The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Chronic urticaria (CU) is one of the most common diseases in dermatology clinics, mainly characterized by recurrent wheals and pruritus. CU often co-exists with various comorbidities, including autoimmune diseases, infectious diseases, allergic diseases, mental diseases, metabolic syndrome, malignant tumors and endocrine system-related diseases. Currently, Chinese and international guidelines have not provided specific recommendations for screening comorbidities in CU. This review summarizes common comorbidities associated with CU, aiming to provide a reference for clinical diagnosis and treatment.

Chronic urticaria (CU) is one of the most common diseases in dermatology clinics, mainly characterized by recurrent wheals and pruritus. CU often co-exists with various comorbidities, including autoimmune diseases, infectious diseases, allergic diseases, mental diseases, metabolic syndrome, malignant tumors and endocrine system-related diseases. Currently, Chinese and international guidelines have not provided specific recommendations for screening comorbidities in CU. This review summarizes common comorbidities associated with CU, aiming to provide a reference for clinical diagnosis and treatment.

Objective To study the inhibitory activities of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells.Methods With pentacyclic triterpene saponin glycyrrhizic acid(a natural SARS-CoV-2 entry inhibitor)as the lead compound,a series of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle,and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirus-infected cells.The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance(SPR)assay,and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion.Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein.Results The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28μmol/L(P<0.05),and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus.Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S protein-mediated cell-cell fusion.Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment(S1)and fusion(S2)subunits at the 3-fold axis,where it formed multiple hydrophobic interactions with Glu309,Ser305,Arg765 and Lys964 residues with a KD value of-8.6 kcal/mol.The compound 1b at 10,5,2.5 and 1.25 μmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765,Lys964,Glu309 and Leu303(P<0.01).Conclusion 3-O-β-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane,and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

Objective To study the inhibitory activities of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells.Methods With pentacyclic triterpene saponin glycyrrhizic acid(a natural SARS-CoV-2 entry inhibitor)as the lead compound,a series of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle,and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirus-infected cells.The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance(SPR)assay,and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion.Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein.Results The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28μmol/L(P<0.05),and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus.Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S protein-mediated cell-cell fusion.Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment(S1)and fusion(S2)subunits at the 3-fold axis,where it formed multiple hydrophobic interactions with Glu309,Ser305,Arg765 and Lys964 residues with a KD value of-8.6 kcal/mol.The compound 1b at 10,5,2.5 and 1.25 μmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765,Lys964,Glu309 and Leu303(P<0.01).Conclusion 3-O-β-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane,and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

