Single-cell profiling reveals kidney CD163+ dendritic cell participation in human lupus nephritis.

OBJECTIVES: The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment. METHODS: Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced. Multiplex immunohistochemical analysis was performed on an independent cohort of 60 patients and validated using flow cytometric characterisation of human kidney tissues and in vitro assays. RESULTS: We uncovered a notable enrichment of CD163+ dendritic cells (DC3s) in LN kidneys, which exhibited a positive correlation with the severity of LN. In contrast to their counterparts in blood, DC3s in LN kidney displayed activated and highly proinflammatory phenotype. DC3s showed strong interactions with CD4+ T cells, contributing to intrarenal T cell clonal expansion, activation of CD4+ effector T cell and polarisation towards Th1/Th17. Injured proximal tubular epithelial cells (iPTECs) may orchestrate DC3 activation, adhesion and recruitment within the LN kidneys. In cultures, blood DC3s treated with iPTECs acquired distinct capabilities to polarise Th1/Th17 cells. Remarkably, the enumeration of kidney DC3s might be a potential biomarker for induction treatment response in LN patients. CONCLUSION: The intricate interplay involving DC3s, T cells and tubular epithelial cells within kidneys may substantially contribute to LN pathogenesis. The enumeration of renal DC3 holds potential as a valuable stratification feature for guiding LN patient treatment decisions in clinical practice.

Prognostic significance of blood urea nitrogen/creatinine ratio in chronic HFpEF.

BACKGROUND: The prognostic significance of blood urea nitrogen (BUN)/creatinine ratio specifically in chronic heart failure with preserved ejection fraction (HFpEF) patients remained unclear. We aimed to evaluate the association of BUN/creatinine ratio (baseline level and visit-to-visit variation) with the risk of adverse clinical outcomes among patients with chronic HFpEF. METHODS AND RESULTS: This is a secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Of the enrolled 3445 participants in the TOPCAT trial, associations between BUN/creatinine and clinical outcomes were examined in a subset of 1521 (baseline measurements level) and 1453 (visit-to-visit variation) participants. A multivariable Cox proportional hazard model was used to assess the prognostic significance of BUN/creatinine ratio and BUN/creatinine ratio variation for the prespecified clinical outcomes. A higher BUN/creatinine ratio was associated with a higher risk of all-cause mortality (hazard ratio [HR] = 1.52, 95%CI, 1.21-1.91; p < .001) as well as cardiovascular disease mortality (HR = 1.83, 95%CI, 1.35-2.49; p < .001) in the fully adjusted model. Greater visit-to-visit variability in BUN/creatinine ratio tended to be independently associated with a higher risk of heart failure hospitalization and primary endpoint (p < .001 for both outcomes). Furthermore, those findings were consistent across participants stratified by the presence of chronic kidney disease at baseline. CONCLUSIONS: Higher BUN/creatinine ratio and greater BUN/creatinine ratio variability are independently associated with adverse outcomes in HFpEF participants in the TOPCAT trial.

Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19.

BACKGROUND: The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. METHODS: A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. RESULTS: On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells. CONCLUSIONS: A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Chest pain in a mid-aged woman, not simply myopericarditis: a case report of anti-Ku positive polymyositis.

BACKGROUND: Anti-Ku is a rare antibody which can be positive in some rheumatic diseases and it might be related to cardiac involvement. Polymyositis is an inflammatory myopathy, and its cardiac involvement seldom presents as myopericarditis and anti-Ku positive. CASE PRESENTATION: In this case, we report a mid-aged woman with chest pain, upper limbs weakness and fever unrelated with infection. The diagnosis of this case was unquestionably myopericarditis supported by ECG, cardiac MRI and negative findings in coronary arteries. Diagnosis of polymyositis was further clarified by the evidence of persistently increased CK, degeneration of proximal muscle in MRI, muscular dystrophy with lymphocytes infiltration in muscle biopsy. In the analysis of autoantibodies, we surprisingly discovered positive anti-Ku. Glucocorticoid and mycophenolate mofetil were then prescribed for polymyositis. Patient follow-up indicated remission of both myopericarditis and polymyositis. We finally clarified this rare case as a positive anti-Ku polymyositis with myopericarditis as cardiac involvement. CONCLUSION: This report presents a rare case with anti-Ku positive polymyositis and the cardiac involvement of polymyositis was manifested as myopericarditis. Therefore, positive anti-Ku might explain the myopericarditis as cardiac involvement in polymyositis. More cases and longer duration of follow-up is required for the comprehensive understanding of the disease.

