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The aim of this study was to systematically review the cost-effectiveness of HPV vaccination in Asia.We performed a systematic review of papers indexed in PubMed, Scopus, and Web of Science covering the period from 1 January 2000 to 13 August 2020.Sixteen studies were included in the review. Half of them (8 studies) evaluated the cost-effectiveness of HPV vaccination in high-income countries and regions (HICs) while the other eight studies were set in low- and middle-income countries and regions (LMICs). In HICs, the implementation of bivalent, quadrivalent and nine-valent HPV vaccination was all shown to be cost-effective. Most studies (7/8) also showed that it was cost-effective to implement bivalent, quadrivalent, and nine-valent HPV vaccines in LMICs. However, one study concluded that it was not cost-effective to implement bivalent HPV vaccination in Thailand.In general, the implementation of bivalent, quadrivalent and nine-valent HPV vaccination for adolescent girls was cost-effective in both high-income countries and regions and low- and middle-income countries and regions in Asia. Policy makers in HICs could consider expanding the target vaccinated population, while for LMICs it is essential to reduce HPV vaccine price to a level at which the implementation of HPV vaccination is cost-effective.

Crizotinib, a multitargeted MET/ALK/ROS1 tyrosine kinase inhibitor, has been approved for the treatment of ROS1 fusion–positive non‐small cell lung cancers (NSCLCs). However, “on‐target” or “off‐target” resistance alterations often emerge that confer the drug resistance. Patients with ROS1‐rearranged NSCLC who develop crizotinib resistance, especially those acquiring “off‐target” resistance mutations, still lack effective therapeutic options for after crizotinib treatment. Herein, we reported a patient with stage IVb lung adenocarcinoma harboring ROS1 fusion, who acquired a BRAF V600E and lost the ROS1 fusion after progression on crizotinib. It was deduced that the V600E may originate from a subclone with an extremely low fraction that was independent of ROS1 fusion–positive cells. The patient was subsequently treated with dabrafenib and trametinib combination and achieved a partial response lasting for more than 6 months. Our study revealed that BRAF V600E can confer the crizotinib resistance in ROS1 fusion–positive NSCLC and presented the first case showing that the treatment with dabrafenib and trametinib can serve as an effective option for later‐line treatment for this molecular‐defined subgroup. Key Points Patients with ROS1‐rearranged non‐small cell lung cancer (NSCLC) who acquire “off‐target” resistance mutations to crizotinib still lack effective therapeutic options for after crizotinib treatment.This report describes the case of a patient with ROS1‐rearranged NSCLC who acquired a BRAF V600E and lost the ROS1 fusion after crizotinib failure.The case was subsequently treated with dabrafenib and trametinib combination and achieved a partial response lasting for more than 6 months.This is the first article reporting that treatment with dabrafenib and trametinib may serve as an effective option for later‐line treatment for patients harboring resistant BRAF V600E., Rearrangements of the ROS1 gene occur in 1%–2% of non‐small cell lung cancers, characterizing a distinct molecular subgroup. This article reports a case of stage IVb lung cancer in a patient with ROS1 fusion who acquired a BRAF V600E fusion after progression on crizotinib.

This multicenter phase 1b/2 trial aimed to explore the maximum tolerated dose (MTD), activity, and safety of anlotinib plus chemotherapy in patients with T790M-negative epidermal growth factor receptor (EGFR)-mutant advanced nonsquamous non-small cell lung cancer (NSCLC) after resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs).In the phase 1b stage, patients received anlotinib (8/10/12 mg, days 1-14) combined with cisplatin (75 mg/mThe study was prematurely terminated due to slow accrual after 19 patients had been enrolled between January 18, 2019, and March 21, 2021. The MTD of anlotinib was 12 mg. The median PFS was 5.75 (95% confidence interval, 4.37-7.52) months. The objective response rate was 47.4% (95% confidence interval, 24.5%-71.1%). In the 12 mg group, seven (58.3%) patients experienced grade 3-4 treatment-related adverse events, and the most common ones were hypertension (6 [50.0%]), decreased platelet count (2 [16.7%]), and hypertriglyceridemia (1 [8.3%]). No treatment-related deaths occurred.Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs.

