Comparison of Efficacy of Baricitinib and Dupilumab in the Treatment of Chinese Moderate-To-Severe Atopic Dermatitis: A Retrospective Study.

INTRODUCTION: The treatment of atopic dermatitis (AD) patients with insufficient response or intolerance to topical medication remains clinical challenges, and there is a paucity of head-to-head trials comparing the efficacy of novel biological agents such as JAK inhibitor and antibody. METHODS: To compare the efficacy of selective JAK1/JAK2 inhibitor baricitinib and interleukin-4 monoclonal antibody dupilumab in the treatment of patients with moderate-to-severe AD, a retrospective cohort study method was adopted. Clinical data from June 2020 to April 2022 were systematically reviewed. Eligible patients who received baricitinib or dupilumab were screened according to the following inclusion criteria: (1) age ≥ 18 years; (2) moderate-to-severe AD: baseline investigator global assessment (IGA) score ≥ 3, baseline eczema area and severity index (EASI) score ≥ 16; (3) poor response or intolerance to at least one topical drug in the past 6 months; (4) no topical glucocorticoids were used in the past 2 weeks and no systematic treatment was given in the past 4 weeks. Patients of the baricitinib group were treated with oral baricitinib in doses of 2 mg per day for 16 weeks, and patients of the dupilumab group were treated with standardized use of dupilumab for 16 weeks, with the initial 600 mg subcutaneous injection and the following 300 mg subcutaneous injection every 2 weeks. The clinical efficacy score indexes including the IGA score, EASI score, and Itch Numeric Rating Scale (NRS) score. These scores at 0, 2, 4, 8, 12, and 16 weeks after the start of treatment were collected. RESULTS: A total of 54/45 patients treated with baricitinib/dupilumab were included. There was no significant difference in the decrease of all scores between the two groups at the 4th week (p > 0.05). There was no difference in the EASI score and Itch NRS score (p > 0.05), but the IGA score of the baricitinib group was lower at the 16th week (Z = 4.284, p < 0.001). Within the first 4 weeks, the Itch NRS score of the baricitinib group decreased rapidly, but with the prolongation of treatment time, there was no significant difference between the two groups at the 16th week (Z = 1.721, p = 0.085). CONCLUSIONS: The efficacy of baricitinib at a dose of 2 mg daily was similar to dupilumab, and the improvement in pruritus was significantly faster in the early stage of treatment (the first 4 weeks) than that of dupilumab.

Impact of Omalizumab on Anaphylaxis in Patients Treated for Chronic Urticaria.

BACKGROUND: Anaphylaxis is a life-threatening systemic allergic reaction. Omalizumab (OMA) is an established treatment in chronic urticaria (CU), but experience in anaphylaxis is limited. OBJECTIVES: The objective was to evaluate the efficacy and safety of OMA on anaphylaxis in patients with CU who are resistant to antihistamine therapy and have a history of anaphylaxis. METHOD: Patients with antihistamine-resistant CU and a history of anaphylaxis were eligible. OMA was given 300 mg/150 mg every 4 weeks. Urticaria control test (UCT) scores, the episodes of anaphylaxis, and adverse events were recorded during the OMA treatment. RESULTS: A total of 7 adults were included. After starting OMA, all of them achieved a complete control (UCT = 16) after 3 months of OMA treatment; 6 of them did not suffer any attack of anaphylaxis in the follow-up periods (5 patients for more than 12 months and 1 patient for 4 months). No adverse events were observed. CONCLUSION: The study indicated the efficacy and safety of OMA for antihistamine-resistant CU patients with a history of anaphylaxis and its potential as a prevention option for anaphylaxis.

An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke.

