Effectiveness of Ixekizumab in Chinese Patients with Moderate-Severe Plaque Psoriasis with Special Area Involvement: Subanalysis of a Prospective, Multicenter, Observational Real-World Study.

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). METHODS: A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. RESULTS: In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. CONCLUSION: Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

A novel adaptive filter with a heart-rate-based reference signal for esophageal pressure signal denoising.

Esophageal pressure (Peso) is one of the most common and minimally invasive methods used to assess the respiratory and lung mechanics in patients receiving mechanical ventilation. However, the Peso measurement is contaminated by cardiogenic oscillations (CGOs), which cannot be easily eliminated in real-time. The field of study dealing with the elimination of CGO from Peso signals is still in the early stages of its development. In this study, we present an adaptive filtering-based method by constructing a reference signal based on the heart rate and sine function to remove CGOs in real-time. The proposed technique is tested using clinical data acquired from 20 patients admitted to the intensive care unit. Lung compliance ( QUOTE ) and esophageal pressure swings (△Pes) are used to evaluate the performance and efficiency of the proposed technique. The CGO can be efficiently suppressed when the constructional reference signal contains the fundamental, and second and third harmonic frequencies of the heart rate signal. The analysis of the data of 8 patients with controlled mechanical ventilation reveals that the standard deviation/mean of the QUOTE is reduced by 28.4-79.2% without changing the QUOTE and the △Pes measurement is more accurate, with the use of our proposed technique. The proposed technique can effectively eliminate the CGOs from the measured Peso signals in real-time without requiring additional equipment to collect the reference signal.

Time-series analysis of meteorological factors and emergency department visits due to dog/cat bites in Jinshan area, China.

Background: Meteorological factors play an important role in human health. Clarifying the occurrence of dog and cat bites (DCBs) under different meteorological conditions can provide key insights into the prevention of DCBs. Therefore, the objective of the study was to explore the relationship between meteorological factors and DCBs and to provide caution to avoid the incidents that may occur by DCBs. Methods: In this study, data on meteorological factors and cases of DCBs were retrospectively collected at the Shanghai Climate Center and Jinshan Hospital of Fudan University, respectively, in 2016-2020. The distributed lag non-linear and time series model (DLNM) were used to examine the effect of meteorological elements on daily hospital visits due to DCBs. Results: A total of 26,857 DCBs were collected ranging from 1 to 39 cases per day. The relationship between ambient temperature and DCBs was J-shaped. DCBs were positively correlated with daily mean temperature (rs = 0.588, P < 0.01). The relative risk (RR) of DCBs was associated with high temperature (RR = 1.450; 95% CI [1.220-1.722]). Female was more susceptible to high temperature than male. High temperature increased the risk of DCBs. Conclusions: The extremely high temperature increased the risk of injuries caused by DCBs, particularly for females. These data may help to develop public health strategies for potentially avoiding the occurrence of DCBs.

Single-injection subunit vaccine for rabies prevention using lentinan as adjuvant.

Current rabies vaccines require 5 doses to provide full protection from the deadly virus, which significantly reduce the compliance of recipients. To minimize the number of immunizations herein single injection vaccines were developed. First a single injection vaccine was designed using rabies virus glycoprotein (G protein) as antigen. A time-controlled release system which uses dynamic layer-by-layer films as erodible coating was employed to accomplish multiply pulsatile releases of G protein. The single-injection vaccine elicits potent humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of G protein. To further improve its performance, a second single injection vaccine, in which lentinan was added as adjuvant, was designed. This single-injection vaccine again elicits humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of antigen and adjuvant. In addition, the second single-injection vaccine elicits higher level immune response and provides higher efficiency on virus inhibition than the first one because lentinan can booster immune response.

Three cases of refractory bullous pemphigoid in the elderly treated successfully with ultra-low-dose rituximab.

Rituximab has proven effective for the treatment of steroid-refractory bullous pemphigoid (BP), but there is controversy over the dosing protocol. We report three cases of refractory BP treated successfully with ultra-low-dose rituximab (100 mg weekly for 4 weeks). Our cases confirmed the efficacy and good follow-up outcomes of this treatment strategy for refractory BP. The ultra-low-dose rituximab regimen (100 mg weekly for 4 weeks) may be a useful alternative therapy in patients with refractory BP.

Can second language metaphorical competence be taught through instructional intervention? A meta-analysis.

