Search

Objective: To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents. Methods: The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors. Results: Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P <0.001; median PFS: 16.0 months vs 3.0 months, P <0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P =0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P =0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P <0.001; median PFS: 20.0 months vs 2.0 months, P <0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor ( HR =3.204, 95% CI 1.068-9.610, P =0.038) for patients with pPCL, while receiving maintenance therapy ( HR =0.075, 95% CI 0.022-0.253, P <0.001) and post-treatment response of VGPR or better ( HR =0.175, 95% CI 0.048-0.638, P =0.008) were independent protective factors for patients with pPCL. Conclusions: In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P <0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P <0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) ( P <0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P <0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P =0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P =0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg ( P <0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d ( P =0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d ( P =0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P <0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR =2.37, 95% CI 1.30-4.30; HR =4.50, 95% CI 2.35-9.01) and OS ( HR =4.20, 95% CI 1.50-11.80; HR =9.53, 95% CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months ( P <0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively ( P =0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached ( P= 0.324 and P= 0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months ( P =0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months ( P =0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

Objective: To explore the effect of the combined effect of noise and heat on occupational hearing loss of workers by using Meta-analysis method. Methods: In August 2020, the Chinese and English literature on the relationship between exposure to noise and heat and occupational hearing loss published from January 2005 to August 2020 by CNKI, China Biomedical Literature Service System, Wanfang Data Knowledge Service Platform, VIP Official Database, Medline and PubMed Databases were searched, using noise, heat or hyperthermia, hearing as keywords. The selected data were analyzed by Stata 12.0 software, and the combined OR (95% CI ) value included in the literature was calculated. Sensitivity analysis was used to explore the source of heterogeneity and analyze publication bias. Results: A total of 14 literatures (14 in Chinese, 0 in English) were included in the analysis, and 38654 subjects were included, including 6411 workers in the noise and heat combined effect group and 32243 workers in the noise alone group. The probability of hearing loss in the noise and heat combined effect group was 1.39 times higher than that in the noise alone group (95% CI : 1.14-1.69). The effect size OR was stable after sensitivity analysis, and there was no publication bias in the included literatures tested by Egger's and Begg's Method ( z =0.38, P =0.702, t =-0.74, P =0.476) . Conclusion: Simultaneous exposure to noise and heat may increase the risk of hearing loss for workers in noisy workplaces.

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P= 0.024) and PFS (28.7 vs. 24.1 months, P= 0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS ( HR =0.644, 95 %CI 0.438-0.947, P= 0.025) and a favorable prognostic factor for PFS ( HR =0.646, 95 %CI 0.457-0.913, P= 0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis ( HR =0.705, 95 %CI 0.497-0.998, P= 0.049), but OS was not affected ( P> 0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P= 0.047), but not OS (63.4 vs.43.1 months, P= 0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P <0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Ultrasounds (US) are one of the most used imaging techniques in medicine for assessing the physiological and pathological state of soft tissue. Apart from therapeutic applications, most of the interaction of the acoustic beams with tissues occur passively and without substantial modification to the physiology of the latter. However, US can also be used to remotely power implantable devices with sensing capabilities. In this study, we propose small-form devices interfaced with functionalized electrochemical electrodes for the detection of pH and lactate levels, powered by ultrasounds and data transmission through a Frequency Shift Keying (FSK) modulation technique. A custom-made piezoelectric transducer is responsible for converting the acoustic waves into electrical voltage at the device with operational levels as low as 0.5 V (power consumption of 10 μW) obtained from implantation distances of 50 mm inside tissue. This conjugated with the high sensitivity of the developed electrochemical sensors allows to detect and transmit local parameter variations below 0.1 pH (4.2 mV) and 1 mM lactate (70 nA). Potential applications include real-time access to intrabody tissue monitoring post-operatively, with the view of assessing proper soft tissue healing or infection detection by bacteria, as well as tissue cancer screening in structures such as the human breast., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effect of autologous stem cell transplantation (auto-HSCT) on treatment remission and survival of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 243 new diagnosed MM patients (age ≤65 years) who had received auto-HSCT were selected, and 176 MM patients (age ≤65 years) who had not received auto-HSCT were selected as the control group to evaluate the effect of auto-HSCT on the remission and survival. To balance the distribution of prognostic factors between auto-HSCT and non-auto-HSCT patients, the propensity score matching technique was used to reduce the bias between groups in a 1∶1 scale, 64 in each group, and correlation analysis was performed. Results: A total of 128 patients (64 cases in each group) were screened by propensity score matching analysis. 64 patients received auto-HSCT after induction therapy. After auto-HSCT, 24 patients (37.5%) obtained sCR, 16 patients (25.0%) obtained CR, 15 patients (23.4%) obtained VGPR, and 9 patients (14.1%) obtained PR. The efficacy of patients with auto-HSCT was significantly better than that of non-auto-HSCT patients ( P =0.032) . Progression-free survival (PFS) and overall survival (OS) were significantly longer in auto-HSCT patients compared with non-auto-HSCT patients[PFS: 42.2 (95% CI 29.9-54.5) months vs 22.4 (95% CI 17.1-27.7) months, P =0.007; OS: 87.6 (95% CI 57.3-117.9) months vs 53.9 (95% CI 36.1-71.7) months, P =0.011]. Multivariate analysis confirmed that auto-HSCT had a favorable effect on OS ( HR =0.448, 95% CI 0.260-0.771, P =0.004) and PFS ( HR =0.446, 95% CI 0.280-0.778, P =0.003) . Conclusion: These results demonstrated that auto-HSCT was a favorable prognostic factor for newly diagnosed MM patients.