Clinical outcome in pediatric refractory gastrointestinal Henoch-Schönlein purpura treated with mycophenolate mofetil.

The aim of the present study was to investigate the clinical outcome of mycophenolate mofetil in pediatric refractory gastrointestinal (GI) Henoch-Schönlein purpura (HSP). Most of the HSP patients with GI symptoms may benefit from early introduction of glucocorticoid; however, a number of patients still do not achieve remission following the administration of steroids. Therefore, the present study was to investigate the clinical features and the clinical outcome of mycophenolate mofetil in refractory GI HSP. A total of 110 HSP patients with a median onset age of 6.3 years were included. Sixty-one (55.5%) exhibited GI involvement, and 18 (18/61, 29.5%) presented with refractory GI involvement, with a median onset age of 6.3 years. Intractable abdominal pain, GI hemorrhage, intussusception, and chronic ulcers were common presentations of GI involvement. Of those refractory ones, Arthralgia was observed in 9 cases and renal involvement was observed in 13 cases. Glucocorticoids were administered in all 18 patients, but remission was not achieved. However, complete remission of abdominal pain was achieved in all patients within a median time of 3 days (1-14 days) after mycophenolate mofetil therapy. The infection rate of Epstein-Barr virus and cytomegalovirus in the refractory group was significantly higher compared with that in non-refractory group.Conclusion: GI symptoms in HSP patients with refractory GI involvement were more severe compared with non-refractory cases. Epstein-Barr virus and cytomegalovirus infection may be risk factors for refractory GI HSP. The efficacy of mycophenolate mofetil treatment was evident in these patients. What is Known: • Abdominal pain, gastrointestinal hemorrhage, intussusceptions, and intestinal perforation were the main presentations of gastrointestinal involvement in Henoch-Schönlein purpura. What is New: • Epstein-Barr virus and Cytomegalovirus infection may be the high risk factor of refractory GI. Refractory gastrointestinal Henoch-Schönlein purpura was associated with renal involvement. • Mycophenolate mofetil treatment was effective for refractory gastrointestinal Henoch-Schönlein purpura.

The vascular densities of the macula and optic disc in normal eyes from children by optical coherence tomography angiography.

PURPOSE: This study aims to describe the variation and characteristics of vessel density (VD) of the macula and optic disc in the normal eyes of children. METHODS: This was a retrospective study where subjects aged 5-18 years with normal eyes were enrolled. The macula and optic disc were scanned by optical coherence tomography angiography (OCTA). The influences of age, gender, and axial length (AL) on VD were analyzed. RESULTS: A total of 71 normal eyes from 71 subjects were enrolled. For the macula, the mean VD of fovea, parafovea, and perifovea at superficial retina and deep retina were 20.1%, 50.2%, 49.4%, 36.1%, 53.9%, and 48.1%, respectively. The mean foveal avascular zone (FAZ) was 0.277 mm2. For optic disc, the mean VD of radial peripapillary capillary (RPC) and inside-disc areas were 51.8% and 51.7%, respectively. Significant differences were found between the superior-hemi and inferior-hemi VD of the superficial retinal parafovea, deep retinal perifovea, and perifovea. The fovea VD of the superficial and deep retina and FAZ areas were different between genders. The inside-disc VD was positively correlated with AL, while other VDs had no significant correlation with age and AL. CONCLUSIONS: The parafovea VD of the superficial retina, parafovea, and perifovea of the deep retina had superior-hemi VD; boys had a higher fovea VD and smaller FAZ area than those of girls, the macular VD and peripapillary RPC density were steady for 5-18 year-olds. This study provided useful information for furthering the understanding of the development mode of vessel in children and the OCTA clinical applications in children.