ALK-positive histiocytosis is a rare malignancy which was first described in 2008 and recognized as a systemic histiocytic disorder that can affect multiple organs. Less than 20 cases were reported to date, and much fewer cases were presented as disseminated disease, especially with lung and central nervous system (CNS) involvement. The clinical presentation, cytologic and histologic features were diverse in prior reported cases. Diagnosis relied on clinical, pathological findings and might be determined by molecular identification of anaplastic lymphoma kinase (ALK) gene translocation. Exclusion of other tumors such as Erdheim-Chester disease, Langerhans cell histiocytosis (LCH) and histiocytic sarcoma are required. Because of their rarity and diverse features, no standard treatment was applied so far. Here we reported a 51-year-old Asian female patient documented as ALK-positive histiocytosis with lung, intracranial and lymph nodes involvement. Surgery for left frontal tumor resection was performed. Of note was the presence of foam-like histiocytes, epithelioid cells and Touten-like histiocytes scattered in the lesion, emperipolesis also could be observed. Histiocytes were positive immunostaining for CD68/PGM-1, CD163 and ALK1 in cytoplasmic pattern. Fluorescence in situ hybridization (FISH) analysis confirmed ALK gene translocation and next generation sequencing (NGS) revealed KIF5B-ALK fusion. The patient received treatment of second-generation ALK inhibitor-alectinib after diagnosed and showed durable remission. Therefore, our case highlights a new treatment option for this rare entity.

The study was to determine the analgesic effect of ultrasound-guided intercostal nerve block (ICNB) and single-injection erector spinae plane block (ESPB) in comparison with multiple-injection paravertebral block (PVB) after thoracoscopic surgery.Randomized, controlled, double- blinded study.Operating room, postoperative recovery room and ward.Seventy-five patients, aged 18-75 years, ASA I-II and scheduled for elective thoracoscopic partial pulmonary resection surgery were enrolled in the study. Seventy-two patients were left for final analysis.Patients were randomly assigned into the three groups (PVB group, ICNB group or ESPB group). After anesthesia induction, a single anesthesiologist performed PVB at T5-T7 levels or ICNB at T4-T9 levels or ESPB at T5 level under ultrasound guidance using 20 ml of 0.375% ropivacaine. Patients were connected to the patient-controlled morphine analgesia device after surgery.Cumulative morphine consumption at 24 h postoperatively as primary outcome was compared. Visual analog scale pain scores at rest and while coughing at 0, 2, 4, 8, 24 and 48 h postoperatively, cumulative morphine consumption at other observed time and rescue analgesia requirement were also recorded.There was a significant difference in median [interquartile range, IQR] morphine consumption at 24 h postoperatively among the three groups (PVB, 10.5 [9-15] mg; ICNB, 18 [13.5-22.1] mg; ESPB, 22 [15-25.1] mg; p = 0.000). This difference was statistically significant for PVB group vs ESPB group (median difference, -7.5; 95% confidence interval [CI], -12 to -4.5; p = 0.000) and PVB group vs ICNB group (median difference, -6; 95% CI, -9 to -3; p = 0.001), but not for ICNB vs ESPB (median difference, -3; 95% CI, -6 to 1.5; p = 0.192). PVB group had significantly lower VAS scores at rest and while coughing than ESPB group at 0, 2, 4, 8 h postoperatively and than ICNB group at 8 h postoperatively. There was no significant difference in the VAS scores between ICNB group and ESPB group at all time. Median VAS scores at rest and while coughing at all time were low (4) in all groups. More rescue analgesia was needed in ESPB group during 48 postoperative hours (PVB vs ICNB vs ESPB; 13% vs 29% vs 46%; p 0.05).Ultrasound-guided multiple-injection PVB provided superior analgesia to ICNB and single-injection ESPB, while ICNB and single-injection ESPB were equally effective in reducing pain after thoracoscopic surgery.

Objective: To investigate the perioperative anesthetic management of patients diagnosed with renal cell carcinoma (RCC) metastasized into the renal vein or inferior vena cava (IVC) after undergoing radical nephrectomy to provide clinical evidence for rational anesthetic interventions. Methods: A total of 81 patients with RCC extending into the renal vein or IVC, aged 17–73 years, undergoing radical nephrectomy were recruited. Preoperative status, intraoperative management, average operation time, average estimated blood loss, postanesthesia outcomes, and postoperative complications were retrospectively analyzed. Results: The mean operation time was 288 minutes (range 146–825 minutes). The mean estimated blood loss was recorded as 1905 mL (range 200–7000 mL). Among 81 cases, 9 patients (11.1%, 1 level II, 3 level III, and 5 level IV) were switched to undergo cardiopulmonary bypass. Significant hemodynamic fluctuations were observed in 39 patients who presented with level II–IV of tumor thrombus. One patient had pulmonary embolism and died of active cardiopulmonary resuscitation. The mean postoperative hospital stay was 12.8 days. Twenty-five cases with level III–IV tumor thrombus were transferred to the intensive care unit with endotracheal intubation due to massive intraoperative blood loss. The remaining 55 cases were transferred to the postanesthesia care unit 2 hours before being transferred to the ward. One patient had postoperative acute coronary syndrome and was discharged after effective interventions. Conclusion: Anesthetic management and intensive postoperative care play a pivotal role in the success of complete resection of RCC that metastasize into the IVC.

