Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Objective To analyze the epidemiological characteristics of newly diagnosed occupational diseases in Guangdong Province from 2019 to 2023. Methods Data on newly diagnosed occupational diseases reported in Guangdong Province from 2019 to 2023 were collected from the national occupational disease network reporting system. The spectrum of occupational diseases and their distribution by region, industry, and population were analyzed. Results A total of 4 136 newly diagnosed occupational disease cases were reported in Guangdong Province from 2019 to 2023, showing an overall downward trend. Newly diagnosed cases were classified into eight categories and 53 types of occupational diseases. In terms of the number of cases, the top five categories were occupational diseases of the ear, nose, throat and oral cavity;occupational pneumoconiosis and other respiratory diseases; occupational diseases caused by physical factors; occupational chemical poisoning; and occupational tumors, accounting for 98.62% of all cases. The top ten specific disease types were occupational noise-induced deafness, occupational silicosis, occupational other pneumoconiosis, occupational chronic benzene poisoning, occupational heatstroke, occupational hand-arm vibration disease, occupational coal workers′ pneumoconiosis, occupational welders′ pneumoconiosis, occupational tumor (leukemia caused by benzene exposure), and occupational chronic n-hexane poisoning, accounting for 94.85% of all cases. Most of the cases were distributed in the Pearl River Delta region, accounting for 89.19%; as well as manufacturing industry, accounting for 84.89%. Male cases accounted for 87.02%. Most diagnoses occurred in individuals aged >40-60 years, accounting for 74.73%. Conclusion Newly diagnosed occupational diseases in Guangdong Province from 2019 to 2023 showed the following characteristics: concentration of categories and disease types, polarization of regional distribution, industry clustering, and population difference. The disease spectrum is evolving from a dual-disease predominance toward a multi-disease predominance.

Objective To establish a set of scientific and standardized quality control indicator system for occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") medical care. Methods A research group was set up to establish an indicator pool of quality control indicator system for pneumoconiosis, including three first-level indicators and 48 second-level indicators, based on literature review, analysis and sorting, and the current national quality control indicators of respiratory diseases in disease-specific quality monitoring. Two rounds of consultation were conducted with 15 experts through Delphi method to establish the quality control indicator system for pneumoconiosis medical care. Results The questionnaire recovery rates of the two rounds of expert consultations were 100%, and the effective questionnaire recovery rates of both consultations were 100%. The expert authority coefficient was 0.91, and the expert coordination coefficients were 0.208 and 0.209, respectively (both P<0.001). The coefficient of variation ranged from 0.10 to 0.37, with nine indicators having a coefficient of variation >0.25. The constructed quality control indicator system for pneumoconiosis medical care includes three primary indicators, 15 secondary indicators, and 32 tertiary indicators. Conclusion The constructed quality management indicator system for pneumoconiosis medical care has high scientificity and reliability. It provides a basis for the quality evaluation of pneumoconiosis medical care. However, continuous improvement is needed in practical applications.

Objective To develop and validate a deep learning model for automatic identification of liver CT contrast-enhanced phases.Methods A total of 766 patients with liver CT contrast-enhanced images were retrospectively collected.A three-phase classification model and an arterial phase(AP)classification model were developed,so as to automatically identify liver CT contrast-enhanced phases as early arterial phase(EAP)or late arterial phase(LAP),portal venous phase(PVP),and equilibrium phase(EP).In addition,221 patients with liver CT contrast-enhanced images in 5 different hospitals were used for external validation.The annotation results of radiologists were used as a reference standard to evaluate the model performances.Results In the external validation datasets,the accuracy in identifying each enhanced phase reached to 90.50%-99.70%.Conclusion The automatic identification model of liver CT contrast-enhanced phases based on residual network may provide an efficient,objective,and unified image quality control tool.