Paramyxoviruses respiratory syncytial virus, parainfluenza virus, and human metapneumovirus infection in pediatric hospitalized patients and climate correlation in a subtropical region of southern China: a 7-year survey.

To investigate the features of paramyxovirus respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (HMPV) infection and determine the effect of meteorological conditions in Guangzhou, a subtropical region of southern China. We collected 11,398 respiratory samples from hospitalized pediatric patients with acute respiratory illness between July 2009 and June 2016 in Guangzhou. The samples were tested simultaneously for 18 respiratory pathogens using real-time PCR. Local meteorological data were also collected for correlation analysis. Of 11,398 patients tested, 5606 (49.2%) patients tested positive for one or more pathogens; RSV, PIV, and HMPV were the first, sixth, and ninth most frequently detected pathogens, in 1690 (14.8%), 502 (4.4%), and 321 (2.8%) patients, respectively. A total 17.9% (4605/5606) of patients with positive results had coinfection with other pathogens. Significant differences were found in the prevalence of RSV, PIV, and HMPV among all age groups (p < 0.001). RSV and HMPV had similar seasonal patterns, with two prevalence peaks every year. PIV appeared alternatively with RSV and HMPV. Multiple linear regression models were established for RSV, PIV, and HMPV prevalence and meteorological factors (p < 0.05). RSV and PIV incidence was negatively correlated with monthly mean relative humidity; RSV and HMPV incidence was negatively correlated with sunshine duration; PIV incidence was positively correlated with mean temperature. We described the features of paramyxovirus infection in a subtropical region of China and highlighted the correlation with meteorological factors. These findings will assist public health authorities and clinicians in improving strategies for controlling paramyxovirus infection.

Increased Group 2 Innate Lymphoid Cells Are Correlated with Eosinophilic Granulocytes in Patients with Allergic Airway Inflammation.

The T helper 2 (Th2)-type response was considered the hypostasis of allergic airway diseases, including asthma and allergic rhinitis (AR). However, more recent studies have suggested that allergic airway inflammation also depends on innate immunity and is closely related to group 2 innate lymphoid cells (ILC2s). This study evaluated the ILC2 levels of asthma subjects, patients with asthma and AR, and healthy individuals, regarding how to investigate the relationship between clinical data and ILC2 levels. It was found that asthma patients and asthma with AR patients had higher ILC2 levels compared to healthy subjects. ILC2s were positively correlated with the percentage of eosinophils in patients with asthma and AR, but not with pulmonary function. ILC2 levels were higher in mild asthma subjects than in patients with severe asthma. This study provides a new interpretation of the pathogenesis of allergic airway inflammation and may provide a new direction for the diagnosis and assessment of allergic airway diseases.

Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China.

Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7-12 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (≥ 38 °C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.

Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region.

BACKGROUND: Human bocavirus 1 (HBoV1) is an important cause of acute respiratory illness (ARI), yet the epidemiology and effect of meteorological conditions on infection is not fully understood. To investigate the distribution of HBoV1 and determine the effect of meteorological conditions, hospitalized pediatric patients were studied in a subtropical region of China. METHODS: Samples from 11,399 hospitalized pediatric patients (≤14 years old), with ARI were tested for HBoV1 and other common respiratory pathogens using real-time PCR, between July 2009 and June 2016. In addition, local meteorological data were collected. RESULTS: Of the 11,399 patients tested, 5606 (49.2%) were positive for at least one respiratory pathogen. Two hundred forty-eight of 11,399 (2.2%) were positive for HBoV1 infection. Co-infection was common in HBoV1-positive patients (45.2%, 112/248). A significant difference in the prevalence of HBoV1 was found in patients in different age groups (p < 0.001), and the peak prevalence was found in patients aged 7-12 months (4.7%, 56/1203). Two HBoV1 prevalence peaks were found in summer (between June and September) and winter (between November and December). The prevalence of HBoV1 was significantly positively correlated with mean temperature and negatively correlated with mean relative humidity, and the mean temperature in the preceding month had better explanatory power than the current monthly temperature. CONCLUSIONS: This study provides a better understanding of the characteristics of HBoV1 infection in children in subtropical regions. Data from this study provide useful information for the future control and prevention of HBoV1 infections.

