Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Objective:To investigate the efficacy,safety,and prognostic factors associated with immune checkpoint inhibitors(ICIs)in pa-tients with non-small cell lung cancer(NSCLC)comorbid with chronic obstructive pulmonary disease(COPD).Methods:Clinical and patholo-gical data were collected from 100 patients with stage Ⅲ-Ⅳ NSCLC who received one or more cycles of ICI treatment at Peking University Shougang Hospital between January 2018 and October 2024 were collected.Based on COPD diagnosis,patients were assigned into the NSCLC with COPD(LC-COPD,n=52)and NSCLC without COPD(non-COPD,n=48)groups.The efficacy,safety,and prognostic factors of ICIs treatment were retrospectively analyzed in both groups.Survival analysis was performed using the Kaplan-Meier method,and survival rates were compared using the Log-rank test.Results:Among the patients who received ICIs treatment,median progression-free survival(PFS)in the LC-COPD group was longer than that in the non-COPD group(11.97 vs.7.83 months,P=0.022),but no significant difference was detec-ted in overall survival(OS)(22.37 vs.16.80 months,P=0.110).Compared with the LC-COPD group and patients with normal lung function,the preserved ratio impaired spirometry(PRISm)subgroup showed worse median PFS and OS following immunotherapy(all P<0.05).Multivari-ate analysis revealed that COPD comorbidity,programmed cell death-ligand 1(PD-L1)expression,treatment line,and neutrophil to lympho-cyte ratio(NLR)were independently associated with PFS(P<0.05).Additionally,PD-L1 expression,immunotherapy efficacy,NLR,and inhaled corticosteroids(ICS)use were significantly associated with OS(P<0.05).The incidence of immune-related adverse events was comparable between the two groups.Conclusions:ICI treatment demonstrated a greater positive impact on PFS in patients with NSCLC and COPD than in patients with NSCLC alone in a real-world study,with a good safety profile in both groups.NSCLC patients with PRISm showed poorer out-comes following ICI treatment.PD-L1 expression,FeNO,NLR,and ICS may serve as potential predictive biomarkers for immunotherapy effic-acy in NSCLC patients with COPD.

Objective:To investigate the efficacy,safety,and prognostic factors associated with immune checkpoint inhibitors(ICIs)in pa-tients with non-small cell lung cancer(NSCLC)comorbid with chronic obstructive pulmonary disease(COPD).Methods:Clinical and patholo-gical data were collected from 100 patients with stage Ⅲ-Ⅳ NSCLC who received one or more cycles of ICI treatment at Peking University Shougang Hospital between January 2018 and October 2024 were collected.Based on COPD diagnosis,patients were assigned into the NSCLC with COPD(LC-COPD,n=52)and NSCLC without COPD(non-COPD,n=48)groups.The efficacy,safety,and prognostic factors of ICIs treatment were retrospectively analyzed in both groups.Survival analysis was performed using the Kaplan-Meier method,and survival rates were compared using the Log-rank test.Results:Among the patients who received ICIs treatment,median progression-free survival(PFS)in the LC-COPD group was longer than that in the non-COPD group(11.97 vs.7.83 months,P=0.022),but no significant difference was detec-ted in overall survival(OS)(22.37 vs.16.80 months,P=0.110).Compared with the LC-COPD group and patients with normal lung function,the preserved ratio impaired spirometry(PRISm)subgroup showed worse median PFS and OS following immunotherapy(all P<0.05).Multivari-ate analysis revealed that COPD comorbidity,programmed cell death-ligand 1(PD-L1)expression,treatment line,and neutrophil to lympho-cyte ratio(NLR)were independently associated with PFS(P<0.05).Additionally,PD-L1 expression,immunotherapy efficacy,NLR,and inhaled corticosteroids(ICS)use were significantly associated with OS(P<0.05).The incidence of immune-related adverse events was comparable between the two groups.Conclusions:ICI treatment demonstrated a greater positive impact on PFS in patients with NSCLC and COPD than in patients with NSCLC alone in a real-world study,with a good safety profile in both groups.NSCLC patients with PRISm showed poorer out-comes following ICI treatment.PD-L1 expression,FeNO,NLR,and ICS may serve as potential predictive biomarkers for immunotherapy effic-acy in NSCLC patients with COPD.