With the continuous development of integrated circuit technology and digital processing technology, this article designed a portable low-power multifunction digital oscilloscope based on STM32F407ZGT6. The input signal can be processed through the signal conditioning circuit, and the ADC module carried by the main control chip STM32 is used to collect external signals, using a 3.5-inch TFT-LCD to display the processed signal waveform. The added touch screen makes the operation more convenient. The software ported the UCOS-II embedded operating system and the graphical support system UCGUI in embedded applications to form a complete real-time operating system. After actual testing, the oscilloscope has the characteristics of high real-time performance, low power consumption, stable and practical performance. And it has strong practical value and promotion value.

Early detection of prostate cancer is critical for the success of cancer therapy. It is believed that the biochemical changes that cause the optical spectra changes would appear earlier than the histological aberration. The aim of this ex vivo study was to evaluate the ability of Stokes Shift Spectra (S3) to identify human prostate cancerous tissues from the normal. Fifteen (15) pairs of with pathologically confirmed human prostate cancerous and normal tissues underwent Stokes Shift Spectra measurements with selective wavelength interval of 40 nm. The spectra were then analyzed using machine learning (ML) algorithms to classify the two types of tissues. The ML algorithms including principal component analysis (PCA) and nonnegative matrix factorization (NMF) were used for dimension reduction and feature detection. The characteristic component spectra were used to identify the key fluorophores related to carcinogenesis. The results show that these key fluorophores within tissue, e.g., tryptophan, collagen, and NADH, have different relative concentrations between cancerous and normal tissues. A multi-class classification was performed using support vector machines (SVMs). A leave-one- out cross validation was used to evaluate the performance of the classification with the gold standard histopathological results as the ground truth. The results with high sensitivity and specificity indicate that the S3 method is effective for detecting changes of fluorophore composition in human prostate tissues due to the development of cancer.

Background: Growing evidences indicate that neuropathic pain is frequently accompanied with cognitive impairments, which aggravate the decrease in the quality of life of chronic pain patients. Furthermore, it has been shown that the activation of Glucagon-like-peptide-1receptor (GLP-1R) improved memory deficit in multiple diseases such as Alzheimer’s disease (AD), stroke and so on. However, whether activating GLP-1R could improve memory impairment induced by neuropathic pain and the mechanism by which this improvement would occur remain unclear. Methods: The spared nerve injury (SNI) model was established as a kind of neuropathic pain. And novel-object recognition memory (hippocampus-dependent memory) was tested by the novel object recognition test (NORT).The expression levels of GLP-1,GLP-1R,adenosine monophosphate-activated protein kinase (AMPK),p-AMPKThr172, nuclear factor κ B p65 (NF-κB p65), interleukin-1β p17(IL-1β p17),and the synaptic associated proteins were tested in the murine hippocampus with memory deficits caused by neuropathic pain. Then, exenatide acetate (Ex-4, a GLP-1R agonist), exendin(9-39)(Ex(9-39),a GLP-1R antagonist) and Compound C dihydrochloride ( CC, an AMPK inhibitor) were used to test the effects of activating GLP-1R in mice with neuropathic pain.Results: First, we uncovered that neuropathic pain could inhibit GLP-1/GLP-R axis, disturb inflammatory signaling pathway, increase the expression of IL-1β and downregulate the synaptic associated proteins (postsynaptic density protein 95(PSD95) and Arc). Subsequently, we reported that Ex-4 treatment could improve recognition memory impairment and increase the ratio of p-AMPKThr172/AMPK, decrease the expression of NF-κB p65 and IL-1β p17, upregulate the levels of PSD95 and Arc. Moreover, we uncovered that Ex(9-39) and CC treatment could abrogate the neuroprotection of Ex-4 in mice with memory impairment induced by neuropathic pain.Conclusions: The results indicated that the activation of GLP-1R could improve recognition memory impairment caused by neuropathic pain via activating AMPK signaling pathway, then, which could inhibit NF-κB activating and its downstream IL-1β expression, upregulate the levels of PSD95 and Arc proteins.

To realize the full benefits of the high brightness and ultra-small beam sizes of NSLS-II, it is essential that the photon beams are exceedingly stable. In the circumstances of implementing local bumps, changing ID gaps, and long term drifting, the fast orbit feedback (FOFB) requires shifting the fast corrector strengths to the slow correctors to prevent the fast corrector saturation and to make the beam orbit stable in the sub-micron level. As the result, a reliable and precise technique of fast-to-slow corrector strength shift has been developed and tested at NSLS-II. This technique is based on the fast corrector response to the slow corrector change when the FOFB is on. In this article, the shift technique is described and the result of proof-of-principle experiment carried out at NSLS-II is presented. The maximum fast corrector current was reduced from greater than 0.45 A to less than 0.04 A with the orbit perturbation within ± 1 μ m.

