Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients.

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.

Interplay of OATP1A/1B/2B1 uptake transporters and ABCB1 and ABCG2 efflux transporters in the handling of bilirubin and drugs.

Transmembrane drug transporters can be important determinants of the pharmacokinetics, efficacy, and safety profiles of drugs. To investigate the potential cooperative and/or counteracting interplay of OATP1A/1B/2B1 uptake transporters and ABCB1 and ABCG2 efflux transporters in physiology and pharmacology, we generated a new mouse model (Bab12), deficient for Slco1a/1b, Slco2b1, Abcb1a/1b and Abcg2. Bab12 mice were viable and fertile. We compared wild-type, Slco1a/1b/2b1-/-, Abcb1a/1b;Abcg2-/- and Bab12 strains. Endogenous plasma conjugated bilirubin levels ranked as follows: wild-type = Abcb1a/1b;Abcg2-/- << Slco1a/1b/2b1-/- < Bab12 mice. Plasma levels of rosuvastatin and fexofenadine were elevated in Slco1a/1b/2b1-/- and Abcb1a/1b;Abcg2-/- mice compared to wild-type, and dramatically increased in Bab12 mice. Although systemic exposure of larotrectinib and repotrectinib was substantially increased in the separate multidrug transporter knockout strains, no additive effects were observed in the combination Bab12 mice. Significantly higher plasma exposure of fluvastatin and pravastatin was only found in Slco1a/1b/2b1-deficient mice. However, noticeable transport by Slco1a/1b/2b1 and Abcb1a/1b and Abcg2 across the BBB was observed for fluvastatin and pravastatin, respectively, by comparing Bab12 mice with Abcb1a/1b;Abcg2-/- or Slco1a/1b/2b1-/- mice. Quite varying behavior in plasma exposure of erlotinib and its metabolites was observed among these strains. Bab12 mice revealed that Abcb1a/1b and/or Abcg2 can contribute to conjugated bilirubin elimination when Slco1a/1b/2b1 are absent. Our results suggest that the interplay of Slco1a/1b/2b1, Abcb1a/1b, and Abcg2 could markedly affect the pharmacokinetics of some, but not all drugs and metabolites. The Bab12 mouse model will represent a useful tool for optimizing drug development and clinical application, including efficacy and safety.

The Effect of Depth of Anesthesia on Postoperative Pain in Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.

Preoperative systemic immune-inflammation index-based nomogram for lung carcinoma following microwave ablation -a real world single center study.

Background: The preoperative inflammatory condition significantly influences the prognosis of malignancies. We aimed to investigate the potential significance of preoperative inflammatory biomarkers in forecasting the long-term results of lung carcinoma after microwave ablation (MWA). Method: This study included patients who received MWA treatment for lung carcinoma from Jan. 2012 to Dec. 2020. We collected demographic, clinical, laboratory, and outcome information. To assess the predictive capacity of inflammatory biomarkers, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of inflammatory biomarkers in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: A total of 354 individuals underwent MWA treatment, of which 265 cases were included in this study, whose average age was 69.1 ± 9.7 years. The AUC values for the Systemic Inflammatory Response Index (SIRI) to overall survival (OS) and disease-free survival (DFS) were 0.796 and 0.716, respectively. The Cox proportional hazards model demonstrated a significant independent association between a high SIRI and a decreased overall survival (hazard ratio [HR]=2.583, P<0.001). Furthermore, a high SIRI independently correlated with a lower DFS (HR=2.391, P<0.001). We developed nomograms utilizing various independent factors to forecast the extended prognosis of patients. These nomograms exhibited AUC of 0.900, 0.849, and 0.862 for predicting 1-year, 3-year, and 5-year OS, respectively. Additionally, the AUC values for predicting 1-year, 3-year, and 5-year DFS were 0.851, 0.873, and 0.883, respectively. Conclusion: SIRI has shown promise as a valuable long-term prognostic indicator for forecasting the outcomes of lung carcinoma patients following MWA.

Preparation and Performance of Ceramic Tiles with Steel Slag and Waste Clay Bricks.