Objective: To explore the influence of lateral patellofemoral joint degeneration on the treatment of anteromedial osteoarthritis of knee joint by Oxford medial unicompartmental knee arthroplasty. Methods: The clinical data of 73 patients (73 knees) with knee osteoarthritis underwent unicompartmental knee arthroplasty at Department of Orthopaedic Surgery, Xuanwu Hospital, Capital Medical University from March 2016 to December 2017 were analysed respectively.There were 18 males and 55 females, aged (68.6±7.5) years(range: 53 to 89 years).The lateral patellofemoral joints of patients were evaluated by Ahlback grading system. Patients with Ahlback 0 andⅠ were in the non degenerative group (37 cases), and those with Ahlback Ⅱ and above were in the degenerative group (36 cases). Hospital for special surgery knee score(HSS) and the Western Ontario and McMaster Universities(WOMAC) osteoarthritis index, as well as the condition of kneeling, sit to stand movement, up stair and down stair were recorded. The data before and after operation were compared by paired sample t test, and the data between groups were compared by independent sample t test. χ(2) test was used for counting data. Pearson correlation analysis was used to compare the correlation between ahlback score, HSS and WOMAC osteoarthritis index. Results: The follow-up time was (35.1±6.6) months (range: 25 to 47 months).The knee function of the patients improved significantly after operation.The HSS score increased from 57.7±11.8 preoperative to 81.8±7.8 postoperative ( t= 16.64, P= 0.00) and WOMAC osteoarthritis index decreased from 48.9±13.4 preoperative to 15.6±8.8 postoperative ( t= 20.48, P= 0.00). There was no statistical difference in the change of HSS between the degenerative group and the non-degenerative group before and after surgery(27.5±12.2 vs . 22.5±12.3, t=- 1.65, P= 0.10) as well as the change of WOMAC osteoarthritis index(31.8±14.0 vs . 36.4±13.7, t=- 1.35, P= 0.18), but the lateral patellofemoral joint degeneration was related to inability to complete squats (χ(2)=5.17, P= 0.04) and sitting up (χ(2)=7.22, P= 0.01). Conclusion: The degeneration of lateral patellofemoral joint has no effect on the early functional recovery of patients with anteromedial knee osteoarthritis after Oxford medial unicompartmental knee arthroplasty.

This paper presents the use of tubing to store clinical microdialysis samples for delayed analysis with high temporal resolution, offering an alternative to traditional discrete offline microdialysis sampling. Samples stored in this way were found to be stable for up to 72 days at -80 °C. Examples of how this methodology can be applied to glucose and lactate measurement in a wide range of in vivo monitoring experiments are presented. This paper presents a general model, which allows for an informed choice of tubing parameters for a given storage time and flow rate avoiding high back pressure, which would otherwise cause the microdialysis probe to leak, while maximising temporal resolution.

Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) Ⅰ-Ⅱ, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.