Objective:To analyze the clinical features of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to evaluate the accuracy of the TEN-specific severity-of-illness score (SCORTEN) in predicting death.Methods:A retrospective analysis was conducted on 104 patients with SJS/TEN at the First Affiliated Hospital of Army Medical University between December 2003 and December 2023. Clinical data, such as sensitizing drugs, clinical manifestations, laboratory tests, SCORTEN scores, and treatment regimens, were collected and retrospectively analyzed. The efficacy of different treatment modalities for TEN was analyzed. The receiver operating characteristic (ROC) curve was used to assess the accuracy of SCORTEN in predicting death in TEN patients.Results:Among the 104 patients, 57 were males and 47 were females, with ages ranging from 12 to 93 years (45.45 ± 19.76 years). There were 52 cases of SJS and 52 cases of TEN (including 1 case of SJS-TEN overlap). The ages of SJS patients (40.42 ± 17.06 years) were significantly lower than those of TEN patients (50.48 ± 21.13 years; t = 2.67, P = 0.009) ; the total hospital stay was 14.47 ± 7.24 days, and the TEN patients had significantly longer hospital stays (16.65 ± 7.82 days) compared with the SJS patients (12.29 ± 5.92 days; t = 3.21, P = 0.002). Definite sensitizing drugs were identified in 82 patients; combined drugs were the most common sensitizing cause (26 cases, 25.00%), and 20 patients reported combination treatment with antibiotics; 56 patients (53.85%) were treated with single drugs, and the common sensitizing drugs included carbamazepine (16 cases, 15.38%), nonsteroidal anti-inflammatory drugs (13 cases, 12.50%), and allopurinol (9 cases, 8.65%). Laboratory test results showed that the proportions of patients with decreased lymphocyte counts, elevated alanine aminotransferase and/or aspartate aminotransferase levels, decreased albumin levels, and with increased creatinine levels were significantly higher in the TEN patients than in the SJS patients (all P < 0.05), while the proportion of patients with increased monocyte counts was significantly lower in the TEN patients than in the SJS patients ( P = 0.006). Among the 52 TEN patients, 33 had SCORTEN scores < 3 points and 19 had scores ≥ 3 points, with 12.32 expected deaths and 4 actual deaths; the ROC curve analysis indicated that the area under the curve for SCORTEN in predicting death in TEN patients was 0.784 (95% CI: 0.558 - 1.00). Of the 104 patients, 57 (54.81%) received a monotherapy regimen (glucocorticoids only), and 47 (45.19%) received combination therapies, including glucocorticoids combined with intravenous immunoglobulin (IVIG) in 42 cases. Among the TEN patients, 30 started combination therapy with IVIG within 7 days after glucocorticoid treatment (early combination therapy group), and 7 patients started IVIG after 7 days of glucocorticoid treatment (late combination therapy group). The early combination therapy group showed a shorter time to lesion stabilization (10.82 ± 3.35 days) compared with the late combination therapy group (15.50 ± 4.04 days; LSD- t = 2.87, P = 0.006) . Conclusions:The main sensitizing cause in SJS/TEN patients was the combination of antibiotics. Early combination of glucocorticoids and IVIG could shorten the disease course in TEN patients to some extent. SCORTEN still holds a certain clinical value in predicting the prognosis of TEN patients.

Objective:To analyze the clinical features of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to evaluate the accuracy of the TEN-specific severity-of-illness score (SCORTEN) in predicting death.Methods:A retrospective analysis was conducted on 104 patients with SJS/TEN at the First Affiliated Hospital of Army Medical University between December 2003 and December 2023. Clinical data, such as sensitizing drugs, clinical manifestations, laboratory tests, SCORTEN scores, and treatment regimens, were collected and retrospectively analyzed. The efficacy of different treatment modalities for TEN was analyzed. The receiver operating characteristic (ROC) curve was used to assess the accuracy of SCORTEN in predicting death in TEN patients.Results:Among the 104 patients, 57 were males and 47 were females, with ages ranging from 12 to 93 years (45.45 ± 19.76 years). There were 52 cases of SJS and 52 cases of TEN (including 1 case of SJS-TEN overlap). The ages of SJS patients (40.42 ± 17.06 years) were significantly lower than those of TEN patients (50.48 ± 21.13 years; t = 2.67, P = 0.009) ; the total hospital stay was 14.47 ± 7.24 days, and the TEN patients had significantly longer hospital stays (16.65 ± 7.82 days) compared with the SJS patients (12.29 ± 5.92 days; t = 3.21, P = 0.002). Definite sensitizing drugs were identified in 82 patients; combined drugs were the most common sensitizing cause (26 cases, 25.00%), and 20 patients reported combination treatment with antibiotics; 56 patients (53.85%) were treated with single drugs, and the common sensitizing drugs included carbamazepine (16 cases, 15.38%), nonsteroidal anti-inflammatory drugs (13 cases, 12.50%), and allopurinol (9 cases, 8.65%). Laboratory test results showed that the proportions of patients with decreased lymphocyte counts, elevated alanine aminotransferase and/or aspartate aminotransferase levels, decreased albumin levels, and with increased creatinine levels were significantly higher in the TEN patients than in the SJS patients (all P < 0.05), while the proportion of patients with increased monocyte counts was significantly lower in the TEN patients than in the SJS patients ( P = 0.006). Among the 52 TEN patients, 33 had SCORTEN scores < 3 points and 19 had scores ≥ 3 points, with 12.32 expected deaths and 4 actual deaths; the ROC curve analysis indicated that the area under the curve for SCORTEN in predicting death in TEN patients was 0.784 (95% CI: 0.558 - 1.00). Of the 104 patients, 57 (54.81%) received a monotherapy regimen (glucocorticoids only), and 47 (45.19%) received combination therapies, including glucocorticoids combined with intravenous immunoglobulin (IVIG) in 42 cases. Among the TEN patients, 30 started combination therapy with IVIG within 7 days after glucocorticoid treatment (early combination therapy group), and 7 patients started IVIG after 7 days of glucocorticoid treatment (late combination therapy group). The early combination therapy group showed a shorter time to lesion stabilization (10.82 ± 3.35 days) compared with the late combination therapy group (15.50 ± 4.04 days; LSD- t = 2.87, P = 0.006) . Conclusions:The main sensitizing cause in SJS/TEN patients was the combination of antibiotics. Early combination of glucocorticoids and IVIG could shorten the disease course in TEN patients to some extent. SCORTEN still holds a certain clinical value in predicting the prognosis of TEN patients.

