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General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

Abstract. Background:. Whether regional anesthesia may help to prevent disease recurrence in cancer patients is still controversial. The stage of cancer at the time of diagnosis is a key factor that defines prognosis and is one of the most important sources of heterogeneity for the treatment effect. We sought to update existing systematic reviews and clarify the effect of regional anesthesia on cancer recurrence in late-stage cancer patients. Methods:. Medline, Embase, and Cochrane Library were searched from inception to September 2020 to identify randomized controlled trials (RCTs) and cohort studies that assessed the effect of regional anesthesia on cancer recurrence and overall survival (OS) compared with general anesthesia. Late-stage cancer patients were primarily assessed according to the American Joint Committee on Cancer Cancer Staging Manual (eighth edition), and the combined hazard ratio (HR) from random-effects models was used to evaluate the effect of regional anesthesia. Results:. A total of three RCTs and 34 cohort studies (including 64,691 patients) were identified through the literature search for inclusion in the analysis. The risk of bias was low in the RCTs and was moderate in the observational studies. The pooled HR for recurrence-free survival (RFS) or OS did not favor regional anesthesia when data from RCTs in patients with late-stage cancer were combined (RFS, HR = 1.12, 95% confidence interval [CI]: 0.58–2.18, P = 0.729, I2 = 76%; OS, HR = 0.86, 95% CI: 0.63–1.18, P = 0.345, I2 = 48%). Findings from observational studies showed that regional anesthesia may help to prevent disease recurrence (HR = 0.87, 95% CI: 0.78–0.96, P = 0.008, I2 = 71%) and improve OS (HR = 0.88, 95% CI: 0.79–0.98, P = 0.022, I2 = 79%). Conclusions:. RCTs reveal that OS and RFS were similar between regional and general anesthesia in late-stage cancers. The selection of anesthetic methods should still be based on clinical evaluation, and changes to current practice need more support from large, well-powered, and well-designed studies.

Introduction: Cervical cancer is common in women. The present standardized therapies including surgery, chemotherapy, and radiotherapy are still not enough for treatment. Propofol is the most commonly used intravenous anesthetic agent for induction and maintenance of anesthesia and has been shown to exert anti-malignancy effects on cancer cells, inducing oxidative stress and apoptosis. However, the biological effects of propofol have not yet been systematically assessed. In this study, we examined the ferroptosis-related changes caused by propofol and the chemotherapeutic agent paclitaxel besides apoptosis in vitro.Methods: Cervical cancer cell lines (C-33A and HeLa) were treated with propofol alone (1, 2, 5, 10, and 20 μg/ml) or in combination with paclitaxel (0.5, 1, and 5 μg/ml). The viability was assessed using cell counting kit-8 (CCK8), apoptosis was detected by flow cytometry, morphological changes of mitochondria were examined using transmission electron microscope (TEM), cellular reactive oxygen species (ROS), and intracellular ferrous ions were determined by fluorescence microscope or confocal microscopy. The expression and cellular localization of apoptosis and ferroptosis-related molecules were detected by Western blot and multiplex immunohistochemistry (mIHC), respectively. Calcusyn software was used to determine whether propofol has a synergistic effect with paclitaxel.Results: Propofol and paclitaxel inhibited C-33A and HeLa cell viability. There were also synergistic effects when propofol and paclitaxel were used in combination at certain concentrations. In addition, propofol promoted paclitaxel-induced cervical cancer cell death via apoptosis. ROS level and Fe2+ concentrations were also influenced by different drug treatments. Furthermore, propofol, propofol injectable emulsion, and paclitaxel induced ferroptosis-related morphological changes of mitochondria in C-33A and HeLa cells. Ferroptosis-related signaling pathways including SLC7A11/GPX4, ubiquinol/CoQ10/FSP1, and YAP/ACSL4/TFRC were found to be changed under drug treatments.Conclusion: Propofol showed synergistic anticancer effects with paclitaxel in cervical cancer cells. Propofol and paclitaxel may induce ferroptosis of cervical cancer cells besides apoptosis.

