Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer.

BACKGROUND: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer. METHODS: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice. RESULTS: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1. CONCLUSIONS: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.

[Analysis of the correlative factors of long-term positive nucleic acid and the characteristics of nucleic acid conversion in novel coronavirus infected patients].

To analyze the correlative factors of long-term positive nucleic acid and the characteristics of negative nucleic acid conversion in novel coronavirus infected patients.Novel coronavirus infected patients who were hospitalized in Beijing Tsinghua Changgung Hospital from December 2022 to June 2023 were retrospectively included. Patients who were positive for novel coronavirus nucleic acid for ≥30 days were selected as the long-positive group, and age-and sex-matched patients with novel coronavirus nucleic acid for <30 days were selected as the control group. The clinical data of all enrolled patients were collected. Binary logistic regression was used to analyze the influencing factors of the positive duration of nucleic acid ≥30 days. The Cox risk ratio model was used to analyze the risk factors for the prognosis of severe patients during hospitalization, and the difference in the time of nucleic acid conversion between the upper and lower respiratory tract was compared between the groups. A total of 30 patients were included in the long-positive group, including 24 males and 6 females, aged [M (Q1, Q3)] 77 (64, 86) years. Fifty-eight patients were included in the control group, including 46 males and 12 females, aged 78 (66, 86) years. Transplantation status (OR=50.32, 95%CI: 1.98-1 278.63, P=0.018), malignant tumor (OR=12.85, 95%CI: 1.65-99.88, P=0.015), CD4+T cell count (OR=0.99, 95%CI: 0.99-1.00, P=0.005) were correlative factors for positive nucleic acid≥30 days. Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score (HR=1.12, 95%CI: 1.03-1.22, P=0.012) and nucleic acid positive time (HR=1.16, 95%CI: 1.01-1.33, P=0.031) were correlative factors for death in severe patients. The nucleic acid conversion time of the lower respiratory tract specimens in both groups was later than that of the upper respiratory tract specimens (all P<0.001). Weakened underlying immunity is a correlative factor for long-term novel coronavirus nucleic acid positivity, and long-term positive novel coronavirus nucleic acid in severe patients indicates high risk of death. The nucleic acid of the lower respiratory tract specimen turned negative later than the upper respiratory tract specimen.

[Evaluation effect of COMPERA 2.0 risk assessment model on prognosis of Chinese patients with pulmonary arterial hypertension].

Objectives: To clarify the evaluation effect of COMPERA 2.0 risk assessment model on prognosis of pulmonary arterial hypertension (PAH) in China. Methods: Patients with newly diagnosed PAH admitted in Fuwai hospital between April 2019 and March 2022 were enrolled retrospectively and divided in low, intermediate-low, intermediate-high and high strata by scores of COMPERA 2.0 risk assessment model. All the patients were followed up by clinic or telephone. The primary endpoint was defined as a composite of all-cause mortality, exacerbated heart failure and aggravated symptoms. Kaplan-Meier analysis and log-rank trend test were used to determine the risk of endpoints among the 4 groups. Multivariate Cox proportional hazards regression were used to analyze the association between COMPERA 2.0 scores and prognosis in patients with PAH. Results: A total of 951 patients with PAH were enrolled in this study. The age [M (Q1, Q3)] of the patients was 35 (28, 47) years, of which 706 cases (74.2%) were females. A total of 328 cases (34.5%) were assigned in low strata, 264 cases (27.8%) in intermediate-low strata, 193 cases (20.3%) in intermediate-high strata, and 166 cases (17.5%) in high strata. During the duration [M (Q1, Q3)] of follow-up after discharge of 1.8 (1.0, 2.8) years, the primary endpoint was occurred in 12.8% (42/328), 21.2% (56/264), 28.5% (55/193) and 42.8% (71/166) of low, intermediate-low, intermediate-high and high strata, respectively. The rates of primary endpoint were significantly increased with strata rising (P<0.001). Multivariate Cox proportional hazards regression showed that COMPERA 2.0 risk scores were associated with the primary endpoints in PAH patients (HR=1.801, 95%CI: 1.254-2.588, P=0.001) after adjusting confounders. Conclusion: COMPERA 2.0 risk assessment model is a simple and effective tool for evaluating the prognosis of newly diagnosed PAH patients in China.

