Supportive or Confining? The Impact of War Metaphors From the COVID-19 Pandemic on Persons With Disabilities in Mainland China.

Ensuring the well-being of persons with disabilities (PWDs) is a priority in the public sector during the coronavirus disease 2019 (COVID-19) pandemic. To contain this unprecedented public crisis in China, a set of nationwide anti-epidemic discourse systems centered on war metaphors has guided the epidemic's prevention and control. While the public is immersed in the joy brought by the stage victory, most ignore the situation of the disadvantaged PWDs. Accordingly, this study adopts and presents a qualitative research method to explore the impact of war metaphors on PWDs. The results showed that while there was some formal and informal support for PWDs during this period, they were increasingly marginalized. Owing to the lack of a disability lens and institutional exclusion, PWDs were placed on the margins of the epidemic prevention and control system like outsiders. Affected by pragmatism under war metaphors, PWDs are regarded as non-contributory or inefficient persons; therefore, they are not prioritized and are thus placed into a state of being voiceless and invisible. This research can provide inspiration for improving public services for PWDs in the context of COVID-19.

Genetic Modification of Mesenchymal Stem Cells Overexpressing Angiotensin II Type 2 Receptor Increases Cell Migration to Injured Lung in LPS-Induced Acute Lung Injury Mice.

Although mesenchymal stem cells (MSCs) transplantation has been shown to promote the lung respiration in acute lung injury (ALI) in vivo, its overall restorative capacity appears to be restricted mainly because of low retention in the injured lung. Angiotensin II (Ang II) are upregulated in the injured lung. Our previous study showed that Ang II increased MSCs migration via Ang II type 2 receptor (AT2R). To determine the effect of AT2R in MSCs on their cell migration after systemic injection in ALI mice, a human AT2R expressing lentiviral vector and a lentivirus vector carrying AT2R shRNA were constructed and introduced into human bone marrow MSCs. A mouse model of lipopolysaccharide-induced ALI was used to investigate the migration of AT2R-regulated MSCs and the therapeutic potential in vivo. Overexpression of AT2R dramatically increased Ang II-enhanced human bone marrow MSC migration in vitro. Moreover, MSC-AT2R accumulated in the damaged lung tissue at significantly higher levels than control MSCs 24 and 72 hours after systematic MSC transplantation in ALI mice. Furthermore, MSC-AT2R-injected ALI mice exhibited a significant reduction of pulmonary vascular permeability and improved the lung histopathology and had additional anti-inflammatory effects. In contrast, there were less lung retention in MSC-ShAT2R-injected ALI mice compared with MSC-Shcontrol after transplantation. Thus, MSC-ShAT2R-injected group exhibited a significant increase of pulmonary vascular permeability and resulted in a deteriorative lung inflammation. Our results demonstrate that overexpression of AT2R enhance the migration of MSCs in ALI mice and may provide a new therapeutic strategy for ALI. Stem Cells Translational Medicine 2018;7:721-730.

Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

BACKGROUND: Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. METHODS: Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. RESULTS: Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but not Losartan, indicating that FAK activation and F-actin reorganization were downstream of AT2R. CONCLUSIONS: These data indicate that Ang II-AT2R regulates human bone marrow MSC migration by signaling through the FAK and RhoA/Cdc42 pathways. This study provides insights into the mechanisms by which MSCs home to injury sites and will enable the rational design of targeted therapies to improve MSC engraftment.

