Adjusting Effects of Baicalin for Nuclear Factor-κB and Tumor Necrosis Factor-α on Rats With Caerulein-Induced Acute Pancreatitis

Forty Wistar rats were divided into 5 groups, including the control group, the acute pancreatitis group (AP group, induced by intraperitoneal injections of caerulein), and the AP group treated with baicalin, the AP group treated with LPS, and the AP group treated with LPS and baicalin. Pathological damage of pancreatic tissue was scored with hematoxylin and eosin (HE) staining. The mRNA expression of TNF-α was measured with semiquantitative RT-PCR, and activation of NF-κB was detected with flow cytometry assay. It was shown in the results that the expression of TNF-α mRNA, activation of NF-κB, and pathological score of AP group were all obviously higher than those of control group (P < .01). In AP group treated with LPS, further rise of these values were observed (P < .01). In the AP group treated with baicalin, activation of NF-κB decreased (P < .05), and expression of TNF-α mRNA also obviously decreased (P < .01), while pancreatic pathological damage was alleviated at the same time (P < .01); similar results were observed in AP group treated with LPS and baicalin (P < .01), which indicated that baicalin might be applied to inhibit NF-κB activating and TNF-α expressing so as to treat AP

The association between frailty and the risk of mortality in critically ill congestive heart failure patients: findings from the MIMIC-IV database

BackgroundFrailty is a severe, common co-morbidity associated with congestive heart failure (CHF). This retrospective cohort study assesses the association between frailty and the risk of mortality in critically ill CHF patients.MethodsEligible patients with CHF from the Medical Information Base for Intensive Care IV database were retrospectively analyzed. The frailty index based on laboratory tests (FI_Lab) index was calculated using 33 variables to assess frailty status. The primary outcomes were in-hospital mortality and one-year mortality. The secondary outcomes were the incidence of acute kidney injury (AKI) and the administration of renal replacement therapy (RRT) in patients with concurrent AKI. Survival disparities among the FI_Lab subgroups were estimated with Kaplan-Meier survival analysis. The association between the FI_Lab index and mortality was examined with Cox proportional risk modeling.ResultsA total of 3273 adult patients aged 18 years and older were enrolled in the study, with 1820 men and 1453 women included. The incidence rates of in-hospital mortality and one-year mortality rate were 0.96 per 1,000 person-days and 263.8 per 1,000 person-years, respectively. Multivariable regression analysis identified baseline FI_Lab &gt; 0.45 as an independent risk factor predicting in-hospital mortality (odds ratio = 3.221, 95% CI 2.341–4.432, p &lt; 0.001) and one-year mortality (hazard ratio=2.152, 95% CI: 1.730-2.678, p &lt; 0.001). In terms of predicting mortality, adding FI_Lab to the six disease severity scores significantly improved the overall performance of the model (all p &lt; 0.001).ConclusionsWe established a positive correlation between the baseline FI_Lab and the likelihood of adverse outcomes in critical CHF patients. Given its potential as a reliable prognostic tool for such patients, further validation of FI_Lab across multiple centers is recommended for future research

IL-2-Free Tumor-Infiltrating Lymphocyte Therapy With PD-1 Blockade Demonstrates Potent Efficacy in Advanced Gynecologic Cancer

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. RESULTS: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p \u3c 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3-61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8 CONCLUSIONS: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer

The Design of a Vapor-Condensing Plume Abatement System and Devices for Mechanical Draft Cooling Towers

Cooling towers are widely used in many fields, but the generation of visible plumes has a serious impact on the environment. Moreover, the evaporation losses also cause a great waste of water. In this paper, a vapor-condensing plume abatement system was designed for a mechanical-draft cooling tower based on the mechanism of vapor plume generation. An effective method to achieve water-saving and eliminate the water fog generated in the cooling tower was proposed, and its feasibility was verified by using thermodynamic analysis. Next, the vapor-condensing plume abatement device was designed and used for both the confined space cooling tower (CSCT) and the free space cooling tower (FSCT). The surface type heat exchanger was adopted to design the vapor-condensing plume abatement device. Then a basic calculation flow and method were proposed to obtain thermodynamic operating parameters. According to the comparison between the results of theoretical calculation and practical engineering application, it was found that the designed vapor-condensing plume abatement system obviously benefits the water-saving of a mechanical-draft cooling tower and considerable economic benefits can be obtained. The contents presented provide the theoretical basis and technical support for the upgrade of the cooling tower and the design of the new cooling tower

COM33 suppresses carboplatin-induced epithelial-mesenchymal transition via inhibition of Twist1 in ovarian cancer

Despite favorable responses to platinum-based chemotherapy in ovarian cancer (OC), chemoresistance is still a major cause of treatment failure. Hence, we develop a novel synthetic agent, COM33, to relieve the chemoresistance caused by carboplatin. The anti-cancerous effects of the combination of COM33 and carboplatin on OC are evaluated by cell viability, wound healing, and transwell invasion assays. A mechanistic investigation is carried out by using RNA-Seq analysis and then verified by western blot analysis and immunofluorescence microscopy. The safety and efficacy in vivo are evaluated using SKOV3 tumor-bearing nude mice. Results show that the co-administration of COM33 enhances the inhibitory effects of carboplatin on cancer cell viability, migration, and invasion in vitro and tumor growth in vivo. Furthermore, COM33 suppresses the carboplatin-induced epithelial-mesenchymal transition (EMT) by inhibiting the ERK signaling pathway. Additionally, we show that Twist1, the effector of the ERK signaling pathway, participates in carboplatin-induced EMT and is also inhibited by COM33. Our data show that the combination of carboplatin with COM33 is beneficial for chemotherapy against OC, which may be a potential novel anti-tumor strategy

Coal Burst Prevention Technology and Engineering Practice in Ordos Deep Mining Area of China

With the coal mines in western China entering the field of deep mining, the problem of coal burst is becoming more and more serious. According to the characteristics of deep mining, it is an urgent problem that requires the development of an efficient and reasonable coal burst prevention and control plan to guide project practices. This study takes the typical deep mining area in Ordos as the research background, according to the stress state of the coal mining area and the load form of induced coal burst, which, in Ordos deep mining, is divided into the typical and atypical type. The former is caused by the superposition of high in situ stress and strong mining-induced stress, while the latter is due to the combination of high in situ stress, strong mining-induced stress, and external stress disturbances. Combined with theoretical analysis, numerical simulation, and field measurement, it is shown that the stress level of the Ordos deep mining area is higher than that of the shallow original rock, and the difference of the three-dimensional stress between coal and rock mass is greater. The concentration degree and influence range of mining-induced stress obviously increase. Coal and rock mass are more prone to instability and failure due to external disturbances. Based on the stress control theory, the prevention and control strategies of coal burst in different types of deep mining are put forward. In addition, the prevention and control technology system of coal burst in the Ordos deep mining area is established. The field engineering practice has been carried out to realize the efficient prevention and control of coal burst