[Preliminary analysis of seasonal pollen allergens of allergic rhinitis in a hospital of Nanchang City].

The study was aimed to analyze the seasonal pollen allergen spectrum of patients with allergic rhinitis (AR) in Nanchang city, and to provide evidence for improving the clinical diagnosis, treatment, prevention and epidemiology of seasonal AR. A retrospective analysis was conducted on the results of skin prick test (SPT) among 1 752 patients with AR in outpatient at Department of Otolaryngology, the First Affiliated Hospital of Nanchang University from September 2020 to August 2021 (a total of 1 069 males and 683 females, age ranged from 2 to 84 years old). SPSS 22.0 software was used to analyze the positive rates of main allergens and their differences in gender, age, and month of visit. Differences among groups were compared by student t test, Wilcox rank sum test, or χ2 test. The results showed that among 1 752 SPT-positive patients, the number of simple seasonal AR and the number of perennial combined seasonal AR were 102 (5.82%) and 281 (16.04%), respectively. There was no significant difference between male and female patients in positive seasonal pollen allergens (χ2=2.181, P>0.05), but the positive rate of indoor seasonal pollen allergens in males was higher than that in females (χ2=7.901, P<0.05). The seasonal pollen allergens ranking top 5 of the positive rates were willow (6.62%, 116/1 752), humulus scandens (5.71%, 100/1 752), rape (5.54%, 97/1 752), grey pigweed (4.62%, 81/1 752) and birch (3.60%, 63/1 752). The positive rates of indoor and seasonal pollen allergens increased first and then decreased in different age groups, and the highest positive rates of seasonal pollen allergens were in the age group of 31-40 years old, with statistical significance compared with other groups (χ2=61.269, P<0.05). The seasonal allergen positive rate showed two peaks in time: March to May and September to November. The positive rate of pollen in spring was 60.27% (132/219), which was significantly higher than that in autumn (39.73%,87/219) (χ2=9.247, P<0.05). The positive rate of pollen combination in spring and autumn was 68.29% (112/164), which was significantly higher than that in spring and autumn alone (18.9%,31/164) and (12.8%, 21/164) (χ2=14.731, P<0.05). In summary, pollen allergy in Nanchang City cannot be ignored, accounting for more than 20% of the total number of AR. The incidence of seasonal AR in Nanchang City showed two peaks (March to May and September to November). The common allergens for seasonal AR in Nanchang City were willow, humulus scandens, rape, grey chenopods and birch.

[Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

[Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad].

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

[Comparison of three different measurement methods to determine resting energy expenditure in patients with decompensated hepatitis B cirrhosis].

Objective: To compare the differences to determine resting energy expenditure (REE) measured with indirect calorimetry and REE predicted by formula method and body composition analyzer in patients with decompensated hepatitis B cirrhosis, so as to provide theoretical guidance for the implementation of precision nutrition intervention. Methods: Patients with decompensated hepatitis B cirrhosis who were admitted to Henan Provincial People's Hospital from April 2020 to December 2020 were collected. REE was determined by the body composition analyzer and the H-B formula method. Results: were analyzed and compared to REE measured by the metabolic cart. Results A total of 57 cases with liver cirrhosis were included in this study. Among them, 42 were male, aged (47.93 ± 8.62) years, and 15 were female aged (57.20 ± 11.34) years. REE measured value in males was (1 808.14 ± 201.47) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.002 and 0.003, respectively). REE measured value in females was (1 496.60 ± 131.28) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.016 and 0.004, respectively). REE measured with the metabolic cart had correlation with age and area of visceral fat in men (P = 0.021) and women (P = 0.037). Conclusion: Metabolic cart use will be more accurate to obtain resting energy expenditure in patients with decompensated hepatitis B cirrhosis. Body composition analyzer and formula method may underestimate REE predictions. Simultaneously, it is suggested that the effect of age on REE in H-B formula should be fully considered for male patients, while the area of visceral fat may have a certain impact on the interpretation of REE in female patients.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

Effect of ventilation mode on postoperative pulmonary complications following lung resection surgery: a randomised controlled trial.