Steel slag and waste clay bricks are two prevalent solid waste materials generated during industrial production. The complex chemical compositions of these materials present challenges to their utilization in conventional alumina silicate ceramics manufacturing. A new type of ceramic tile, which utilizes steel slag and waste clay brick as raw materials, has been successfully developed in order to effectively utilize these solid wastes. The optimal composition of the ceramic material was determined through orthogonal experimentation, during which the effects of the sample molding pressure, the soaking time, and the sintering temperature on the ceramic properties were studied. The results show that the optimal ceramic tile formula was 45% steel slag, 35% waste clay bricks, and 25% talc. The optimal process parameters for this composition included a molding pressure of 25 MPa, a sintering temperature of 1190 °C, and a soaking time of 60 min. The prepared ceramic tile samples had compositions in which solid waste accounted for more than 76% of the total material. Additionally, they possessed a modulus of rupture of more than 73.2 MPa and a corresponding water absorption rate of less than 0.05%.

Surgery challenges and postoperative complications of lung cancer after neoadjuvant immunotherapy.

BACKGROUND: In China, real-world data on surgical challenges and postoperative complications after neoadjuvant immunotherapy of lung cancer are limited. METHODS: Patients were retrospectively enrolled from January 2018 to January 2023, and their clinical and pathological characters were subsequently analyzed. Surgical difficulty was categorized into a binary classification according to surgical duration: challenging or routine. Postoperative complications were graded using Clavien-Dindo grades. Logistic regression was used to identify risk factors affecting the duration of surgery and postoperative complications greater than Clavien-Dindo grade 2. RESULTS: In total, 261 patients were included. Of these, stage III patients accounted for 62.5% (163/261) at initial diagnosis, with 25.3% (66/261) at stage IIIB. Central-type non-small-cell lung cancer accounted for 61.7% (161/261). One hundred and forty patients underwent video-assisted thoracoscopic surgery and lobectomy accounted for 53.3% (139/261) of patients. Surgical time over average duration was defined as challenging surgeries, accounting for 43.7%. The postoperative complications rate of 261 patients was only 22.2%. Smoking history (odds ratio [OR] = 9.96, 95% [CI] 1.15-86.01, p = 0.03), chemoimmunotherapy (OR = 2.89, 95% CI 1.22-6.86, p = 0.02), and conversion to open surgery (OR = 11.3, 95% CI 1.38-92.9, p = 0.02) were identified as independent risk factors for challenging surgeries, while pneumonectomy (OR = 0.36, 95% CI 0.15-0.86, p= 0.02) was a protective factor. Meanwhile, pneumonectomy (OR = 7.51, 95% CI 2.40-23.51, p < 0.01) and challenging surgeries (OR = 5.53, 95% CI 1.50-20.62, p = 0.01) were found to be risk factors for postoperative complications greater than Clavien-Dindo grade 2. CONCLUSIONS: Compared to immunotherapy alone or in combination with apatinib, neoadjuvant chemoimmunotherapy could increase the difficulty of surgery while the incidence of postoperative complications remained acceptable. The conversion to open surgery and pneumonectomy after neoadjuvant immunotherapy should be reduced.

MR-guided percutaneous microwave coagulation of small breast tumors.

BACKGROUND: To evaluate the technical success and patient safety of magnetic resonance-guided percutaneous microwave coagulation (MR-guided PMC) for breast malignancies. METHODS: From May 2018 to December 2019, 26 patients with breast tumors measuring 2 cm or less were recruited to participate in a prospective, single-institution clinical study. The primary endpoint of this study was the evaluation of treatment efficacy for each patient. Histochemical staining with α-nicotinamide adenine dinucleotide and reduced (NADH)-diaphorase was used to determine cell viability following and efficacy of PMC. The complications and self-reported sensations from all patients during and after ablation were also assessed. The technical success of the PMC procedure was defined when the area of the NADH-diaphorase negative region fully covered the hematoxylin-eosin (H&E) staining region in the tumor. RESULTS: All patients had a complete response to ablation with no residual carcinoma on histopathological specimen. The mean energy, ablation duration, and procedure duration per tumor were 36.0 ± 4.2 kJ, 252.9 ± 30.9 S, and 104.2 ± 13.5 min, respectively. During the ablation, 14 patients underwent prolonged ablation time, and 1 patient required adjusting of the antenna position. Eleven patients had feelings of subtle heat or swelling, and 3 patients experienced slight pain. After ablation, one patient took two painkillers because of moderate pain, and no patients had postoperative oozing or other complications after PMC. Induration around the ablation area appeared in 16 patients. CONCLUSION: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. CRITICAL RELEVANCE STATEMENT: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. KEY POINTS: • MR-guided PMC of small breast tumors is feasible. • PMC was successfully performed for all patients. • All patients were satisfied with the final cosmetic result.

