Fully recyclable and tough thermoplastic elastomers from simple bio-sourced δ-valerolactones.

While a large number of chemically recyclable thermoplastics have been developed in recent years, technologically important thermoplastic elastomers (TPEs) that are not only bio-based and fully recyclable but also exhibit mechanical properties that can rival or even exceed those petroleum-based, non-recyclable polyolefin TPEs are critically lacking. The key challenge in developing chemically circular, bio-based, high-performance TPEs rests on the complexity of TPE's block copolymer (BCP) structure involving block segments of different suitable monomers required to induce self-assembled morphologies responsible for performance as well as the control and monomer compatibility in their synthesis and the selectivity in their depolymerization. Here we demonstrate the utilization of bio-sourced δ-valerolactone (δVL) and its simple α-alkyl-substituted derivatives to produce all δVL-based polyester tri-BCP TPEs, which exhibit not only complete (closed-loop) chemical recyclability but also excellent toughness that is 2.5-3.8 times higher than commercial polyolefin-based TPEs. The visualized cylindrical morphology formed via crystallization-driven self-assembly in the new all δVL tri-BCP is postulated to contribute to the excellent TPE property.

The Attitudes and Experiences of Hospice Nurses Regarding Palliative Sedation: A Cross-Sectional Descriptive Study.

Background: Despite the global acceptance of palliative sedation, China's engagement in this field remains comparatively restricted. There exists a scarcity of information regarding the attitudes and experiences of hospice nurses concerning palliative sedation. Objectives: This survey aimed at investigating the attitudes of Chinese hospice nurses toward palliative sedation, as well as their practices in palliative sedation. Design: A cross-sectional descriptive study. Setting/Subjects: In 2023, the survey on palliative sedation was introduced during the opening ceremony of the largest National Symposium on New Advances in Hospice Nursing in China. Subsequently, the study questionnaire was disseminated through email to a cohort of 806 hospice nurses attending the conference. Measurements/Results: The statistical analysis was based on 641 valid responses. Among them, 508 had no experience with palliative sedation, while only 133 had such experience. Around 92.5% of hospice nurses with experience in palliative sedation agreed with the physician's instructions to begin palliative sedation. Nurses were present at the start of sedation in nearly all cases (97.0%), and most doctors (79.7%) and family members (82.0%) were also present. However, 8.3% of them perceived that there was no difference between palliative sedation and euthanasia. Furthermore, 13.5% of participants believed that the purpose of palliative sedation was to hasten death. Conclusions: Hospice nurses play a crucial role in the process of palliative sedation, yet they also face significant challenges. It suggests that there is an urgent need in China for the development of consensus or guidelines for palliative sedation to clarify the roles of team members, including hospice nurses.

Polyoxovanadate-Based Metal-Organic Frameworks with Dual Active Sites for the Synthesis of p-Benzoquinones.

p-Benzoquinones are important organic intermediates in the synthesis of biopharmaceuticals and fine chemicals. In this study, two crystalline 3D polyoxovanadate-based metal-organic frameworks, H[Cu(tpi)2]{Cu2V7O21}·H2O (1, tpi = C18N5H13) and [Co(Htpi)2]{V4O12} (2, Htpi = C18N5H14), were synthesized, which as heterogeneous catalysts showed excellent catalytic activities for the synthesis of p-benzoquinones. Both compounds were characterized by IR, UV-vis diffuse reflectance spectroscopy, TG, XPS, X-ray diffraction, etc. In 1, {Cu2V7} clusters are connected together by copper cations and 1D Cu-organic coordination chains to yield a 3D polyoxometalate-based metal-organic framework (POMOF); in 2, adjacent 2D bimetallic oxide layers, constructed from 1D polyoxovanadate chains and cobalt ions, are further connected by 1D Co-organic coordination chains to form a 3D POMOF. Noteworthily, in the synthesis of trimethyl-p-benzoquinone, the key intermediate of vitamin E, using 2,3,6-trimethylphenol as the model substrate, the turnover frequency values for compounds 1 and 2 can, respectively, reach 607 and 380 h-1 in 8 min. Furthermore, both compounds demonstrated excellent recyclability and structural stability, characterized by PXRD and IR. The catalytic mechanism reveals that both the homolytic radical mechanism and heterolytic oxygen atom transfer mechanism are involved.