Sestrin 1 ameliorates cardiac hypertrophy via autophagy activation.

Cardiac hypertrophy is one of the major risk factors of cardiovascular morbidity and mortality. Autophagy is acknowledged to be an important mechanism regulating cardiac hypertrophy. Sestrin 1, a downstream target gene of p53, has been proven to regulate autophagy. However, the role of Sestrin 1 in cardiac hypertrophy remains unknown. Our study showed that Sestrin 1 mRNA and protein expression declined in pressure overload cardiac hypertrophy and phenylephrine (PE)-induced cardiac hypertrophy. Knockdown of Sestrin 1 by RNAi deteriorated PE-induced cardiac hypertrophy, whereas the overexpression of Sestrin 1 by adenovirus transfection blunted hypertrophy. We discovered that knockdown of Sestrin 1 resulted in impaired autophagy while overexpression of Sestrin 1 resulted in increased autophagy without affecting lysosomal function. In addition, the antihypertrophic effect of Sestrin 1 overexpression was eliminated by autophagy blockade. Importantly, Sestrin 1 targets at the AMPK/mTORC1/autophagy pathway to inhibit cardiac hypertrophy by interaction with AMPK which is responsible for autophagy regulation. Taken together, our data indicate that Sestrin 1 regulates AMPK/mTORC1/autophagy axis to attenuate cardiac hypertrophy.

Detection of IL-9 producing T cells in the PBMCs of allergic asthmatic patients.

BACKGROUND: Interleukin-9 (IL-9) was reported as an active participant in the pathogenesis of allergic asthma. This study aimed to investigate the major source ofIL-9 and its effect on interferon γ (IFN-γ) and immunoglobulin (Ig) secretion by B cells. METHODS: We isolated peripheral blood mononuclear cells from children with allergic asthma and healthy children. IL-9, IL-4 and IFN-γ expression were detected by ELISA, ELISpot and Flowcytometry. Expression of transcription factor PU.1 was measured by Western Blot. We evaluated the effect of IL-9 on B cell activation and Ig production. RESULTS: Results showed that compared with healthy children, levels of IL-9, IL-4 and PU.1 were elevated and levels of IFN-γ were lower in children with allergic asthma. IL-9-expressing CD4+ T cells did not co-express IL-4. Exogenous IL-9 inhibited IFN-γ production in a dose-dependent manner. Antigen-specific Th9 cells existed in children with house dust mite allergic asthma. IL-9 up-regulated expression of CD69 and CD25 on B cells and combination of IL-9 and IL-4 enhanced IgE production. CONCLUSIONS: In conclusion, our results showed that Th9 cells may be the major source of IL-9 in children with allergic asthma. In these patients, IL-9 impairs IFN-γ production and synergistically promotes IL-4-induced IgE secretion.

DJ-1 activates autophagy in the repression of cardiac hypertrophy.