α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4ß2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-ß-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.

Chest tube removal at different gas flows in prolonged air leak: a randomized non-inferiority trial.

OBJECTIVES: To evaluate the safety and feasibility of removing drainage tubes at larger size of air leak in patients with prolonged air leak after pulmonary surgery. METHODS: Ninety-five patients who underwent pulmonary surgery with prolonged air leak in our centre were enrolled in this randomized controlled, single-centre, non-inferiority study. The drainage tube was clamped with a stable size of air leak observed over the last 6 h, which was quantified by gas flow rate using the digital drainage system. The control group (n = 48) and the study group (n = 46) had their drainage tube clamped at 0-20 ml/min and 60-80 ml/min, respectively. We continuously monitored clinical symptoms, conducted imaging and laboratory examinations, and decided whether to reopen the drainage tube. RESULTS: The reopening rate in the study group was not lower than that in the control group (2.08% vs 6.52%, P > 0.05). The absolute difference in reopening rate was 4.44% (95% confidence interval -0.038 to 0.126), with an upper limit of 12.6% below the non-inferiority margin (15%). There were significant differences in the length of stay [16.5 (13-24.75) vs 13.5 (12-19.25), P = 0.017] and the duration of drainage [12 (9.25-18.50) vs 10 (8-12.25), P = 0.007] between the control and study groups. No notable differences were observed in chest X-ray results 14 days after discharge or in the readmission rate. CONCLUSIONS: For patients with prolonged air leak, removing drainage tubes at larger size of air leak demonstrated similar safety compared to smaller size of air leak, and can shorten both length of stay and drainage duration. CLINICAL TRIAL REGISTRATION NUMBER: Name of registry: Gas flow threshold for safe removal of chest drainage in patients with alveolar-pleural fistula prolonged air leak after pulmonary surgery. Registration number: ChiCTR2200067120. URL: https://www.chictr.org.cn/.

A hydrodynamic-based dual-function microfluidic chip for high throughput discriminating tumor cells.

A hydrodynamic-based microfluidic chip consisted of two function units that could not only separate tumor cells (TCs) from whole blood but also remove residual blood cells was designed. The separation of TCs was achieved by a straight contraction-expansion array (CEA) microchannel on the front end of the chip. The addition of contractive structure brought a micro-vortex like Dean vortex that promoted cell focusing in the channel, while when cells entered the dilated region, the wall-induced lift force generated by the channel wall gave cells a push away from the wall. As the wall-induced lift force is proportional to the third power of the cell diameter, TCs with larger diameter will have a larger lateral migration under the wall-induced lift force, realizing the separation of TCs from blood sample. Fluorescent particles with diameters of 19.3 µm and 4.5 µm were used to simulate TCs and red blood cells, respectively, to verify the separation capacity of the proposed CEA microchannel for particles with different diameter. And a separation efficiency 98.7% for 19.3 µm particles and a removal rate 96.2% for 4.5 µm particles was observed at sample flow rate of 10 µL min-1 and sheath flow rate of 190 µL min-1. In addition, a separation efficiency about 96.1% for MCF-7 cells (stained with DiI) and removal rates of 96.2% for red blood cells (RBCs) and 98.7% for white blood cells (WBCs) were also obtained under the same condition. However, on account of the large number of blood cells in the blood, there will be a large number of blood cells remained in the isolated TCs, so a purification unit based on hydrodynamic filtration (HDF) was added after the separation microchannel. The purification channel is a size-dictated cell filter that can remove residual blood cells but retain TCs, thus achieving the purification of TCs. Combined the CEA microchannel and the purifier, the microchip facilitates sorting of MCF-7 cells from whole blood with a separation rate about 95.3% and a removal rate over 99.99% for blood cells at a sample flow rate of 10 µL min-1, sheath flow rate of 190 µL min-1 and washing flow rate of 63 µL min-1.