Background: For a long time, the traditional view regarded metaphor as merely a rhetorical device that served to enrich linguistic expression. With the continuous development of cognitive linguistics, foreign language educators began to realize the vital role of metaphor in foreign language education. Objectives: This study looked at how well pedagogical interventions improve metaphorical competence by looking at how well teachers teach metaphors. Methods: After a rigorous literature search and selection process from the Chinese and English databases, 13 Chinese and 7 international studies with 51 effect sizes were included in this meta-analysis. With the help of the meta-analysis 3.0 software, the literature and heterogeneity tests were performed to ensure that the meta-analysis results were as accurate and valid as possible. Results: The effect size tests revealed that the metaphorical instructional intervention was significantly effective in general and produced a large effect size (d = 0.888) on improving learners' metaphorical abilities. Meta-regression analyses were also conducted to examine how other factors might change the effects of the interventions. Findings: Research has shown that instructional interventions that combine prolonged input of metaphorical concepts with reinforcement of metaphorical practice can help second language learners develop metaphorical competence. Teaching puts more pressure on teachers and the learning environment, and the results of this study could help teachers teach metaphors in the future.

Carbon-economic inequality in global ICT trade.

The expansion of information and communications technology (ICT) trade has contributed to rising trade imbalances and international tensions. A detailed assessment of the potential carbon and economic impacts of ICT trade is pertinent. We assess to what extent and how the carbon costs and economic benefits embodied in ICT trade were unevenly distributed among global regions in the period 2000-2018 using multiregional input-output models. We show that in 2018, emerging economies received 82% of the CO2 emissions while developed economies gained 42% of the value-added in ICT exports. This carbon-economic inequality (CEI) decreased (i.e., improved) by 16% from 2000 to 2018, arising from global production fragmentation, with developed economies retaining downstream high value-added ICT marketing but outsourcing upper- and middle-stream carbon-intensive material extraction and manufacturing to emerging economies. This study provides insights for enhancing negotiations and cooperation among global regions to light a path toward sustainable ICT trade.

Anthracene dimer cross-linked, washing- and sterilization-free hydrogel films for multicellular spheroid generation.

Three-dimensional multicellular spheroids are better in vitro cell models than two-dimensional cell monolayers; however, their applications are limited by their difficult production. PHEMA hydrogel films with honeycomb-like wrinkled patterns have been developed for high-throughput generation of multicellular spheroids with a uniform shape and size; however, the films are prepared by polymerization of the HEMA monomer, and should be washed extensively before use. Here to synthesize washing-free PHEMA hydrogel films, linear anthracene-functionalized PHEMA polymers were first synthesized by the free-radical copolymerization of HEMA and an anthracene-containing vinyl monomer. Smooth films were then prepared from the linear polymers in the wells of cell culture plates by solution casting. They were cross-linked via photo-dimerization of anthracene groups by exposing to 365 nm UV light, and patterned spontaneously by adding water to swell them. The swelling degree of the films and hence the shape of the wrinkled patterns could be facilely adjusted by adjusting the anthracene content in the linear polymers. If necessary, the cross-link density of the film and thus the shape of the wrinkled patterns could be callbacked by irradiating with 254 nm UV light, thanks to the reversibility of the photo-dimerization of anthracene. The as-prepared films exhibit a high biocompatibility and support cell growth well even without washing and sterilization. The high biocompatibility is attributed to the facts that no low molecular weight monomer, crosslinker and initiator were involved in the film preparation, and the photo-dimerization of anthracene groups produces no by-products. The films are sterilized simultaneously when cross-linked with UV irradiation, thus avoiding an additional sterilization step. PHEMA films with long-range ordered hexagonal wrinkled patterns were selected to generate multicellular spheroids of tumor cell lines. The resulting spheroids exhibit a narrow size distribution and high cell viability. Preliminary tests demonstrated their potential in the screening of anti-cancer drugs.

Asiaticoside delays senescence and attenuate generation of ROS in UV­exposure cells through regulates TGF­ß1/Smad pathway.

Asiaticoside, isolated from Centella asiatica, shows great improvement on wound healing and anti-oxidation function in vitro and in vivo. From previous research, asiaticoside possesses the potential capability to delay skin aging and reduce wrinkles clinically, but its underlying mechanism to regulate aging have not well-investigated. The present study found that asiaticoside could improve the viability and maintains a normal morphology in ultraviolet (UV)-exposure cells. In addition, ß-galactosidase release was inhibited by treatment of asiaticoside in UV damaged cells was observed. The present study confirmed that UV-induced ROS generation and SOD reduction could be attenuated by incubation of asiaticoside. By using RNA sequencing technology, differential genes between UV and asiaticoside treatment were demonstrated and enriched genes suggested that asiaticoside is able to negatively regulate cell cycle and MAPK pathways. Western blotting was employed to clarify the variation of key proteins in TGF-ß1/Smad pathway and cell cycle and the result implied that asiaticoside is capable of attenuating upregulation of TGF-ß1, Smad2 and Smad3 to reverse cell senescence. The present study investigated regulation of asiaticoside to TGF-ß1/Smad pathway in UV-induced HaCat cells, showing its potential to against photoaging.

