Recent advances in photothermal nanomaterials-mediated detection of circulating tumor cells.

Photothermal materials have shown great potential for cancer detection and treatment due to their excellent photothermal effects. Circulating tumor cells (CTCs) are tumor cells that are shed from the primary tumor into the blood and metastasize. In contrast to other tumor markers that are free in the blood, CTCs are a collective term for all types of tumor cells present in the peripheral blood, a source of tumor metastasis, and clear evidence of tumor presence. CTCs detection enables early detection, diagnosis and treatment of tumors, and plays an important role in cancer prevention and treatment. This review summarizes the application of various photothermal materials in CTC detection, including gold, carbon, molybdenum, phosphorus, etc. and describes the significance of CTC detection for early tumor diagnosis and tumor prognosis. Focus is also put on how various photothermal materials play their roles in CTCs detection, including CT, imaging and photoacoustic and therapeutic roles. The physicochemical properties, shapes, and photothermal properties of various photothermal materials are discussed to improve the detection sensitivity and efficiency and to reduce the damage to normal cells. These photothermal materials are capable of converting radiant light energy into thermal energy for highly-sensitive CTCs detection and improving their photothermal properties by various methods, and have achieved good results in various experiments. The use of photothermal materials for CTCs detection is becoming more and more widespread and can be of significant help in early cancer screening and later treatment.

Aggressive intraoperative warming and postoperative pulmonary complications in elderly patients recovering from esophageal cancer surgery: sub-analysis of a randomized trial.

Background: Elderly patients having esophagectomies often become hypothermic which may promote complications. We tested the hypothesis that aggressive warming to a core temperature of 37°C reduces postoperative pulmonary complications (PPCs) in elderly patients having esophageal cancer resections. Methods: This study was a pre-defined sub-study of a multi-center, parallel group, superiority trial (PROTECT). Patients aged >65 years and having elective radical resection of esophageal cancer in a single center were randomly allocated into either aggressive warming group (target intraoperative core temperatures of 37°C) or routine thermal management group (target intraoperative core temperatures of 35.5°C). The primary endpoint was the incidence of PPCs. Secondary endpoints included duration of chest tube drainage and other postoperative complications. Results: A total of 300 patients were included in the primary analysis. PPCs occurred in 27 (18%) of 150 patients in the aggressive warming group and 31 (21%) of 150 patients in the routine thermal management group. The relative risk (RR) of aggressive versus routine thermal management was 0.9 (95% CI: 0.5, 1.4; p = 0.56). The duration of chest drainage in patients assigned to aggressive warming was shorter than that assigned to routine thermal management: 4 (3, 5) days vs. 5 (4, 7) days; hazard ratio (HR) 1.4 [95% CI: 1.1, 1.7]; p = 0.001. Fewer aggressively warmed patients needed chest drainage for more than 5 days: 30/150 (20%) vs. 51/150 (34%); RR:0.6 (95% CI: 0.4, 0.9; p = 0.03). The incidence of other postoperative complications were similar between the two groups. Conclusion: Aggressive warming does not reduce the incidence of PPCs in elderly patients receiving esophagectomy. The duration of chest drainage was reduced by aggressive warming. But as a secondary analysis of a planned sub-group study, these results should be considered exploratory. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=37099, ChiCTR1900022257.

Hypoxemia in thoracoscopic lung resection surgery using a video double-lumen tube versus a conventional double-lumen tube: A propensity score-matched analysis.