BACKGROUND: Ischemic stroke is one of the most serious global public health problems. However, the performance of current therapeutic regimens is limited due to their poor target specificity, narrow therapeutic time window, and compromised therapeutic effect. To overcome these barriers, we designed an ischemia-homing bioengineered nano-scavenger by camouflaging a catalase (CAT)-loaded self-assembled tannic acid (TA) nanoparticle with a M2-type microglia membrane (TPC@M2 NPs) for ischemic stroke treatment. RESULTS: The TPC@M2 NPs can on-demand release TA molecules to chelate excessive Fe2+, while acid-responsively liberating CAT to synergistically scavenge multiple ROS (·OH, ·O2-, and H2O2). Besides, the M2 microglia membrane not only can be served as bioinspired therapeutic agents to repolarize M1 microglia into M2 phenotype but also endows the nano-scavenger with ischemia-homing and BBB-crossing capabilities. CONCLUSIONS: The nano-scavenger for specific clearance of multiple pathogenic elements to alleviate inflammation and protect neurons holds great promise for combating ischemic stroke and other inflammation-related diseases.

Prevalence and risk factors of allergic rhinitis among Chinese adults: A nationwide representative cross-sectional study.

Background: The prevalence of allergic rhinitis (AR) has been increasing steadily worldwide, especially in countries with increasing industrialization such as China. However, available evidence regarding AR prevalence among Chinese adults is scarce and limited to regional data collected in earlier years. We therefore aimed to provide a more recent and robust estimate of AR prevalence using a nationwide representative cross-sectional study in China. Methods: Data of 184 326 participants aged 18 years or older were obtained from the China Chronic Disease and Risk Factor Surveillance conducted in 2018-2019. AR was determined by self-reported sneezing, nasal itching, obstruction, or rhinorrhea symptoms for at least 1 h in the absence of a cold or flu within the last 12 months. Multivariable logistic model was used to examine the risk factors of AR, and a possible non-linear relationship was further tested by restricted cubic spline. Potential additive interactions of risk factors with sex, residence, and geographic region were assessed by relative excess risk due to interaction (RERI). Results: The weighted prevalence of AR was 8.1% (95% confidence interval [CI], 7.4%-8.7%), of whom 23.7% (95% CI, 21.3%-26.0%) were aware of their diagnosis. Increased odds of AR were associated with younger age, men, living in urban area or north region, more education, smoking, underweight, and higher income. Despite the nonsignificant linear trend, the spline regression demonstrated a non-linear association between AR and sleep duration, with higher odds at both ends. Additionally, the observed associations were generally stronger among men and people living in urban area and north region, with significant RERI ranging from 0.07 (95% CI, 0.00-0.14) to 0.40 (95% CI, 0.12-0.67). Conclusions: AR is prevalent in China and the associated factors and interactions are helpful to design targeted preventive strategies towards certain subpopulations. The low awareness of AR calls for a national effort on AR screening.

The Emerging Role of Mast Cells in Response to Fungal Infection.

Mast cells (MCs) have been considered as the core effector cells of allergic diseases. However, there are evidence suggesting that MCs are involved in the mechanisms of fungal infection. MCs are mostly located in the border between host and environment and thus may have easy contact with the external environmental pathogens. These cells express receptors which can recognize pathogen-associated molecular patterns such as Toll-like receptors (TLR2/4) and C-type Lectins receptors (Dectin-1/2). Currently, more and more data indicate that MCs can be interacted with some fungi (Candida albicans, Aspergillus fumigatus and Sporothrix schenckii). It is demonstrated that MCs can enhance immunity through triggered degranulation, secretion of cytokines and chemokines, neutrophil recruitment, or provision of extracellular DNA traps in response to the stimulation by fungi. In contrast, the involvement of MCs in some immune responses may lead to more severe symptoms, such as intestinal barrier function loss, development of allergic bronchial pulmonary aspergillosis and increased area of inflammatory in S. schenckii infection. This suggests that MCs and their relevant signaling pathways are potential treatment regimens to prevent the clinically unwanted consequences. However, it is not yet possible to make definitive statements about the role of MCs during fungal infection and/or pathomechanisms of fungal diseases. In our article, we aim to review the function of MCs in fungal infections from molecular mechanism to signaling pathways, and illustrate the role of MCs in some common host-fungi interactions.

Induced Pluripotent Stem Cells for Ischemic Stroke Treatment.

