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.

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.

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.

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.

To explore the predictive efficacy of fragmented red blood cells (FRC) and fragmented red blood cells percentage(FRC%) with regarding for the prognosis of septic patients, along with comparing with routine coagulation parameters. A prospective study was conducted. A total of 101 patients with sepsis who met the requirements admitted to the Intensive Care Department of the Third Xiangya Hospital of Central South University from June 1, 2022 to January 10, 2023 were selected as the research objects, they were divided into survival group and death group according to the 30-day prognosis. The clinical data and laboratory indexes such as FRCs, FRC% and Platelet (PLT) were compared between the survival group and the death group. Univariate logistic regression analysis was used first, then multivariate logistic regression analysis was used to analyze the factors affecting the prognosis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each parameter in the regression model for the prognosis of sepsis. The results showed that the levels of FRCs, FRC%, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer in death group were significantly higher than those in survival group, and PLT in death group were significantly lower than those in survival group (Z or t values were -3.712,-3.793,-2.119,-2.007,-2.209,all P<0.05). FRCs or FRC% and PLT could be independent predictors of 30-day mortality. The area under the ROC curve (AUC) of PLT for predicting 30-day death in sepsis patients was 0.727 (95%CI 0.629-0.811, P<0.01), when the optimal threshold was 137 ×10⁹/L, the sensitivity was 83.87% and the specificity was 57.14%. The AUC of FRCs for predicting 30-day death in sepsis patients was was 0.732 (95%CI 0.635-0.815, P<0.01), when the optimal threshold was 10.1×10⁹/L, the sensitivity was 77.42%, and the specificity was 67.14%. The AUC of FRC% for predicting 30-day death in sepsis patients was 0.737 (95%CI 0.640-0.820, P<0.01), When the optimal threshold was 0.34%, the sensitivity was 77.42%, and the specificity was 65.71%. In conclusion,PLT, FRCs and FRC% have great application value in the prognosis of sepsis. When the PLT, FRCs and FRC% of sepsis patients are more than 137 ×10⁹/L, 10.1×10⁹/L and 0.34% respectively, it is necessary to take necessary and reasonable clinical intervention measures as soon as possible.

To explore the predictive efficacy of fragmented red blood cells (FRC) and fragmented red blood cells percentage(FRC%) with regarding for the prognosis of septic patients, along with comparing with routine coagulation parameters. A prospective study was conducted. A total of 101 patients with sepsis who met the requirements admitted to the Intensive Care Department of the Third Xiangya Hospital of Central South University from June 1, 2022 to January 10, 2023 were selected as the research objects, they were divided into survival group and death group according to the 30-day prognosis. The clinical data and laboratory indexes such as FRCs, FRC% and Platelet (PLT) were compared between the survival group and the death group. Univariate logistic regression analysis was used first, then multivariate logistic regression analysis was used to analyze the factors affecting the prognosis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each parameter in the regression model for the prognosis of sepsis. The results showed that the levels of FRCs, FRC%, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer in death group were significantly higher than those in survival group, and PLT in death group were significantly lower than those in survival group (Z or t values were -3.712,-3.793,-2.119,-2.007,-2.209,all P<0.05). FRCs or FRC% and PLT could be independent predictors of 30-day mortality. The area under the ROC curve (AUC) of PLT for predicting 30-day death in sepsis patients was 0.727 (95%CI 0.629-0.811, P<0.01), when the optimal threshold was 137 ×10⁹/L, the sensitivity was 83.87% and the specificity was 57.14%. The AUC of FRCs for predicting 30-day death in sepsis patients was was 0.732 (95%CI 0.635-0.815, P<0.01), when the optimal threshold was 10.1×10⁹/L, the sensitivity was 77.42%, and the specificity was 67.14%. The AUC of FRC% for predicting 30-day death in sepsis patients was 0.737 (95%CI 0.640-0.820, P<0.01), When the optimal threshold was 0.34%, the sensitivity was 77.42%, and the specificity was 65.71%. In conclusion,PLT, FRCs and FRC% have great application value in the prognosis of sepsis. When the PLT, FRCs and FRC% of sepsis patients are more than 137 ×10⁹/L, 10.1×10⁹/L and 0.34% respectively, it is necessary to take necessary and reasonable clinical intervention measures as soon as possible.

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*

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m² group (P_interaction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans ; Male ; Arsenic/urine* ; Creatinine ; East Asian People ; Testosterone/blood* ; Urinalysis ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Life Style ; Risk Factors ; Smoking/epidemiology* ; Aged