Background: Malposition of the double-lumen tubes (DLTs) may lead to hypoxemia during one-lung ventilation (OLV). Video double-lumen tubes (VDLTs) enable continuous observation of DLT position and avoid displacement. We aimed to investigate whether VDLTs could reduce the incidence of hypoxemia during OLV compared with conventional double-lumen tubes (cDLT) in thoracoscopic lung resection surgery. Methods: This was a retrospective cohort study. Adult patients who underwent elective thoracoscopic lung resection surgery and required VDLTs or cDLTs for OLV at Shanghai Chest Hospital from January 2019 to May 2021 were included. The primary outcome was the incidence of hypoxemia during OLV between VDLT and cDLT. Secondary outcomes included bronchoscopy use, the degree of PaO2 decline, and arterial blood gas indices. Results: A total of 1,780 patients were finally analyzed in propensity score-matched cohorts (VDLT vs. cDLT 1:1 n = 890). The incidence of hypoxemia decreased from 6.5% (58/890) in cDLT group to 3.6% (32/890) in VDLT group (Relative Risk [RR]: 1.812, 95% CI: 1.19-2.76, p = 0.005). The use of bronchoscopy was reduced by 90% in VDLT group (VDLT 10.0% (89/890) vs. cDLT 100% (890/890), p < 0.001). PaO2 after OLV was 221 [136.0-325.0] mmHg in cDLT group compared to 234 [159.7-336.2] mmHg in VDLT group, p = 0.003. The percentage of PaO2 decline was 41.4 [15.4-61.9] % in cDLT group, while it was 37.7 [8.7-55.9] % in the VDLT group, p < 0.001. In patients who suffered from hypoxemia, there were no significant differences in arterial blood gas indices or the percentage of PaO2 decline. Conclusion: VDLTs reduce the incidence of hypoxemia and the use of bronchoscopy during OLV compared with cDLTs. VDLT may be a feasible option for thoracoscopic surgery.

Circ_0002984 induces proliferation, migration and inflammation response of VSMCs induced by ox-LDL through miR-326-3p/VAMP3 axis in atherosclerosis.

Atherosclerosis can result in multiple cardiovascular diseases. Circular RNAs (CircRNAs) have been reported as significant non-coding RNAs in atherosclerosis progression. Dysfunction of vascular smooth muscle cells (VSMCs) is involved in atherosclerosis. However, up to now, the effect of circ_0002984 in atherosclerosis is still unknown. Currently, we aimed to investigate the function of circ_0002984 in VSMCs incubated by oxidized low-density lipoprotein (ox-LDL). Firstly, our findings indicated that the expression levels of circ_0002984 were significantly up-regulated in the serum of atherosclerosis patients and ox-LDL-incubated VSMCs. Loss of circ_0002984 suppressed VSMC viability, cell cycle distribution and migration capacity. Then, we carried out ELISA assay to determine TNF-α and IL-6 levels. The data implied that lack of circ_0002984 obviously repressed ox-LDL-stimulated VSMC inflammation. Meanwhile, miR-326-3p, which was predicted as a target of circ_0002984, was obviously down-regulated in VSMCs treated by ox-LDL. Additionally, after overexpression circ_0002984 in VSMCs, a decrease in miR-326-3p was observed. Subsequently, miR-326-3p was demonstrated to target vesicle-associated membrane protein 3 (VAMP3). Therefore, we hypothesized that circ_0002984 could modulate expression of VAMP3 through sponging miR-326-3p. Furthermore, we confirmed that up-regulation of miR-326-3p rescued the circ_0002984 overexpressing-mediated effects on VMSC viability, migration and inflammation. Additionally, miR-326-3p inhibitor-mediated functions on VSMCs were reversed by knockdown of VAMP3. In conclusion, circ_0002984 mediated cell proliferation, migration and inflammation through modulating miR-326-3p and VAMP3 in VSMCs, which suggested that circ_0002984 might hold great promise as a therapeutic strategy for atherosclerosis.

Frequency domain analysis and clinical outcomes of pulsatile and non-pulsatile blood flow energy during cardiopulmonary bypass.

INTRODUCTION: The superiority of pulsatile perfusion during cardiopulmonary bypass remains controversial. We analyzed the frequency-domain characteristics and organ protection of pulsatile and nonpulsatile flow in adult patients with valvular disease. METHODS: EEP and SHE were used to calculate blood flow energy in 60 patients. The Fast Fourier Transform was employed to analyze the power spectral density and power density ratio (Rvpd) of flow energy. Changes in endothelin-1, nitric oxide, interleukin-6,10, tumor necrotic factor, S100ß, NSE, blood and urinary ß2-microglobulin levels were investigated to assess the endothelial function, inflammatory reaction, kidney and brain injury during CPB. RESULTS: EEP and SHE in PP group at each time point were 1.52-1.62 times and 2.03-2.22 times higher respectively compared with NP group. Power spectral density analysis demonstrated that the blood flow energy frequencies in each group were all within 40 Hz and the low frequency energy (0-5 Hz) was dominant in physiological perfusion (>90%). The energy ratio of 0-5 Hz at radial artery was significantly decreased compared with that of post arterial filter in PP (81% vs 64%) and NP (63% vs 37%) group. The power density ratio (Rvpd) was higher than that of NP in all frequency ranges at the radial artery (9.51 vs 4.68 vs 3.59) and arterial filter (3.87 vs 2.69 vs 2.38). The S100ß, NSE Urinary and plasma ß2-microglobulin level were significantly increased at 6 and 24 hours after surgery in two group, and significantly higher in group NP. CONCLUSION: PP provided more energy than NP. The proportion of low frequency energy in the pulsatile or nonpulsatile flow is significantly reduced. The low-frequency energy is significantly attenuated during conduction to peripheral tissues in nonpulsatile flow. The surplus pulsatile energy influences the secretion of endothelial and inflammatory factors, and demonstrate better cerebral and kidney protective effect at the biological marker level.