Ischemic stroke is one of the main central nervous system diseases and is associated with high disability and mortality rates. Recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy are the optimal therapies available currently to restore blood flow in patients with stroke; however, their limitations are well recognized. Therefore, new treatments are urgently required to overcome these shortcomings. Recently, stem cell transplantation technology, involving the transplantation of induced pluripotent stem cells (iPSCs), has drawn the interest of neuroscientists and is considered to be a promising alternative for ischemic stroke treatment. iPSCs are a class of cells produced by introducing specific transcription factors into somatic cells, and are similar to embryonic stem cells in biological function. Here, we have reviewed the current applications of stem cells with a focus on iPSC therapy in ischemic stroke, including the neuroprotective mechanisms, development constraints, major challenges to overcome, and clinical prospects. Based on the current state of research, we believe that stem cells, especially iPSCs, will pave the way for future stroke treatment.

Tailored Design of an ROS-Responsive Drug Release Platform for Enhanced Tumor Therapy via "Sequential Induced Activation Processes".

The reactive oxygen species (ROS)-responsive intelligent drug delivery system has developed rapidly in recent years. However, because of the low concentration of ROS in most types of tumor cells, it is not possible to rapidly and effectively stimulate the drug delivery system to release the active drug. Here, we introduced "sequential induced activation processes" for efficient tumor therapy by designing a new ROS-responsive drug release platform. ß-Lapachone, a positively charged nitrogen mustard (NM) prodrug, and two diblock molecules (mPEG-AcMH and PAsp-AcMH) are self-assembled to form prodrug primary micelles, which are further aggregated into nanoparticles that facilitate drug codelivery. When administered by intravenous injection, the nanoparticles reach the tumor site and enter the tumor cells by endocytosis. The ß-lapachone released in the tumor cells induces a large amount of H2O2, and the ROS-responsive NM prodrug is activated to form activated NM, quinone methide, and boric acid under the induction of H2O2. The activated NM leads to tumor cell apoptosis.

Entirely oligosaccharide-based supramolecular amphiphiles constructed via host-guest interactions as efficient drug delivery platforms.

Entirely oligosaccharide-based supramolecular amphiphiles were constructed via host-guest interactions between ferrocene-terminated acetylated-maltoheptaose (Fc-AcMH) and ß-cyclodextrin-terminated four-arm star maltoheptaose (MH4-ß-CD). The amphiphiles could self-assemble to form spherical supramolecular nanoparticles to provide efficient drug delivery platforms. The combination of a pH-sensitive covalent acetal group and the oxidation-sensitive noncovalent host-guest interaction of ß-CD and ferrocene provided the obtained fully oligosaccharide-based supramolecular amphiphiles. The structures of these amphiphiles could respond to the intracellular microenvironment.

Characteristics and risk factor analysis of 410 cases of tracheobronchial tuberculosis.

The present study analyzed the characteristics and risk factors associated with tracheobronchial tuberculosis (TBTB) in 410 patients with TBTB. Retrospective analysis was performed on the clinical features, bronchoscopy performance, bacteriological examination, imaging and treatment of 410 patients who were diagnosed with TBTB using bronchoscopy. Among the 410 patients, 10 patients underwent chest X-ray which revealed two cases of atelectasis, eight cases of patch or spot shadows, three cases of cavity, one case of nodule and one case with no abnormalities. The remaining 400 patients underwent computed tomography chest scans and/or airway reconstruction examinations. Among all the lesion types, the cavity type was found to be the most likely to cause bronchial stenosis or obstruction, with statistically significant differences when compared with the congestion, stenosis or scar lesion types (P<0.01). Moreover, for the cavity type, there were 194 sites of obstruction prior to therapy; however, only 23 sites of obstruction remained following therapy. Furthermore, there were 34 sites without stenosis prior to therapy and 205 sites without stenosis following therapy. The number of sites of obstruction was significantly decreased and the number of sites without stenosis was increased upon therapy. These findings suggest that the cavity type is the most sensitive type to therapy among the five types of TBTB lesion.