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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.

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.

Objectives This study aimed to explore the expression profile of the Forkhead box protein L2 gene ( FOXL2) and to determine its prognostic value and associated epigenetic and genetic alterations in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods Data for a subset of patients with LSCC (N = 116) were extracted from the head and neck squamous cell carcinoma dataset of The Cancer Genome Atlas and analyzed in relation to FOXL2 expression and survival. Results Aberrant FOXL2 expression was an independent prognostic factor for progression-free survival (PFS) (hazard ratio (HR): 2.63, 95% confidence interval (CI): 1.34–5.18) and overall survival (OS) (HR: 2.39, 95%CI: 1.28–4.46). Two gene-body CpG sites (cg10554436 and cg23637494) were moderately and positively correlated with FOXL2 expression. DNA amplification (+2/+1) was common (82/115, 71%) in LSCC, and FOXL2 expression was significantly upregulated in the high-amplification group (+2) compared with copy-neutral (0) cases. Conclusion Aberrant FOXL2 expression may be a novel prognostic biomarker for PFS and OS among patients with LSCC. FOXL2 upregulation may be related to gene-body hypermethylation and DNA amplification.

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.

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.

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.

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.

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.

Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model.Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo.Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1βand IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group.Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.

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.

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.

Our previous study suggested that early dantrolene treatment reduced amyloid plaque burden and nearly abolished learning and memory loss in a triple transgenic Alzheimer's disease (3xTg-AD) mouse model. In this study, we investigated the long term treatment of dantrolene on amyloid and tau neuropathology, brain volume and cognitive function in aged 3xTg-AD mice. Fifteen month old 3xTg-AD mice and wild type controls were treated with oral dantrolene (5 mg/kg) or vehicle control twice a week for 6 months. Learning and memory were examined using the Morris Water Maze at 21 and again at 22 months of age. After the behavioral testing, hippocampal and cortical brain volumes were calculated with magnetic resonance imaging and motor function was evaluated using the rotorod. The amyloid burden and tau neurofibrillary tangles in the hippocampus were determined using immunohistochemistry. We found that dantrolene significantly decreased the intraneuronal amyloid accumulation by as much as 76% compared to its corresponding vehicle control, together with a trend to reduce phosphorylated tau in the hippocampus. No significant differences could be detected in hippocampal or cortical brain volume, motor function or cognition among all experimental groups, indicating that the mice were still pre-symptomatic for Alzheimer's disease. Thus, pre-symptomatic and long term dantrolene treatment significantly decreased the intraneuronal amyloid burden in aged 3xTg-AD mice prior to significant changes in brain volume, or cognition.