Objective: To investigate the effects of berberine in combination with bortezomib on proliferation and apoptosis of multiple myeloma (MM) cell line. Methods: MM cell line U266 cells were treated with berberine and/or bortezomib. The effects of berberine and/or bortezomib on proliferation of cells were measured by methylthiazolyl tetrazolium bromide (MTT). Flow cytometric Annexin Ⅴ/PI double staining method was used to detect effect of either drug alone or in combination on apoptosis of MM cell line U266. ELISA was used to measure the expression of casepase-3,-8,-9 affected by the two drugs. Western blot was used to detect the expression of the apoptosis-related protein TRADD and FADD. King formula was used to determine if there was a synergistic effect of berberine in combination with bortezomib. Results: ① Both berberine and bortezomib as single agent had dose- and time-dependent effects of proliferation inhibition on U266 cells. Berberine (20 μmol/L) and bortezomib (5 nmol/L) had a synergistic effect of proliferation inhibition (Q value: 1.31-1.65). ② The proportion of early stage apoptosis in both single agent groups and combination group significantly increased compared to control group ( P < 0.05). Berberine and bortezomib had a synergistic effect on cell apoptosis (Q value after 6 h and 12 h were 0.896 and 1.197, respectively). ③ Berberine in combination with bortezomib significantly upregulated expressions of caspase-3, -8 and -9, which were statistically significant ( P <0.05). ④Berberine in combination with bortezomib significantly upregulated expressions of TRADD (0.91±0.01, 0.70±0.01) and FADD (0.98±0.01, 0.98±0.01) compared with control group (both P <0.05). Conclusion: Berberine in combination with bortezomib had synergistic effects on proliferation inhibition and apoptosis, which were mediated by up-regulated levels of TRADD and FADD.

Conventional catheter-based systems used for ambulatory esophageal pH monitoring have been reported to affect patient behavior. As physical activity has been associated with gastroesophageal reflux disease (GERD), there is a risk that abnormal behavior will degrade the value of this diagnostic investigation and consequent management strategies. The aim of this study was to quantify the effect of conventional pH monitoring on behavior and to investigate the temporal association between activity and reflux. A total of 20 patients listed for 24 hours pH monitoring underwent activity monitoring using a lightweight ear-worn accelerometer (e-AR sensor, Imperial College London) 2 days prior to, and during their investigation. PH was measured and recorded using a conventional nasogastric catheter and waist-worn receiver. Daily activity levels, including subject-specific activity intensity quartiles, were calculated and compared. Physical activity was added to the standard pH output to supplement interpretation. Average patient activity levels decreased by 26.5% during pH monitoring (range -4.5 to 51.0%, P = 0.036). High-intensity activity decreased by 24.4% (range -4.0 to 75.6%, P = 0.036), and restful activity increased on average by 34% although this failed to reach statistical significance (-24.0 to 289.2%, P = 0.161). Some patients exhibited consistent associations between bouts of activity and acidic episodes. The results of this study support the previously reported reduction in activity during ambulatory esophageal pH monitoring, with the added reliability of objective data. In the absence of more pervasive pH monitoring systems (e.g. wireless), quantifying activity changes in the setting of activity-induced reflux might guide the physicians' interpretation of patient DeMeester scores resulting in more appropriate management of GERD., (© 2015 International Society for Diseases of the Esophagus.)

In this study we quantified and characterised the return of functional mobility following open tibial fracture using the Hamlyn Mobility Score. A total of 20 patients who had undergone reconstruction following this fracture were reviewed at three-month intervals for one year. An ear-worn movement sensor was used to assess their mobility and gait. The Hamlyn Mobility Score and its constituent kinematic features were calculated longitudinally, allowing analysis of mobility during recovery and between patients with varying grades of fracture. The mean score improved throughout the study period. Patients with more severe fractures recovered at a slower rate; those with a grade I Gustilo-Anderson fracture completing most of their recovery within three months, those with a grade II fracture within six months and those with a grade III fracture within nine months. Analysis of gait showed that the quality of walking continued to improve up to 12 months post-operatively, whereas the capacity to walk, as measured by the six-minute walking test, plateaued after six months. Late complications occurred in two patients, in whom the trajectory of recovery deviated by > 0.5 standard deviations below that of the remaining patients. This is the first objective, longitudinal assessment of functional recovery in patients with an open tibial fracture, providing some clarification of the differences in prognosis and recovery associated with different grades of fracture., (©2015 The British Editorial Society of Bone & Joint Surgery.)