The effect of intra-operative mechanical ventilation modes on pulmonary outcomes after thoracic surgery with one-lung ventilation has not been well established. We evaluated the impact of three common ventilation modes on postoperative pulmonary complications in patients undergoing lung resection surgery. In this two-centre randomised controlled trial, 1224 adults scheduled for lung resection surgery with one-lung ventilation were randomised to one of three groups: volume-controlled ventilation; pressure-controlled ventilation; and pressure-control with volume guaranteed ventilation. Enhanced recovery after surgery pathways and lung-protective ventilation protocols were implemented in all groups. The primary outcome was a composite of postoperative pulmonary complications within the first seven postoperative days. The outcome occurred in 270 (22%), with 87 (21%) in the volume control group, 89 (22%) in the pressure control group and 94 (23%) in the pressure-control with volume guaranteed group (p = 0.831). The secondary outcomes also did not differ across study groups. In patients undergoing lung resection surgery with one-lung ventilation, the choice of ventilation mode did not influence the risk of developing postoperative pulmonary complications. This is the first randomised controlled trial examining the effect of three ventilation modes on pulmonary outcomes in patients undergoing lung resection surgery.

Psoriasis may increase the risk of lung cancer: a two-sample Mendelian randomization study.

BACKGROUND: Although many studies have indicated that Psoriasis (PsO) could contribute to the risk of lung cancer, no study has reported a clear causal association between them. Our aim was to explore the potential causal association between PsO and the lung cancer risk using Mendelian randomization (MR) design. METHODS: To explore a causal association between the PsO and lung cancer, we used large-scale genetic summary data from genome-wide association study (GWAS), including PsO (n = 337 159) and lung cancer (n = 361 586), based on previous observational studies. Our main analyses were conducted by inverse-variance weighted (IVW) method with random-effects model, with a complementary with the other two analyses: weighted median method and MR-Egger approach. RESULTS: The results of IVW methods demonstrated that genetically predicted PsO was significantly associated with higher odds of lung cancer, with an odds ratio (OR) of 1.06 (95%CI, 1.01-1.12; P = 0.02). Weighted median method and MR-Egger regression also demonstrated directionally similar results (All P < 0.05). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between PsO and lung cancer. CONCLUSIONS: Our study provided potential evidence between genetically predicted PsO and lung cancer, which suggested that enhanced screening for lung cancer allows early detection of lung cancer.

[Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes].

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

[Lipid metabolism in idiopathic pulmonary fibrosis].

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology, which was characterized by irreversible lung function decrease and high mortality. Up till now, only two drugs, i.e. Pirfenidone and Nintedanib,have been approved by Food and Drug Administration (FDA) for therapy of IPF, and the treatment is less effective. Therefore, it is urgent to develop new therapeutic drugs. In recent years, studies had paid attention to lipid metabolism in IPF. In this review, we discussed recent major advances of lipid metabolism, biomarkers and clinical trials in IPF.

[Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure].

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.

Trends towards revealing the genetic architecture of sheep tail patterning: Promising genes and investigatory pathways.

Different sheep breeds have evolved after initial domestication, generating various tail phenotypic patterns. The phenotypic diversity of sheep tail patterns offers ideal materials for comparative analysis of its genetic basis. Evolutionary biologists, animal geneticists, breeders, and producers have been curious to clearly understand the underlying genetics behind phenotypic differences in sheep tails. Understanding the causal gene(s) and mutation(s) underlying these differences will help probe an evolutionary riddle, improve animal production performance, promote animal welfare, and provide lessons that help comprehend human diseases related to fat deposition (i.e., obesity). Historically, fat tails have served as an adaptive response to aridification and climate change. However, the fat tail is currently associated with compromised mating and animal locomotion, fat distribution in the animal body, increased raising costs, reduced consumer preference, and other animal welfare issues such as tail docking. The developing genomic approaches provide unprecedented opportunities to determine causal variants underlying phenotypic differences among populations. In the last decade, researchers have performed several genomic investigations to assess the genomic causality underlying phenotypic variations in sheep tails. Various genes have been suggested with the prominence of several potentially significant causatives, including the BMP2 and PDGFD genes associated with the fat tail phenotype and the TBXT gene linked with the caudal vertebrae number and tail length. Although the potential genes related to sheep tail characteristics have been revealed, the causal variant(s) and mutation(s) of these high-ranking candidate genes are still elusive and need further investigation. The review discusses the potential genes, sheds light on a knowledge gap, and provides possible investigative approaches that could help determine the specific genomic causatives of sheep tail patterns. Besides, characterizing and revealing the genetic determinism of sheep tails will help solve issues compromising sheep breeding and welfare in the future.

