Selection of indicators reporting response rate in pharmaceutical trials for systemic lupus erythematosus: preference and relative sensitivity.

OBJECTIVE: SLE is a common multisystem autoimmune disease with chronic inflammation. Many efficacy evaluation indicators of randomised clinical trials (RCTs) for SLE have been proposed but the comparability remains unknown. We aim to explore the preference and comparability of indicators reporting response rate and provide basis for primary outcome selection when evaluating the efficacy of SLE pharmaceutical treatment. METHODS: We systematically searched three databases and three registries to identify pharmacological intervention-controlled SLE RCTs. Relative discriminations between indicators were assessed by the Bayesian hierarchical linear mixed model. RESULTS: 33 RCTs met our inclusion criteria and we compared eight of the most commonly used indicators reporting response rate. SLE Disease Activity Index 4 (SLEDAI-4) and SLE Responder Index 4 were considered the best recommended indicators reporting response rate to discriminate the pharmacological efficacy. Indicator preference was altered by disease severity, classification of drugs and outcome of trials, but SLEDAI-4 had robust efficacy in discriminating ability for most interventions. Of note, BILAG Index-based Combined Lupus Assessment showed efficacy in trials covering all-severity patients, as well as non-biologics RCTs. The British Isles Lupus Assessment Group response and Physician's Global Assessment response were more cautious in evaluating disease changes. Serious adverse event was often applied to evaluate the safety and tolerability of treatments rather than efficacy. CONCLUSIONS: The impressionable efficacy discrimination ability of indicators highlights the importance of flexibility and comprehensiveness when choosing primary outcome(s). As for trials that are only evaluated by SLEDAI-4, attention should be paid to outcome interpretation to avoid the exaggeration of treatment efficacy. Further subgroup analyses are limited by the number of included RCTs. PROSPERO REGISTRATION NUMBER: CRD42022334517.

Global, regional, and national incidence and prevalence of systemic sclerosis.

OBJECTIVES: To estimate the global and country-specific unbiased epidemiological data of SSc. METHODS: Epidemiological studies were systematically searched in four databases. A Bayesian hierarchical linear mixed model was constructed to estimate epidemiological data. RESULTS: 82 studies were included and epidemiological data on SSc were missing for 83.9% of countries worldwide. The global SSc incidence and newly diagnosed population were estimated to be 8.64 per 100,000 person-years (1.78-23.57) and 0.67 million (0.14-1.84) people annually, respectively. Regarding prevalence, the global SSc prevalence and affected population were 18.87 per 100,000 persons (1.55-25.28) and 1.47 million (0.12-1.97) people, respectively. Relatively higher incidence and prevalence were observed in females, adults, and high-income level countries. CONCLUSIONS: We provide a comprehensive synthesis of SSc epidemiology and fill data gaps in most countries. Especially in low- and middle-income countries, epidemiological studies of SSc are insufficient. Further large-scale and standardized reported epidemiological investigations of SSc are imperative.

C. acnes qPCR-Based Antibiotics Resistance Assay (ACQUIRE) Reveals Widespread Macrolide Resistance in Acne Patients and Can Eliminate Macrolide Misuse in Acne Treatment.

Background: Macrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences. Objective: We developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care. Methods: A cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne. Results: The high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies. Conclusion: The macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.

Original Hosts, Clinical Features, Transmission Routes, and Vaccine Development for Coronavirus Disease (COVID-19).

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to public concern worldwide. Although a variety of hypotheses about the hosts of SARS-CoV-2 have been proposed, an exact conclusion has not yet been reached. Initial clinical manifestations associated with COVID-19 are similar to those of other acute respiratory infections, leading to misdiagnoses and resulting in the outbreak at the early stage. SARS-CoV-2 is predominantly spread by droplet transmission and close contact; the possibilities of fecal-oral, vertical, and aerosol transmission have not yet been fully confirmed or rejected. Besides, COVID-19 cases have been reported within communities, households, and nosocomial settings through contact with confirmed COVID-19 patients or asymptomatic individuals. Environmental contamination is also a major driver for the COVID-19 pandemic. Considering the absence of specific treatment for COVID-19, it is urgent to decrease the risk of transmission and take preventive measures to control the spread of the virus. In this review, we summarize the latest available data on the potential hosts, entry receptors, clinical features, and risk factors of COVID-19 and transmission routes of SARS-CoV-2, and we present the data about development of vaccines.