This review comprehensively summarizes clinical assessment tools which have been developed and validated for cholinergic urticaria (CholU) , involving diagnosis and severity assessment of CholU, assessment of patients′ quality of life, and assessment of disease control. The application methods and status of relevant tools in clinical practice are introduced in detail.

Objective:To explore the efficacy and safety of microneedle radiofrequency combined with supramolecular salicylic acid in improving facial photoaging.Methods:Thirty patients treated for facial photoaging were randomly divided into the combined treatment group and the microneedle radiofrequency group. All patients were female, aged between 30 and 50 years, with an average age of (39.4±4.1) years. The combined treatment group was treated with microneedle radiofrequency combined with supramolecular salicylic acid, and the Microneedle radiofrequency group was treated with microneedle radiofrequency alone. The patients were followed up 3 days, 7 days, 14 days, 28 days and 3 months after treatment. The results of VISIA, skin physiology and patients' satisfaction were used to compare the two groups of patients after treatment.Results:After 3 months of treatment, the skin pores (11.98±2.14 vs. 15.54±1.52), brown spots (12.40±1.85 vs. 15.84±1.42), ultraviolet spots (6.74±0.87 vs. 11.20±1.70), skin physiological status (transepidermal water loss): 11.84±1.80 vs 13.09±1.96 g/(h·m) 2, stratum corneum water content: 84.91±2.86 % vs 80.29±3.58 %, melanin index: 110.07±15.02 vs. 122.30±9.97, erythema index: 220.43±19.69 vs. 236.30±16.55), elasticity (75.98±3.94 vs. 69.89±3.58), epidermal thickness (1401.33±178.43 vs. 1217.13±139.77), skin color improvement (effective rate 86.7% vs. 40.0%) and patients' satisfaction (total satisfaction was 93.3% vs 67.0%) in the combined treatment group were significantly superior than those in the microneedle radiofrequency group, and the differences were statistically significant ( P<0.05). The reaction of moderate and severe erythema (the incidence rate 40.0% vs. 86.7%) and edema (the incidence rate 26.7% vs. 80.0%) in the combined treatment group was also significantly lower than that in the microneedle radiofrequency group ( P<0.05). No adverse pigmentation was reported in both groups after treatment. Conclusions:The combination of microneedle radiofrequency and supramolecular salicylic acid in the treatment of facial photoaging has definite clinical effect and high safety, which is worthy of clinical application.

A large number of studies have shown that immunoglobulin E (IgE) not only participates in the occurrence and development of allergic reactions, but also induces and aggravates autoimmune reactions through various mechanisms. IgE autoantibodies have been confirmed to be present in a variety of autoimmune skin diseases, and may be involved in the occurrence and development of related diseases by affecting multiple immune cells such as dendritic cells, mast cells, and basophils via binding to autoantigens. This review summarizes the role and possible mechanism of action of IgE in the induction and exacerbation of autoimmune skin diseases such as systemic lupus erythematosus, bullous pemphigoid and chronic idiopathic urticaria, and provides a theoretical basis for clinical diagnosis and treatment.