografts].

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

[Is low-dose anticoagulation a therapeutic option for patients at high risk of bleeding with high-risk pulmonary thromboembolism].

This issue of Chinese Journal of Tuberculosis and Respiratory Diseases published an interesting case illustrating the identification, treatment, and post-treatment management of a high-risk pulmonary thromboembolism (PTE) that occurred during surgery. It was a high-risk case of PTE, but during treatment, the risk stratification changed to medium-high risk. We should dynamically assess risk stratification and develop diagnosis and treatment plans based on changes in the patient's condition. At the same time, there was a high risk of bleeding in this patient. We should try to decrease the risk of bleeding as much as possible, consider all the conditions that can be applied at that time and on a local level, and devise a safe and effective treatment plan. The socio-economic status of patients may have an impact on how the final diagnosis and treatment plan are implemented. We need to communicate fully with patients, consider comprehensively, and prepare contingency plans to ensure patients' life safety to the greatest extent possible.

Differentially Expressed Circulating Long-Noncoding RNAS in Premature Infants with Respiratory Distress Syndrome.

Purpose: Recent studies have addressed the association between lung development and long-noncoding RNAs (lncRNAs). But few studies have investigated the role of lncRNAs in neonatal respiratory distress syndrome (RDS). Thus, this study aimed to compare the expression profile of circulating lncRNAs between RDS infants and controls. Methods: 10 RDS infants and 5 controls were enrolled. RDS patients were further divided into mild and severe RDS subgroups. Blood samples were collected for the lncRNA expression profile. Subsequently, differentially expressed lncRNAs were screened out. Bioinformatics analysis was applied to establish a co-expression network of differential lncRNAs and mRNAs, and predict the underlying biological functions. Results: A total of 135 differentially expressed lncRNAs were identified, including 108 upregulated and 27 downregulated lncRNAs (fold-change>2 and P<0.05) among the three groups (non-RDS, mild RDS and severe RDS groups). Of these lncRNAs, four were selected as showing higher fold changes and validated by qRT-PCR. ENST00000470527.1, ENST00000504497.1, ENST00000417781.5, and ENST00000440408.5 were increased not only in the plasma of total RDS patients but also in the severe RDS subgroup. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses showed that differentially expressed lncRNAs may play important roles in RDS through regulating PI3KAkt, RAS, MAPK, and TGF-ß signaling pathways. Conclusion: The present results found that ENST00000470527.1, ENST00000504497.1, ENST00000417781.5, and ENST00000440408.5 may be invol ved in RDS. This could provide new insight into research of the potential pathophysiological mechanisms of preterm RDS.

[Clinical features and CT findings of fibrosing mediastinitis associated pulmonary hypertension].

Objective: To investigate the clinical features and CT findings of pulmonary hypertension (PH) in patients with fibrosing mediastinitis (FM). Methods: Thirteen patients with FM diagnosed between September 2015 and June 2022 were studied retrospectively, including patients with PH (FM-PH group) and patients without PH (FM group) confirmed on right heart catheterization. The t test of two independent samples, Mann-Whitney U rank sum and Fisher's test were used to compare the general information, symptoms, laboratory examination, right ventricular and pulmonary artery measurement data and pulmonary artery CT findings between the two groups, respectively. Results: Compared with the 7 FM patients aged 28-79 (60.00±17.69) years, the 6 patients in the FM-PH group, aged from 60 to 82 (68.83±8.35) years, had more peripheral edema, lower percentage of PaO2, wider inner diameters of pulmonary artery and right ventricle, a higher ratio of right ventricle and left ventricular transverse diameter, faster tricuspid regurgitation velocity and higher estimated systolic pulmonary artery pressure (P<0.05). There were no differences in BNP levels and tricuspid annular plane systolic excursion between groups (P>0.05). Of the 6 patients with PH, 5 had precapillary PH and 1 had mixed PH. Except that the pulmonary vascular resistance in patients of the FM-PH group was significantly higher than that in the FM group (P<0.05), there were no significant differences in cardiac output, mixed venous oxygen saturation and pulmonary capillary wedge pressure between the two groups. CT pulmonary angiography (CTPA) showed pulmonary artery and vein stenosis. Patients in the FM-PH group had more severe stenosis and occlusion of pulmonary artery and pulmonary vein (P<0.05), and more involvement of multiple pulmonary veins (P<0.05). Conclusions: The clinical manifestation of FM complicated with PH is related to the degree of involvement of pulmonary artery, vein and airway. It is recommended that the disease be evaluated in combination with multiple parameters such as clinical manifestations, cardiac ultrasound, right cardiac catheter and CTPA.

HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.

Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling.

Risk of herpesvirus, serious and opportunistic infections in atopic dermatitis: a population-based cohort study.

BACKGROUND: Staphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections. OBJECTIVES: To determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD. METHODS: We conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections. RESULTS: Among 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50-52% greater risk of HSV and 18-33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38-4·54] and adults with severe AD (HR 4·45, 95% CI 1·76-11·25). Patients with AD had a 26-40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20-1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD. CONCLUSIONS: AD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.

[A study on the burden of myocarditis in China in 1990 and 2019].

Objective: To investigate Chinese myocarditis burden and trends in 1990 and 2019. Methods: Based on the Global Burden of Disease (GBD) 2019 data, the number of patients, the number of new cases, the number of deaths, the disability-adjusted life years (DALYs), as well as the morbidity, mortality, DALYs rate and their age-standardized rates were used to analyze the trend and the burden of myocarditis in the Chinese population in 1990 and 2019. Results: In 2019, the number of patients, the number of new cases and the number of deaths with myocarditis in China were 234 900, 275 100 and 13 100 respectively, increasing by 85.62%, 47.51% and 50.22% compared with 1990. The age-standardized incidence and mortality were 16.94/100 000 and 0.92/100 000, respectively. Compared with 1990, the age-standardized incidence in 2019 decreased by 6.06%, and the mortality decreased by 16.04% respectively. The age-standardized incidence and mortality of Chinese male patients with myocarditis were higher than that of female. Compared with 1990, the age group with the largest incidence and mortality of myocarditis in China in 2019 all shifted to the elder group. And, DALYs and age-normalized DALYs due to myocarditis in China showed a decreasing trend in 2019, from 458 600 and 42.51/100 000 in 1990 to 341 300 and 25.39/100 000 in 2019, respectively. The rate of DALYs and age-standardized DALYs in male patients was always higher than female. Conclusions: Compared with 1990, the overall burden of myocarditis in China showed a downward trend in 2019, and the burden of myocarditis in male patients was higher than female. More attention should be paid to the burden of myocarditis in Chinese elderly population.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Induction of peripheral blood mononuclear cells to hepatocyte-like cells and preliminary study of cell response to injury under the effect of acetaminophen].

Objective: To establish a method for the induction of peripheral blood mononuclear cells to hepatocyte-like cells, and preliminarily investigate cell response to injury under the effect of acetaminophen (APAP). Methods: The surface marker CD45 of peripheral blood mononuclear cells wase detected cells by using flow cytometry and immunofluorescence methods. The cellular morphology of induced hepatocyte-like cells was observed under an inverted microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the expression level of hepatocyte-specific genes, such as cytochrome (CY) P1A2, CYP3A4, CYP2C9, albumin (ALB), alpha-fetoprotein (AFP), and hepatocyte nuclear factor (HNF)4α mRNA. Immunofluorescence method was used to detect intracellular hepatocyte markers AFP, HNF4α, and ALB expression at the protein level. Biochemical analyzer was used to detect hepatocyte-specific secretory functions of AFP, ALB, and urea. Luciferase chemiluminescence method was used to detect the activity of key drug metabolizing enzyme CYP3A4. Colorimetric assay was used to detect the effect of the drug acetaminophen on hepatocyte-like cells, and alanine aminotransferase (ALT) was used as an indicator of liver cell injury. The statistical differences between the data were compared with t-test and rank-sum test. Results: The positive expression rate of CD45 cell surface markers isolated from peripheral blood mononuclear cells was about 98%, and hepatocyte-like cell morphology changes appeared on 15th day of induction. Compared with isolated mononuclear cells, CYP1A2, CYP3A4, CYP2C9, ALB, AFP and HNF4α mRNA was markedly elevated. The expression level of AFP, ALB and HNF4α protein were equally increased, and the secretory function of AFP, ALB and urea were enhanced. Compared with primary hepatocytes, CYP1A2, CYP2C9, AFP, HNF4α mRNA, and CYP3A4 mRNA did not decrease. The expression levels of AFP, ALB, and HNF4α proteins in the cells did not decrease, and the secretory function of AFP, ALB, and urea did not decrease. In addition, the CYP3A4 enzyme activity produced by hepatocyte-like cells was similar to that of primary hepatocytes. Compared with hepatocyte-like cells incubated without APAP, hepatocyte-like cells incubated with APAP had higher ALT level. Under the effect of APAP, the ALT level of hepatocyte-like cells was higher than isolated mononuclear cells. Conclusion: Peripheral blood mononuclear cells can be induced into hepatocyte-like cells with partial characteristics of hepatocytes, including the activity of CYP3A4, a key enzyme of hepatocyte drug metabolism. Additionally, preliminarily ALT secretory features reflect the hepatocytes injury under the effect of acetaminophen.