Efficacy and safety of intravenous tranexamic acid in microscopic modified radical mastoidectomy: a study protocol for a prospective, randomised, double-blind controlled trial.

INTRODUCTION: Radical mastoidectomy is a common procedure for chronic suppurative otitis media, typically performed under a microscope. The smooth operation is closely related to the clarity of the operative field. Our trial is designed to investigate whether the intravenous administration of tranexamic acid (TXA) can improve the clarity of the operative field, reduce the operative time, and increase surgeon satisfaction. METHODS AND ANALYSIS: This study is a prospective, randomised, double-blinded, controlled trial that aims to investigate the effects of TXA on patients with otitis media. The trial will include patients between the ages of 18 and 65 who will be randomly assigned to either the TXA group or the control group. In the TXA group, patients will receive 1 g of TXA diluted to 20 mL of normal saline before anaesthesia induction while the control group will receive 20 mL of normal saline. The primary outcome measure will be the Modena Bleeding Score, which will assess the clarity of the surgical field. Secondary outcomes will include the surgeon's satisfaction with surgical conditions, operation time, laboratory measurements (prothrombin time, activated partial thromboplastin time, fibrin degradation products, D-dimer) and levels of inflammatory factors (such as IL-6) at 24 hours postoperatively. In addition, the incidence of general adverse reactions such as postoperative nausea, vomiting and dizziness; serious adverse events such as arterial and venous thromboembolism, myocardial infarction and epilepsy within 90 days will be compared between the two groups. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee of Peking University People's Hospital (2021PHB173-001), on 19 July 2021. The trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100049183.

Intravenous tranexamic acid significantly improved visualization and shortened the operation time in microscopic middle ear surgery: a randomized controlled trial.

BACKGROUND: The microscopic middle ear surgery involves a limited operating space and numerous important anatomical structures in which good visualization is crucial, as even a small amount of bleeding can greatly affect the clarity of surgical field. This study aims to investigate whether intravenous 1 g of tranexamic acid can improve surgical visualization and further shorten the operation time in microscopic middle ear surgery. METHODS: This study is a prospective, randomized, double-blind, controlled trial conducted from December 2021 to December 2022, enrolling patients who were scheduled for microscopic modified radical mastoidectomy due to chronic otitis media. In addition to standard techniques to optimize the surgical field, participants were randomized into the TXA (tranexamic acid) group (1 g diluted to 20 ml normal saline) and the control group (20 ml normal saline). The primary outcome was assessed based on the clarity of the surgical field using the Modena Bleeding Score. Secondary outcomes included operation time, the surgeon satisfaction with the visual clarity, postoperative 24 h coagulation parameters, and the incidence of adverse events. Student's t -test, χ2 test, and ANOVA of repeated measures were used for statistical analyses. RESULTS: A total of 28 patients were enrolled in each group using a 1:1 randomized allocation with similar demographic characteristics, including 24 male and 32 female individuals, and the mean age is 45.6±11.9 years. The surgical visualization in the TXA group was significantly better than that of the control group (2.29±0.46 vs. 2.89±0.31, P <0.001) as assessed by the Modena Bleeding Score. Furthermore, the TXA group demonstrated a shorter operation time compared to the control group (88.61±10.9 vs. 105.2±15.9, P <0.001) and higher surgeon satisfaction with surgical field (7.82±0.55 vs. 6.50±0.64, P <0.001). No statistically significant differences were found in postoperative coagulation parameters in the two groups. No TXA-related adverse events or complications occurred during the 12-month follow-up. CONCLUSION: Intravenous 1 g of TXA can further significantly improve the visual clarity in the microscopic middle ear surgery and shorten the operation time based on other standard measures implemented.

A Coordination-Derived Cerium-Based Amorphous-Crystalline Heterostructure with High Electrocatalytic Oxygen Evolution Activity.