Purpose: The number of cancer cases in China has increased rapidly from 2.1 million in 2000 to 4.3 million in 2015. As a consequence, pain management as an integral part of cancer treatment became an important health care issue. In March 2011, the Good Pain Management (GPM) program was launched to standardize the treatment of cancer pain and improve the quality of life for patients with cancer. With this work, we will describe the GPM program, its implementation experience, and highlight key lessons that can improve pain management for patients with cancer. Methods: We describe procedures for the selection, implementation, and assessment procedures for model cancer wards. We analyzed published results in areas of staff training and patient education, pain management in practice, analgesic drugs administration, and patient follow-up and satisfaction. Results: Pain management training enabled medical staff to accurately assess the level of pain and to provide effective pain relief through timely dispensation of medication. Patients with good knowledge of treatment of pain were able to overcome their aversion to opioid drugs and cooperate with nursing staff on pain assessment to achieve effective drug dose titration. Consumption of strong opioid drugs increased significantly; however, there was no change for weaker opioids. Higher pain remission rates were achieved for patients with moderate-to-severe pain levels. Proper patient follow-up after discharge enabled improved outcomes to be maintained. Conclusion: The GPM program has instituted a consistent and high standard of care for pain management at cancer wards and improved the quality of life for patients with cancer.

Background: Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain (CIBP). In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity. Methods: A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III (MDL28170, 1 mg/kg) on mechanical withdrawal threshold (MWT) of bilateral hind paws was examined on postoperative days (PODs) 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor′s effect on tumor bone tartrate-resistant acid phosphatase (TRAP) stain and radiology was also carefully investigated. Results: Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 (P < 0.05). TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05). However, bone resorption and destruction measured by radiographs showed no difference between the two groups. Conclusions: Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

Asynchronous parallel multisplitting relaxation methods for solving large sparse linear complementarity problems are presented, and their convergence is proved when the system matrices are H-matrices having positive diagonal elements. Moreover, block and multi-parameter variants of the new methods, together with their convergence properties, are investigated in detail. Numerical results show that these new methods can achieve high parallel efficiency for solving the large sparse linear complementarity problems on multiprocessor systems. [ABSTRACT FROM AUTHOR]

Presents a class of relaxed asynchronous parallel multisplitting iterative methods for solving the linear complementarity problem on multiprocessor systems. Establishment of the methods; Convergence theories; Numerical results.

Objective To investigate the changes of perioperative serum levels of interleukin-6 ( IL-6 ), C-reactive protein (CRP), and cortisol, as well as gastric intramucosal pH (pHi) and plasma lactate, aiming to compare systemic changes and tissue perfusion during colorectal and orthopaedic surgical procedures. Methods Twenty patients were randomly assigned to two groups, 10 cases of operation on vertebral canal, 10 cases of colorectal radical operation. Venous blood was drawn at l day before operation, 2, 4, and 6 hours following skin incision, and 1 day after operation, in order to measure serum IL-6, CRP, and cortisol, pHi and plasma lactate were also measured at the same time points. Results Serum concentrations of IL-6 and cortisol increased gradually following operation, reaching the peak value at 6 hours from the beginning of operation. CRP was not detectable until the first day after operation. Peak concentration of IL-6 had positive relationship with CRP. These variables changed more significantly in colorectal group than that in orthopaedic group (P < 0.05). pHi decreased gradually, reaching the lowest level at 4 hours from the beginning of operation, and to more extent in colorectal group than that in orthopaedic group (P < 0. 05). Conclusion IL-6 may reflect tissue damage more sensitively than CRP. Colorectal surgery might induce systemic disorder to more extent, in terms of immuno-endocrinal aspect as well as tissue perfusion, reflected with pHi. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of intraoperative Combined forced-air warming and fluid warming system on patient's core temperature, blood loss, transfusion demand, extubation time, and incidence of postoperative shivering. Methods Forty patients with American Society of Anesthesiologists physical status I and II, aged 18–70 years, scheduled for elective abdominal surgery were randomly assigned to receive intraoperative warning from a forced-air blanket and fluid warming system or conventional cotton blanket, 20 in each group. The core temperature was recorded every 20 minutes during the operation, as well as the blood loss, blood transfusion, extubation time, and incidence of postoperative shivering. Results The core temperature at the end of the surgery in the warming group was significantly different from that in the control group (36.4±0.4°C vs. 35.3±0.5°C, P<0.001). Application of intraoperative warming significantly shortened the time between the end of the surgery and extubation (P<0.01). Postoperative shivering occurred in 30% of the patients in the control group compared to no patient in the warming group (P<0.01). Connection Active warming with air-forced blanket and fluid warming system provides sufficient heat to prevent hypothermia during abdominal surgery. [ABSTRACT FROM AUTHOR]