Objective To investigate the role and mechanism of milk fat globule-EGF factor 8(MFG-E8)in neuroprotection in glaucoma rats.Methods A glaucoma rat model was constructed,and MFG-E8 or D89E was injected into the vitreous cavity of the rats.The intraoc-ular pressure of the rats was measured.HE staining,TUNEL staining and immunofluorescence staining were used to detect the patholog-ical injury,apoptosis and microglia activation of the retina.The protein expressions of cleaved caspase-3,caspase-3,cleaved caspase-9,caspase-9 and Bax were detected by Western blotting,and the expression levels of IL-10,TGF-βand NGFwere detected by ELISA and RT-qPCR.Results Compared with the control group,the intraocular pressure of glaucoma rats significantly increased,the retinal GCC layer became thinner,the apoptotic cells increased,the levels of cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9 and Bax increased,and the number of IBA1 positive cells increased,after treatment with MFG-E8,retinal GCC layer thickness increased,and the levels of cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,Bax decreased,the number of IBA1 positive cells and the levels of IL-10,TGF-β,NGFincreased,but the progression of glaucoma was aggravated after the treatment of MFG-E8 inactivated isomer D89E.Conclusion MFG-E8 can mediate microglia activation,inhibit apoptosis of ganglion cells,and slow down the progression of glaucoma in rats.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To investigate the protective effect of ulinastatin on sepsis-acute kidney injury (SA-AKI) by NF-κB signaling pathway.Methods:Total of 60 mice were randomly(random number) divided into sham group, cecal ligation puncture group (CLP group) and ulinastatin treatment group (CLP+UTI group). Ulinastatin treatment group was intraperitoneally injected with ulinastatin 50 000 U/kg once a day. 24 hours after operation, five mice were sacrificed, the kidney tissues were collected to observe renal histopathology by HE staining. The macrophage infiltration was observed by immunohistochemistry. The remaining mice in each group were used to calculate the survival rate of 7-day after operation. HK-2 cells were stimulated by LPS to obtain the SA-AKI model, and the cells were divided into control group, LPS group and LPS + UTI group. CCK-8 assay was used to detect cell viability, EdU assay was used to detect cell proliferation, and JC-1 assay was used to detect mitochondrial damage. The phosphorylation degree of NF-κB was detected by western blot. Inflammatory factors concentrations of cellular supernatant were detected by ELISA assay.Results:Compared with the sham group, the kidney tissue of mice in CLP group showed that kidney pathological obvious changed, the infiltration of macrophages increased, and the survival rate of mice decreased. CLP+ UTI group reduced the pathological changes and the infiltration of macrophages, improved the survival rate of mice. Compared with control group, LPS group obviously inhibited the cells activity and proliferation of HK-2 cells, damaged the mitochondrial membrane potential of HK-2 cells. Compared with LPS group, LPS+ UTI group attenuated the phosphorylation of NF-κB, decreased the secretion of inflammatory factors, rescued the activity and proliferation of HK-2 cells, and reduced the damage of HK-2 mitochondrial membrane potential.Conclusions:Ulinastatin can reduce mitochondrial damage, inhibit the secretion of inflammatory factors and improve the function of renal tubular epithelial cells through regulating NF-κB signaling pathway.

Objective:To investigate the risk factors of surgical site infection (SSI) after colorectal surgery, and to establish and validate a risk prediction model nomogram.Methods:An observational study was conducted to retrospectively collect data of 6527 patients aged ≥16 years who underwent colorectal surgery in 56 domestic hospitals from March 1, 2021 to February 28, 2022 from the national Surgical Site Infection Surveillance network. The incidence of SSI after surgery was 2.3% (149/6527). According to the ratio of 7:3, 6527 patients were randomly divided into the modeling cohort (4568 cases) and the validation cohort (1959 cases), and there was no statistically significant difference between the two datasets ( P>0.05). Univariate analysis was performed using t test /Mann-Whitney U test /χ 2 test. Multivariate analysis was performed using binary logistic regression to establish a preliminary model and select variables using Lasso analysis to establish an optimized model nomogram. The discrimination and calibration of the model were evaluated by ROC curve, calibration curve, and Hosmer-Lemeshow test. AUC value>0.7 is considered a good discrimination of the model. The Bootstrap method (repeated self-sampling 1000 times) was used to verify the constructed model internally and externally to evaluate the accuracy of the constructed model. Results:Multivariate analysis showed that history of chronic liver disease (OR=3.626, 95%CI: 1.297-10.137, P<0.001) and kidney disease (OR=1.567,95%CI:1.042-2.357, P=0.038), surgical antibiotic prophylaxis (OR=1.564, 95%CI:1.038-2.357, P=0.035), and emergency surgery (OR=1.432,95%CI: 1.089-1.885, P=0.021), open surgery (OR=1.418, 95%CI:1.045-1.924, P=0.042), preoperative stoma (OR=3.310, 95%CI:1.542-7.105, P<0.001), postoperative stoma (OR=2.323,95%CI: 1.537-8.134, P<0.001), surgical incision type above grade II (OR=1.619,95%CI:1.097-2.375, P=0.014), and each unit increase in total bilirubin (OR=1.003,95%CI:-0.994-1.012, P=0.238), alanine aminotransferase (OR=1.006, 95%CI:1.001-1.011, P=0.032), blood urea nitrogen (OR=1.003,95%CI:0.995-1.011, P=0.310), blood glucose (OR=1.024, 95%CI:1.005-1.043, P=0.027), C-reactive protein (OR=1.007, 95%CI:1.003-1.011, P<0.001), length of incision (OR=1.042, 95%CI:1.002-1.087, P=0.031), surgical duration (OR=1.003,95%CI:1.001-1.005, P=0.017), and surgical blood loss (OR=1.001,95%CI: 1.000-1.002, P=0.045) were risk factors for SSI after colorectal surgery. Each unit increase in albumin level (OR=0.969,95%CI:0.941-0.998, P=0.036) was an independent protective factor for SSI after colorectal surgery. The area under the curve of the optimized model obtained by internal and external validation were 0.768 (95%CI: 0.723-0.813) and 0.753 (95%CI: 0.680-0.832), respectively. The predicted value of the calibration curve was basically consistent with the actual value. Conclusions:The risk prediction model for SSI after colorectal surgery constructed in this study has good discrimination and calibration. The nomogram created in this model can provide an evaluation basis for the observed rate and expected event rate of SSI after clinical colorectal surgery.

