The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective:To evaluate the clinical efficacy of omalizumab in the treatment of patients with chronic spontaneous urticaria accompanied by other allergic diseases.Methods:Clinical data were retrospectively collected from 74 patients, who were clinically diagnosed with chronic spontaneous urticaria and other allergic diseases, and received subcutaneous injections of omalizumab in the Department of Allergy, Tianjin Medical University General Hospital from June 2020 to September 2022. Types of allergic diseases, serum total IgE (tIgE) and allergen-specific IgE (sIgE) levels before treatment, treatment outcomes and adverse drug reactions were analyzed. Differences before and after treatment were assessed using paired t-test and Wilcoxon signed-rank sum test. Results:A total of 74 patients with chronic spontaneous urticaria were involved, including 29 with complicated allergic asthma (39.2%) , 61 with complicated allergic rhinitis (82.4%) , 6 with complicated atopic dermatitis (8.1%) , and 4 with food allergy (5.4%) . Before treatment, elevated serum tIgE or sIgE levels were observed in 44 (59.5%) patients. After the first omalizumab treatment, the urticaria control test (UCT) score significantly increased compared with that before treatment (16.00 [13.0.0, 16.00] vs. 6.00 [5.75, 9.00], Z = 7.39, P < 0.001) ; after 4 sessions of the omalizumab treatment, 82.5% (33/40) of the patients achieved complete control of urticaria symptoms or showed complete response. After omalizumab treatment, asthmatic attacks were decreased in 29 patients with allergic asthma, and asthma control test (ACT) scores significantly increased compared with those before treatment (21.07 ± 2.88 points [after the first treatment] vs. 18.48 ± 3.20 points [before treatment], t = 8.87, P < 0.001) ; among 61 patients with allergic rhinitis, global rhinitis symptom-based visual analog scale (VAS) scores (before treatment: 5.89 ± 1.29 points; after the first treatment: 3.28 ±1.46 points) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores (before treatment: 60.10 ± 20.53 points; after the first treatment: 37.26 ± 18.83 points) both significantly decreased after the first treatment ( t = 15.04, 10.01, respectively, both P < 0.001) , and rhinitis symptoms were relieved at the same time; skin itching was relieved in 4 patients with atopic dermatitis, and allergic symptoms after contact with food allergens were also relieved in the 2 patients with food allergy after omalizumab treatment. During the treatment, only 1 patient experienced erythematous swelling, induration, and pain at the injection site. Conclusions:In the treatment of chronic spontaneous urticaria accompanied by allergic diseases, the use of omalizumab not only effectively improved urticaria symptoms, but also well controlled allergic diseases, with a good safety profile. Multiple benefits may be achieved by the use of omalizumabin in patients with chronic spontaneous urticaria accompanied by other allergic diseases.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

With human placed in the whole nature, by following the biologic evolution path, the property of channel structure for "imprinting template" in meridian andwas explored with supramolecular chemistry. In the history of biologic evolution, each molecule in "molecule society" gradually developed into various highly-ordered supramolecular bodies based on self-identification, self-assembly, self-organization, self-replicating of"imprinting template", and thereby the original biochemical system was established, and finally evolved into human. In the forming process of supramolecular bodies, the channel structure of"imprinting template" in guest supramolecular bodies would be kept by host supramolecular bodies, and communicate with the outside to exchange materials, energy, information, otherwise life phenomenon could not continue, for which it was the chemical nature of biolo-gical supramolecular bodies for body to develop meridian. Therefore, the human was a gigantic and complicated supramolecules body in biological nature, and possessed the supramolecules "imprinting template" at each stage of evolution, for which the meridians were formed. When meridians converged, acupoints appeared; when acupointsconverged,appeared. With the promotion of the blood from heart, according to"imprinting template", the guest supramolecular bodies and host meridian produced-analysis, which was the-phenomenon of guest in meridian. It presented asimage of physiology and pathology as well as action regularities of medication and acupuncture tolerance, by which current various meridian viewpoints could be explained and propose the hypothesis of meridian supramolecular bodies. The meridian and its phenomenon was decide by its "imprinting template" of supramolecular bodies and self-reaction regularities, which abided through the living nature. This was the substance for meridian biology.

Acute myocardial ischemia (AMI) was induced by occlusion of the left anterior descending (LAD) coronary artery in rats.AMI rats and normal rats were administered with protocatechuic aldehyde(Pal) at a single dose of 20 mg/kg through peritoneal injection.Concentrations of Pal,protocatechuic acid (PAC) and vanillic acid (VAC) in plasma were determined by HPLC to evaluate the effect of AMI on pharmacokinetics of Pal in rats.Pal was quickly metabolized to PAC,which was then methylated into VAC.Compared to the normal group,AUC_(0-∞) of PAC significantly increased from 14.01 ±3.11 to 22.31 ±4.96 μg·h/mL in AMI group (P ＜ 0.01),and AUC_(0-∞) of VAC markedly elevated from 19.64 ±4.36 to 38.76±5.75 μg·h/mL (P＜0.01).Both MRT of PAC and VAC increased (0.43 ± 0.08 h vs 0.27 ± 0.04 h,0.61 ± 0.11 h vs 0.38 ± 0.05 h,P ＜ 0.01).Metabolic ratio M/P of PAC increased from 1.43 ±0.31 to 1.77 ±0.22 (P ＜0.05).Results indicated that AMI status had great influence on pharmacokinetic behavior of Pal.Meanwhile,the level of methylation was greatly increased.

Here four cases of folliculotropic mycosis fungoides are reported.Of these patients,one was a female and three were males with the age varying from 32 to 52 vears.Three patients presented with multiple,densely distributed,irregularly shaped,dark red infiltrated plaques,nodules,tumors,follicular papules and acneiform lesions preferentially distributed on the head and neck,as well as patches and mildly infiltrated plaques.foilicular papules and aeneifotin lesions on the trunk and extremities.One patient presented with follicular papules all over the bodv with the exception of head and face.Characteristic findings of histopathology included massive lymphoid cell infiltration.heteromorphism of some cells and migration of infiltrated cells into follicular epithelium.No typical epidermotropism was noticed.Two cases showed mnciprotein deposition in follicular epithelium,which was positive for alcian blue staining.The infiltrates were predominated bv CD4+ T lymphocytes.Folliculotropic mycosis fungoides is a refractory disense with poor response to conventional therapy of classical mycosis fungoides.Relapse is common in patients with partial remission.