Objective Heat shock protein 90α (HSP90α) is associated with cancer development, progression, and metastasis. This study assessed the relationships of plasma HSP90α levels with treatment efficacy and prognosis in lung cancer. Methods In this retrospective cross-sectional study, 231 patients with lung cancer were enrolled from 1 September 2016 to 31 December 2019. HSP90α levels were measured before and after treatment, and their relationships with outcomes were assessed. Results Patients with elevated HSP90α levels before treatment had a better overall response rate (ORR, 44.1% vs. 30.6%), whereas the disease control rate did not differ between patients with elevated and normal HSP90α levels (81% vs. 78.5%). Median progression-free survival (PFS) was 6.9 months in patients with elevated baseline HSP90α levels, versus 9 months in patients with normal HSP90α levels, whereas the median overall survival (OS) times in these groups were 12 and 14.1 months, respectively. Concerning HSP90α levels after treatment, ORR (20% vs. 47.1%) and DCR (67.3% vs. 90.9%) were lower in patients with increased HSP90α levels, and PFS and OS were also significantly different between the groups. Conclusions HSP90α levels before and after treatment were associated with treatment response and patient prognosis in lung cancer.

A fast and precise technique of local impedance measurement has been developed and tested at NSLS-II. This technique is based on in-phase sine-wave (AC) excitation of four fast correctors adjacent to the vacuum chamber section, impedance of which is measured. The beam position is measured using synchronous detection. Use of the narrow-band sine-wave signal allows us to improve significantly the accuracy of the orbit bump method. Beam excitation by fast correctors results in elimination of the systematic error caused by hysteresis effect. The systematic error caused by orbit drift is also eliminated because the measured signal is not affected by the orbit motion outside the excitation frequency range. In this article, the measurement technique is described and the result of proof-of-principle experiment carried out at NSLS-II is presented.

We discuss recent work on the construction of a numerical simulation of the fast orbit feedback system at NSLS-II. The simulation operates in the time domain and also includes the spatial domain, i.e. all beam position monitors (BPMs) and correctors. It can accept inputs of the real beam orbit and the measured orbit response matrix. It can also add errors to every stage of the calculation. We present methods to verify the simulation results by comparing the simulation results with experimental data collected at NSLS-II. The results are in very good agreement. The effects of errors from BPMs and correctors, as well as the amplitude of excitation, on the feedback performance, are also explored. This simulation can be used to predict the behavior and performance of the system for a future upgrade.

Pulmonary infections and lung cancer can resemble each other on radiographic images, which makes it difficult to diagnosis accurately and apply an appropriate therapy. Here we report two cases that two postoperative patients with lung adenocarcinoma developed diffuse nodules in bilateral lungs in a month which needed to be distinguished between metastatic malignancies and infectious diseases. Although there are much similarities in disease characteristics of two cases, patient in case one was diagnosed as acute miliary pulmonary tuberculosis (TB) while patient in case two was diagnosed as metastatic disease. The symptoms and pulmonary foci on CT scan of patient in case one improved distinctly after the immediate anti-TB treatment, but the disease of patient in case two progressed after chemotherapy. These findings caution us that differential diagnosis is crucial and have significance in guiding clinical work.

This paper discusses improvements made to the fast orbit feedback (FOFB) system at NSLS-II in 2019. We first characterized the system by measuring the transfer function and the closed-loop gain of the system. We also constructed a model to predict the performance, which was based on physical behaviors. After finding and fixing the sources of the latency, we improved the closed-loop gain’s bandwidth from 250 Hz to 400 Hz in the horizontal plane and 250 Hz to 300 Hz in the vertical plane. The orbit beam instability improved by 30% and 10% in the horizontal and vertical planes, respectively.

To investigate the feasibility to restore functional endometrium using bone marrow mesenchymal stem cells (BMSCs) in the Sprague Dawley (SD[“SD” has been defined as both “Sprague Dawley” and “standard deviation.” Please clarify which one is to be followed.]) rat model for Asherman syndrome (AS). Basic research on treatment of AS utilizing an optimized rat model. University research laboratories. Sprague Dawley rat model in which AS was induced in accordance to an optimized protocol. Bone marrow mesenchymal stem cells were harvested from the rat’s bone marrow and labeled with green fluorescent protein (GFP) in the second passage of BMSCs. The fifth passage of GFP-labeled BMSCs was injected systemically through the tail vein in the optimized AS rat model. We examined the reproliferation of the endometrial lining and the expression of markers for endometrium and endometrial receptivity. The localization of engrafted GFP-labeled BMSCs was determined by a laser scanning confocal microscope and a fluorescence microscope. The number of pregnant rats and implanted embryos in each uterus was recorded to evaluate the function of endometrium. We had demonstrated that in the in vivo experiments on our rat model for AS, the group which received BMSC injection had significantly improved reproductive outcomes—70% of these rats conceived, whereas none of the rats in the control group got pregnant (P