Supplemental Intraoperative Oxygen and Long-term Mortality: Subanalysis of a Multiple Crossover Cluster Trial.

BACKGROUND: Whether supplemental oxygen worsens long-term mortality remains unclear, with contradictory trial results. The authors therefore tested the hypothesis that supplemental oxygen (80% vs. 30%) increases the hazard for long-term mortality. METHODS: The authors conducted a post hoc analysis of a large multiple crossover cluster trial in which more than 5,000 colorectal surgeries on 4,088 adults were allocated to receive either 30% or 80% inspired oxygen during general anesthesia. The authors assessed the effect of 80% versus 30% target-inspired oxygen on long-term mortality and calculated Kaplan-Meier survival estimates. Analysis was restricted to patients with a home address in Ohio because the authors could obtain reliable vital status information from the Ohio Department of Health (Columbus, Ohio) for them. RESULTS: A total of 3,471 qualifying colorectal surgeries performed in 2,801 patients were analyzed, including 1,753 (51%) surgeries in 1,577 patients given 80% oxygen and 1,718 surgeries in 1,551 patients given 30% oxygen. The observed incidence of death after a median of 3 yr was 13% (234 of 1,753) in the 80% oxygen group and 14% (245 of 1,718) in the 30% oxygen group. The estimated hazard ratio for mortality was 0.94 (95% CI, 0.78 to 1.13; P = 0.493). CONCLUSIONS: In this post hoc analysis of a large, controlled trial, supplemental oxygen did not increase postoperative mortality.

Propofol exerts neuroprotective functions by down-regulating microRNA-19a in glutamic acid-induced PC12 cells.

BACKGROUND: Propofol, a kind of intravenous sedative drug, is certified that exerts anti-inflammation and antitumor functions. However, the influence of propofol in cerebral injury and the corresponding mechanism remains unexplained, that our article focuses on. METHODS: PC12 cells were treated with propofol and exposed in glutamic acid (Glu) solutions. Cell viability, apoptotic potential, apoptosis-related and autophagy-linked proteins were tested via CCK-8, flow cytometry, and western blot assays. Reverse transcription-quantitative real-time PCR was utilized to test miR-19a expression in Glu-stimulated cells. Next, miR-19a mimic transfection was used to assess the effects of miR-19a on cell apoptosis and autophagy in Glu or propofol treated cells. Finally, western blot was performed to test AMPK and mTOR pathways. RESULTS: Glu exposure promoted cell apoptosis and autophagy of PC12 cells, while propofol attenuated cell apoptosis and autophagy triggered by Glu. Additionally, propofol decreased the miR-19a expression in Glu-stimulated PC12 cells. Meanwhile, over-expression of miR-19a reversed the effects of propofol on Glu-induced cell apoptosis and autophagy. Moreover, propofol potentiated AMPK and mTOR pathways in Glu-stimulated PC12 cells via impeding miR-19a expression. CONCLUSIONS: These finding revealed that propofol relieved Glu-triggered apoptosis and autophagy of PC12, and activated AMPK and mTOR pathways by suppressing miR-19a expression.

Upregulation of bone morphogenetic protein 2 ( Bmp2) in dorsal root ganglion in a rat model of bone cancer pain.