RNA methylation and neurovascular unit remodeling. / RNAç”²åŸºåŒ–ä¸Žç¥žç»è¡€ç®¡å•å ƒé‡å¡‘.

RNA methylation is of great significance in the regulation of gene expression, among which the more important methylation modifiers are N6-methyladenosine (m6A) and 5-methylcytosine (m5C). The methylation process is mainly regulated by 3 kinds of proteins: methyltransferase, demethylase, and reader. m6A, m5C, and their related proteins have high abundance in the brain, and they have important roles in the development of the nervous system and the repair and remodeling of the vascular system. The neurovascular unit (NVU) is a unit of brain structure and function composed of neurons, capillaries, astrocytes, supporting cells, and extracellular matrix. The local microenvironment for NVU has an important role in nerve cell function repair, and the remodeling of NVU is of great significance in the prognosis of various neurological diseases.

Knowledge, attitudes and anxiety toward COVID-19 among domestic and overseas Chinese college students.

BACKGROUND: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad. METHOD: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad. RESULTS: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72). CONCLUSIONS: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad.

Multi-organ Dysfunction in Patients with COVID-19: A Systematic Review and Meta-analysis.

This study aimed to provide systematic evidence for the association between multiorgan dysfunction and COVID-19 development. Several online databases were searched for articles published until May 13, 2020. Two investigators independently selected trials, extracted data, and evaluated the quality of individual trials. Single-arm meta-analysis was performed to summarize the clinical features of confirmed COVID-19 patients. Fixed effects meta-analysis was performed for clinically relevant parameters that were closely related to the patients' various organ functions. A total of 73 studies, including 171,108 patients, were included in this analysis. The overall incidence of severe COVID-19 and mortality were 24% (95% confidence interval [CI], 20%-28%) and 2% (95% CI, 1%-3%), respectively. Patients with hypertension (odds ratio [OR] = 2.40; 95% CI, 2.08-2.78), cardiovascular disease (CVD) (OR = 3.54; 95% CI, 2.68-4.68), chronic obstructive pulmonary disease (COPD) (OR=3.70; 95% CI, 2.93-4.68), chronic liver disease (CLD) (OR=1.48; 95% CI, 1.09-2.01), chronic kidney disease (CKD) (OR = 1.84; 95% CI, 1.47-2.30), chronic cerebrovascular diseases (OR = 2.53; 95% CI, 1.84-3.49) and chronic gastrointestinal (GI) disease (OR = 2.13; 95% CI, 1.12-4.05) were more likely to develop severe COVID-19. Increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity cardiac troponin I (hs-cTnI), myoglobin, creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were highly associated with severe COVID-19. The incidence of acute organ injuries, including acute cardiac injury (ACI); (OR = 11.87; 95% CI, 7.64-18.46), acute kidney injury (AKI); (OR=10.25; 95% CI, 7.60-13.84), acute respiratory distress syndrome (ARDS); (OR=27.66; 95% CI, 18.58-41.18), and acute cerebrovascular diseases (OR=9.22; 95% CI, 1.61-52.72) was more common in patients with severe COVID-19 than in patients with non-severe COVID-19. Patients with a history of organ dysfunction are more susceptible to severe conditions. COVID-19 can aggravate an acute multiorgan injury.

The Functional Role of Voltage-Gated Sodium Channel Nav1.5 in Metastatic Breast Cancer.

Voltage-gated sodium channels (VGSCs), which are abnormally expressed in various types of cancers such as breast cancer, prostate cancer, lung cancer, and cervical cancer, are involved in the metastatic process of invasion and migration. Nav1.5 is a pore-forming α subunit of VGSC encoded by SCN5A. Various studies have demonstrated that Nav1.5, often as its neonatal splice form, is highly expressed in metastatic breast cancer cells. Abnormal activation and expression of Nav1.5 trigger a variety of cellular mechanisms, including changing H+ efflux, promoting epithelial-to-mesenchymal transition (EMT) and the expression of cysteine cathepsin, to potentiate the metastasis and invasiveness of breast cancer cells in vitro and in vivo. Here, we systematically review the latest available data on the pro-metastatic effect of Nav1.5 and its underlying mechanisms in breast cancer. We summarize the factors affecting Nav1.5 expression in breast cancer cells, and discuss the potential of Nav1.5 blockers serving as candidates for breast cancer treatment.

Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment.

Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.

LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s.

Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of lncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein l splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/XBP1s axis.