As anode material used in power storage device, lithium ion battery (LIB) for example, ZnO has not been recognized as a promising candidate, although which shows advantages like environmental benign, low cost, and large reservation. Several problems, such as volume expansion, pulverization, and active substance detachment because of the particular lithiation kinetics, which result in very high irreversible capacity and following fading, can account for the present situation. Here in this work, we report the self-assembly of ZnxGe1-xO three-dimensional (3D) micronano structures and achieve enormous improvement on both recyclability and rate performance. After the 100th cycle, the capacity remains ∼690 mAh/g at the rate of 100 and ∼510 mA/g at the rate of 500 mAh/g. The capacity recovered rapidly even the rates alternating repeatedly between 50 mA/g and 3.5A/g. Ex situ observation reveals that substance detachment and nanoparticle agglomeration were avoided, benefiting from the firm 3D space configuration. As the Li(+) insertion, the 3D architectures fracture hierarchically with releasing the volume-expansion produced strain. Stable and smooth Li(+)/electrons path would form in these nanoparticles integrated microfragments, which act as the working unit free of further detachment. These facts demonstrate that ZnO based anode materials are anticipant to be good candidate in LIB device through rational design of advanced mirco-nano structures without introduction of carbon coating.

Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), which are responsible for tumor relapse and metastases. Portal vein tumor thrombus (PVTT) is raised from HCC and strongly correlated to a poor prognosis. However, the mechanism underling the formation of PVTT is largely unknown. Herein, we provide evidence that RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) was progressively upregulated in PVTT and overexpressed RMP appeared to increase T-ICs self-renewal. Moreover, RMP promoted metastases of PVTT cells and HCC cells in vitro and in vivo. Knockdown of RMP attenuated T-ICs self-renewal and reversed epithelial-mesenchymal transition (EMT) in HCC and PVTT cells. The neutralizing assays suggested that interleukin-6 (IL-6) had an indispensable role in RMP regulating metastases and self-renewal of HCC cells. Furthermore, the transcription of IL-6 was verified to be modulated by RMP via interaction with p65 and RPB5, through which expanding the T-IC/cancer stem cell populations, as well as inducing EMT was promoted. These results suggested that RMP may promote PVTT formation by promoting IL-6 transcription. Thus, RMP serves as a potent factor contributed to develop PVTT and a promising therapeutic target for HCC patients.

Objectives: The aim of this paper is to discuss how recent developments in the field of big data may potentially impact the future use of wearable sensor systems in healthcare., Methods: The article draws on the scientific literature to support the opinions presented by the IMIA Wearable Sensors in Healthcare Working Group., Results: The following is discussed: the potential for wearable sensors to generate big data; how complementary technologies, such as a smartphone, will augment the concept of a wearable sensor and alter the nature of the monitoring data created; how standards would enable sharing of data and advance scientific progress. Importantly, attention is drawn to statistical inference problems for which big datasets provide little assistance, or may hinder the identification of a useful solution. Finally, a discussion is presented on risks to privacy and possible negative consequences arising from intensive wearable sensor monitoring., Conclusions: Wearable sensors systems have the potential to generate datasets which are currently beyond our capabilities to easily organize and interpret. In order to successfully utilize wearable sensor data to infer wellbeing, and enable proactive health management, standards and ontologies must be developed which allow for data to be shared between research groups and between commercial systems, promoting the integration of these data into health information systems. However, policy and regulation will be required to ensure that the detailed nature of wearable sensor data is not misused to invade privacies or prejudice against individuals.

Measuring gait asymmetry is an important feature when characterizing functional imbalance between limbs. This could be due to pathologies, such as osteoarthritis, stroke, or associated with the effects of surgeries such as hip arthroplasty. Generally, the study of asymmetry or imbalance has required the use of a gait lab or force plates, which could be expensive and difficult to use in home settings. This work validates the use of a light weight ear sensor (7.4 g) with an instrumented treadmill for 64 subjects (age (60.04 (15.36)) including healthy subjects (14) as well as subjects who had been treated for hip (17), knee-replacement surgery (21) and knee osteoarthritis (12). Subjects performed treadmill walking at several speeds on flat surfaces, inclines and declines. Accelerometer data from the ear sensor were segmented into consecutive steps and temporal features were extracted. The measures of gait cycle time and step-period asymmetry obtained from the ear sensor matched well those of the treadmill for flat surfaces, inclines and declines. The key implication of the study is that the proposed method could replace expensive equipment for monitoring temporal gait features in clinics as well as free-living environments, which is important for monitoring rehabilitation after surgery and the progress of diseases affecting limb imbalance.