COVID-19, students satisfaction about e-learning and academic achievement: Mediating analysis of online influencing factors.

Background: The current study examines student satisfaction with e-learning, the adaption of online learning channels, digital competency of students' involvement, and academic achievement during COVID-19. Purpose: The purpose of this study is to examine the online influencing components for learning among University students in Pakistan during the COVID-19 Pandemic. Methods: The study population comprised Pakistani University students in Punjab province who tooke online lessons throughout the epidemic. In accordance with the study's purpose, a questionnaire survey was employed to gather primary data. SPSS-23 is used for analyzing the demographic data, and cleaning and preparing data for testing hypotheses. SmartPLS 3.0 was used to investigate the suggested study framework using structural equation modeling (SEM). Results: The analysis of the SEM model shows that all planned hypotheses (Adaptation of Online Education Channels -> Satisfaction about E-learning, COVID-19 Pandemic -> Adaptation of Online Education Channels, COVID-19 Pandemic -> Digital Competence, COVID-19 Pandemic -> Motivation for Online Learning, COVID-19 Pandemic -> Willingness for Online Learning, Digital Competence -> Satisfaction about E-learning, Motivation for Online Learning -> Satisfaction about E-learning, Satisfaction about E-learning -> Academic Achievement, Willingness for Online Learning -> Satisfaction about E-learning) are confirmed. Conclusion: The results linked e-learning satisfaction to academic success and Pakistani students who utilized e-learning throughout the outbreak reported higher levels of academic satisfaction and achievement.

Construction of single-injection vaccine using new time-controlled release system.

Single-injection vaccines may overcome issues, such as high cost and poor patient compliance, of the multi-bolus regimes dominantly used in vaccination. However no such vaccine has been commercialized because time-controlled release, an unconventional release kinetics, is difficult to achieve. Here a new time-controlled release system using dynamic layer-by-layer (LBL) film as erodible coating was used to design single-injection vaccine. Unlike commonly used degradable polymers, dynamic LBL film disintegrates at a constant rate, thus allowing distinct pulsatile release of antigen at predetermined intervals. The release pattern of the single-injection vaccine mimics closely to that of ordinary multi-dose regimes. It elicits both humoral and cellular immune responses which are comparable to or even stronger than the corresponding multi-dose regime. In addition, it inhibits tumor growth more effectively. The new vaccine will not only improve patient compliance but also therapeutic outcome.

Single-injection COVID-19 subunit vaccine elicits potent immune responses.

Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO3 microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.

Therapy of paraneoplastic pemphigus with Rituximab: A case report.

We report a case of 39-year-old female patient with paraneoplastic pemphigus (PNP) associated with thymoma treated with rituximab plus corticosteroids and methotrexate. After rituximab therapy for 8 weeks, oral ulcerations had cured, lesions on the trunk and limbs improved. Rituximab may be useful for PNP therapy, but further studies are necessary to confirm this hypothesis.

Recalcitrant paradoxical pustular psoriasis induced by infliximab: Two case reports.

BACKGROUND: Paradoxical psoriasis induced by tumor necrosis factor alpha antagonists is a rare side effect of those drugs and has similarities with and differences from classical psoriasis in clinical and pathological characteristics. Treating severe paradoxical psoriasis is challenging because the reported cases are rare, with treatment experience being only anecdotal. CASE SUMMARY: We report 2 cases of paradoxical psoriasis caused by infliximab. Both cases manifested with a significant number of pustular lesions and had protracted and complicated clinical courses. In case 1, secukinumab alone could not control the eruptions, but colchicine supplementation markedly decreased disease activity. In case 2 miscellaneous medications were administered, including the systemic drug acitretin, the immunosuppressive drug cyclosporine, and the biologic agent ustekinumab. However, multiple applications of those medications failed to prevent new lesions from occurring. Both cases showed moderate-to-high anti-nuclear antibody titers. CONCLUSION: Based on these cases, moderate-to-high anti-nuclear antibody titer seems to be a risk factor for paradoxical psoriasis. In addition, extensive pustular presentation may be a negative prognostic indicator and may portend a protracted clinical course refractory to therapy.