Bone cancer pain is one of the most severe and intractable complications in patients suffering from primary or metastatic bone cancer and profoundly compromises the quality of life. Emerging evidence indicates that the dorsal root ganglion play an integral role in the modulation of pain hypersensitivity. However, the underlying molecular mechanisms during dorsal root ganglion-mediated bone cancer pain remain elusive. In this study, RNA-sequencing was used to detect the differentially expressed genes in dorsal root ganglion neurons of a rat bone cancer pain model established by intratibial inoculation of Walker 256 breast cancer cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes (fold change > 1.5; false discovery rate < 0.05) were enriched in the bone morphogenetic protein (BMP) signaling pathway, transforming growth factor-ß signaling pathway, and positive regulation of cartilage development. Importantly, serum deprivation-response protein ( Sdpr), hephaestin ( Heph), transthyretin ( Ttr), insulin receptor substrate 1 ( Irs1), connective tissue growth factor ( Ctgf ), and Bmp2 genes were associated with bone pain and degeneration. Of note, Bmp2, a pleiotropic and secreted molecule mediating pain and inflammation, was one of the most significantly upregulated genes in dorsal root ganglion neurons in this bone cancer pain model. Consistent with these data, upregulation of Bmp2 in the bone cancer pain model was validated by immunohistochemistry, real-time quantitative polymerase chain reaction, and western blotting. Importantly, intrathecal administration of siRNA significantly reduced Bmp2 transcription and ameliorated bone cancer pain in rat as shown by paw withdrawal mechanical threshold and spontaneous and movement-evoked pain-like behaviors. In conclusion, we have characterized the comprehensive gene expression profile of dorsal root ganglion from a bone cancer pain rat model by RNA-sequencing and identified Bmp2 as a potential therapeutic target for bone cancer pain treatment.

Comparison of deep or moderate neuromuscular blockade for thoracoscopic lobectomy: a randomized controlled trial.

BACKGROUND: Laparoscopic surgery typically requires deep neuromuscular blockade (NMB), but whether deep or moderate NMB is superior for thoracoscopic surgery remains controversial. METHODS: Patients scheduled for thoracoscopic lobectomy under intravenous anesthesia were randomly assigned to receive moderate [train of four (TOF) 1-2] or deep NMB [TOF 0, post-tetanic count (PTC) 1-5]. Depth of anesthesia was controlled at a Narcotrend rating of 30 ± 5 in both groups. The primary outcome was the need to use an additional muscle relaxant (cisatracurium) during surgery. Secondary outcomes included surgeon satisfaction, recovery time of each stage after drug withdrawal [time from withdrawal until TOF recovery to 20% (antagonists administration), 25, 75, 90, 100%], blood gas data, VAS pain grade after extubation, the time it takes for patients to begin walking after surgery, postoperative complications and hospitalization time. Results were analyzed on an intention-to-treat basis. RESULTS: Thirty patients were enrolled per arm, and all but one patient in each arm was included in the final analysis. Among patients undergoing moderate NMB, surgeons applied additional cisatracurium in 8 patients because of body movement and 5 because of coughing (13/29, 44.8%). Additional cisatracurium was not applied to any of the patients undergoing deep NMB (p < 0.001). Surgeons reported significantly higher satisfaction for patients undergoing deep NMB (p < 0.001, Wilcoxon rank sum test). The mean difference between the two groups in the time from withdrawal until TOF recovery of 25% or 90% was 10 min (p < 0.001). The two groups were similar in other recovery data, blood gas analysis, VAS pain grade, days for beginning to walk and mean hospitalization time. CONCLUSIONS: Deep NMB can reduce the use of additional muscle relaxant and increase surgeon satisfaction during thoracoscopic lobectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-15007117 , 22 September 2015.

Evaluation of local anesthetic effects of Lidocaine-Ibuprofen ionic liquid stabilized silver nanoparticles in Male Swiss mice.

A simple approach for the synthesis of Lidocaine-Ibuprofen ionic liquid stabilized silver nanoparticles (IL-AgNPs) was reported in this work. The shape, size and surface morphology of the Lidocaine-Ibuprofen ionic liquid stabilized AgNPs were characterized by using spectroscopic and microscopic techniques such as Ultraviolet-visible spectroscopy (UV-Visible), X-ray diffraction (XRD) analysis, Selected area electron diffraction (SAED), Transmission electron microscopy (TEM). TEM analysis showed the formation of 20-30nm size of IL-AgNPs with very clear lattice fringes. SAED pattern confirmed the highly crystalline nature of fabricated IL stabilized AgNPs. EDS results confirmed the formation of nanosilver. The fabricated IL-AgNPs were studied for their local anesthetic effect in rats. The results of local anesthetic effect showed that the time for onset of action by IL-AgNPs is 10min, which is significantly higher than that for EMLA. Further, tactile test results confirmed the stronger and faster local anesthetic effect of IL-AgNPs when compared to that of EMLA.