Cardiac hypertrophy is the risk factor of heart failure when the heart is confronted with pressure overload or neurohumoral stimuli. Autophagy, a conserved degradative pathway, is one of the important mechanisms involved in the regulation of cardiac hypertrophy. DJ-1 is a traditional anti-oxidative protein and emerging evidence suggested that DJ-1 might modulate autophagy. However, the regulation of autophagy by DJ-1 in the process of cardiac hypertrophy remains unknown. In our study, we firstly discovered that the expression of DJ-1declined in the process of pressure overload cardiac hypertrophy, and its alteration was parallel with the impairment of autophagy. Furthermore, we proved that DJ-1 knockout mice exhibited a more hypertrophied phenotype than wildtype mice in cardiac hypertrophy which indicated that DJ-1 is responsible for the repression of cardiac hypertrophy. Furthermore, DJ-1 knockout significantly exacerbated pulmonary edema due to cardiac hypertrophy. In the process of cardiac hypertrophy, DJ-1 knockout significantly impaired autophagy activation and enhanced mTORC1 and mTORC2 phosphorylation were found. Similarly, our in vitro study proved that DJ-1 overexpression ameliorated phenylephrine (PE)-induced cardiac hypertrophy and promoted autophagy activation. Taken together, DJ-1 might repress both pressure overload and PE-induced cardiac hypertrophy via the activation of autophagy.

Methylprednisolone pulse therapy rescued life-threatening pulmonary hemorrhage due to idiopathic pulmonary hemosiderosis.

Idiopathic pulmonary hemosiderosis (IPH) is an extremely rare cause of massive pulmonary hemorrhage in children. During the acute phase, death due to massive alveolar hemorrhage and subsequent severe respiratory failure. We report two cases of IPH children who developed hypoxemic respiratory failure and massive pulmonary hemorrhage. One case of a 10-year-old boy was treated with methylprednisolone pulse therapy (10mg/kg/d) for the first three days and followed by systemic steroid therapy, he successfully decannulated 10days later and discharged with a favorable quality of life. Another case of a 4year-old female child with Down's syndrome diagnosed as IPH for over one year and treated with oral corticosteroids for maintenance therapy. She sudden suffered severe hypoxemia with rapid falls in the hemoglobin level. We applied methylprednisolone pulse therapy (10mg/kg/d) for three days and other supportive therapies, the girl survived through complicated with oxygen dependence. We suggest that methylprednisolone pulse therapy provides a chance of recovery and survival for patients with IPH at the acute phase, even if accompanied by severe pulmonary hemorrhage.

A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes.

PIWI interacting RNAs (piRNAs) are highly expressed in germline cells and are involved in maintaining genome integrity by silencing transposons. These are also involved in DNA/histone methylation and gene expression regulation in somatic cells of invertebrates. The functions of piRNAs in somatic cells of vertebrates, however, remain elusive. We found that snoRNA-derived and C (C')/D' (D)-box conserved piRNAs are abundant in human CD4 primary T-lymphocytes. piRNA (piR30840) significantly downregulated interleukin-4 (IL-4) via sequence complementarity binding to pre-mRNA intron, which subsequently inhibited the development of Th2 T-lymphocytes. Piwil4 and Ago4 are associated with this piRNA, and this complex further interacts with Trf4-Air2-Mtr4 Polyadenylation (TRAMP) complex, which leads to the decay of targeted pre-mRNA through nuclear exosomes. Taken together, we demonstrate a novel piRNA mechanism in regulating gene expression in highly differentiated somatic cells and a possible novel target for allergy therapeutics.

Corticosteroid in Combination with Leflunomide and Mesenchymal Stem Cells for Treatment of Pediatric Idiopathic Pulmonary Hemosiderosis.

Background: This study evaluated the efficiency of corticosteroid, leflunomide and mesenchymal stem cells (MSCs) in the treatment of pediatric idiopathic pulmonary hemosiderosis (IPH). Methods: Ten patients were included in the study. The diagnosis of IPH was based on clinical symptoms, laboratory examinations and pulmonary hemosiderosis. Induction therapy consisted of methylprednisolone pulse therapy, followed by prednisone plus leflunomide. Maintenance therapy consisted of low-dose prednisone, leflunomide and administration of MSCs. Results: All the patients achieved complete response after treatment with corticosteroid, leflunomide and MSCs. The median follow-up was 23 months (range: 4-34 months). Moreover, administration of MSCs induced an increase in the percentage of CD4+ CD25+ regulatory T cells but a decrease in the percentage of Th17 cells. Conclusion: Treatment with corticosteroid, leflunomide and MSCs for pediatric IPH was safe and effective.