Supplementary_Images_2018 for Bone Marrow Mesenchymal Stem Cells (BMSCs) Restore Functional Endometrium in the Rat Model for Severe Asherman Syndrome by Lufen Gao, Zhongwei Huang, Haiyingjie Lin, Yuke Tian, Ping Li, and Shaoqiang Lin in Reproductive Sciences

We compared the McGrath® Series 5 videolaryngoscope with the Macintosh laryngoscope for double-lumen tracheal tube placement in patients with a predicted good glottic view on assessment of the airway. An initial laryngoscopy was performed using the Macintosh laryngoscope; 96 patients with Cormack and Lehane grade-1 or -2a views were randomly assigned to undergo intubation using either the McGrath or Macintosh device. Compared with the Macintosh laryngoscope, the McGrath videolaryngoscope provided more Cormack and Lehane grade-1 views (47 (97.9%) vs 29 (60.4%), p < 0.05), a longer mean (SD) intubation time (39.6 (10.0) s vs 24.4 (7.3) s, p < 0.05) and a higher incidence of double-lumen tube malposition (6 (12.5%) vs 0, p < 0.05). However, in 18 non-randomised patients with Cormack and Lehane grade ≥ 2b on initial laryngoscopy using the Macintosh, the glottic view was improved on intubation with the McGrath videolaryngoscope, with a total success rate of double-lumen tube placement of 94.4% and mean (SD) intubation time of 50.0 (18.6) s. We recommend that in patients with a low airway risk index score requiring intubation with a double-lumen tracheal tube, the Macintosh laryngoscope is used as the first device and the McGrath videolaryngoscope is used only if this provides a poor glottic view.

Bone cancer pain is a major clinical problem and remains difficult to treat. ATP-sensitive potassium (KATP) channels may be involved in regulating nociceptive transmission at the spinal cord level. We determined the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat model of bone cancer pain. The rat model of bone cancer pain was induced by implanting rat mammary gland carcinoma cells (Walker256) into the tibias. KATP modulators (pinacidil and glibenclamide) or the specific Kir6.2-siRNA were injected via an intrathecal catheter. The mechanical withdrawal threshold of rats was tested using von Frey filaments. The Kir6.2 mRNA and protein levels were measured by quantitative PCR and western blots, respectively. Intrathecal injection of pinacidil, a KATP channel opener, significantly increased the tactile withdrawal threshold of cancer cell-injected rats in a dose-dependent manner. In contrast, intrathecal delivery of glibenclamide, a KATP channel blocker, or the specific Kir6.2-siRNA significantly reduced the tactile withdrawal threshold of cancer cell-injected rats. The mRNA and protein levels of Kir6.2 in the spinal cord of cancer cell-injected rats were significantly lower than those in control rats. Our findings suggest that the KATP channel expression level in the spinal cord is reduced in bone cancer pain. Activation of KATP channels at the spinal level reduces pain hypersensitivity associated with bone cancer pain.

Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. No causative genes have been reported to date. In this study, we investigated a large five-generation Chinese family with DUH. After excluding the two known DUH loci, we performed genome-wide linkage analysis and identified a DUH locus on chromosome 2q33.3-q36.1 with a maximum LOD score of 3.49 with marker D2S2382. Exome sequencing identified a c.1067T>C (p.Leu356Pro) mutation in exon 3 of ABCB6 (ATP-binding cassette subfamily B, member 6) in the DUH family. Two additional missense mutations, c.508A>G (p.Ser170Gly) in exon 1 and c.1736G>A (p.Gly579Glu) in exon 12 of ABCB6, were found in two out of six patients by mutational screening using sporadic DUH patients. Immunohistologic examination in biopsy specimens showed that ABCB6 is expressed in the epidermis and had a diffuse cytoplasmic distribution. Examination of subcellular localization of wild-type ABCB6 in a B16 mouse melanoma cell line revealed that it is localized to the endosome-like compartment and dendrite tips, whereas disease-causing mutations of ABCB6 resulted in its retention in the Golgi apparatus. Our studies identified ABCB6 as the first pathogenic gene associated with DUH. These findings suggest that ABCB6 may be a physiological factor for skin pigmentation.

Background Paravertebral block is often used to provide postoperative analgesia after renal surgery. In this case-series report, we present our experience with 3 patients in whom percutaneous nephrolithotomy was performed successfully under ultrasound-guided 3-segment lumbar-thoracic paravertebral block. Case summary Three patients were scheduled for percutaneous nephrolithotomy. All 3 patients were high-risk cases for both general and neuraxial anesthesia. After due deliberation and with the consent of patient and his family, ultrasound-guided paravertebral block was performed. Seven to 10 mL of 0.5% ropivacaine was injected at T10/T11, T11/T12, and T12/L1 paravertebral place, respectively. Sensory loss to pinprick from T8 to L2 was achieved in all 3 patients 20 min after administration of block. Surgical procedures for all 3 patients were successful, and none of the patients complained of pain during the operation. Conclusions Ultrasound-guided multilevel paravertebral block may be an attractive option for anesthetic management of percutaneous nephrolithotomy in clinical practice.