Risk Factors for Postoperative Delirium in Patients Undergoing Major Head and Neck Cancer Surgery: A Meta-analysis.

BACKGROUND: Postoperative delirium (POD) is a common and serious complication after extensive surgery. Understanding the independent and potential modifiable risk factors leading to POD in patients with head and neck cancer (HNC) can provide information for future intervention trials aimed at reducing this risk. OBJECTIVE: To systematically analyze influencing factors of POD in patients with HNC and identify high-risk individuals for delirium. METHODS: PubMed, EMBASE, Scopus, OVID, and Cochrane Library were searched for publications prior to June 2023. Comparative studies in which POD risk factors were investigated were identified following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Newcastle-Ottawa Scale was used to evaluate the study quality. Pooled odds ratios or mean differences for individual risk factors were estimated using the Mantel-Haenszel and inverse-variance methods. RESULTS: This review included 17 studies with a total of 4188 patients undergoing HNC surgery. The pooled prevalence of POD was 15.44%. Based on pooled analysis, 8 significant risk factors were identified including age older than 70 years, male sex, history of smoking, history of psychiatric disorder, American Society of Anesthesiologists score, albumin level, postoperative insomnia, and fluid intake. CONCLUSION: In the present study, 8 factors that correlated with POD were identified: 6 preoperative, 1 intraoperative, and 1 postoperative. IMPLICATIONS FOR PRACTICE: The influencing factors for POD in patients with HNC were identified that can provide a reference for improving the psychological state of the patient population and further development of effective treatment interventions.

How does patient-centered communication influence patient trust?: The roles of patient participation and patient preference.

OBJECTIVE: The aim of this study was to examine the effects of patient-centered communication, patient participation, and patient preference on patient trust in the context of China. METHODS: A cross-sectional survey was conducted involving 217 cancer patients in China. Mediation and moderation analyses were performed to examine the relationships among the study variables. RESULTS: First, patient-centered communication increased patient participation in decision-making, which, in turn, enhanced patient trust. Second, patient-centered communication did not have a direct effect on patient trust. Third, patient preference for a passive role in decision-making weakened the relationship between patient participation and patient trust. CONCLUSION: The results underscore the significant effect of facilitating patient participation in linking patient-centered communication to patient trust. However, medical communication should also respond to patients' preferred roles in the decision-making process. PRACTICE IMPLICATIONS: Doctors should provide patients with opportunities to ask questions and express their concerns. In addition, they should evaluate patients' preferred degree of involvement before inviting them to contribute so as to respect their preferences and values.

Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma.

Malignant mesothelioma is a highly aggressive tumor with a survival of only 4-18 months after diagnosis. Treatment options for this disease are limited. Immune checkpoint blockade using ipilimumab and nivolumab has recently been approved as a frontline therapy, but this led to only a small improvement in overall patient survival. As more than half of patients with mesothelioma have alterations in the gene encoding for BAP1 this could be a potential marker for targeted therapies. In this study, we investigated the synergistic potential of combining EZH2 inhibition together with FGFR inhibition for treatment of BAP1-deficient malignancies. The efficacy of the combination was evaluated using human and murine preclinical models of mesothelioma and uveal melanoma in vitro. The efficacy of the combination was further validated in vivo by using BAP1-deficient mesothelioma xenografts and autochthonous mouse models. In vitro data showed sensitivity to the combined inhibition in BAP1-deficient mesothelioma and uveal melanoma tumor cell lines but not for BAP1-proficient subtypes. In vivo data showed susceptibility to the combination of BAP1-deficient xenografts and demonstrated an increase of survival in autochthonous models of mesothelioma. These results highlight the potential of this novel drug combination for the treatment of mesothelioma using BAP1 as a biomarker. Given these encouraging preclinical results, it will be important to clinically explore dual EZH2/FGFR inhibition in patients with BAP1-deficient malignant mesothelioma and justify further exploration in other BAP1 loss-associated tumors. SIGNIFICANCE: Despite the recent approval of immunotherapy, malignant mesothelioma has limited treatment options and poor prognosis. Here, we observe that EZH2 inhibitors dramatically enhance the efficacy of FGFR inhibition, sensitising BAP1-mutant mesothelioma and uveal melanoma cells. The striking synergy of EZH2 and FGFR inhibition supports clinical investigations for BAP1-mutant tumors.