[The disease burden of degenerative mitral valve disease in the Chinese population from 1990 to 2019].

Objective: To explore the trend of disease burden of degenerative mitral valve disease (DMVD) in the Chinese population from 1990 to 2019. Methods: Based on the 2019 Global Burden of Disease database (GBD 2019), the number of patients, the number of new cases, the number of deaths, the disability-adjusted life years (DALY) as well as the prevalence, incidence and death rate, DALY rate and their age-standardized rates were used to analyze the trend of the burden of DMVD in the Chinese population from 1990 to 2019. Results: In 2019, the number of patients, the number of new cases, and the number of deaths with DMVD in China were 461.2, 27.0 and 0.129 ten thousand, respectively, which increased by 209.0%, 199.1% and 13.2% when compared with 1990. In 2019, the age-standardized prevalence, incidence and death rate were 228.1/100 000, 12.7/100 000 and 0.075/100 000, respectively. Compared with 1990, the change of the age-standardized prevalence, incidence and death rate were 32.6%, 42.8% and -54.1%, respectively. In addition, the 2019 data also showed that the age-standardized prevalence and incidence were higher in females than in males (the age-standardized prevalence was 190.1 (181.5-198.9)/100 000 for males and 262.0 (250.3-273.9)/100 000 for females); the age-standardized incidence was 10.5 (10.0-11.0)/100 000 for males and 14.9 (14.3-15.6)/100 000 for females. The age group with the largest number of DMVD patients was 65 to 69 years old, and the highest incidence was 60 to 64 years old. From 1990 to 2019, DALY caused by DMVD showed an upward trend in China, from 46 439 person-years in 1990 to 69 402 person-years in 2019, with an increase of 49.4%. While the age-standardized DALY rate continued to decline, from 5.5/100 000 in 1990 to 3.8/100 000 in 2019, with a drop of 30.8%. The DALY and the age-standardized DALY rate of females were always higher than that of males in different years. Conclusion: From 1990 to 2019, DALY and the age-standardized prevalence and incidence of DMVD in China shows an increasing trend, and the disease burden caused by DMVD is severe in China.

Human milk immunomodulatory proteins are related to development of infant body composition during the first year of lactation.

BACKGROUND: To investigate relationships between infant body composition (BC) and human milk (HM) immunomodulatory proteins (IMPs) during the first 12 months of lactation. METHODS: BC of breastfeeding dyads (n = 20) was measured with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers) at 2, 5, 9, and/or 12 months post partum. Breastfeeding frequency, 24-h milk intake, and IMP concentrations (lactoferrin, lysozyme, secretory immunoglobulin A (sIgA)) were measured, and calculated daily intakes (CDIs) were determined. We used linear regression/mixed-effects models and adjusted results for multiple comparisons. RESULTS: No associations were seen between maternal characteristics and IMP concentrations/CDIs or between IMP concentrations and infant BC. Lactoferrin CDI was negatively associated with infant fat-free mass index (P = 0.002); lysozyme CDI was positively associated with infant fat mass (P = 0.004) and fat mass index (P = 0.004) measured with ultrasound skinfolds. CONCLUSION: In this small cohort of infants breastfed on demand during first year of life, we report differential associations of HM IMPs with infant BC, showing that in addition to their critical role in shaping infant immunity, lactoferrin, and lysozyme also influence development of infant BC, highlighting the importance of breastfeeding for 12 months and beyond. IMPACT: HM IMPs (concentrations and, most importantly, daily intakes) time-dependently and differentially associate with development of infant lean mass and adiposity during first 12 months of lactation. There is no information on how intakes and concentrations of these components affect development of infant BC. HM contains IMPs-lactoferrin, lysozyme, and sIgA, which not only play a critical role in shaping infant's immunity, but also influence infant growth and development of BC, highlighting the importance of breastfeeding for 12 months and beyond and warranting careful consideration of the dose effects of supplemented formula.

