Increased TMEM166 Level in Patients with Postoperative Stroke after Carotid Endarterectomy.

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

Predictive Factors of Intestinal Ischaemia in Adhesive Small Bowel Obstruction.

OBJECTIVE: To identify the predictive factors of intestinal ischaemia in adhesive small bowel obstruction (ASBO) and develop an intestinal ischaemia risk score. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China, from January 2017 to February 2022. METHODOLOGY: ASBO was determined by findings at laparotomy. The assessment of small bowel's viability was conducted through surgical inspection and subsequent histological examination of the surgical specimen. Univariate and multivariate analyses were conducted to ascertain the risk factors associated with intestinal ischaemia. RESULTS: In total, 79 patients were included. Factors entered into multivariate analysis associated with intestinal ischaemia were; rebound tenderness (odds ratio (OR): 7.8, 95% confidence interval (CI):1.7-35.3; p=0.008), procalcitonin (PCT) >0.5 ng/mL (OR: 11.7, 95% CI: 2.3-58.1; p=0.003), and reduced bowel wall enhancement on computerised tomography (CT) scan (OR: 12.2, 95% CI:2.4-61.5; p=0.003). Among patients with 0, 1, 2, and 3 factors, the rate of intestinal ischaemia increased from 0% to 49%, 72%, and 100%, respectively. According to the number of risk factors, the area under the receiver operating characteristic curve for the determination of intestinal ischaemia was 0.848 (95% CI: 0.764-0.932). CONCLUSION: Rebound tenderness, PCT levels >0.5 ng/mL, and reduced bowel wall enhancement are risk factors of intestinal ischemic injury that require surgery within the context of ASBO. These factors need to be closely monitored that could assist clinicians in avoiding unnecessary laparotomies and selecting patients eligible for surgery. KEY WORDS: Intestinal obstruction, Ischaemia, Adhesions.

Mesoporous polydopamine Targeting CDK4/6 Inhibitor toward Brilliant Synergistic Immunotherapy of Breast Cancer.

Immunotherapy utilizing anti-PD-L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti-tumor immunity effectively. However, developing simple but versatile, highly efficient but low-toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable. Herein, a multifunctional ICD inducer is purposefully developed A6-MPDA@PAL by integrating photothermal therapy (PTT) nanoplatforms mesoporous polydopamine (MPDA), CDK4/6 inhibitor palbociclib (PAL), and CD44-specific targeting A6 peptide in a simple way for augmenting the immune antitumor efficacy of anti-PD-L1 therapy. Remarkably, the light-inducible nanoplatforms exhibit multiple favorable therapeutic features ensuring a superior and biosafe PTT/chemotherapy efficacy. Together with stronger accumulative ICD induction, single administration of A6-MPDA@PAL can trigger robust systemic antitumor immunity and abscopal effect with the assistance of anti-PD-L1 blockade by fascinating the intratumoral infiltration of T lymphocytes and reversing the immunosuppressive tumor microenvironment simultaneously, therapy achieving brilliant synergistic immunotherapy with effective tumor ablation. This study presents a simple and smart ICD inducer opening up attractive clinical possibilities for reinforcing the anti-PD-L1 therapy against breast cancer.

Regulating pyroptosis by mesenchymal stem cells and extracellular vesicles: A promising strategy to alleviate intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate a heavy burden on society. IVDD is characterized by a decrease in nucleus pulposus cells (NPCs) and endogenous mesenchymal stem cells (MSCs), degradation of the extracellular matrix, macrophage infiltration, and blood vessel and nerve ingrowth. To date, the therapeutic approaches regarding IVDD mainly include conservative treatment and surgical intervention. However, both can only relieve symptoms rather than stop or revert the progression of IVDD, since the pathogenesis of IVDD is not yet clear. Pyroptosis, which is characterized by Caspase family dependence and conducted by the Gasdermin family, is a newly discovered mode of programmed cell death. Pyroptosis has been observed in NPCs, annulus fibrosus cells (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial cells and neurons and may contribute to IVDD. MSCs are a kind of pluripotent stem cell that can be found in almost all tissues. MSCs have a strong ability to secrete extracellular vesicles (EVs), which contain exosomes, microvesicles and apoptotic bodies. EVs derived from MSCs play an important role in pyroptosis regulation and could be beneficial for alleviating IVDD. This review focuses on clarifying the regulation of pyroptosis to improve IVDD by MSCs and EVs derived from MSCs.