Discovery of ellagic acid as a competitive inhibitor of Src homology phosphotyrosyl phosphatase 2 (SHP2) for cancer treatment: In vitro and in silico study.

Targeting SHP2 has become a potential cancer treatment strategy. In this study, ellagic acid was first reported as a competitive inhibitor of SHP2, with an IC50 value of 0.69 ± 0.07 µM, and its inhibitory potency was 34.86 times higher that of the positive control NSC87877. Ellagic acid also had high inhibitory activity on the SHP2-E76K and SHP2-E76A mutants, with the IC50 values of 1.55 ± 0.17 µM and 0.39 ± 0.05 µM, respectively. Besides, the IC50 values of ellagic acid on homologous proteins SHP1, PTP1B, and TCPTP were 0.93 ± 0.08 µM, 2.04 ± 0.28 µM, and 11.79 ± 0.83 µM, with selectivity of 1.35, 2.96, and 17.09 times, respectively. The CCK8 proliferation experiment exhibited that ellagic acid would inhibit the proliferation of various cancer cells. It was worth noting that the combination of ellagic acid and KRASG12C inhibitor AMG510 would produce a strong synergistic effect in inhibiting NCI-H358 cells. Western blot experiment exhibited that ellagic acid would downregulate the phosphorylation levels of Erk and Akt in NCI-H358 and MDA-MB-468 cells. Molecular docking and molecular dynamics studies revealed the binding information between SHP2 and ellagic acid. In summary, this study provides new ideas for the development of SHP2 inhibitors.

Epidemiology Characteristics and Potential Clinical Value of Vulvar Human Papillomavirus in Chinese Women: A Multicenter Cross-Sectional Study.

CONTEXT.­: Noninvasive self-sampling is a convenient option that may be highly accepted by women for home-based detection, which could increase the screening rate for cervical cancer (CC) and reduce its incidence and mortality. OBJECTIVE.­: To compare the distribution of high-risk human papillomavirus (hr-HPV) between the vulva and cervix and to explore the clinical value of vulvar HPV detection in CC screening. DESIGN.­: The study was nested within a clinical trial on recombinant HPV 9-valent vaccine for women ages 20 to 45 years. Women with paired vulvar and cervical specimens were included and received cytology and HPV detection. The consistency of HPV detection between vulvar and cervical specimens was evaluated using Cohen κ statistics. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the diagnostic accuracy of primary CC screening. The primary end points were cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+). RESULTS.­: A total of 7999 women were enrolled, and 83/33 cases were diagnosed as CIN2+/CIN3+. The HPV-positive rate in vulvar specimens (1785 of 7999; 22.32%) was higher than that in cervical specimens (1390 of 7999; 17.38%), and there were no significant differences in the distribution of hr-HPV genotypes between the vulva and cervix in patients with CIN2+/CIN3+. Vulva-based HPV primary screening showed sensitivity, specificity, PPV, and NPV comparable to those for cervix-based HPV primary CC screening in the detection of CIN3+. CONCLUSIONS.­: The distribution of vulvar and cervical HPV was similar in patients with CIN2+/CIN3+. Vulva-based HPV primary CC screening had acceptable diagnostic efficacy and might be used as a modality for primary CC screening.