A novel common gamma chain mutation in a Chinese family with X-linked severe combined immunodeficiency (X-SCID; T(-)NK(-)B(+)).

X-linked severe combined immunodeficiency (X-SCID) is one of the most common causes of primary immunodeficiencies in humans. A 4-month-old boy with recurrent pulmonary infection had decreased numbers of CD3(+), CD4(+), CD8(+) T lymphocytes, and NK cells and increased levels of CD19(+) B cells but no memory B cells or plasma cells. The production of cytokines by T cells and the activation of T and B cells were either absent or inefficient. While B cell levels were high, they were all IgM-positive, and the secretion of all Ig isotypes by activated B cells in vitro was defective. Genomic DNA sequencing revealed that the patient had missense mutations in the IL2RG (exon 5, 718 T > C) and IL7R genes (exon 2, 197 T > C; exon 4, 412G > A). Although the patient's father and one of his sisters have the same missense homozygous mutations of the IL7R gene, neither of them exhibited the immunological phenotype of SCID. The results indicate that the IL2RG gene mutation or a combination of the IL7R and IL2RG mutations in the sick boy had resulted in T(-)NK(-)B(+) SCID.

REDD1 attenuates cardiac hypertrophy via enhancing autophagy.

Cardiac hypertrophy is a major risk factor of cardiovascular morbidity and mortality. Autophagy is established to be involved in regulating cardiac hypertrophy. REDD1, a stress-responsive protein, is proved to contribute in autophagy induction. However, the role of REDD1 in cardiac hypertrophy remains unknown. Our study demonstrated that REDD1 knockdown by RNAi exacerbated phenylephrine (PE)-induced cardiac hypertrophy, manifested by increased hypertrophic markers such as ANP and cell surface area. In addition, we discovered that ERK1/2 signaling pathway was involved in the effect of REDD1 on hypertrophy. Moreover, our study showed that REDD1 knockdown impaired autophagy in hypertrophied cardiomyocytes. mTOR, a signaling molecule governing autophagy induction, was activated by the knockdown of REDD1 under PE stress. Importantly, the pro-hypertrophic effect of REDD1 knockdown was significantly reversed by the autophagy enhancer rapamycin. Taken together, we firstly prove that REDD1 is essential for inhibiting cardiac hypertrophy by enhancing autophagy.

Efficacy and safety of tocilizumab in Chinese patients with systemic juvenile idiopathic arthritis: a multicentre phase IV trial.

OBJECTIVES: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA. METHOD: In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12. RESULTS: Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%-95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred. CONCLUSION: This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.

Chinese expert consensus on the diagnosis, treatment, and management of asthma in women across life.

Background: The epidemiology and severity of asthma vary by sex and age. The diagnosis, treatment, and management of asthma in female patients are quite challenging. However, there is hitherto no comprehensive and standardized guidance for female patients with asthma. Methods: Corresponding search strategies were determined based on clinical concerns regarding female asthma. Search terms included "sex hormones and lung development", "sex hormone changes and asthma", "hormones and asthma immune response", "women, asthma", "children, asthma", "puberty, asthma", "menstruation, asthma", "pregnancy, asthma", "lactation, asthma", "menopause, asthma", "obesity, asthma", and "women, refractory, severe asthma". Literature was retrieved from PubMed/Medline, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Data with the search date of July 30, 2022 as the last day. This consensus used the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the strength of recommendation and quality of evidence. Results: We collected basic research results and clinical evidence-based medical data and reviewed the effects of sex hormones, classical genetics, and epigenetics on the clinical presentation and treatment response of female patients with asthma under different environmental effects. Based on that, we formulated this expert consensus on the management of female asthma throughout the life cycle. Conclusions: This expert consensus on the management of asthma in women throughout the life cycle provides diagnosis, treatment, and research reference for clinical and basic medical practitioners.