Introduction: Postoperative delirium is a common mental complication that is often neglected by medical professionals. This survey aimed to determine the current opinions regarding postoperative delirium in anesthetists from Chinese university affiliated hospitals. Methods: A paper-based survey was administrated during an anesthesia forum held in Wuhan, China. A total of 320 copies of the questionnaire were distributed to the attendees from university affiliated hospitals. Results: Two hundred and twenty-five (70.3%) valid responses were collected. Postoperative delirium was regarded as a serious problem by 82.2% of respondents; 70.9% and 64.7%, respectively believed that regular assessment and active intervention should be implemented. However, 36.4% underestimated the incidence of postoperative delirium. Only 7.7% of respondents knew the exact diagnosis criteria according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and less than half were aware that haloperidol could treat delirium. As to assessment practices, 86.1% respondents had never assessed delirium or performed assessments occasionally. Over 60% had never heard of the commonly applied delirium screening instruments. Discussion: An obvious disparity was found between the perceived significance and current practice of postoperative delirium among the population of anesthetists in Chinese university hospitals, suggesting that further education regarding postoperative delirium is required.

Neuropathic pain due to nerve injury is associated with overactivity of spinal N-methyl-D-aspartate (NMDA) receptors and nitric oxide synthases (NOS). Spinal NOS and NMDA receptors could act in a concerted manner to excite each other in nociceptive signaling. Among the 3 major NOS isoforms, neuronal NOS (nNOS) has the most functional relationship with NMDA receptors through a PDZ-PDZ (PSD-95, Dlg, ZO-1 homology) postsynapse interaction. However, some nNOS variants lack the PDZ domain, which may result in the changes in the interaction with the NMDA receptor and subsequent localization and enzymatic activity. The aim of this study was to determine which nNOS variants are expressed in the spinal cord in neuropathic rats and deduce their role in neuropathic pain by testing the effects of these kinds of nNOS on nuclear factor-kappaB (NF-kappaB) activity in PC12 cells. Western blot analysis revealed that there were at least 3 bands of nNOS (155, 135, and 125 kDa) in the spinal cord and, moreover, that nNOS at 135 kDa decreased significantly after development of neuropathic pain. 5'-RACE-PCR and Southern blots determined that the nNOS at 155 and 135 kDa corresponded to nNOSalpha and nNOSbeta, respectively, which was confirmed by RT-PCR. PC12 cells transfected with the nNOSalpha gene had no effect on NF-kappaB activity, but nNOSbeta without the PDZ domain significantly decreased that in PC12 cells. Considering the importance of spinal NF-kappaB signaling in neuropathic rat, it could be concluded that changes in spinal nNOS variants and quantity after peripheral nerve injury implicate nNOS in the generation of neuropathic pain.This article presents data demonstrating that nNOS variants change in the spinal cord of the rats after neuropathic pain and result in differential effects on NF-kappaB activity in PC12 cells. These changes in nNOS variants and their different characteristics may account for the spinal NO paradox role in neuropathic pain. Furthermore, these data suggest that nNOSbeta may represent a new therapeutic target for the treatment of chronic neuropathic pain.

The effects of intracerebroventricular (icv) agonists and antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors on the general anesthesia of propofol were studied. A total of 144 Kunming mice, male and female with body mass of (22±3) g, were used. Part One of the Experiment: a total of 104 Kunming mice, male and female, were randomly divided into 13 groups. Intracerebroventricular artificial cerebral fluid (aCSF) or different doses of NMDA, AMPA, MK-801 or NBQX was injected immediately after intravenously administered propofol 25 mg/kg and the recovery time following the loss of righting reflex (LORR) was recorded. Part Two of the Experiment: a total of 40 Kunming female mice were divided randomly into 5 groups and injected with icv aCSF or NMDA, AMPA, MK-801 or NBQX after intraperitoneally administered propofol 50 mg/kg. The pain threshold of the mice was then investigated by hot-plate test (HPPT). NMDA (0.05 or 0.075μg, icv) or AMPA (0.05 μg, icv) exhibited no effects on the LORR, but NMDA (0.1 μg, icv) or AMPA (0.075 or 0.1 μg, icv) prolonged the LORR significantly compared with the aCSF group (P