Based on the requirements for studying the dynamic process of proteinase action substrates in life science, we selected six random proteins including 1L-10, SCGB2A2, CENPQ, GST, HK1, KLHL7, as well as five different concentrations of 1L-10 proteins of 1 mg/ml, 0.5 mg/ml, 0.25 mg/ml, 0.125 mg/ml, and 0.0625 mg/ml, and fabricated two types of substrate protein microarrays, respectively. We detected the dynamic processes of proteins degraded by proteinase K using oblique-incidence reflectivity difference (OIRD) method in a label-free and real-time manner. We obtained the relevant degradation velocities and the degradation time. The experimental results demonstrate that OIRD has the ability to study proteinase action substrates which is out of reach of label methods and is expected to offer opportunities to determine protease-substrate relationships on the systems biology level.

The feasibility of robotic surgery has been extensively explored over the past decade with a more recent shift towards defining focused clinical applications for which quantifiable patient benefits can be directly attributed to its use. The aim of this article is to review the current literature on the use of daVinci robotic surgery for the management of rectal cancer and identify the potential benefits, if any, that robotic-assisted total mesorectal excision (RTME) may provide over the current conventional approach. A comprehensive search strategy was used to identify relevant evidence in order to explore the oncological, operative and functional outcome measures for the RTME in addition to quantifying the level of evidence which describes the clinical effectiveness of the daVinci robot in oncological surgery. Both robotic assisted techniques and the primary outcomes are discussed. In total, 23 studies were reviewed across 11 institutions, including one pilot randomised control trial. When data repetition is disregarded, a total of 452 robotic assisted laparoscopic anterior resections and 60 robotic-assisted laparoscopic abdomino-perineal excision of the rectum have been published since the introduction of the daVinci into clinical practice. Feasibility of the daVinci robotic assisted total mesorectal excision is demonstrated, with comparable oncological outcomes presented for rectal cancer excision. A demonstration of a reduced open conversion rate as well as of reduced hospital stay with the use of the robot is highlighted, although further trials are required to confirm both these findings. No functional benefit in using the daVinci could be confirmed due to the lack of focused trials in this area.

Background: It is well established that disorientation during laparoscopic operations such as cholecystectomy is associated with increased morbidity and mortality. The aim of the present study was to evaluate whether high-performance orientation strategies could be taught to a cohort without relevant experience of laparoscopic cholecystectomy, resulting in improved performance and spatial awareness, thereby reducing the need for operative experience to command this skill., Methods: Thirty medical students participated in a randomized controlled trial, with half randomized to a tutorial teaching orientation strategies at specific stages of laparoscopic cholecystectomy and half to a control group without any teaching. Attention as represented by gaze was captured using eye tracking as subjects were presented with 12 images of various stages of the operation, with the task of interpreting the orientation of the image. The primary outcome measure was subject performance in orientation. Secondary outcome measures were gaze dwell time on relevant anatomical structures within the images and comparison of individual behaviour using a visual behaviour profiling algorithm., Results: The intervention group was significantly more likely to orientate correctly than the control group (mean 75·6 versus 56·1 per cent; P = 0·019). A difference in visual attention behaviour between the two groups was apparent for the majority of images when examining the output of the visual profiling algorithm, in the form of increased homogeneity of visual behaviour and/or an overall difference in orientation strategy. The mean orientation rate of all surgeons under identical conditions in a previously published study was 78·6 per cent., Conclusion: Training novices in orientation strategies improved their performance significantly and it could reach the level of a surgeon with several years of experience in laparoscopic surgery., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Estrogen plays an important role in bone metabolism and only high dose can stimulate osteoblast bone formation. However, the underlying mechanisms have not been elucidated. The epithelial sodium channel (ENaC) is a key pathway for sodium transport in epithelia, vascular endothelium, and other tissues; although the expressions of α and γ ENaC mRNA were found in osteoblasts, the regulation of ENaC by estrogen in osteoblasts has not been studied. Our recent data confirmed the ENaC expression in mouse primary osteoblasts by immunocytofluorescence, RT-PCR, western blot, and patch clamp. Furthermore, we found estrogen (10(-5)M) increased the expression of α and γ ENaC subunits at both the mRNA and protein levels in osteoblasts. On the other hand, 17β estradiol (20 nM) increased inward Na+ currents which were inhibited by amiloride. The estrogen dose used in patch clamp is much lower than those of mRNA and protein analysis, which means single cell ENaC electrophoretic mobility is much more sensitive to estrogen than the mRNA and protein production by estrogen stimulation. Our results suggest that estrogen regulates expression and function of ENaC in osteoblasts may provide a new clue that the mechanism of high dose of estrogen influence osteoblast bone formation via ENaC activity.

