CSE regulates LINC000665/XBP-1 in the progress of pulmonary fibrosis.

INTRODUCTION: Cigarette smoking may impact the progression of idiopathic pulmonary fibrosis (IPF), and the intensity of smoking presents a dose-response association with IPF. METHODS: We retrospectively analyzed IPF patients diagnosed in our hospital from 2014 to 2018 and performed follow-up to confirm survival status and duration, and determine the effect of smoking on the prognosis of IPF. We retrieved information on IPF from a bioinformatics database to identify the differential expression of lncRNAs and proteins in smokers. Therefore, we explored and verified the mechanism by which cigarette smoke exposure (CSE) regulates LINC00665/XBP-1 involvement in pulmonary fibrosis through cell experiments. We clarified the mechanism between LINC00665 and XBP-1 through cellular and molecular experiments, and verified the inhibitory effect of silencing LINC00665 on pulmonary fibrosis by using a bleomycin (BLM)-induced pulmonary fibrosis model. RESULTS: We found that smokers with IPF had a poor prognosis compared with non-smokers. Both the expression of LINC00665 and XBP-1 in IPF lung tissue and smoker lung tissue were significantly upregulated, moreover, LINC00665 was higher in smoker IPF lung tissue than in smoker healthy people. Exposure to CSE could upregulate LINC00665/XBP-1 in lung fibroblast-to-myofibroblast transition. Cellular and molecular experiments showed that LINC00665 regulates the expression of XBP-1 by targeting miR-214-3p. LINC00665 expression, was significantly upregulated in BLM-induced mouse lung fibrosis tissues, and LINC00665 knockdown inhibited fibrogenesis in BLM-induced lung fibrosis. CONCLUSIONS: Our study found that the high expression of LINC00665 is involved in the pathogenesis of smoker IPF and that CSE may positively regulate LINC00665/XBP-1 to participate in lung fibroblast-to-myofibroblast transition. These findings help elucidate the pathogenesis of smoker IPF and may contribute to the development of new targeted drugs for IPF therapy.

The prognostic role of C-reactive protein to albumin ratio and anti-MDA5 antibody-positive in idiopathic inflammatory myopathy: a retrospective study.

This cohort study aimed to identify the characteristics and risk factors of adult idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) and further explore the prognostic factors of IIM-ILD. We extracted data regarding 539 patients with laboratory-confirmed idiopathic inflammatory myopathy (IIM) with or without interstitial lung disease (ILD) from the Second Xiangya Hospital of Central South University between January 2016 and December 2021. The regression analysis was conducted to identify the possible risk factors for ILD as well as mortality. Of 539 IIM patients, 343 (64.6%) were diagnosed with IIM-ILD. The median (IQR) baseline neutrophil-to-lymphocyte ratio (NLR), C-reactive protein to albumin ratio (CAR) and ferritin were 4.1371 (2.6994-6.8143), 0.1685 (0.0641-0.5456) and 393.6 (210.6-532.2), respectively. Risk factors associated with IIM-ILD were older age (p = 0.002), arthralgia (p = 0.014), lung infection (p = 0.027), hemoglobin (p = 0.022), high CAR (p = 0.014), anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive (p < 0.001), and anti-MDA5 antibody-positive (p < 0.001). The IIM-ILD patients whose age at diagnosis of disease ≥ 59.5 (HR = 2.673, 95% CI 1.588-4.499, p < 0.001), NLR ≥ 6.6109 (HR = 2.004, 95% CI 1.193-3.368, p = 0.009), CAR ≥ 0.2506 (HR = 1.864, 95% CI 1.041-3.339, p = 0.036), ferritin ≥ 397.68 (HR = 2.451, 95% CI 1.245-4.827, p = 0.009) and anti-MDA5 antibody-positive (HR = 1.928, 95% CI 1.123-3.309, p = 0.017) had a higher mortality rate. High CAR and anti-MDA5 antibody-positive are more likely to be associated with a high mortality rate of IIM-ILD, which can be used as serum biomarkers, especially the CAR, a simple, objective tool to assess the prognosis of IIM.