Study objective To investigate the effects and optimal concentration of chloroprocaine for epidural analgesia after lower limb orthopedic surgery. Design Prospective, randomized, observational, multicenter clinical study. Setting Operating room, postoperative recovery area, university hospital. Patients One hundred and twenty patients from 4 hospitals were enrolled and randomized into 5 groups after lower limb orthopedic surgery under epidural anesthesia with lidocaine. Interventions Epidural chloroprocaine mixed with 0.4 μ g/mL fentanyl was administered via a patient-controlled analgesia pump at the concentration of 0.6%, 0.8%, 1.0%, 1.2%, or 1.4% after the surgery. Measurements Systolic blood pressure, heart rate, visual analog score at rest and during activity, as well as the Bromage score at 0 minute, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours after the surgery were recorded and compared. Use of morphine and incidence of adverse effects were also recorded. Main results Patients given 1.2% chloroprocaine showed the lowest visual analog score compared with other groups. There was no significant difference in the Bromage score among 5 groups. The Bromage score returned to 0 in 89.7% of the patients 48 hours after surgery. No difference in postoperative morphine usage, blood pressure, or heart rate was found among 5 groups. Conclusions Epidural 1.2% chloroprocaine with 0.4 μ g/mL fentanyl could generate proper analgesic effects with little influence on mobility in patients undergoing lower limb orthopedic surgery. In addition, it could generate a good sense and movement separation, facilitating the early functional training.

To explore the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on the levels of toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), and tumor necrosis factor (TNF-α) in spinal cord tissue of rat model of spinal cord injury (SCI). BMSCs from 4-week-old male SD rats were isolated, cultured, and characterized after three generations using specific surface markers CD34 and CD44. Fifty four SD male rats were divided into sham group, model group, and cell transplantation group (18 rats each group). SCI model was generated using an improved Allen's method. Rats in cell transplantation group were treated with BMSCs in caudal vein. Rats were sacrificed at 24 h, 72 h, and 7 d post-injury, and spinal cord tissues were taken out for detection of IL-1β and TNF-α tissue content by enzyme-linked immunosorbent assay. IL-1β and TNF-α mRNA expression was evaluated by qPCR and TLR4 protein expression was analyzed by Western blotting. IL-1β and TNF-α protein levels, as well as IL-1β, TNF-α mRNA, and TLR4 expression were significantly increased in rats with established SCI, and reached its peak in spinal cord tissues at 72 h after the initial injury (p < 0.01 comparing to sham group). BMSC transplantation resulted in significant decrease in IL-1β and TNF-α tissue content, as well as IL-1β, TNF-α mRNA, and TLR4 expression as compared with model group (p < 0.01). BMSCs may alleviate the damaging effect of spinal cord inflammation by weakening TLR4-mediated signaling pathways and reducing tissue content of IL-1β and TNF-α.

The effect of morphine and naloxone on release of the excitatory amino acids (EAAs) of spinal astrocytes induced by TNF-a was studied. Astrocytes were purified from 2- to 3-day old SD rats and divided into 8 groups: group 1 (without any stimulatants); group 2 (10 ng/ml TNF-alpha); group3 (10 ng/ml TNF-alpha + 0.5 micromol/L morphine); group 4 (10 ng/ml TNF-alpha + 1.0 micromol/L morphine); group 5 (10 ng/ml TNF-alpha + 2. 0 micromol/L morphine); group 6 (10 ng/ml TNF-alpha + 0.5 micromol/L naloxone); group 7 (10 ng/ml TNF-alpha + 1.0 0Lmol/L naloxone); group 8 (10 ng/ml TNF-alpha + 2. 0 micromol/L naloxone). In group 2, 3, 4 and 5, 0, 0.5, 1.0 or 2.0 micromol/L morphine was added to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-alpha respectively, while in group 6, 7 and 8, 0.5, 1.0 or 2.0 micromol/L naloxone was added respectively to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-alpha. After 30 min incubation, high-pressure liquid chromatography (HPLC) was used to measure the levels of EAAs in all cultured cells. The results showed the level of EAAs in group 2 was significant higher than in group 1 (P < 0.01). As compared with group 2, the levels of EAAs in group 3, 4 and 5 were decreased with the difference being significant between group 5 and group 2 (P < 0.01) or between group 4 and group 2 (P < 0.05). The levels of EAAs in group 6, 7 and group 8 was significantly lower than in group 2 (P < 0.05 or P < 0.01). It was concluded that TNF-alpha could promote the release of glutamate and aspartate from astrocytes, and morphine and naloxone might reduce the release of EAAs in cultured spinal astrocytes induced by TNF-alpha.