The rational design of heterogeneous catalysts is crucial for achieving optimal physicochemical properties and high electrochemical activity. However, the development of new amorphous-crystalline heterostructures is significantly more challenging than that of the existing crystalline-crystalline heterostructures. To overcome these issues, a coordination-assisted strategy that can help fabricate an amorphous NiO/crystalline NiCeOx (a-NiO/c-NiCeOx) heterostructure is reported herein. The coordination geometry of the organic ligands plays a pivotal role in permitting the formation of coordination polymers with high Ni contents. This consequently provides an opportunity for enabling the supersaturation of Ni in the NiCeOx structure during annealing, leading to the endogenous spillover of Ni from the depths of NiCeOx to its surface. The resulting heterostructure, featuring strongly coupled amorphous NiO and crystalline NiCeOx, exhibits harmonious interactions in addition to low overpotentials and high catalytic stability in the oxygen evolution reaction (OER). Theoretical calculations prove that the amorphous-crystalline interfaces facilitate charge transfer, which plays a critical role in regulating the local electron density of the Ni sites, thereby promoting the adsorption of oxygen-based intermediates on the Ni sites and lowering the dissociation-related energy barriers. Overall, this study underscores the potential of coordinating different metal ions at the molecular level to advance amorphous-crystalline heterostructure design.

Interfacing Lanthanide Metal-Organic Frameworks with ZnO Nanowires for Alternating Current Electroluminescence.

Alternating current electroluminescence (ACEL) devices are attractive candidates in cost-effective lighting, sensing, and flexible displays due to their uniform luminescence, stable performance, and outstanding deformability. However, ACEL devices have suffered from limited options for the light-emitting layer, which presents a significant constraint in the progress of utilizing ACEL. Herein, a new class of ACEL phosphors based on lanthanide metal-organic frameworks (Ln-MOFs) is devised. A synthesis of lanthanide-benzenetricarboxylate (Ln-BTC) thin film on a brass grid substrate seeded with ZnO nanowires (NWs) as anchors is developed. The as-synthesized Ln-BTC thin film is employed as the emissive layer and shows visible electroluminescence driven by alternating current (2.9 V µm-1 , 1 kHz) for the first time. Mechanistic investigations reveal that the Ln-based ACEL stems from impact excitation by accelerated electrons from ZnO NWs. Fine-tuning of the ACEL color is also demonstrated by controlling the Ln-MOF compositions and introducing an extra ZnS emitting layer. The advances in these optical materials expand the application of ACEL devices in anti-counterfeiting.

Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection: A randomized controlled trial.

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Analysis of Results of Continuous Invasive Arterial Blood Pressure Monitoring in Postoperative Patients.

Objective: In patients with postoperative circulatory instability, the exploration of invasive arterial blood pressure (IABP) monitoring is of great significance because it can provide real-time cardiovascular function information and help medical staff to better assess and manage the patient's circulatory status. To explore the value of IABP monitoring for patients with postoperative circulatory instability in the postanesthesia care unit (PACU). Methods: From January to December 2021, 160 postoperative patients with circulatory instability were randomly divided into a control group and a study group (80 patients in each group). A random number sequence is generated through a random number table, and random numbers are distributed to different patients to achieve random grouping. SPSS was used for data processing and statistical analysis, t test was used for continuous variables, chi-square test was used for count data, and the significance level was P < .05.We compared various parameters, such as systolic blood pressure (SBP), PACU observation time, arterial partial pressure of oxygen (PaO2), total hospitalization time, heart rate (HR), arterial partial pressure of carbon dioxide (PaCO2), re-intubation rate, mean arterial pressure (MAP), adverse events, and blood oxygen saturation (SaO2), between the two groups. Flow cytometry was used to analyze changes in immune lymphocyte subsets in the patient's peripheral blood. Results: During the postoperative observation period, there were no significant differences in SBP, PaCO2, HR, SaO2, MAP, and PaO2 between the two groups (P > .05)The study group showed higher SBP, SaO2, MAP, and PaO2, and lower HR and PaCO2 compared to the control group (P < .05). The study group also had shorter PACU observation time, total hospitalization time, and a lower re-intubation rate compared to the control group (P < .05). There was no significant difference in the overall incidence of adverse events between the two groups (7.50% vs 3.75%) (P > .05). The study group showed significantly higher proportions of lymphocytes, CD3+ T cells, CD3+ CD4+ T cells, and CD3+ CD4+/CD3+ CD8+ ratio compared to the control group (P < .05). This change may reflect the patients with a positive response of the immune system, help to resist disease progress and infection. Conclusion: IABP monitoring can continuously, dynamically and accurately collect arterial blood pressure data of patients with postoperative circulatory instability, contributing to the recovery of immune competence in patients to help formulate the best clinical treatment and intervention plan. The dynamic and accurate arterial blood pressure data collection provided by IABP monitoring contributes not only to immune competence recovery but also to overall patient management and treatment planning.