Objective To identify the characteristics of anesthesia and perioperative management for ankylosing spondylitis (AS) patients undergoing total hip arthroplasty (THA). Methods Totally 63 patients scheduled for single THA in PUMC Hospital from January 1st 2013 to June 1st 2015 were included in this retrospective analysis,among whom 21 patients were diagnosed of AS. The perioperative clinical data included:demographic data,American Society of Anesthesiologists (ASA) classification,medical history,airway assessment,preoperative laboratory examinations,electrocardiogram,pulmonary function tests,intubation information,operation time,intraoperative intake and output volume,postoperative hospital stay,and postoperative complications. Results Significantly fewer AS patients undergoing THA were evaluated as ASA classification I than non-AS patients (9.5% vs. 33.3%,P=0.041). AS patients had significantly higher level of preoperative high-sensitivity C-reactive protein [(17.0±14.8)mg/L vs.(4.3±7.1)mg/L,P<0.001],platelets [(275.0±71.3)×10(9)/L vs. (237.7±68.0)×10(9)/L,P=0.048] and neutrophils [(4.7±1.7)×10(9)/L vs. (3.9±1.4)×10(9)/L,P=0.044] and higher incidence of pulmonary function abnormality (42.9% vs.16.7%,P=0.024).More AS patients were induced with scoline (14.3% vs.0,P=0.012). More AS patients underwent THA with Mallampati classification 3 (28.6% vs.7.1%,P=0.022),reduced neck extension(47.6% vs.2.4%,P<0.001),Cormack-Lehane classification2(56.3% vs.15.4%,P=0.002)and 3 (18.8% vs.0,P=0.005),while much fewer AS patients had Cormack-Lehane classification1 (25.0% vs.84.6%,P<0.001).A variety of difficult airway tools were used in intubation (AS group:Macintosh laryngoscope:14%,Macintosh laryngoscope with stylet:38%,visualization laryngoscope:24%,visualization stylet:10% and fiber bronchoscope:14%;non-AS group:57%,24%,12%,5% and 2%,respectively). The use of intraoperative autologous blood transfusion (33.3% vs.11.9%,P=0.041) and postoperative 24 h drainage (61.9% vs.31.0%,P=0.019) were more common in AS group. However,no statistical difference existed in the success rate of first intubation,postoperative hemoglobin,postoperative hematocrit,and postoperative hospitalization(all P>0.05). Conclusions AS patients undergoing THA have elevated preoperative inflammatory markers,with high incidence of pulmonary function abnormality and difficult airway. In consideration of high risk of surgery and anesthesia,adequate airway evaluation and optimization of perioperative management are needed to ensure the patients' safety.

Objective: To observe the effects of PSD95 gene specific siRNAs on neuropathic pain relief, neuron viability, and postsynaptic calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) phosphorylation in vitro and in vivo., Methods: Gene-specific siRNAs of rat PSD95 were synthesized chemically for transfection. Adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups: naïve group (n=6), sham group (n=6), and sciatic nerve chronic constriction injury (CCI) group (n=24). The CCI group was further divided into 4 groups (n=6 in each group), which were pretreated with normal saline, transfection vehicle, negative control siRNAs, and PSD95 gene specific siRNAs respectively. All the subgroups received corresponding agents intrathecally for 3 days, started one day before the CCI of sciatic nerve. Both mechanical allodynia and thermal hyperalgesia were measured on post-operative day 3 and 7. PSD95 gene silenced NG108-15 cells were further stimulated by glutamate, with the cell viability and the expression/phosphorylation of CaMKIIα measured by MTT cell proliferation assay and Western blot, respectively., Results: The siRNAs decreased PSD95 mRNA level significantly both in vivo and in vitro. Neuropathic pain rats pretreated with PSD95 gene specific siRNAs exhibited significant elevation in the mechanical withdrawal threshold and paw withdrawal thermal latency, without affecting the baseline nociception. PSD95 gene silencing enhanced neuronal tolerance against the glutamate excitotoxicity, meanwhile the phosphorylation of CaMKIIα Thr286 was attenuated., Conclusion: Pre-emptive administration of PSD95 gene specific siRNAs may attenuate the central sensitization CaMKIIα-related signaling cascades, leading to the relief of neuropathic pain.