The analgesic efficacy of parecoxib in postsurgical pain management has been confirmed in minimally invasive surgery. However, little is known about its effects used in combination with opioids and about its potential for opioid-sparing effects in complex operations. This study was performed to investigate the influence of parecoxib on morphine analgesia after gynecological tumor surgery.Eighty patients undergoing gynecological tumor resection were randomized to receive either intravenous parecoxib at a dose of 40 mg (Group P, n = 40) followed by 40 mg every 12 h for 48 h or saline as a control (Group C, n = 40) 30 min before induction of anesthesia, followed by saline at the same time points after the operation. All patients had access to patient-controlled analgesia with intravenous morphine. Patients were assessed with respect to pain score (visual analog scale from 0-10), cumulative morphine requirement, satisfaction score, and side effects at 2, 6, 12, 24, and 48 h after surgery.A total of 79 patients were evaluated. The cumulative dose of morphine administered at each time point was lower in Group P than in Group C (P 0.05), at 2 h (3.81 ± 0.35 versus 4.13 ± 0.45; P = 0.01), 6 h (16.20 ± 1.49 versus 19.60 ± 0.35; P 0.001), 12 h (26.29 ± 2.75 versus 32.49 ± 2.42; P 0.001), 24 h (41.72 ± 2.70 versus 49.97 ± 4.53; P 0.001), and 48 h (60.06 ± 4.00 versus 65.68 ± 3.23; P 0.001). Compared with Group C, Group P had significantly lower visual analog scale scores at rest and with movement, respectively, at 2 h (4.2, P 0.001 and 5.0, P 0.001), 6 h (3.6, P 0.001 and 4.5, P 0.001), 12 h (3.0, P = 0.017 and 4.0, P 0.001), 24 h (2.1, P 0.001 and 3.4, P 0.001), and 48 h (1.8, P 0.001 and 2.6, P 0.001). The satisfaction score was higher in Group P than in Group C (8.6 ± 0.3 versus 6.8 ± 0.7, P 0.001). There were no significant differences in side effects between the two groups (P 0.05).The use of parecoxib with patient-controlled analgesic morphine in postoperative analgesia resulted in comprehensive enhancement of the analgesic efficacy, reducing the opioid requirement and increasing patient satisfaction after gynecological tumor surgery.

Previous studies have indicated that estrogen protects the brain from ischemic damage and regulates K(ATP) channel activity; the present study was designed to address the involvement of K(ATP) channels in the neuroprotective effects of estrogen in focal cerebral ischemia: in experiment 1, K(ATP) mRNA and protein in the cortices of rats were compared among groups of ovariectomized rats (Ovx-1), Sham-operated rats (Sham-1), and ovariectomized rats administered 17β-estradiol (Estr-1). In experiment 2, neurobehavioral scores and infarct volume of rats were evaluated after middle cerebral artery occlusion in ovariectomized rats (Ovx-2), Sham-operated rats (Sham-2), ovariectomized female rats administered 17β-estradiol (Estr-2), and ovariectomized rats administered both 17β-estradiol and stereotactic injections of glibenclamide (Estr+G). Our results showed that the Kir6.2 and SUR1 mRNA and protein levels in the brain cortices of female ovariectomized rats were lower than those in Sham rats. However, the expression levels of Kir6.2 and SUR1 in brain cortices of ovariectomized rats recovered after supplementation with 17β-estradiol. The protective effects of 17β-estradiol were abolished by glibenclamide, a K(ATP) channel blocker. This indicates that estradiol significantly upregulates the expression of K(ATP) channel subunits and channel activity in the brain cortices of ovariectomized rats. This regulation is associated with the neuroprotective effects of estradiol.

The objective of this study is to construct and identify an inducible lentiviral vector containing improved tet-on system and FasL gene and observe its effects on pristane-induced arthritis (PIA). FasL gene was amplified from the spleen of Lewis rats by RT-PCR. The tet-on system was improved with insertion of a chicken chromatin insulator (cHS4) element and an rtTA-dependent, tet-responsive element containing modifications of the tetO sequence (TRE-tight1). Pro-apoptosis effect of the vector pTREFasLcHS4V16 on synovial cells was evaluated by flow cytometer in vitro. Anti-arthritis effects of the vector on PIA after intra-articular injection were observed by clinical evaluation and joint histology. Cytokines in synovial tissue were measured by ELISA. The recombinant inducible lentiviral vector pTREFasLcHS4V16 was successfully constructed. The expression response and the pro-apoptosis effects of the vector were doxycycline dose-dependent. The vector injected intra-articularly attenuated the severity of PIA and decreased the level of cytokines in inflamed joints. pTREFasLcHS4V16 with an improved tet-on system can precisely regulate the expression of FasL gene and apoptosis. Anti-arthritis effects were observed after intra-articular injection of the inducible vector.

The ultrasound-guided transversus abdominis plane block and ilioinguinal-iliohypogastric nerve block have been shown to provide pain relief after abdominal surgery. A combination of the 2 blocks may provide acceptable surgical anesthesia for cesarean delivery. We describe 4 women who had contraindications to neuraxial anesthesia, who underwent cesarean delivery with ultrasound-guided bilateral transversus abdominis plane block combined with ilioinguinal-iliohypogastric nerve block using 40 mL 0.5% ropivacaine. Breakthrough pain during the delivery of the fetus was treated with small doses of IV ketamine and propofol. We suggest that this technique may be an alternative to local anesthesia for cesarean delivery in clinical practice.