Noninvasive Ventilation in Acute Hypoxemic Nonhypercapnic Respiratory Failure: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of noninvasive ventilation in patients with acute hypoxemic nonhypercapnic respiratory failure unrelated to exacerbation of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. DATA SOURCES: PubMed, EMBASE, Cochrane library, Web of Science, and bibliographies of articles were retrieved inception until June 2016. STUDY SELECTION: Randomized controlled trials comparing application of noninvasive ventilation with standard oxygen therapy in adults with acute hypoxemic nonhypercapnic respiratory failure were included. Chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients were excluded. The primary outcome was intubation rate; ICU mortality and hospital mortality were secondary outcomes. DATA EXTRACTION: Demographic variables, noninvasive ventilation application, and outcomes were retrieved. Internal validity was assessed using the risk of bias tool. The strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. DATA SYNTHESIS: Eleven studies (1,480 patients) met the inclusion criteria and were analyzed by using a random effects model. Compared with standard oxygen therapy, the pooled effect showed that noninvasive ventilation significantly reduced intubation rate with a summary risk ratio of 0.59 (95% CI, 0.44-0.79; p = 0.0004). Furthermore, hospital mortality was also significantly reduced (risk ratio, 0.46; 95% CI, 0.24-0.87; p = 0.02). Subgroup meta-analysis showed that the application of bilevel positive support ventilation (bilevel positive airway pressure) was associated with a reduction in ICU mortality (p = 0.007). Helmet noninvasive ventilation could reduce hospital mortality (p = 0.0004), whereas face/nasal mask noninvasive ventilation could not. CONCLUSIONS: Noninvasive ventilation decreased endotracheal intubation rates and hospital mortality in acute hypoxemia nonhypercapnic respiratory failure excluding chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients. There is no sufficient scientific evidence to recommend bilevel positive airway pressure or helmet due to the limited number of trials available. Large rigorous randomized trials are needed to answer these questions definitely.

A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study.

INTRODUCTION: The effect of mean arterial pressure titration to a higher level on microcirculation in septic shock patients with previous hypertension remains unknown. Our goal is to assess the effect of mean arterial pressure titration to a higher level on microcirculation in hypertensive septic shock patients. METHODS: This is a single-center, open-label study. Hypertensive patients with septic shock for less than 24 hours after adequate fluid resuscitation and requiring norepinephrine to maintain a mean arterial pressure of 65 mmHg were enrolled. Mean arterial pressure was then titrated by norepinephrine from 65 mmHg to the normal level of the patient. In addition to hemodynamic variables, sublingual microcirculation was evaluated by sidestream dark field imaging. RESULTS: Nineteen patients were enrolled in the study. Increasing mean arterial pressure from 65 mmHg to normal levels was associated with increased central venous pressure (from 11 ± 4 to 13 ± 4 mmHg, P = 0.002), cardiac output (from 5.4 ± 1.4 to 6.4 ± 2.1 l/minute, P = 0.001), and central venous oxygen saturation (from 81 ± 7 to 83 ± 7%, P = 0.001). There were significant increases in small perfused vessel density (from 10.96 ± 2.98 to 11.99 ± 2.55 vessels/mm(2), P = 0.009), proportion of small perfused vessels (from 85 ± 18 to 92 ± 14%, P = 0.002), and small microvascular flow index (from 2.45 ± 0.61 to 2.80 ± 0.68, P = 0.009) when compared with a mean arterial pressure of 65 mmHg. CONCLUSIONS: Increasing mean arterial pressure from 65 mmHg to normal levels is associated with improved microcirculation in hypertensive septic shock patients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01443494; registered 28 September 2011.

MSCs modified with ACE2 restore endothelial function following LPS challenge by inhibiting the activation of RAS.

Angiotensin (Ang) II plays an important role in the process of endothelial dysfunction in acute lung injury (ALI) and is degraded by angiotensin-converting enzyme2 (ACE2). However, treatments that target ACE2 to injured endothelium and promote endothelial repair of ALI are lacking. Mesenchymal stem cells (MSCs) are capable of homing to the injured site and delivering a protective gene. Our study aimed to evaluate the effects of genetically modified MSCs, which overexpress the ACE2 protein in a sustained manner via a lentiviral vector, on Ang II production in endothelium and in vitro repair of lipopolysaccharide (LPS)-induced endothelial injury. We found that the efficiency of lentiviral vector transduction of MSCs was as high as 97.8% and was well maintained over 30 passages. MSCs modified with ACE2 showed a sustained high expression of ACE2 mRNA and protein. The modified MSCs secreted soluble ACE2 protein into the culture medium, which reduced the concentration of Ang II and increased the production of Ang 1-7. MSCs modified with ACE2 were more effective at restoring endothelial function than were unmodified MSCs, as shown by the enhanced survival of endothelial cells; the downregulated production of inflammatory mediators, including ICAM-1, VCAM-1, TNF-α, and IL-6; reduced paracellular permeability; and increased expression of VE-cadherin. These data demonstrate that MSCs modified to overexpress the ACE2 gene can produce biologically active ACE2 protein over a sustained period of time and have an enhanced ability to promote endothelial repair after LPS challenge. These results encourage further testing of the beneficial effects of ACE2-modified MSCs in an ALI animal model.