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[Detection and analysis of serum food-specific IgG antibody in Beijing area].

Objective: The level of food specific IgG antibody in serum of patients with suspected food intolerance in Beijing area was detected and analyzed, so as to provide a basis for patients to eliminate the food that causes disease in their diet. Methods: Data were retrospectively analyzed in a total of 2368 suspected chronic food intolerance patients (all resident population in Beijing) admitted to Beijing Jishuitan Hospital from October 2015 to December 2019, including 859 males and 1509 females. The age range ranged from 2 months to 90 years, (40.2±18.6) years, and the median age was 36 years. Serum specific IgG (sIgG) antibody concentrations in 14 kinds of food (beef, chicken, pork, cod, shrimp, crab, egg, milk, corn, wheat, mushroom, soybean, tomato and rice) were determined by enzym-linked immunosorbentassay (ELISA).SPSS V22.0 was used for statistical analysis, and χ2 was used to compare the positive rate of each group. Results: The positive rate of food sIgG in 2 368 patients was 82.7% (1959/2368), the higher sIgG positive rates were found in eggs (54.7%), shrimp (29.0%) and milk (26.0%), and the lowest sIgG positive rates were found in pork (4.1%) and beef (1.2%) (P<0.05).There was significant gender difference in egg (χ²=10.885) and shrimp (χ²=6.607) sIgG, and female was significantly higher than male (P<0.05).The sIgG positive rates of egg (χ²=515.645), shrimp (χ²=74.20.4), milk (χ²=305.65), soybean (χ²=39.413), wheat (χ²=133.222), cod (χ²=25.540), crab (χ²=55.521), corn (χ²=20.645), tomato (χ²=118.108), chicken (χ²=32.821), pork (χ²=26.539), beef (χ²=21.632) and rice (χ²=25.335) were significant in different age groups. The positive rate of shrimp and crab sIgG increased with age (P<0.05).The positive rate of tomato sIgG decreased with age, and then increased slightly after 45 years. However, egg, milk, soybean, wheat, corn, and rice all showed a decreasing positive rate with the increase of age. The increase of chicken, pork and cod was observed in childhood, and then decreased with age, and then increased in middle and old age. Conclusions: There may be a certain correlation between food intolerance and elevated food sIgG levels in Beijing area. It is suggested that patients of different genders and ages should be optimized and adjusted according to their own characteristics, and children patients are still the key population for food intolerance control.

[Human bone marrow mesenchymal stem cells improve steroid resistance of human airway epithelial BEAS-2B cells in vitro].

Objective: To explore the effect of human bone marrow mesenchymal stem cells(MSC) on the steroid resistance of human airway epithelial cells. Methods: Ovalbumin (OVA)/lipopolysaccharide (LPS) were used to construct steroid resistant BEAS-2B cells, which were then co-cultured with MSC. Groups were set as follows: blank group, model group, Glucocorticoid group, MSC group, MSC+Glucocorticoid group (MSC+bud group). The expression of interleukin (IL)-8 in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA); the expression of reactive oxygen species (ROS) in the cells was detected by flow cytometry; the expression of glucocorticoid receptor α (GRα) and histone deacetylase 2 (HDAC2) protein in the cell was detected by Western blotting; and the expression of GRα and HDAC2 mRNA was detected by reverse transcription-polymerase chain reaction (RTPCR). Results: The expression level of IL-8 in the MSC group was significantly lower than that in the Glucocorticoid group (31.7±0.7 vs. 49.8±3.6, P<0.01). The expression of ROS in the MSC group was significantly lower than that in the Glucocorticoid group (2754±154 vs.4624±228, P<0.05). The expression level of HDAC2 mRNA in the MSC group was significantly higher than that in the Glucocorticoid group(1.749±0.005 vs. 1.283±0.098, P<0.05). The expression level of GRα mRNA in the MSC group was significantly higher than that in the Glucocorticoid group (1.623±0.079 vs.1.047±0.220, P<0.01). The expression of HDAC2 protein in the MSC group was significantly higher than that in the Glucocorticoid group (1.067±0.100 vs. 0.620±0.083, P<0.01). The expression of GRα protein in the MSC group was significantly higher than that in the Glucocorticoid group (0.834±0.053 vs. 0.579±0.017, P<0.01). ROS was positively correlated with the IL-8 expression (r=0.796, P<0.01) and negatively correlated with the HDAC2 and GRα mRNA expression (r=-0.893 3, P<0.01; r=0.931 4, P<0.01, respectively), as well as the HDAC2 and GRα Protein expression (r=-0.929 5, P<0.01;r=-0.864 3, P<0.01, respectively). Conclusions: Human MSC can improve steroid resistance of airway epithelial cells in an exocrine manner. The mechanism may be related to the down-regulation of ROS and up-regulation of HDAC2, which lead to GRα overexpression. In addition, MSC may improve the steroid resistance by reducing the expression of IL-8.