Performance of different methods for testing polymyxin B: comparison of broth microdilution, agar dilution and MIC test strip in mcr-1 positive and negative Escherichia coli.

Antimicrobial susceptibility testing with the last-resort antibiotics polymyxins (polymyxin B and colistin) is associated with several methodological issues. Currently, broth microdilution (BMD) is recommended for colistin and polymyxin B. BMD is laborious and the utility of alternative methods needs to be evaluated for polymyxin B susceptibility testing. In this study, using BMD as a reference method, the performance of agar dilution (AD) and MIC test strips (MTS) were evaluated in polymyxin B susceptibility testing. BMD, AD and MTS were used to determine MICs of 193 clinical isolates of Escherichia coli. Seventy-nine were positive for the polymyxin resistance gene mcr-1. Method performances were evaluated based on pair-wise agreements with the reference method (BMD) and statistical testing. AD and MTS showed an unacceptable number of very major errors (VMEs) compared with BMD, 9·3 and 10·7%, respectively. The essential agreement (EA) was low for AD (49·7%), but high for MTS (97·8%). However, statistical testing showed that MTS tended to yield a one-step lower MIC (P < 0·01) compared with BMD. The discordances observed with MTS and AD in comparison with BMD for polymyxin B susceptibility testing for E. coli suggest their inapplicability in routine testing. A large number of isolates clustered around the susceptibility breakpoint (2-4 mg l-1 ) and several mcr-1 positive isolates (17%) were determined as susceptible with BMD. A screening breakpoint for mcr-1 of 2 mg l-1 should also be considered.

Plasma metabolome alteration in dairy cows with left displaced abomasum before and after surgical correction.

Left displaced abomasum (LDA) leads to substantial changes in the metabolism of dairy cows. Surgical correction of LDA can rapidly improve the health of cows; however, changes in metabolism following surgery are rarely described. To investigate the changes of plasma metabolome in cows with LDA before and after surgical correction, blood samples were collected from 10 healthy postpartum cows and 10 cows with LDA on the day of diagnosis, then again from the LDA cows 14 d after surgery. Serum nonesterified fatty acid, ß-hydroxybutyric acid, cortisol and histamine concentration, and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities were evaluated, and the metabolic profile in plasma was analyzed using ultra-high-performance liquid chromatography time-of-flight mass spectrometry. The results demonstrated that cows with LDA experienced severe negative energy balance and oxidative stress, which can be improved by surgical correction. The metabolic profile was analyzed using multidimensional and univariate statistical analyses, and different metabolites were identified. In total, 102 metabolites differed between cows with LDA and healthy cows. After surgical correction, 65 metabolites changed in cows with LDA, compared with these cows during the LDA event. Following surgical correction, AA levels tended to increase, and lipid levels tended to decrease in cows with LDA. Pathway analysis indicated marked changes in linoleic acid metabolism, Arg biosynthesis, and Gly, Ser, and Thr metabolism in cows at the onset of LDA and following surgical correction. Surgical treatment reversed the changes in AA and lipid metabolism in cows with LDA.

[The expression and clinical significance of serum soluble programmed cell death ligand-1 in adult patients with community-acquired pneumonia].