Visible-Light-Responsive 2D Photocatalysts Assembled by Evans-Showell-Type POMs and Metalloviologen Frameworks for Sulfide-Sulfoxide Transformation.

Sulfide-sulfoxide aerobic photo-oxidation is of great interest in organic and medicinal chemistry; however, developing efficient and facile heterogeneous photocatalytic systems without additional additives remains challenging. Herein, we intentionally designed and synthesized two polyoxometalate (POM)-based metalloviologen frameworks, formulated as [MII(4-PBPY)2(H2O)][MII(H2O)4][CoIII2MoVI10H4O38]·nH2O (M = Cu, n = 10 for 1; M = Co, n = 11 for 2), prepared by the mild one-step synthesis strategy and characterized in detail. X-ray single-crystal diffraction analysis shows that they present a two-dimensional layered structure formed by two parallel metalloviologen layers pillared by dimeric Evans-Showell-type POMs. The connection of POM to the metalloviologen framework enables easier flow of electrons to the POM port, which can theoretically further induce O2 to generate reactive oxygen species (O2•-) to oxidize substrates to form target products. As expected, both 1 and 2 exhibit outstanding photocatalytic activity in the oxidation of sulfides. Within 6 h, methyl phenyl sulfide can be quantitatively converted into methyl phenyl sulfoxide. The in-depth mechanism reveals that there is also a synergistic energy-transfer pathway in the catalytic system in addition to the electron-transfer pathway. In addition, the corresponding catalytic activity and structure can be well maintained after at least 10 cycle experiments.

Does the low-carbon city pilot contribute to the blue sky defense? Evidence from China.

China's goal of ecological civilization construction simultaneously faces the dual strategic tasks of pollution control and carbon reduction (PCCR). In addition to carbon reduction, does the low-carbon city pilot (LCCP) further contribute to the blue sky defense? This study investigates the impact of the LCCP on air pollution by employing a multiperiod difference-in-differences (DID) model based on data from 276 Chinese cities. The results show the following: (1) Compared with nonpilot areas, the LCCP reduces PM2.5 levels in pilot areas by approximately 1.50% on average, which is achieved by "industrial restructuring", "government investment in science and technology (S&T)", and "green lifestyle". (2) The LCCP has heterogeneous effects on air quality across cities with different resource endowments and industrial attributes, showing a greater air quality improvement in nonresource-based cities (NREB cities) and old industrial base cities (OIB cities) than in other city types. (3) The positive impact of the LCCP on air improvement in the pilot areas is derived from "pollution control effects" rather than "pollution transfer effects". This study provides useful policy implications for the comprehensive green transition and exploration of synergistic governance for PCCR in China.

Baicalin inhibits hepatocellular carcinoma cell growth and metastasis by suppressing ROCK1 signaling.

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3ß, and ß-catenin, whereas it up-regulated the expressions of GSK-3ß and p-ß-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3ß/ß-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK-3ß/ß-catenin signaling.

Postoperative recovery after breast cancer surgery: A randomised controlled trial of opioid-based versus opioid-free anaesthesia with thoracic paravertebral block.