Tailor-made multiple sequence alignments using the PRALINE 2 alignment toolkit.

SUMMARY: PRALINE 2 is a toolkit for custom multiple sequence alignment workflows. It can be used to incorporate sequence annotations, such as secondary structure or (DNA) motifs, into the alignment scoring, as well as to customize many other aspects of a progressive multiple alignment workflow. AVAILABILITY AND IMPLEMENTATION: PRALINE 2 is implemented in Python and available as open source software on GitHub: https://github.com/ibivu/PRALINE/.

WHITE STRIPE LEAF8, encoding a deoxyribonucleoside kinase, is involved in chloroplast development in rice.

KEY MESSAGE: WSL8 encoding a deoxyribonucleoside kinase (dNK) that catalyzes the first step in the salvage pathway of nucleotide synthesis plays an important role in early chloroplast development in rice. The chloroplast is an organelle that converts light energy into chemical energy; therefore, the normal differentiation and development of chloroplast are pivotal for plant survival. Deoxyribonucleoside kinases (dNKs) play an important role in the salvage pathway of nucleotides. However, the relationship between dNKs and chloroplast development remains elusive. Here, we identified a white stripe leaf 8 (wsl8) mutant that exhibited a white stripe leaf phenotype at seedling stage (before the four-leaf stage). The mutant showed a significantly lower chlorophyll content and defective chloroplast morphology, whereas higher reactive oxygen species than the wild type. As the leaf developed, the chlorotic mutant plants gradually turned green, accompanied by the restoration in chlorophyll accumulation and chloroplast ultrastructure. Map-based cloning revealed that WSL8 encodes a dNK on chromosome 5. Compared with the wild type, a C-to-G single base substitution occurred in the wsl8 mutant, which caused a missense mutation (Leu 349 Val) and significantly reduced dNK enzyme activity. A subcellular localization experiment showed the WSL8 protein was targeted in the chloroplast and its transcripts were expressed in various tissues, with more abundance in young leaves and nodes. Ribosome and RNA-sequencing analysis indicated that some components and genes related to ribosome biosynthesis were down-regulated in the mutant. An exogenous feeding experiment suggested that the WSL8 performed the enzymic activity of thymidine kinase, especially functioning in the salvage synthesis of thymidine monophosphate. Our results highlight that the salvage pathway mediated by the dNK is essential for early chloroplast development in rice.

[The effects of continuous proton pump inhibitor therapy on small intestinal bacterial overgrowth in elderly].