To investigate the clinical significance of serum soluble programmed cell death ligand-1 (PD-L1) in adult patients with community-acquired pneumonia (CAP). A total of 44 CAP patients, 54 severe CAP patients and 30 healthy volunteers were recruited in this study. Serum soluble PD-L1 were detected. Univariate and multivariate regression analyses were used to assess the influence of multiple clinical variables on prognosis. Serum soluble PD-L1 level in severe CAP group was 98.20(57.94, 128.90) ng/L, which was significantly higher than that in the CAP group [59.32(33.55, 92.58) ng/L] and healthy controls [20.44(12.15, 36.20) ng/L] (all P<0.001). PD-L1 level was positively correlated with CRUB-65(r=0.481, P<0.001) and the pneumonia severity index (PSI) score (r=0.442, P<0.001). Univariate regression analysis showed that CURB-65 (HR=2.544, 95%CI 1.324-4.889, P=0.005), PSI score (HR=1.036, 95%CI 1.012-1.061, P=0.004), soluble PD-L1(HR=1.013, 95%CI 1.001-1.026, P=0.041) were risk factors of mortality during hospitalization. Multivariate regression analysis suggested that PSI score (HR=1.042, 95%CI 1.012-1.073, P=0.005), soluble PD-L1 (HR=1.011, 95%CI 1.002-1.071, P=0.020) were independent predictors for mortality risk in CAP patients. CAP patients with soluble PD-L1≥98.20 ng/L had a significantly lower survival rate than those with soluble PD-L1<98.20 ng/L (P=0.033). In conclusion, this study indicates that serum soluble PD-L1 level in CAP patients is correlated with the survival prognosis.

[Clinical characteristics of patients infected with Chlamydia pneumoniae in Beijing from 2015 to 2019].

Objective: To aralyze the clinical characteristics of Chlamydia pneumoniae infection in Beijing. Methods: Based on Beijing Respiratory Pathogen Surveillance System, acute respiratory infection patients were recruited from 35 different types of sentinel hospitals in Beijing. Their epidemiological and clinical data were systematically collected and clinical specimens were also obtained. Nuclear acid testing was performed for 30 types of respiratory pathogens (including Chlamydia pneumoniae). The identified patients of Chlamydia pneumoniae infection were divided into two groups, the acute upper respiratory tract infection (AURI) group and pneumoniae group. The differences in clinical characteristics, laboratory examination and prognosis were compared by using independent sample t test, Mann-Whitney U test, χ2 test or Fisher's exact probability test. Results: A total of 119 patients of Chlamydia pneumoniae infection were included, including 12 patients in the AURI group and 107 patients in pneumoniae group. Chlamydia pneumoniae infection mainly occurred in people aged from 5 to 44 years, accounting for 81.5% (97/119). The three most common clinical symptoms were cough (92.4%, 110/119), fever (88.8%, 95/107), and sputum production (76.5%, 91/119). White blood cell counts increased in 39.3% (46/117) of patients. Neutrophile granulocyte proportion increased in 39.7% (46/116) of patients. Platelet count increased in 36.9% (41/111) of patients. An increase of the creatine kinase MB isoenzyme (CKMB) was observed in 12 pneumonia patients (24.5%, 12/49). Radiological examination showed that 90.6% (87/105) of patients in the pneumoniae group had pulmonary parenchymal changes; the lesion occurred most commonly in the lower right lung lobe (34.3%, 36/105) and the lower left lung lobe (27.6%, 29/105). Although 73.8% (79/107) of patients in the pneumoniae group were hospitalized, no case received intensive care unit or mechanical ventilation. As to outcomes, one patient developed respiratory failure and 6 patients suffered myocardial injury. No death was observed in this study. The median days of hospitalization and course of illness for pneumonia patients M(P25,P75) were 10.0 (7.0, 13.0) days and 18.0 (13.5, 22.0) days, respectively. Conclusion: Generally, Chlamydia pneumoniae infections in Beijing from 2015 to 2019 were mild, and the main clinical manifestations were cough, fever and sputum. However, most patients in the pneumoniae group caused by Chlamydia pneumoniae still required hospitalization but with a better outcome.

Effective Model of Food Allergy in Mice Sensitized with Ovalbumin and Freud's Adjuvant.