BACKGROUND: Perioperative use of opioids has revealed significant adverse effects associated with poor postoperative outcomes. OBJECTIVE: To determine whether opioid-free anaesthesia based on thoracic paravertebral block (TPVB) could improve postoperative recovery after breast cancer surgery. DESIGN: A randomised controlled trial. SETTING: A tertiary teaching hospital. PATIENTS: Eighty adult women undergoing breast cancer surgery were enrolled. Key exclusion criteria included remote metastasis (but not to axillary lymph nodes of the surgical side), contraindication to interventions or drugs and a history of chronic pain or chronic opioid use. INTERVENTIONS: Eligible patients were randomised at a 1 : 1 ratio to receive either TPVB-based opioid-free anaesthesia (OFA group) or opioid-based anaesthesia (control group). MAIN OUTCOME MEASURES: The primary outcome was the global score of the 15-item Quality of Recovery (QoR-15) questionnaire at 24 h after surgery. Secondary outcomes included postoperative pain and health-related quality of life. RESULTS: The QoR-15 global score was 140.3 ±â€Š5.2 in the OFA group and 132.0 ±â€Š12.0 in the control group ( P  < 0.001). The percentage of patients with good recovery (QoR-15 global score ≥118) was 100% (40/40) in the OFA group and 82.5% (33/40) in the control group ( P  = 0.012). Improved QoR in the OFA group was also evident in sensitivity analysis that rated QoR as excellent for a score of 136 to 150, as good at 122 to 135, as moderate at 90 to 121 and as poor at 0 to 89. The OFA group had higher scores in the domains of physical comfort (45.7 ±â€Š3.0 versus 41.8 ±â€Š5.7, P  < 0.001) and physical independence (18.3 ±â€Š2.2 versus 16.3 ±â€Š4.5, P  = 0.014). The two groups did not differ in pain outcomes or health-related quality of life. CONCLUSION: TPVB-based opioid-free anaesthesia improved early postoperative quality of recovery without compromising pain control in patients undergoing breast cancer surgery. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT04390698.

Dual Recycling of Depolymerization Catalyst and Biodegradable Polyester that Markedly Outperforms Polyolefins.

Chemically recyclable, circular polymers continue to attract increasing attention, but rendering both catalysts for depolymerization and high-performance polymers recyclable is a more sustainable yet challenging goal. Here we introduce a dual catalyst/polymer recycling system in that recyclable inorganic phosphomolybdic acid catalyzes selective depolymerization of high-ceiling-temperature biodegradable poly(δ-valerolactone) in bulk phase, which, upon reaching suitable molecular weight, exhibits outstanding mechanical performance with a high tensile strength of ≈66.6 MPa, fracture strain of ≈904 %, and toughness of ≈308 MJ m-3 , and thus markedly outperforms commodity polyolefins, recovering its monomer in pure state and quantitative yield at only 100 °C. In sharp contrast, the uncatalyzed depolymerization not only requires a high temperature of >310 °C but is also low yielding and non-selective. Importantly, the recovered monomer can be repolymerized as is to reproduce the same polymer, thereby closing the circular loop, and the recycled catalyst can be reused repeatedly for depolymerization runs without loss of its catalytic activity and efficiency.

Efficacy and safety of different doses of epidural morphine coadministered with low-concentration ropivacaine after cesarean section: A retrospective cohort study.