Effects of opioid-free anaesthesia on postoperative nausea and vomiting in patients undergoing video-assisted thoracoscopic surgery (OFA-PONV trial): study protocol for a randomised controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after general anaesthesia and is associated with morbidity and prolonged length of stay. Growing evidence suggest that opioid-free general anaesthesia (OFA) may reduce PONV in various surgical settings. We aim to evaluate the efficacy of OFA on the incidence of PONV compared with opioid-based anaesthesia among adults undergoing thoracoscopic surgery. METHODS: This is a prospective, single-centre, randomised controlled trial comparing OFA and opioid-based anaesthesia for thoracoscopic surgery. A total of 168 adults will be randomised with a 1:1 ratio to receive either opioid-free anaesthesia or opioid-based anaesthesia. The primary outcome will be the incidence of PONV within 24 h after operation. The secondary outcomes will include the severity of PONV, quality of recovery, pain at rest, 6-min walking test, and health-related quality of life after operation. DISCUSSION: The benefit-risk of OFA for patients after operation is contradictory in previous studies, so further study is required. This trial will focus on the effect of OFA on the incidence of PONV in patients undergoing thoracoscopic surgery. This trial adopts uniformed PONV and perioperative pain management, standardised randomised and blind, clear-cut inclusion and exclusion criteria, and standardised scales to assess the severity of PONV after surgery, the quality of postoperative recovery, and the health status at 6 months. The findings of this study will help to provide references to promote early recovery of patients after lung surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05411159. Registered on 9 June 2022.

The potential role of gut microbiota outer membrane vesicles in colorectal cancer.

Colorectal cancer (CRC) is a common malignant digestive tract tumor in colorectal regions. Considerable evidence now shows that the gut microbiota have essential roles in CRC occurrence and development. Most Gram-negative bacteria release outer membrane vesicles (OMVs) via outer membrane blistering, which contain specific cargoes which interact with host cells via intercellular communications, host immune regulation, and gut microbiota homeostasis. Studies have also shown that OMVs selectively cluster near tumor cells, thus cancer treatment strategies based on OMVs have attracted considerable research attention. However, little is known about the possible impact of gut microbiota OMVs in CRC pathophysiology. Therefore, in this review, we summarize the research progress on molecular composition and function of OMV, and review the microbial dysbiosis in CRC. We then focus on the potential role of gut microbiota OMVs in CRC. Finally, we examine the clinical potential of OMVs in CRC treatment, and their main advantages and challenges in tumor therapy.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Intra-articular Histone Deacetylase Inhibitor Microcarrier Delivery to Reduce Osteoarthritis.

The histone deacetylase inhibitor (HDACi) was a milestone in the treatment of refractory T-cell lymphoma. However, the beneficial effects of HDACi have not been appreciated in osteoarthritis (OA). Herein, we implemented a microcarrier system because of the outstanding advantages of controlled and sustained release, biodegradability, and biocompatibility. The poly(d,l-lactide-co-glycolide) (PLGA) microcapsules have a regulated and sustained release profile with a reduced initial burst release, which can improve the encapsulation efficiency of the Chidamide. The emulsion solvent evaporation strategy was used to encapsulate Chidamide in PLGA microcapsules. The encapsulation of Chidamide was established by UV-vis spectra and scanning electron microscopy. Additionally, the inhibition of Tnnt3 and immune stimulation by Chidamide helped to inhibit cartilage destruction and prevent articular cartilage degeneration. Based on the results, the Chidamide in PLGA microcapsules provides a transformative therapeutic strategy for the treatment of osteoarthritis patients to relieve symptoms and protect against cartilage degeneration.

GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma.

Glioblastoma is the most common malignant tumor in the central nervous system. The general transcription factor IIE subunit beta (GTF2E2) is crucial for physiological and pathological functions, but its roles in the malignant biological function of glioma remain ambiguous. CCK-8, colony formation assays, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological functions of GTF2E2 both in vitro and in vivo. GTF2E2 was overexpressed in glioma and was associated with poor prognosis of glioma patients. Biological functions of GTF2E2 were investigated both in vitro and in vi0vo by multiple experiments. Moreover, we explored the possible mechanisms of GTF2E2. In our results, we demonstrated that GTF2E2 could be regulated by miR-340-5p directly or indirectly. CCND1 was transcriptionally affected by GTF2E2 and glioma progression was then regulated. Our data presented the overexpression of GTF2E2 in glioma and indicated the association between GTF2E2 and glioma prognosis. GTF2E2 was found to be regulated by miR-340-5p and thus affect downstream gene expressions and glioma progression. Our results indicate that GTF2E2 might be a potential target in the diagnosis and treatments of glioblastoma.