To better explore the pathophysiology of FA and its therapy, we aimed to establish a simple and practicable FA model with Freund's adjuvant and introduce an easy and reliable laboratory evaluation method for assessment of inflammation in intestinal segments at different anatomical locations. BALB/c mice were sensitized with ovalbumin combined with Freund's adjuvant. Complete Freund's adjuvant was chosen for the first sensitization and two weeks later incomplete Freund's adjuvant was used for a second sensitization. Two weeks later, the sensitized mice were challenged with 50 mg ovalbumin every other day. After the 6 challenge, all mice were assessed for systemic anaphylaxis, and then sacrificed for sample collection. All sensitized mice showed anaphylactic symptoms and markedly increased levels of serum ovalbumin-specific IgE and IgG1. The activity of mast cell protease-1 (mMCPT-1) was significantly increased in the serum and interstitial fluid of the duodenum, jejunum, ileum, and colon. A successful FA model was established, of which inflammation occurred in the duodenum, jejunum, ileum, and colon. This model provides a reliable and simple tool for analysis of the mechanism of FA and methods of immunotherapy. Moreover, combined detection of ovalbumin-specific antibody and local mMCPT-1 levels could potentially be used as the major indicator for assessment of food allergy.

[The effects of posterior chamber intraocular lens implantation on accommodative function in high myopia].

Objective: To investigate the effects of implantable Collamer lens (ICL) with a central hole on the accommodative function of patients with high myopia at different ages after implantation. Methods: A retrospective cohort study was conducted on 75 patients (150 eyes, 23 men and 52 women) with high myopia who underwent ICL implantation in Department of Ophthalmology of First Affiliated Hospital of Army Medical University from January 2017 to December 2018. The age was (28.99±7.26) years (range, 18-48 years). Forty patients (80 eyes) aged 18-34 years were included in the younger group and 35 patients (70 eyes) aged 35-48 years were included in the elderly group. To compare the changes and differences of accommodative function between the two groups, the uncorrected visual acuity, best corrected visual acuity, spherical equivalent error, amplitude of accommodation (AMP), negative relative accommodation (NRA), positive relative accommodation, single and both eyes' accommodation of facility (AF), fused cross cylinder, near and far distance horizontal phoria, accommodative convergence/accommodation and visual satisfaction questionnaire before surgery and at 1, 3, 6 and 12 months after surgery were analyzed. ANOVA for repeated design, LSD, unpaired sample t-test, Paired t-test, Chi-square test and Fisher's exact test were used for data analyses. Results: At each time point before and after operation, there were significant differences between the two groups in the AMP (F=16.511, P<0.05). The AMP of the younger group increased from (8.88±2.27) D at baseline to (9.51±1.34) D at 12 months, while it was decreased in the elderly group from (7.67±2.36) D at baseline to (6.56±2.63) D at 12 months. The trend of changes was significantly different (F=15.044,P<0.05). The AMP of the elderly group was significantly lower than that of the younger group at all time points (F=47.678, P<0.05). The NRA of the younger group was better than that of the elderly group (F=13.459, P<0.05), but the NRA had no significant changes in both groups postoperatively (F=1.788, P=0.141). We could not find any significant changes of positive relative accommodation between two groups (F=1.447, P=0.233). The monocular and binocular AF of two groups was increased significantly after surgery (F=34.296, 21.839, P<0.05). The AF of the younger group was better than that of the elderly group (F=80.327, 43.08, P<0.05). The fused cross cylinder was improved from baseline (0.12±0.32) D to (0.38±0.49) D at 12 months (F=4.752, P<0.05), while the difference was not found in the younger group (F=2.110, P=0.151). We could not find any significant changes of accommodative convergence/accommodation between two groups (F=0.389, P=0.505) or in each group (F=1.049, P=0.309) preoperatively and at 1, 3, 6 and 12 months after surgery. Conclusions: ICL implantation is effective in the treatment of high myopia. The visual acuity, AMP, monocular and binocular AF may increase obviously. Big improvements in the accommodative function and high satisfaction of vision can be achieved, especially in younger patients. (Chin J Ophthalmol, 2021, 57: 113-121).