The introduction of surgical robotics to the field of surgical oncology brings with it an expectation not only of improved vision, instrumentation, and precision but also as a result, a potential for improved oncological outcomes. The current interest in the field of oesophagogastric oncology is explored in this review together with the benefits, real and potential, that robotic assistance offers surgical cancer resection as well as some of the limiting factors which may be hampering its uptake into current surgical practice. A systematic review of all the published literature up until April 2010 was examined across the field of esophageal and gastric cancer resection. A quantitative assessment of the oncological, operative, and functional outcomes was determined from each procedure. The level of evidence behind the results was determined using the Oxford Centre for Evidence-based Medicine Levels of Evidence; Therapy and Prevention. Three hundred and five cases from 19 independent studies were included for review. Nine studies explored the outcomes from robotic-assisted esophagectomy and eight, the robotic-assisted gastrectomy. Two articles included small case series of both procedures. The level of evidence was predominantly based on case series or expert opinion (Level 4 or 5) with only three unmatched or poorly matched comparative trials (Level 4) with no randomized trials evident. Improved operative outcomes and hospital stays were demonstrated with a reduction of 2 days when the robotic-assisted gastrectomy technique was employed compared with the open. No improvement in oncological outcomes could be identified with the use of the robot for either oesophageal or gastric cancer resection; however, in terms of short-term oncological outcomes, these were at least equivalent to the open approach for oesophageal cancer and early stage gastric cancer. Robotic-assisted laparoscopic surgery is a feasible technique to use to perform a safe and oncologically sound resection for oesophageal and early gastric cancer. Operative benefits appear to be encouragingly similar to the laparoscopic approach with some demonstration of improvement over the open technique despite a prolonged operative time. However, the level of evidence is suboptimal and more randomized controlled trials and long-term survival studies within a framework of measured and comparable outcomes is required., (© 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Aim of the Study: Proteomic approach was applied to identify differential protein expressed in brain of rats with type 1 diabetes mellitus (T1DM) in order to search for potential biomarkers for pathological changes of brain with T1DM., Methods: Proteins were extracted from brain tissues of T1DM rats and healthy control rats, separated by 2-DE and identified by MALDI-TOF-MS. The results were validated by Western blot analysis and immunohistochemistry (IHC)., Results: A total of 8 proteins from the 24 differentially expressed spots were identified by MALDI-TOF-MS. The proteins identified were vitamin D-dependent calcium-binding protein, creatine kinase B-type (B-CK), myosin light chain kinase (MLCK), HSP60 and HSP71, ATP synthase, cyclin-G, pantothenate kinase-1 (PANK1), respectively. 3 proteins were up-regulated and 5 proteins were down-regulated from the T1DM rats. Of the 8 proteins identified, MLCK was confirmed by Western blot and IHC., Conclusion: This work demonstrates that a comprehensive strategy of proteomic identification should be a useful tool for understanding of diabetic encephalopathy mechanism. And the differential proteins such as MLCK may be give clues about the pathogenesis of diabetic encephalopathy., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

This study examined the validity of 2 kinematic systems for estimating force and power during squat jumps. 12 weight-trained males each performed single repetition squat jumps with a 20-kg, 40-kg, 60-kg and 80-kg load on a Kistler portable force plate. A commercial linear position transducer (Gymaware [GYM]) and accelerometer (Myotest® [MYO]) were attached to the bar to assess concentric peak force (PF) and peak power (PP). Across all loads tested, the GYM and MYO estimates of PF and PP were moderately to strongly correlated ( P≤0.05-0.001) with the force plate measurements ( R=0.59-0.87 and R=0.66-0.97), respectively. The mean PF and PP values were not significantly different between the 2 kinematic systems and the force plate, but the estimates did produce some systematic bias and relatively large random errors, especially with the 20-kg load (PF bias >170 N, PF error >335 N, PP bias >400 W, PP error >878 W). Some proportional bias was also identified. In summary, the estimation of PF and PP by a linear position transducer and accelerometer showed moderate to strong relative validity and equivalent absolute validity, but these estimates are limited by the presence of bias and large random errors., (© Georg Thieme Verlag KG Stuttgart · New York.)