Objective: The optimal dose of epidural morphine after cesarean section (CS) still remains unknown when combined with low-concentration ropivacaine based on a continuous basal infusion (CBI) mode. The aim of this study was to assess the impact of different dose of epidural morphine plus ropivacaine on maternal outcomes. Materials and methods: Data of parturients who received epidural analgesia for CS at a teaching hospital from March 2021 to June 2022 were retrospectively collected. Parturients were divided into two groups (RM3 group and RM6 group) according to different medication regimens of morphine. The implementation of epidural analgesia was performed with 3 mg morphine in RM3 group and 6 mg morphine in RM6 group in combination with 0.1% ropivacaine via a CBI pump. The primary outcomes included pain intensity at rest and movement and the incidence of urinary retention and pruritus within postoperative 48 h. The secondary outcomes included the incidence and severity of postoperative nausea and vomiting (PONV) and pruritus, the rate of rescue analgesia and grading of motor Block. Results: Totally, 531 parturients were eligible for the final analysis, with 428 and 103 parturients in the RM3 group and RM6 group, respectively. There were no statistically significant differences in the visual analogue scores (VAS) at rest and movement within postoperative 48 h between the two groups (all p > 0.05). Compared with the RM6 group, the incidence of urinary retention was lower in the RM3 group within 48 h after CS (4.0% vs. 8.7%, p = 0.044). No significant difference was found in the incidence and severity of PONV and pruritus, the rate of rescue analgesia and grading of motor block between RM3 and RM6 groups. Conclusion: Epidural 3 mg morphine plus 0.1% ropivacaine in a CBI mode can provide equal efficacy and have lower incidence of urinary retention compared with 6 mg morphine after CS.

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema.

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.

Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone-induced DNA damage.

Numerous studies have shown that the release of stress hormones resulting from repeated exposure to chronic psychological stress increases DNA damage and promotes tumorigenesis. However, the mechanisms that enable cancerous cells adapt to stress hormone-induced DNA damage and survive remain unclear. The present study aimed to investigate the impact of stress hormones on the survival of liver cancer cells and the underlying mechanism. HepG2 human liver cancer cells were treated with dexamethasone (DEX), epinephrine (EPI) and norepinephrine (NE) and subjected to the testing of DNA damage, cell survival and cell apoptosis by alkaline comet assay, CCK-8 viability assay and flow cytometry, respectively. The protein expression levels of DNA damage response factors were determined by western blotting analysis. The results revealed that treatment of HepG2 cells with DEX, EPI and NE induced DNA damage without affecting cell survival or inducing apoptosis. The protein levels of wild-type p53-induced phosphatase 1 (Wip1), a type 2C family serine/threonine phosphatase, were increased, and the dephosphorylation of DNA damage response factors, including phosphorylated (p-)ataxia-telangiectasia mutated and p-checkpoint kinase 2, occurred following treatment with DEX, EPI and NE. In addition, a cycloheximide chase assay was performed to explore the protein stability under treatment with stress hormones. Compared with vehicle-treated cells, Wip1 exhibited increased protein stability in stress hormone-treated HepG2 cells. Eventually, the depletion of Wip1 using small interfering RNA verified the role of Wip1 in the modulation of stress hormone-induced DNA damage. These findings suggest that cancerous cells likely adapt to stress hormone-induced DNA damage via Wip1 upregulation. The present study provides an insight into the underlying mechanism that links chronic psychological stress with tumor growth and progression.

Biejiajian pill inhibits progression of hepatocellular carcinoma by downregulating PDGFRß signaling in cancer-associated fibroblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Biejiajian pill (BJJP) is a canonical formula that is clinically used to treat chronic liver disease, especially to decrease the incidence of hepatocellular carcinoma (HCC). However, the mechanisms underlying the prevention of HCC progression by BJJP remain unclear. AIM OF THE STUDY: This study aimed to determine whether BJJP inhibits HCC progression by downregulating platelet-derived growth factor receptor beta (PDGFRß) signaling in cancer-associated fibroblasts (CAFs) in a mouse model of diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced HCC. MATERIALS AND METHODS: C57BL/6 male mice were intraperitoneally injected with DEN 2 weeks after birth, followed by repeated injections of CCl4 weekly from 6 weeks of age onwards, to recapitulate features of HCC. At week 14, BJJP was orally administered to mice. The effects of BJJP on HCC progression were evaluated using histology, immunohistochemistry, and serum biochemical marker levels. Transcriptome analysis, molecular docking, quantitative real-time PCR, and Western blot were used to study the genes targeted by BJJP and the associated signaling pathway. The effects of BJJP on PDGFRß signaling in CAFs and the underlying mechanism were demonstrated. RESULTS: BJJP treatment significantly suppressed carcinogenesis and cancer progression, and it ameliorated liver inflammation in mice with HCC. A total of 176 genes, including PDGFRß, were significantly downregulated after BJJP treatment and five components of BJJP with high binding affinity to PDGFRß were identified. BJJP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK3ß) by suppressing PDGFRß expression in CAFs, and it also downregulated the expression of the downstream proteins hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A). Furthermore, BJJP-containing serum consistently reduced PDGFRß, HGF, and VEGF-A expression levels in HSC-derived CAFs in vitro. Importantly, PDGF-BB induced PDGFRß activation in CAFs and both BJJP and sunitinib (a kinase inhibitor) inhibited PDGF-BB/PDGFRß signaling. CONCLUSION: BJJP inhibits the progression of HCC through suppressing VEGF-A and HGF expression in CAFs by downregulating PDGFRß signaling.