Clinical characteristics analysis of Chlamydia psittaci pneumonia detected by metagenomic next-generation sequencing / 中国热带医学

@#Abstract: Objective　To analyze the clinical characteristics of Chlamydia psittaci pneumonia and improve the diagnosis and treatment skills of clinicians on this disease. Methods The clinical data of thirty-nine Chlamydia psittaci pneumonia cases detected by metagenomic next-generation sequencing (mNGS) from September 2020 to January 2022 at the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. Results There was a history of poultry exposure in 89.7%(35 cases) of the patients. The most common clinical manifestations were high fever (92.3%, 36), cough (76.9%,30), muscle soreness (48.7%,19), headache (38.5%,15), etc. Laboratory examinations showed 76.9% of patients had a normal leukocyte count, and 76.9% had decreased lymphocyte count, often accompanied by elevated C-reactive protein (100%), procalcitonin (97.4%), interleukin-6 (95.8%), interleukin-10 (95.8%), alanine aminotransferase (74.4%), and aspartate aminotransferase (84.6%). Univariate analysis indicated that there were statistically significant differences in the levels of aspartate transaminase, blood urea nitrogen, C-reactive protein, and procalcitonin between severe pneumonia patients and non-severe pneumonia patients（P<0.05）. Multivariate logistic regression analysis showed that an elevated blood urea nitrogen (OR=4.899) had guiding significance for predicting the occurrence of severe pneumonia. Bronchoscopy examination showed no abnormalities in 53.6% of the patients. The imaging manifestations of pulmonary lesions were mainly lobar pneumonia (61.5%) and air bronchograms (94.9%). Therapeutically, it was sensitive to tetracyclines, macrocyclic lactones, and fluoroquinolones. A total of 84.6%(33 cases) of the patients were cured and discharged from the hospital at the end of the treatment. Conclusion Chlamydia psittaci pneumonia is a zoonotic disease that can be detected by mNGS. An elevated blood urea nitrogen level has guiding significance for predicting the occurrence of severe pneumonia. Empirically-selected regimens based on doxycycline are effective for the treatment of Chlamydia psittaci pneumonia.

Clinical profiles of SS-ILD compared with SS-NILD in a Chinese population: a retrospective analysis of 735 patients.

BACKGROUND: Interstitial lung disease (ILD) is a serious complication in patients with Sjögren's syndrome (SS). Most studies on primary SS (pSS) with ILD are limited in sample size, and studies on secondary SS (sSS) with ILD are rare. This study aimed to elucidate both primary and secondary SS-associated ILD (SS-ILD) based on a large cohort. METHODS: The medical records of hospitalized patients diagnosed with SS at the Second Xiangya Hospital of Central South University from January 2010 to May 2020 were retrospectively reviewed. Clinical manifestations, medical history, biological results and imaging data were collected. RESULTS: Of the 735 SS patients enrolled in this study, 563 (76.6%) were diagnosed with pSS, 172 (23.4%) were diagnosed with sSS. Additionally, 316 (43.0%) were diagnosed with SS-ILD. No significant difference was found between the pSS and sSS groups concerning the incidence of ILD (p = .718). Factors associated with SS-ILD were older age (p < .001), male sex (p = .032), female sex at menopause (p = .002), Raynaud's phenomenon (p < .001), low levels of albumin (p = .010) and respiratory symptoms (p < .001). The SS-ILD group showed higher counts of platelets (p < .001). The three most frequent high-resolution CT (HRCT) findings of SS-ILD were irregular linear opacities (42.7%), grid shadows (30.7%) and pleural thickening (28.5%). NSIP (56.3%) was the most frequent HRCT pattern. Compared with pSS patients with ILD (pSS-ILD) patients, sSS patients with ILD (sSS-ILD) patients had a higher incidence of proteinuria (p < .001) and hypercreatinaemia (p = .013), a higher level of erythrocyte sedimentation rate (ESR) (p = .003), low levels of complement 3 (C3) (p = .013), lymphocytes (p = .009) and leukocytes (p = .024), and worse DLCO (%Pred) (p = .035). CONCLUSIONS: ILD is a common pulmonary involvement in both pSS patients and sSS patients. Older age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD. NSIP is important HRCT feature of SS-ILD. sSS-ILD patients showed worse laboratory results and pulmonary function.KEY MESSAGEOlder age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD.SS-ILD patients show higher counts of platelets and less purpura.sSS-ILD patients have worse laboratory results and pulmonary function.

Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis.

Fibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05). The percentages of peripheral blood fibrocytes in the IPF group (4.2550 ± 0.3483%) and CTD-ILD group (4.7100 ± 0.4811%) were higher than that in the control group (1.6340 ± 0.2549%) (both P < 0.05). In vitro, PBMCs transfected with siRNA-CFL-1 showed lower expression of CFL-1, and the percentage of fibrocytes was lower than that of the control (P < 0.05). PBMCs transfected with Lv-CFL-1 to increase the expression of CFL-1 showed a higher percentage of fibrocytes than the control (P < 0.05). In mice with bleomycin-induced pulmonary fibrosis, the relative expression of CFL-1 was increased, and the percentage of fibrocytes was higher than that in the saline group (P < 0.05). In bleomycin-induced mice, interference with Lv-CFL-1 decreased the expression of CFL-1, the percentage of fibrocytes was lower, and the lung tissue showed less fibrosis (P < 0.05). The overexpression of CFL-1 is associated with pulmonary fibrogenesis. CFL-1 could promote the differentiation of fibrocytes from monocyte peripheral blood mononuclear cells and promote pulmonary fibrosis.

Clinical Findings in Diabetes Mellitus Patients with COVID-19.

BACKGROUNDS: Diabetes mellitus (DM) is one of the most common comorbidities in patients with coronavirus disease (COVID-19). We aim to summarize the clinical features of DM patients with COVID-19 and find out potential factors associated with severe disease. METHODS: In this retrospective, single-center study, the medical records of patients with COVID-19 in Changsha, Hunan, China, from January 21, 2020, to February 19, 2020, were reviewed. Epidemiological information, clinical features, and outcomes were compared between DM patients admitted to the intensive care unit (ICU) or not. RESULTS: A total of 241 patients confirmed with COVID-19 were enrolled, including 19 DM patients. There were more patients in DM group admitted to the ICU than non-DM group (36.8% vs. 15.8%, P = 0.045). Compared with non-DM group in the ICU, there were more female patients from DM group in the ICU (85.7% vs. 31.4%, P = 0.024). On admission, the mean level of glycated hemoglobin A1c (HbA1c) was higher in the ICU DM patients than that in the non-ICU DM patients (8.5% vs. 7.1%). There were more DM patients with proteinuria in the ICU group than the non-ICU group (57.1% vs. 33.3%). Twelve DM patients (63.2%) changed diabetic therapy during hospitalization, and all DM patients admitted to the ICU used insulin. As of March 14, all 19 DM patients have been discharged, and no death occurred. CONCLUSIONS: DM patients with COVID-19 are vulnerable to severe disease, especially for female patients. High levels of HbA1c and proteinuria could be potential risk factors for severe COVID-19 in DM patients. In addition to timely systemic therapy, the control of blood glucose and proper diabetic therapy is essential to improve the prognosis of severe DM patients with COVID-19.

Pain is a common problem in patients with ILD.

BACKGROUND: As it is less known about the prevalence and characteristics of pain in the patients with interstitial lung disease (ILD), this paper aims at determining the characteristics of the pain in the patients with ILD. METHODS: Subjects with ILD and health controls with the matched ages and genders completed Short Form McGill Pain Questionnaire (SF-MPQ) and part of the Brief Pain Inventory (BPI) Short Form to elicit the characteristics of the pain. The patients with ILD were also assessed through Pulmonary Function Test, Six Minutes Walking Test (6MWT), modified Medical Research Council Dyspnea Scale (mMRC) for state of the illness and measured health-related quality of life (HRQoL) by Short Form-36 (SF-36) and psychological associations by Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 63 subjects with ILD and 63 healthy controls (HC) were recruited in our study. The prevalence of the pain was 61.9% in ILD versus 25.3% in HC (P = 0.005) and the median score of the pain rank index (PRI) in ILD was higher than that in HC (P = 0.014). Chest (46.1%) accounted for the highest of overall pain locations in subjects with ILD. Associated clinical factors for pain intensity in the patients with ILD included exposure history of risk factors of ILD, with a longer distance of 6MWD (≥ 250 m), and a higher mMRC score (2-4). The patients with ILD and pain are more likely to suffer impaired HRQoL (P = 0.0014) and psychological problems (P = 0.0017, P = 0.044). CONCLUSION: The pain is common in those with ILD and the pain intensity is associated with exposure history, 6MWD, and mMRC score. The patients with ILD and pain were possibly to suffer depression, anxiety, and impaired HRQoL.

Clinical Characteristics of Elderly Patients with COVID-19 in Hunan Province, China: A Multicenter, Retrospective Study.