The fourth Euro-NOTES workshop took place in September 2010 and focused on enabling intensive scientific dialogue and interaction between participants to discuss the state of the practice and development of natural-orifice transluminal endoscopic surgery (NOTES) in Europe. Five working groups were formed, consisting of participants with varying scientific and medical backgrounds. Each group was assigned to an important topic: the correct strategy for dealing with bacterial contamination and related complications, the question of the ideal entry point and secure closure, interdisciplinary collaboration and indications, robotics and platforms, and matters related to training and education. This review summarizes consensus statements of the working groups to give an overview of what has been achieved so far and what might be relevant for research related to NOTES in the near future., (© Georg Thieme Verlag KG Stuttgart · New York.)

We report a novel Al(2)O(3) nanoparticle-decorated tubular SiC nanostructure, which shows a remarkable enhanced field emission property with low turn-on and threshold field. The formation of Al(2)O(3) nanoparticle-decorated tubular SiC on Si substrates is achieved in one-step via simple heating evaporation process for the first time. The nanostructure consists of tubular SiC and the Al(2)O(3) nanoparticles, which homogeneously decorate on the surface of the tubular SiC with an average diameter of 7.8 nm and narrow diameter distribution. Moreover, compared with the same density and sized bare tubular SiC, the Al(2)O(3) nanoparticle-decorated tubular SiC nanostructure has an obvious reduction in turn-on (from 8.8 to 2.4 V μm(-1)) and threshold field (from 23.5 to 5.37 V μm(-1)). The very low turn-on and threshold field is also comparable to that of carbon nanotubes, which indicates the Al(2)O(3) nanoparticle-decorated tubular SiC is of huge potential application in future field emission display devices.

Background and Study Aims: Narrow-band imaging (NBI) is a new imaging methodology for improving the detection rate of gastrointestinal lesions. We aimed to evaluate perception of images by NBI and corresponding standard white-light-endoscopy (WLE) using a computer-guided eye-tracking system., Methods: A total of 23 NBI images of various lesions with the 23 corresponding WLE images were assessed in random order by 18 subjects with various endoscopy experience. Before evaluation, a teaching set of three NBI and corresponding WLE images was shown to highlight the characteristics of lesions. An eye-tracking system (Tobii X series with integrated 17-inch monitor) was used to record the eye movements of the subjects while they examined respective images. The following parameters were measured: total time spent on image, time until first fixation of lesion, total number of fixations per image and per lesion, and number of fixations until finding the lesion., Results: In total, 828 experiments were conducted. Lesions could not be detected in 6.5 % (NBI) and 4.1 % (WLE) of images ( P = NS). The total number of fixations and total time spent on respective figures as a whole were significantly greater for NBI images compared with WLE images ( P < 0.003). However, the number of fixations until the lesion was found, the number of fixations on the lesion, and the time until first fixation of the lesion did not differ between the two image groups ( P > 0.1)., Conclusion: This is the first study using eye tracking to evaluate image perception in gastrointestinal endoscopy. Significant differences in the interpretation of NBI and WLE images were observed, which may be relevant for the detection and characterization of lesions during endoscopy., ((c) Georg Thieme Verlag KG Stuttgart . New York.)

Functional near infrared spectroscopy (fNIRS) is a rapidly developing neuroimaging modality for exploring cortical brain behaviour. Despite recent advances, the quality of fNIRS experimentation may be compromised in several ways: firstly, by altering the optical properties of the tissues encountered in the path of light; secondly, through adulteration of the recovered biological signals (noise) and finally, by modulating neural activity. Currently, there is no systematic way to guide the researcher regarding these factors when planning fNIRS studies. Conclusions extracted from fNIRS data will only be robust if appropriate methodology and analysis in accordance with the research question under investigation are employed. In order to address these issues and facilitate the quality control process, a taxonomy of factors influencing fNIRS data have been established. For each factor, a detailed description is provided and previous solutions are reviewed. Finally, a series of evidence-based recommendations are made with the aim of improving consistency and quality of fNIRS research.

Large scale single-crystalline tubular beta-SiC was prepared via a simple thermal evaporation method without any template and catalyst, and the nanostructure showed excellent field emission properties.