Propofol Inhibits Neurogenesis of Rat Neural Stem Cells by Upregulating MicroRNA-141-3p.

Prolonged or high-dose exposure to anesthetics, such as propofol, can cause brain cell degeneration and subsequent long-term learning or memory deficits, particularly in the developing brain. However, the cellular and molecular mechanisms underlying the deleterious effects of propofol at certain stages of development remain unclear. In this study we found that propofol inhibited the proliferation, neuronal differentiation, and migration of neural stem cells (NSCs) while upregulating miR-141-3p. Silencing of miR-141-3p abrogated the effects of propofol on NSC neurogenesis. Propofol treatment downregulated IGF2BP2, a direct target of miR-141-3p, whereas overexpression of IGF2BP2 attenuated the effects of propofol and miR-141-3p on NSC neurogenesis. In short, propofol inhibits NSC neurogenesis through a mechanism involving the miR-141-3p/IGF2BP2 axis. Our results may provide a potential approach for preventing the neurodegenerative effects of propofol in the developing brain.

The effects of electroacupuncture treatment on the postoperative cognitive function in aged rats with acute myocardial ischemia-reperfusion.

Many literatures have proven that postoperative cognitive dysfunction (POCD) was very common in old patients after the injury of acute myocardial ischemia-reperfusion (AMIR) clinically such as the off-pump coronary artery bypass surgery (OPCAB) without definite mechanism; however, reports on the animal experiments were rarely seen. We hypothesized that AMIR could contribute to cognitive dysfunction, and this severe injury might be impeded by EA via hindering neuroinflammation and oxidative stress response as well as modulating the balance of the autonomic nervous system. The aged male Sprague Dawley rats were randomly assigned into three experimental groups: sham (sham operation), AMIR, and EA (electroacupunture treatment, acupoints GV20 and ST36+AMIR) groups. The survival rate, heart rate variability analysis, examination of pathology within the hippocampal CA1, oxidative stress, systemic inflammation and the behavior testing were evaluated by their corresponding methods. The results showed that the rats subjected to AMIR had lower survival rates, higher malondialdehyde (MDA), decreased superoxide dismutase (SOD) activity, more microglial activation, and presented evidence of severe brain injury and cognitive dysfunction on the 1st, 3rd, 7th days after reperfusion compared to sham-operated controls. Most important of all, the above damages induced by the AMIR were significantly improved by the EA treatment. Our findings indicated that EA treatment could be a neuroprotective therapy for the cognitive dysfunction induced by the AMIR event, which might be attributablefor balancing the autonomic nervous system, inhibiting the neuronic apoptosis, hindering microglial activation, attenuating oxidative stress and restraining the central and peripheral inflammation reactions.

Quality of cardiopulmonary resuscitation affects cardioprotection by induced hypothermia at 34 °C against ischemia/reperfusion injury in a rat isolated heart model.

In this study, we aimed to compare the effects of low- and high-quality cardiopulmonary resuscitation (CPR) on cardioprotection by induced hypothermia (IH) at 34 °C and examine whether extracellular signal-regulated kinase or endothelial nitric oxide synthase mediates this cardioprotection. Left ventricle infarct sizes were evaluated in six groups of rat hearts (n = 6) following Langendorff perfusion and triphenyltetrazolium chloride staining. Controls underwent 30 min of global ischemia at 37 °C, followed by 10 min of simulated low- or high-quality CPR reperfusion and 90 min of reperfusion at 75 mmHg. The IH groups underwent IH at 34 °C during reperfusion. The U0126 group received U0126 (60 µM)-an extracellular signal-regulated kinase inhibitor-during reperfusion at 34 °C. The L-NIO (N-(1-iminoethyl)-L-ornithine dihydrochloride) group received L-NIO (2 µM)-an endothelial nitric oxide synthase inhibitor-5 min before global ischemia at 37 °C to the end of reperfusion at 34 °C. Infarct size did not significantly differ between the control and IH groups receiving low-quality CPR. However, IH with high-quality CPR reduced the infarct size from 47.2% ± 10.2% to 26.0% ± 9.4% (P = 0.005). U0126 reversed the IH-induced cardioprotection (45.9% ± 9.4%, P = 0.010), whereas L-NIO had no significant effect. Cardiopulmonary resuscitation quality affects IH-induced cardioprotection. Extracellular signal-regulated kinase may mediate IH-induced cardioprotection.