[Cd Accumulation Characteristics in Different Populations of Hylotelephium spectabile Under Salt Stress].

A pot experiment was conducted to investigate the growth response and Cd accumulation characteristics among different populations of Hylotelephium spectabile in Cd-contaminated cinnamon soil (2.22 mg·kg-1) with the addition of different concentrations of NaCl. Results showed that the biomasses and Cd concentrations of H. spectabile showed significant differences among different populations under Cd alone or Cd-salt combined stress. Moreover, salt stress aggravated the growth inhibition of H. spectabile and the Cd concentrations in different H. spectabile populations showed a declining trend, which may be related to the salt-derived pH increase leading to a decrease in Cd bioavailability. In addition, the growth and Cd absorption responses of H. spectabile under salt stress were significantly different in the different populations. The shoot biomasses of the LN population were significantly higher than in other populations under different treatment, and showed no significant decrease with the addition of 1% NaCl when compared with the control treatment and the tolerance index remained 0.91. At the same time, the shoot Cd concentration of the LN population was significantly higher than in other populations under different treatments. The result may be attributed to the Cd accumulation and detoxification mechanisms in LN are prior than other populations that may also have important physiological mechanisms for tolerance of salt stress. In summary, although Cd uptake in H. spectabile decreased with salt stress, there were significant differences among different populations. LN populations accumulated 84.4 µg·plant-1 Cd in shoots with 2% NaCl addition, which was 48.4%-89.3% higher than in other populations. Therefore, H. spectabile, especially LN populations, is a good candidate for phytoremediation of Cd-contaminated saline soil.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

hsa_circ_0006916 promotes hepatocellular carcinoma progression by activating the miR-337-3p/STAT3 axis.

BACKGROUND: Circular RNAs (circRNAs) are thought to be involved in the development of various malignancies. The expression and function of hsa_circ_0006916, a newly identified circRNA, in hepatocellular carcinoma remain unclear. METHODS: Quantitative RT-PCR was used to detect hsa_circ_0006916 in hepatocellular carcinoma. In vitro function assays were conducted to explore growth and invasion of hepatocellular carcinoma cells. Next, the mechanism of hsa_circ_0006916 function in hepatocellular carcinoma was determined by luciferase reporter and RIP assays. RESULTS: Hsa_circ_0006916 was substantially overexpressed in hepatocellular carcinoma tissues and cells. High levels of hsa_circ_0006916 in hepatocellular carcinoma patients were associated with advanced clinical characteristics. Down-regulation of hsa_circ_0006916 decreased the growth and invasion of hepatocellular carcinoma cells in vitro. The results suggested that hsa_circ_0006916 acted as a sponge of miR-337-3p and had an important functional use in the regulation of STAT3 levels in hepatocellular carcinoma cells. Moreover, miR-337-3p inhibition or STAT3 overexpression abolished the effect of hsa_circ_0006916 suppression on the progression of hepatocellular carcinoma cells. CONCLUSIONS: Our data suggest a novel hsa_circ_0006916/miR-337-3p/STAT3 axis in hepatocellular carcinoma, and provide a new target for treatment.

[Effect of Nutrient Regulation and Control on Cd Accumulation Efficiency of Hylotelephium spectabile Under Field Conditions].

A field experiment with an orthogonally designed experiment L9(34) was designed to investigate the effect of different N, P, and K levels on plant growth and Cd uptake by Hylotelephium spectabile. The results showed that the biomass of H. spectabile significantly increased with the N application rate. The highest dry weight in the shoot occurred in the treatments with a high level of N (337.5 kg ·hm-2), which was 0.86-2.00 times higher than the value with no fertilizer treatment. The addition of K contributed to promoting the Cd absorption of H. spectabile, while no effect was observed when N and P were added. Consequently, NPK fertilizers contribute to increasing the Cd uptake of H. spectabile, and the N and K fertilizer play important role in plant growth and Cd absorption respectively. Moreover, the effect of fertilizers on Cd uptake of H. spectabile was in the order of N > K > P, which indicated that N fertilizer was the main factor for promoting the Cd phytoextraction efficiency of H. spectabile by increasing the biomass. Therefore, the application of high levels of N combined with moderate levels of P and K will be an effective approach to improve the Cd phytoremediation efficiency of H. spectabile by promoting its growth, and the Cd uptake can be increased by a factor of 0.9-2.2 compared to no fertilizer treatment condition.