Human right coronary artery (RCA) haemodynamics is investigated using computational fluid dynamics (CFD) based on subject-specific information from magnetic resonance (MR) acquisitions. The dynamically varying vascular geometry is reconstructed from MR images, incorporated in CFD in conjunction with pulsatile flow conditions obtained from MR velocity mapping performed on the same subject. The effects of dynamic vessel motion on instantaneous and cycle-averaged haemodynamic parameters, such as wall shear stress (WSS), time-averaged WSS (TAWSS) and oscillatory shear index (OSI), are examined by comparing an RCA model with a time-varying geometry and those with a static geometry, corresponding to nine different time-points in the cardiac cycle. The results show that the TAWSS is similar for the dynamic and static wall models, both qualitatively and quantitatively (correlation coefficient 0.89-0.95). Conversely, the OSI shows much poorer correlations (correlation coefficient 0.38-0.60), with the best correspondence being observed with the static models constructed from images acquired in late diastole (at t = 0 and 800 ms, the cardiac cycle is 900 ms). These findings suggest that neglecting dynamic motion of the RCA is acceptable if TAWSS is the primary focus but may result in underestimation of haemodynamic parameters related to the oscillatory nature of the blood flow.

Aim: To determine whether experience improves the consistency of visual search behaviour in fracture identification in plain radiographs, and the effect of specialization., Material and Methods: Twenty-five observers consisting of consultant radiologists, consultant orthopaedic surgeons, orthopaedic specialist registrars, orthopaedic senior house officers, and accident and emergency senior house officers examined 33 skeletal radiographs (shoulder, hand, and knee). Eye movement data were collected using a Tobii 1750 eye tracker with levels of diagnostic confidence collected simultaneously. Kullback-Leibler (KL) divergence and Gaussian mixture model fitting of fixation distance-to-fracture were used to calculate the consistency and the relationship between discovery and reflective visual search phases among different observer groups., Results: Total time spent studying the radiograph was not significantly different between the groups. However, the expert groups had a higher number of true positives (p<0.001) with less dwell time on the fracture site (p<0.001) and smaller KL distance (r=0.062, p<0.001) between trials. The Gaussian mixture model revealed smaller mean squared error in the expert groups in hand radiographs (r=0.162, p=0.07); however, the reverse was true in shoulder radiographs (r=-0.287, p<0.001). The relative duration of the reflective phase decreases as the confidence level increased (r=0.266, p=0.074)., Conclusions: Expert search behaviour exhibited higher accuracy and consistency whilst using less time fixating on fracture sites. This strategy conforms to the discovery and reflective phases of the global-focal model, where the reflective search may be implicated in the cross-referencing and conspicuity of the target, as well as the level of decision-making process involved. The effect of specialization appears to change the search strategy more than the effect of the length of training.

High-sensitivity and visible-blind ultraviolet (UV) photoconductive detectors based on SrTiO(3) single crystal with interdigitated electrodes are reported. The responsivities of photovoltage and photocurrent can reach 2.13x10(5) V/W and 213 mA/W, respectively, at 330 nm at ambient temperature, and the corresponding quantum efficiency eta reaches 80.2%. The dark current is lower than 50 pA at 10 V bias, and the UV/visible contrast ratio is about four orders of magnitude with a sharp cutoff at 390 nm. The experimental results demonstrate that SrTiO(3) single crystal has potentially wide applications in UV detection.

Patients going home following major surgery are susceptible to complications such as wound infection, abscess formation, malnutrition, poor analgesia, and depression, all of which can develop after the fifth postoperative day and slow recovery. Although current hospital recovery monitoring systems are effective during perioperative and early postoperative periods, they cannot be used when the patient is at home. Measuring and quantifying home recovery is currently a subjective and labor-intensive process. This case report highlights the development and piloting of a wireless body sensor network to monitor postoperative recovery at home in patients undergoing abdominal surgery. The device consists of wearable sensors (vital signs, motion) combined with miniaturized computers wirelessly linked to each other, thus allowing continuous monitoring of patients in a pervasive (unobtrusive) manner in any environment. Initial pilot work with results in both the simulated (with volunteers) and the real home environment (with patients) is presented.

Positron emission tomography, cardiovascular magnetic resonance and multislice computed tomography have contributed to changing our pathophysiological understanding of many conditions. Clinically, they have provided new tools for the identification of preclinical disease and a better understanding of how disease progresses. The application of these imaging modalities to preclinical disease and the use of these techniques in patients with overt cardiovascular disease are reviewed.