BACKGROUND: The aim of this study was to analyze and summarize the clinical characteristics of elderly patients with coronavirus disease 2019 (COVID-19) and compare the differences of young-old patients (60-74 years old) and old-old patients (≥75 years old). METHODS: In thisretrospective, multicenter study, the medical records of elderly patients who were diagnosed with COVID-19 in Hunan province, China, from January 21 to February 19, 2020 were reviewed. The characteristics of young-old patients and old-old patients were compared. RESULTS: Of the 105 elderly patientsconfirmed withCOVID-19, 81.0% were young-old patients, and 19.0% were old-old patients; 54.3% of elderly patients were females. Overall, 69.5% of elderly patients had underlying diseases, and the most common comorbidities included hypertension (43.8%), diabetes (25.7%), and cardiac disease (16.2%). Of the elderly patients, 22.9% were severe and 10.5% were critical severe cases. On admission, the most frequent symptoms in elderly patients included fever (66.7%), cough (64.8%), and fatigue (33.3%). Lymphopenia (31.4%), increased D-dimer (38.1%), depressed albumin (36.2%), elevated lactate dehydrogenase (41.0%), and a high level of C-reactive protein (79.0%) were common among elderly patients with COVID-19. The median prothrombin time (PT) and the activated partial thromboplastin time (APTT) were longer in old-old patients than young-old patients (PT median 12.3 vs. 13.1 s, p = 0.007; APTT median 39.0 vs. 33.5 s, p = 0.045). Young-old patients showed fewer complications (14.1%) than old-old patients (40.0%; p = 0.0014) and fewer received invasive ventilator support (3.5 vs. 25.0%, p = 0.006). As of March 11, 2020, 85.7% of elderly patients had been discharged, 3 deaths had occurred, and 11.4% were still hospitalized. CONCLUSIONS: Elderly patients usually have chronic medical illness and are likely to have a severe or critically severe condition. They could show atypical symptoms without fever or cough and multiple organ dysfunction. Old-old patients tend to have more complications than young-old patients during hospitalization. Careful nursing, observation, and systemic treatment are very important in elderly patients.

Novel coronavirus infection in children outside of Wuhan, China.

BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

Surface-imprinted microspheres prepared by a template-oriented method for the chiral separation of amlodipine.

The surface imprinting technique has been developed to overcome the mass-transfer difficulty, but the utilization ratio of template molecules in the imprinting procedure still remains a challengeable task to be improved. In this work, specifically designed surface-imprinted microspheres were prepared by a template-oriented method for enantioseparation of amlodipine besylate. Submicron mesoporous silica microspheres were surface-modified with double bonds, followed by polymerizing methacrylic acid to generate carboxyl modified mesoporous silica microspheres (PMAA@SiO2 ). Afterwards, PMAA@SiO2 was densely adsorbed with (S)-amlodipine molecules to immobilize template molecules through multiple hydrogen bonding interactions. Then surface molecular imprinting was carried out by cross-linking the carboxyl group of PMAA@SiO2 with ethylene glycol diglycidyl ether. The surface-imprinted microspheres showed fast binding kinetics of only 20 min for equilibrium adsorption, and the saturation adsorption capacity reached 137 mg/g. The imprinted materials displayed appreciable chiral separation ability when used as column chromatography for enantioseparation of amlodipine from amlodipine besylate, and the enantiomeric excess of (S)-amlodipine reached 13.8% with only 2.3 cm column length by no extra chiral additives. Besides, the imprinted materials exhibited excellent reusability, and this allows the potential application for amplification production of amlodipine enantiomer.

Rapid and efficient enantioseparation of (S)-amlodipine by surface-imprinted core-shell polymer microspheres.

We present a protocol for the preparation of surface-imprinted polymer microspheres by core-shell precipitation polymerization for the enantioseparation of (S)-amlodipine. In this work, submicron mesoporous silica microspheres were prepared with gemini cationic surfactant as soft template. Molecularly imprinted polymers were coated on the silica supports with a low level of crosslinking, and the thickness of the thin-walled imprinted shell was about 45 nm. The material showed fast binding kinetics for (S)-amlodipine (within only 20 min for complete equilibrium), and the saturation adsorption capacity reached 309.2 mg/g, indicating the good accessibility of binding sites and improved mass transfer for target molecule. The imprinted microspheres exhibited an appreciable enantiomeric excess of (S)-amlodipine of 11.3% when used as a glass chromatography column for the enantioseparation of (S)-amlodipine from amlodipine besylate without extra chiral additives. The surface-imprinted materials display potentially amplification for industrial enantioseparation of (S)-amlodipine.