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP. METHODS: Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration. RESULTS: A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤ 100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥ 10 cmH2O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04). CONCLUSIONS: PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.

Normolipemic papuloeruptive xanthomatosis in a child.

Normolipemic papuloeruptive xanthomatosis is a very rare skin disorder. We report a child with yellowish papular eruptions on the face that rapidly merged into confluent plaques. Serum lipid profiles showed normolipemia. A diagnosis of normolipemic papuloeruptive xanthomatosis with no associated systemic disorders was made. The skin lesions involuted spontaneously during follow-up.

Binary sub-wavelength diffractive lenses with long focal depth and high transverse resolution.

This study explores two-dimensional binary sub-wavelength diffractive lenses (BSDLs) for implementing long focal depth and high transverse resolution based on the rigorous electromagnetic theory and the finite-difference time-domain method. Focusing performances, such as the actual focal depth, the ratio between the focal depth of the designed BSDL and the focal depth of the conventional sub-wavelength lens and the spot size of the central lobe at the actual focal plane, for different f-numbers, have been studied in the case of TE incidence polarization wave. The rigorous numerical results indicate that the designed BSDLs indeed have long focal depth and high transverse resolution by modulating the binary sub-wavelength characteristic sizes. Because BSDLs have the ability for monolithic integration and can require only single step fabrication, the investigations may provide useful information for BSDLs' application in micro-optical systems.

Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions.

The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.

Multiple tumors of the follicular infundibulum.

BACKGROUND: Tumor of the follicular infundibulum is an uncommon benign neoplasm manifested histopathologically by a superficial epithelial plate-like growth pattern with multiple thin epidermal connections comprised of monomorphic cells with abundant cytoplasm. Cases of multiple tumors of the follicular infundibulum are rare and are described as hypopigmented scar-like macules or flat papules on the face, neck, and upper chest. OBJECTIVE: The objective was to describe a case of multiple tumors of the follicular infundibulum with numerous pigmented macules or papules and extensive involvement including the face, neck, anterior and posterior trunk, upper extremities, and intertriginous areas. METHODS: A case report and literature review are presented. CONCLUSION: Tumor of the follicular infundibulum with its characteristic histopathologic manifestations is a well-recognized entity nowadays. Our case further expands the constellation of the clinical presentation of the multiple variant. Although the possibility of malignant basocellular degeneration seems remote, the multiplicity of the lesions, the possibility of clinical overlook, and the impracticality of complete treatment makes regular follow-up rational.

Tunable high-peak-power, high-energy hybrid Q-switched double-clad fiber laser.

A cw laser-diode-pumped Yb-doped double-clad fiber laser operating in a hybrid Q-switched regime was demonstrated. The output pulses had a duration as short as 4.2 ns, a tunable wavelength range from 1080.8 to 1142.7 nm, and a linewidth of less than 0.05 nm. Maximum peak power of approximately 175 kW and single-pulse energy of 1.57 mJ were obtained.

Narrow-linewidth widely tunable hybrid Q-switched double-clad fiber laser.

A laser-diode-pumped Yb-doped double-clad fiber laser operating in a hybrid Q-switched regime has been demonstrated. With pulsed pump light and stimulated Brillouin scattering of the gain fiber as the Q-switching mechanisms, the laser generated nanosecond pulses with a stable repetition rate. A single-pulse energy of as much as 143.1 microJ with a peak power of 28.6 kW was obtained. Use of an external-cavity diffraction grating in the Littman configuration permitted tuning of the laser wavelength over a 15.7-THz range from 1080 to 1140 nm, and a linewidth of 0.04 nm over the whole tuning range was achieved.