Objective:To investigate the risk factors of surgical site infection (SSI) after colorectal surgery, and to establish and validate a risk prediction model nomogram.Methods:An observational study was conducted to retrospectively collect data of 6527 patients aged ≥16 years who underwent colorectal surgery in 56 domestic hospitals from March 1, 2021 to February 28, 2022 from the national Surgical Site Infection Surveillance network. The incidence of SSI after surgery was 2.3% (149/6527). According to the ratio of 7:3, 6527 patients were randomly divided into the modeling cohort (4568 cases) and the validation cohort (1959 cases), and there was no statistically significant difference between the two datasets ( P>0.05). Univariate analysis was performed using t test /Mann-Whitney U test /χ 2 test. Multivariate analysis was performed using binary logistic regression to establish a preliminary model and select variables using Lasso analysis to establish an optimized model nomogram. The discrimination and calibration of the model were evaluated by ROC curve, calibration curve, and Hosmer-Lemeshow test. AUC value>0.7 is considered a good discrimination of the model. The Bootstrap method (repeated self-sampling 1000 times) was used to verify the constructed model internally and externally to evaluate the accuracy of the constructed model. Results:Multivariate analysis showed that history of chronic liver disease (OR=3.626, 95%CI: 1.297-10.137, P<0.001) and kidney disease (OR=1.567,95%CI:1.042-2.357, P=0.038), surgical antibiotic prophylaxis (OR=1.564, 95%CI:1.038-2.357, P=0.035), and emergency surgery (OR=1.432,95%CI: 1.089-1.885, P=0.021), open surgery (OR=1.418, 95%CI:1.045-1.924, P=0.042), preoperative stoma (OR=3.310, 95%CI:1.542-7.105, P<0.001), postoperative stoma (OR=2.323,95%CI: 1.537-8.134, P<0.001), surgical incision type above grade II (OR=1.619,95%CI:1.097-2.375, P=0.014), and each unit increase in total bilirubin (OR=1.003,95%CI:-0.994-1.012, P=0.238), alanine aminotransferase (OR=1.006, 95%CI:1.001-1.011, P=0.032), blood urea nitrogen (OR=1.003,95%CI:0.995-1.011, P=0.310), blood glucose (OR=1.024, 95%CI:1.005-1.043, P=0.027), C-reactive protein (OR=1.007, 95%CI:1.003-1.011, P<0.001), length of incision (OR=1.042, 95%CI:1.002-1.087, P=0.031), surgical duration (OR=1.003,95%CI:1.001-1.005, P=0.017), and surgical blood loss (OR=1.001,95%CI: 1.000-1.002, P=0.045) were risk factors for SSI after colorectal surgery. Each unit increase in albumin level (OR=0.969,95%CI:0.941-0.998, P=0.036) was an independent protective factor for SSI after colorectal surgery. The area under the curve of the optimized model obtained by internal and external validation were 0.768 (95%CI: 0.723-0.813) and 0.753 (95%CI: 0.680-0.832), respectively. The predicted value of the calibration curve was basically consistent with the actual value. Conclusions:The risk prediction model for SSI after colorectal surgery constructed in this study has good discrimination and calibration. The nomogram created in this model can provide an evaluation basis for the observed rate and expected event rate of SSI after clinical colorectal surgery.