Case report: A case study on the treatment using icaritin soft capsules in combination with lenvatinib achieving impressive PR and stage reduction in unresectable locally progressive pancreatic cancer and a literature review

Background: Pancreatic cancer is one of the most deadly malignancies in the world. It is characterized by rapid progression and a very poor prognosis. The five-year survival rate of pancreatic cancer in China is only 7.2%, which is the lowest among all cancers and the use of combined paclitaxel albumin, capecitabine, and digital has been the clinical standard treatment for advanced pancreatic cancer since 1997. Also, the application of multidrug combinations is often limited by the toxicity of chemotherapy. Therefore, there is an urgent need for a more appropriate and less toxic treatment modality for pancreatic cancer.Case presentation: The patient was a 79-year-old woman, admitted to the hospital with a diagnosis of unresectable locally advanced pancreatic cancer (T3N0M0, stage IIA), with its imaging showing overgrowth of SMV involvement and unresectable reconstruction of the posterior vein after evaluation. As the patient refused chemotherapy, lenvatinib (8 mg/time, qd) and icaritin soft capsules (three tablets/time, bid) were recommended according to our past experience and a few clinical research cases. The tumor lesion was greatly reduced by 57.5% after the treatment, and the extent of vascular involvement also decreased. The aforementioned medication resulted in a significant downstaging of the patient’s tumor.Conclusion: Better results were achieved in the treatment with icaritin soft capsules and lenvatinib in this case. Because of its less toxic effect on the liver and kidney and bone marrow suppression, it was suitable to combine icaritin soft capsules with targeted drugs for treating intermediate and advanced malignancies, which brings hope to patients who cannot or refuse to take chemotherapy

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

H3K27 tri-demethylase JMJD3 inhibits macrophage apoptosis by promoting ADORA2A in lipopolysaccharide-induced acute lung injury

Abstract Acute lung injury (ALI) is a common critical disease, which is characterized by an uncontrolled, acute inflammatory response, diffuse lung damage and ultimately directly deteriorates into acute respiratory distress syndrome. The number of pro-inflammatory macrophages is related to the severity of ALI. Up-regulation of lipopolysaccharide (LPS)-activated macrophage apoptosis can reduce the pro-inflammatory reactions. Jumonji domain-containing protein D3 (JMJD3)-mediated histone 3 lysine 27 trimethylation (H3K27me3) demethylation may promote the pro-inflammatory response of macrophages under LPS stimulation. However, the mechanism of JMJD3 affecting macrophage apoptosis is still not clear. To explore this gap in knowledge, the ALI mice model with intratracheal administration of LPS and RAW264.7 cells with LPS stimulation were used as in vivo and in vitro experiments. The expression of JMJD3 and H3K27me3 and their cellular localization were analysed in lung tissue. Apoptosis was evaluated using TUNEL staining and flow cytometry. Expression of H3K27me3, ADORA2A and C/EBPβ were compared among different treatments and chromatin immunoprecipitation was performed to investigate the regulatory relationship. Our study showed that JMJD3 expression was upregulated in LPS-induced ALI mice and RAW264.7 cells. JMJD3-indued H3K27me3 demethylation inhibited caspase-3 cleavage by upregulating ADORA2A to decrease LPS-stimulated macrophage apoptosis and promoted the inflammatory reaction. This H3K27me3 demethylation also increased C/EBPβ expression, which may enhance ADORA2A expression further. Besides, inhibiting ADORA2A can also promote LPS-limited macrophage apoptosis. Moreover, the inhibition of JMJD3 in vivo and in vitro relieved the inhibition of macrophage apoptosis thus leading to the resolution of the inflammation. JMJD3 might inhibit macrophage apoptosis by promoting ADORA2A expression in LPS-induced ALI

Difference analysis of dissolved gas in natural ester insulating fluids under typical electrical and thermal faults: An experimental study

Abstract Natural ester insulating oil is widely used in transformers due to its good fire resistance and biodegradability. It is mainly composed of triglycerides, and there are some differences in fatty acid composition and content among natural esters. Therefore, the fault diagnosis methods based on dissolved gas analysis are different. Three kinds of natural ester insulating oils are used to study the dissolved gas in oil under typical electrical and thermal faults of power transformers. Thermal faults from 200°C to 800°C and electrical faults with different discharge energies, which include partial discharge, breakdown discharge, and arc discharge, are simulated. The characteristic gases and their variation trends of natural esters under thermal and electrical faults are obtained through the experimental results. The gas generation characteristics of the three natural ester insulating oils under typical electrical and thermal faults are almost similar, but the relative percentages of characteristic gases have certain differences. Natural ester insulating oil with a higher unsaturation degree tends to produce more H2 and less C2H4. Finally, the fault diagnosis methods are used to determine the fault gas data, and the Duval pentagon is modified and improved according to the gas generation characteristics of natural esters