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

Objective To evaluate the perioperative safety and feasibility of day-case transurethral holmium laser enucleation of prostate(HoLEP)under over-night mode.Method From January 2021 to March 2023,83 patients of benign prostatic hyperplasia(BPH)were elected and treated with HoLEP by the one surgeon.According to different management methods,these patients were divided into the over-night day-case HoLEP group and the ordinary HoLEP group.Again,these patients were divided into large volume(≥50 mL)group and small volume(<50 mL)group according to the prostate volume.Record the age and perioperative data of all patients[total prostate volume,prostate resection weight,proportion of prostate resection,operating time,changes in peripheral venous blood hemoglobin(Hb),bladder flushing duration,catheter insertion duration,and success rate of first tube removal],the parameters of each group were compared.Result All of the 83 patients undergoing HoLEP surgery in this study,and there were no cases of HoLEP related reoperation or readmission.Among them,there were 43 cases in the over-night HoLEP group,aged 57～90 with an average of(70.1±7.3)years old,and the prostate volume was 29～161 mL with an average of(63.0±28.8)mL,All of them were discharged within 24 h,and there were no cases transferred to the ordinary HoLEP group,the success rate of first tube removal was 88.4%(38/43),and with average catheterization duration was(17.8±3.6)h;The other 40 cases were included into the ordinary HoLEP group,aged 55～87 with an average of(70.4±8.2)years old,the volume of the prostate was 22～118 mL with an average of(59.4±29.0)mL,the success rate of first tube removal was 90.0%(36/40),and with average catheterization duration was(77.5±25.1)h;There was no statistically significant difference in the perioperative parameters(total prostate volume,prostate resection weight,proportion of prostate resection,operating time,changes in peripheral venous blood Hb,and bladder flushing time)between the two groups(P>0.05),while the difference in catheter duration was statistically significant(P<0.01).Conclusion Regardless of the size of the prostate volume,day-case HoLEP is safe and feasible.Day-case HoLEP under the over-night mode is suitable for widespread and routine implementation in China,especially in medical centers with rich experience of HoLEP.

Chronic kidney disease (CKD) is an important global public health problem that greatly threatens population health. Application of risk prediction model is a crucial way for the primary prevention of CKD, which can stratify the risk for developing CKD and identify high-risk individuals for more intensive interventions. By now, more than twenty risk prediction models for CKD have been developed worldwide. There are also four domestic risk prediction models developed for Chinese population. However, none of these models have been recommended in clinical guidelines yet. The existing risk prediction models have some limitations in terms of outcome definition, predictors, strategies for handling missing data, and model derivation. In the future, the applications of emerging biomarkers and polygenic risk scores as well as advances in machine learning methods will provide more possibilities for the further improvement of the model.
Humans ; Renal Insufficiency, Chronic ; Risk Factors ; Biomarkers

ObjectiveTo investigate the clinical efficacy of Guizhi Shaoyao Zhimutang （GZSYZM） combined with fire needling in the treatment of periarthritis of shoulder with wind-cold-dampness impediment syndrome by stimulating pain points and "shoulder three acupoints". MethodA total of 120 patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome， admitted to Hainan General Hospital from August 2020 to August 2022， were randomly divided into two groups using a random number table. The control group （60 cases） received treatment with GZSYZM for two weeks， while the observation group （60 cases） received treatment with GZSYZM combined with fire needling at pain points and "shoulder three acupoints" for two weeks. The clinical efficacy， adverse reactions， shoulder pain intensity， shoulder joint function， and levels of calcitonin gene-related peptide （CGRP）， cyclooxygenase-2 （COX-2）， interleukin （IL）-2， and IL-17 before and after treatment were compared between the two groups. ResultThe total effective rate in the observation group was 88.33% （53/60）， significantly higher than 68.33% （41/60） of the control group （χ²=7.070， P<0.01）. Compared with the results before treatment， both groups showed significant reductions in pain rating index （PRI）， visual analog scale （VAS） scores， present pain intensity （PPI）， and Simplified McGill Pain Questionnaire （SF-MPQ） total scores， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 after treatment （P<0.01）， and improved pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. Compared with the control group after treatment， the observation group showed significantly reduced PRI， VAS score， PPI， SF-MPQ total score， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 （P<0.01）， and increased pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionGZSYZM combined with fire needling at pain points and "shoulder three acupoints" can effectively reduce the levels of serum inflammatory factors and pain mediators， alleviate pain， and improve shoulder joint function in patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome.

Zona Incerta ; Prefrontal Cortex ; Fear ; Neural Pathways

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.
Humans ; Mesothelioma, Malignant/drug therapy* ; Mesothelioma/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy/adverse effects*