Effect of regional block technique on postoperative high-grade complications according to Clavien-Dindo classification in elderly patients with thoracic and abdominal cancer: a retrospective propensity score matching analysis.

Background: Postoperative complications have an influence on postoperative rehabilitation, length of hospital stay and hospitalization expenses in elderly patients, especially those with higher Clavien-Dindo (C-D) classification. Patients with cancers often experience more serious postoperative complications after surgery. Different anesthesia methods can affect the postoperative outcomes of cancer patients. Regional block techniques have been recommended in guidelines for enhanced recovery after surgery. However, the relationship between regional blocks and high-grade postoperative complications remains unclear, thus, the study explored the relationship between regional block techniques and high-grade postoperative complications graded by C-D classification in elderly patients with thoracic and abdominal cancer. Method: Retrospective enrollment of eligible elderly patients admitted to Peking University People's Hospital between January 2018 and March 2022 was conducted. Propensity score matching (PSM) and univariate and multivariate regression analyses were used to analyze the potential benefits of regional blocks for elderly patients in real world practice. Results: A total of 2769 patients were enrolled in this study, including 568 who underwent colorectal resection, 2201 who underwent video-assisted thoracoscopic pneumonectomy. Among them, 2033 patients received regional block, while 736 patients did not. Statistical analysis indicated that regional blocks could reduce the incidence of postoperative complications of C-D classification Grade II or higher, with an Odds ratio (OR) of 0.742, 95% Confidence interval (CI) (0.552 to 0.996) (P = 0.047). Conclusion: Regional block is associated with a reduction in the occurrence of postoperative complications graded by C-D classification in elderly patients with thoracic and abdominal cancer. The application of regional blocks can lower the risk of high-risk complications and mortality.

LncRNA EBLN3P attributes methotrexate resistance in osteosarcoma cells through miR-200a-3p/O-GlcNAc transferase pathway.

BACKGROUND: Osteosarcoma is highly malignant. The migration, invasion, and chemoresistance contribute to poor prognosis of osteosarcoma. Research reported that endogenous bornavirus-like nucleoprotein 3 pseudogene (EBLN3P) promotes the progression of osteosarcoma. METHODS: In this study, the expression of EBLN3P in osteosarcoma tissue with different methotrexate (MTX) treatment responses was measured. Osteosarcoma cell lines with MTX resistance were constructed, and bioinformatic analysis was performed to explore the potential involved targets and pathways. RESULTS: Higher EBLN3P was associated with MTX resistance. Downregulation of LncEBLN3P decreased the MTX resistance of osteosarcoma cells by sponging miR-200a-3p, an important microRNA that affects epithelial-mesenchymal transition (EMT). The decreased miR-200a-3p resulted in the upregulation of its target gene O-GlcNAc transferase (OGT), which in turn promoted the EMT process of osteosarcoma cells. Further analysis confirmed that the loss of OGT and over-expression of miR-200a-3p could partly abolish the MTX resistance induced by LncEBLN3P. CONCLUSION: LncEBLN3P is upregulated in osteosarcoma and increases the MTX resistance in osteosarcoma cells through downregulating miR-200a-3p, which in turn promoted the EMT process of osteosarcoma cells by increasing the OGT.