Enrichment of Smectite in the REY‐Rich Mud of the Clarion‐Clipperton Fracture Zone in the Eastern Pacific and Its Geological Significance

Abstract REY‐rich mud, consisting of deep‐sea sediments with high concentrations of rare‐earth elements and yttrium (REY), holds significant economic potential. Many studies have been conducted on biogenic apatite, ferromanganese micronodule, and phillipsite within these deposits to ascertain the REY enrichment mechanisms. However, the knowledge of clay minerals in REY‐rich mud, which is the predominant component of pelagic sediments, is still limited. In this study, two adjacent gravity cores (core GC02: REY‐rich mud; core GC03: typical sediments of equatorial Pacific) were collected from the Clarion‐Clipperton Fracture Zone (CCFZ) of the Eastern Pacific to study the role of different clay minerals in REY enrichment. The clay minerals in core GC03 and core GC02 are primarily illite (averaging 60%) and smectite (averaging 63%), respectively, and the smectite in core GC02 was mainly Fe‐rich, which was probably formed via the reaction between opal and FeOOH. Moreover, multiple studies have reported similar smectite enrichment in REY‐rich mud, suggesting that it is a common characteristic. The presumed hydrothermal or volcanic origination of smectite in REY‐rich layers of core GC02 indicates the essential role of hydrothermal and volcanic activities in REY‐rich mud formation during the Oligocene in the western CCFZ

Clinical Experience with First-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients with Brain Metastasis

Background and objective A survival analysis and the influencing factors for non-small cell lung cancer (NSCLC) patients with brain metastases accepting first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) treatment have not yet been elucidated to date. In this study, we collected and analyzed the survival data of NSCLC patients with brain metastasis to obtain evidence and to provide guidance in clinical practice. Methods NSCLC patients with brain metastases who were treated with first-generation EGFR-TKIs were retrospectively collected in 2012-2013 from Shanghai Chest Hospital, Shanghai Jiao Tong University. The Kaplan-Meier method and Cox regression were performed for univariate and multivariate analyses, respectively, to explore the independent predictors influencing the survival of patients with NSCLC brain metastases. Results The median progression-free survival (PFS) and median overall survival (OS) of all patients treated with first-generation EGFR-TKIs were 10.0 months (95%CI: 8.3-11.7) and 28.0 months (95%CI: 22.9-33.1), respectively. Pathological subtypes were the independent predictors of PFS (P=0.001), and tumor differentiations were the independent predictors of OS (P=0.050). Conclusion First-generation EGFR-TKIs showed promising efficacy in NSCLC patients with brain metastases. PFS was longer in patients with adenocarcinoma than in those with a non-adenocarcinoma subtype. OS was longer in patients with differentiated tumors than in those who developed poorly differentiated tumors

Analysis of Survival Predictors in Patients with Lung Cancer and Brain Metastases

Background and objective The prognosis for patients with lung cancer and brain metastases remains poor, with approximately 6 months of survival, despite active measures after treatment. In this study, we determined and analyzed clinical parameters that affect the survival of patients with lung cancer and brain metastases to provide clinical guidance. Methods Lung cancer cases with brain metastases were retrospectively collected during 2002 and 2008 from Shanghai Chest Hospital, Shanghai Jiao Tong University. Kaplan-Meier method and Cox regression were performed for univariate and multivariate analyses, respectively, to explore independent predictors influencing the survival of patients with lung cancer and brain metastases. Results Age, Eastern Cooperative Oncology Group performance status (ECOG PS), metastasis interval, number of metastasis, treatment method, treatment period, symptoms of brain metastases, extracranial metastasis, and brain metastasis order were factors that affect the survival of patients with brain metastases as confirmed through the Kaplan-Meier method. Treatment periods and extracranial metastasis were independent survival predictors in patients with lung cancer and brain metastasis as indicated by Cox proportional hazard model. Conclusion Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis. Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis

Modeling oil-paper insulation frequency domain spectroscopy based on its microscopic dielectric processes

The present study sets out to devise a universal function model to explain the characteristic curve obtained in the frequency domain spectroscopy (FDS) test on oil-paper insulation, based on its microscopic conduction and relaxation processes, and thus to enhance the accuracy and applicability of the test. First, from the analysis of the relationship between the real and imaginary parts of the dielectric's complex permittivity, it is demonstrated that a relaxation peak co-exists with the conduction process in the low-frequency band of an FDS curve obtained for oil-impregnated paper sample. Second, values for polarization barrier heights, essential to the determination of the microscopic polarization mechanisms, are presented as results of FDS and thermally stimulated depolarization current experiments carried out on oil-impregnated paper samples. The polarization peaks obtained in the imaginary permittivity frequency spectrum are determined as, respectively, space charge polarization and interface polarization. Finally, a function model in good agreement with experiment data is proposed, which quantitatively describes the FDS curve in oil-impregnated sample, including two relaxation processes and one conduction process