OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.

Objective To discuss the application of gelatin sponge-hemocoagulase plugging agent in patients with pulmonary puncture bleeding.Methods The clinical data of 43 patients with hemorrhage caused by DSA-guided lung puncture biopsy,who received gelatin sponge-hemocoagulase plugging agent treatment at the Jining Municipal First People's Hospital of China between September 2021 and May 2023,were collected,and the hemostatic effect of gelatin sponge-hemocoagulase plugging agent was analyzed.Results Successful lung puncture needle biopsy was achieved in all the 43 patients.The puncture needle channel occlusion was accomplished by using gelatin sponge-hemocoagulase plugging agent.Five minutes after occlusion treatment,in one patient,whose moderate hemoptysis with moderate bleeding shadow before puncture needle biopsy changed to bloody sputum,the intrapulmonary bleeding shadow displayed on image became slightly enlarged when compared the size five minutes ago,while in all the remaining patients successful hemostasis was achieved,the hemoptysis disappeared and the pulmonary hemorrhage shadow was similar to that five minutes ago.No occlusion-related complications occurred in all patients.Conclusion For the treatment of pulmonary hemorrhage caused by DSA-guided lung puncture biopsy,gelatin sponge-hemocoagulase plugging agent is clinically safe and effective.

Objective To discuss the application value of XperCT combined with needle-guided Glubran-2 glue for small pulmonary nodule localization in thoracoscopic pulmonary nodule resection.Methods The clinical data of 67 patients,who received XperCT combined with needle-guided Glubran-2 glue for small pulmonary nodule localization before thoracoscopic resection of a single small pulmonary nodule at the Jining Municipal First People's Hospital of China between June 2018 and February 2023,were retrospectively analyzed.The size of the pulmonary nodule,the maximum vertical distance from the visceral pleura to the lesion,the technical success rate of localization,the number of puncturing times,the complications,the time spent for operation,and the postoperative pathological diagnosis were recorded.Results The average size of the small pulmonary nodules in the 67 patients was 8.7 mm,and the average vertical distance from the visceral pleura to the lesion was 19.4 mm.Successful preoperative localization of nodule was accomplished in all patients.The average number of puncturing times was 1.1,and no serious complications occurred.The average time spent for operation was 12.7 min.Definite pathological results were obtained in all 67 patients.Conclusion XperCT combined with needle-guided Glubran-2 glue for small pulmonary nodule localization carries advantage of accurate localization with fewer complications.Therefore,this technique is a highly-efficient and quickly-accomplished positioning method,and it is highly valuable in clinical practice.(J Intervent Radiol,2024,33:623-626)

Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Objective To observe the effect of transcatheter arterial embolization(TAE)with Glubran-2 glue for treating hemorrhage after percutaneous transhepatic cholangial drainage(PTCD).Methods Data of 17 patients with hemorrhage after PTCD who underwent TAE with Glubran-2 glue were retrospectively analyzed.The technical success rate,clinical success rate and complications were observed.The red blood cell(RBC)and hemoglobin(Hb)on the day of TAE and the next day of TAE were compared,also the glutamic-pyruvic transaminase(GPT)level before TAE,on the next day of TAE,on the second and the fourth day after TAE,respectively.Results The offending vessel of bleeding was successfully embolized in all 17 cases,both technical success rate of TAE and clinical success rate of hemostasis were 100%.There was no serious complication such as liver abscess,septicemia nor pulmonary embolism.No significant difference of RBC nor Hb was found between the day of TAE and the next day of TAE(both P＞0.05).GPT before TAE was lower than the next day of TAE and the second day after TAE(P＜0.05),while no significant difference of GPT was found before TAE and 4 days after TAE(P＞0.05).Conclusion TAE with Glubran-2 glue for treating hemorrhage after PTCD was safe and effective.

A young female patient presented with fever, arthralgia, and rash was diagnosed with adults still's disease. When treated with glucocorticoid steroid, the above patient progressed to anuria, sudden, and confusion. After a teamwork involving different departments, the patient was finally diagnosed with atypical hemolytic uremic syndrome (aHUS) and treated with good outcome. aHUS is a rare disease, while Eculizumab is an orphan drug. The diagnosis and treatment of the patient reveals the importance of multidisciplinary team on the diagnosis and treatment of rare and difficult diseases.