Objective: Long-term proton pump inhibitor(PPI) therapy may increase the risk of small intestinal bacterial overgrowth(SIBO). Few studies on the effect of on-demand and continuous PPI therapy are available in elderly. To investigate the prevalence of SIBO and the effect of on-demand and continuous PPI therapy on SIBO in elderly. Methods: A total of 200 elderly outpatients admitted to Department of Gastroenterology at the Second Medical Center of PLA General Hospital were enrolled and divided into 3 groups: continuous PPI group, on-demand PPI group and control group. SIBO was diagnosed according to methane and hydrogen lactulose breath test (LBT).The prevalence of SIBO in the 3 groups was analyzed. Results: The prevalence of SIBO was 71.5% in 200 elderly. PPI therapy and diabetes mellitus (DM) were independent risk factors for SIBO. The prevalence of SIBO was 77.1% (108/140) in elderly who underwent long-term PPI therapy and 58.3% (35/60) in those without PPI therapy (P<0.01).The prevalence of SIBO was significantly higher in continuous PPI therapy group than that in on-demand PPI group and control group(88.6% vs. 65.7% and 58.3%, all P<0.01).However, no significant difference was found in the prevalence of SIBO between on-demand PPI group and control group (P>0.05). In elderly who underwent long-term PPI therapy, the prevalence of SIBO increased significantly if administration time was longer than 61 months. Conclusions: SIBO usually occurs in elderly patients who receive continuous PPI rather than on-demand use. If elderly require long-term PPI therapy, on demand administration is suggested as long as primary diseases are properly treated.

[Analysis of comorbidity and polypharmacy in middle-aged and elderly patients].

Objective: To investigate the characteristics of comorbidities and polypharmacy in middle-aged and elderly patients and assess the potential risk of drug-drug interactions. Methods: Retrospective analysis was carried out among the outpatients aged ≥45 years in the Second Medical Center of the PLA General Hospital from January to December 2016. The patient's comorbidities and polypharmacy were collected from the electronic medical records and annual physical examination reports. The frequency and grade of drug-drug interactions (DDIs) were summarized and ranked by Lexicomp(®) Drug Interactions database. Results: A total of 1 340 patients were enrolled in the study, of which 930 patients (69.40%) used 5 or more drugs, and 660 patients (49.25%) used 10 or more drugs. Multivariate analysis showed that age and the number of comorbidities were independent factors of excessive polypharmacy. The total frequency of detecting clinically significant DDIs (C+D+X) was 857 cases, with 0.8 cases per person by Lexicomp(®) Drug Interactions database. Among them, medications for nervous system accounted for the highest proportion of X-level DDIs. Conclusions: The comorbidities and polypharmacy in middle-aged and elderly patients are very prominent. More attention should be paid to drug interactions, especially in patients with neurological medication.

[Imaging findings of CT pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension].

Objective: To investigate the imaging findings of CT pulmonary angiography (CTPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Consecutive CTEPH cases admitted to receive CTPA in China-Japan Friendship Hospital from December 2015 to December 2019 were enrolled with prospective data collected. The medical histories, imaging manifestation and hemodynamic parameters were analyzed. Patients were divided into proximal lesions group and distal lesions group according to the site of thrombus, and imaging findings were compared between these two groups. Results: In 135 cases of CTEPH, CTPA showed thrombus in both lungs in the majority of patients (133 cases, 98.5%) with location of thromboembolic disease in level Ⅰ, Ⅱ and Ⅲ for most patients, only 8 cases with level Ⅳ(7.3%) and no level 0 patients. The most common signs of chronic thrombus were vessel cutoffs (134 cases, 99.3%), eccentric wall-adherent filling defects (111 cases, 88.2%), web or bands (80 cases, 59.3%), stenosis (41 cases, 30.4%). Compared to patients with distal lesions, eccentric wall-adherent filling defects, irregular vessel wall were more common in patients with proximal lesions, stenosis was more common in distal lesions, all P<0.05. The most common lung parenchymal signs were mosaic attenuation (104 cases, 77.0%), and pulmonary infarction (79 cases, 58.5%). Pulmonary infarction included pleura-based consolidation opacity (35/79, 44.3%), linear opacities (23/79, 29.1%), or both (13/79, 16.5%). Pulmonary artery enlargement (132 cases, 97.8%) and right ventricular hypertrophy (130 cases, 96.3%) were common, other signs included contrast reflux into the inferior vena cava (70 cases, 51.9%), enlargement of bronchial arteries (68 cases, 50.3%). No differences were found for all the secondary signs between patients with proximal lesions and those with distal lesions, all P>0.05. Conclusions: Vessel cutoffs, eccentric wall-adherent filling defects, web or bands are the most common CTPA findings of chronic thrombus in CTEPH. Secondary signs include mosaic attenuation, pulmonary infarction, pulmonary artery enlargement, right ventricular hypertrophy and enlargement of bronchial arteries. Eccentric wall-adherent filling defects are more common in patients with proximal lesions than those with distal lesions.