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Aims This study aims to determine procedural characteristics, acute success rates, and medium-term outcomes of consecutive patients undergoing His bundle pacing (HBP); and learning curves of experienced electrophysiologists adopting HBP. Methods and results Consecutive HBP patients at three hospitals were recruited. Clinical characteristics, acute procedural details, and medium-term outcomes were extracted from electronic medical records. Two hundred and thirty-three patients [mean age 74.6 ± 10.1 years, 48% female, 68% narrow QRS, 71% normal left ventricular ejection fraction (LVEF), 55.8% atrioventricular block] underwent HBP. Acute procedural success was 81.1% (mean procedural and fluoroscopic times of 105.5 ± 36.5 and 13.8 ± 9.3 min). Broad QRS was associated with lower HBP success (odds ratio 0.39, P = 0.02). Fluoroscopic and procedural times decreased and plateaued after 30–40 cases per operator. Implant HBP threshold was 1.3 ± 0.7 V at 1.0 ± 0.2 ms and R wave was 5.0 ± 3.9 mV. During follow-up, loss of HBP occurred in a further 12.4% and 11.3% of patients experienced a ≥1 V increase in HBP threshold. Five (2.6%) patients required HBP revision for pacing difficulties. About 8.6% of patients had a >50% decrease in R wave but lead revision for sensing issues was not necessary. On an intention to treat basis, 56.7% of patients in whom HBP was attempted had persisting HBP capture and thresholds of Conclusion Physicians adopting HBP should be cognizant of the learning curve and preferentially select non-dependent patients with normal QRS and LVEF, to minimize risk of lead revision. Further rises in HBP threshold may increase battery drain and need for reoperations, important considerations when choosing HBP for cardiac resynchronization therapy.

After total knee arthroplasty, the ability to weight bear symmetrically during the sit-to-stand task provides important information regarding altered movement patterns. Despite this, comprehensive recovery curves and validity data for sit-to-stand weight-bearing symmetry are lacking in the total knee arthroplasty population. Our study aimed to (1) develop recovery curves with reference ranges, (2) identify the correlates of standard and constrained sit-to-stand weight-bearing symmetry, and (3) evaluate their predictive validity with gait speed.We performed a retrospective longitudinal study of 706 patients with primary unilateral total knee arthroplasty. Monthly, for 4 mos after surgery, sit-to-stand weight-bearing symmetry, knee pain, knee range of motion, quadriceps strength, and gait speed were quantified.Standard and constrained sit-to-stand weight-bearing symmetry measures improved nonlinearly over time. Standard sit-to-stand weight-bearing symmetry was most strongly associated with bilateral quadriceps strength, whereas constrained sit-to-stand weight-bearing symmetry was most strongly associated with ipsilateral quadriceps strength. Knee range of motion and contralateral knee pain were additional correlates. Both standard sit-to-stand and constrained sit-to-stand weight-bearing symmetry were independently and nonlinearly associated with gait speed in multivariable models.Our study provided recovery curves and validity data to support routine clinical measurement of sit-to-stand weight-bearing symmetry in total knee arthroplasty. Our results also indicate that constrained sit-to-stand may promote greater use of the operated limb than standard sit-to-stand.

Background To assess the value of peptidoglycan recognition protein 2 (PGLYRP2) in assessing the disease activity and lipid metabolism in patients with systemic lupus erythematosus (SLE). Methods SLE patients with stable disease (n = 15), active lupus nephritis (LN) (n = 15) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (n = 15) admitted to Northern Jiangsu People’s Hospital (Jiangsu, China) in 2019–2020 were recruited. In addition, volunteers with matched age and sex (n = 15) were enrolled as controls. The level of PGLYRP2 in the serum and its expression in peripheral blood mononuclear cells (PBMCs) were measured. The link between PGLYRP2 level and clinical parameters (including lipid profile) was described. Results Serum PGLYRP2 level in SLE cases exceeded that in healthy volunteers (3938.56 ± 576.07 pg/mL), and significantly higher in active LN (5152.93 ± 446.13 pg/mL) and NP-SLE patients (5141.52 ± 579.61 pg/mL). As shown by quantitative real-time PCR results, the expression of PGLYRP2 in PBMCs of SLE patients with active LN and NP-SLE surpassed that in healthy volunteers (P P = 0.000). PGLYRP2 level positively correlated with SLEDAI of SLE patients (r = 0.5783, P P Conclusions Serum PGLYRP2 level significantly increases in SLE patients, and is positively correlated to SLEDAI. Moreover, serum PGLYRP2 level is correlated with renal damage parameters and the abnormal lipid profile of SLE. PGLYRP2 could be used to predict SLE activity, dyslipidemia and cardiovascular disease risks in SLE patients.

Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2 (ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPK kinases, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.

Objectives: The GOG240 trial introduced a doublet chemotherapy with bevacizumab as the new standard of care for first-line (1L) recurrent or metastatic cervical cancer (r/mCC). While this regimen has been shown to prolong survival compared with chemotherapy alone in this advanced population, there is no standard systemic treatment for r/mCC after failure of 1L. The objectives of this study were to characterize the real-world patient characteristics, treatment patterns, and clinical outcomes of patients who initiated second-line (2L) therapy for r/mCC in the US community oncology setting. Methods: This was an observational study of women with r/mCC who initiated 2L systemic therapy within the US Oncology Network (USON) between 2014 and 2019. USON's electronic health record was used to identify eligible patients and abstract data. Overall survival (OS), time to treatment discontinuation (TTD), and time to first subsequent treatment (TFST) were estimated using Kaplan-Meier methods. Results: A total of N=130 patients were identified (mean age: 52.8 years). At initiation of 2L systemic therapy, over 60% of patients had ECOG score of 0 or 1. Cytotoxic monotherapy was the most frequently prescribed regimen (N=60, 46%) in 2L, followed by combination therapies that included platinum doublet chemotherapy, or bevacizumab doublet or triplet combination therapy (N=45, 35%), pembrolizumab monotherapy (N=19, 15%), and bevacizumab monotherapy (N=6, 5%). Majority of patients initiating 2L had prior bevacizumab exposure in 1L (N=81, 62%), mostly as a triplet or doublet combination therapy. Median OS was 9.1 months (95% confidence interval (CI): 7.2-12.2) after initiation of 2L treatment. Median TTD was 2.8 months (95% CI: 2.5, 3.3), and median TFST was 4.9 months (95% CI: 4.2, 5.7). No statistically significant difference in the outcomes were found when stratified by 2L treatments, although sample sizes were small. Conclusions: Diverse treatment patterns were observed in the 2L r/mCC setting. Clinical outcomes in these patients were suboptimal and they did not vary significantly by 2L regimen. Additionally, many patients received combination therapies in 2L after having received similar treatments in 1L, even though there is no evidence to support this practice. These findings demonstrate the unmet medical need for new effective treatment options in this setting.

Understanding the health care system's ability to move patients through the hepatitis C virus (HCV) care cascade from screening to treatment is essential for HCV elimination. This retrospective study describes real-world HCV screening rates and care cascade steps to identify gaps in care for patients with HCV in the United States. Eligible patients were aged ≥18 years as of the measurement year (calendar year between January 1, 2010-December 31, 2016) and were commercial and Medicare Advantage with Part D members in the Optum Research database with continuous health plan enrollment 5 years prior to and during the measurement year. Incident and prevalent screening rates were calculated for each measurement year. Care cascade steps were analyzed via Kaplan-Meier analysis and logistic regression among patients with a positive HCV ribonucleic acid test. Cohorts were selected based on birth year (pre-1945 birth cohort, 1945-1965 birth cohort, post-1965 birth cohort). Among the 1945-1965 birth cohort, incident and prevalent screening rates increased from 1.6% to 4.7% and 10% to 18%, respectively, from 2010 to 2016. The proportion of patients attaining each independent cascade step within 1 year of screening increased significantly over time for genotype testing (

Background To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. Methods In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. Results The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). Conclusions Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. Trial registration NCT01349348. Retrospectively registered May 2011.

In order to meet the requirement of ultrahigh-speed, low latency, and wide bandwidth (BW) in the next 5G mobile network and internet of things (IoT) applications, the parasitic capacitance specification of electrostatic discharge (ESD) protection devices should become much stricter. Reducing the capacitance always degrades the ESD performance in terms of shrinking the size of the ESD protection device. The distributed ESD protection network is one of the solutions which mitigates the capacitance issue and provides a broadband design. However, while the ESD devices are put under the I/O pad in the distributed ESD protection network, back-end-of-line (BEOL) capacitance starts to play an important role in the advanced 28-nm CMOS process. Therefore, a tapered metal structure is proposed to significantly reduce 30% BEOL capacitance of the ESD device, which can gain a 2.8-GHz increase in the operational BW in the distributed network. Meanwhile, it can enhance the human-body-model (HBM) level up to 16% higher than the original layout style under the same front-end-of-line (FEOL) layout size.

Background and aims Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. Methods and results Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. Conclusion NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

Female sex workers (FSWs) have a notably high risk of acquiring human papillomavirus (HPV) infections. Relatively few studies address the type-specific prevalence and incidence of HPV among FSWs in sub-Saharan Africa. FSWs (n = 348) attending the Korogocho clinic in Nairobi, Kenya participated from August 2009 to March 2011. HPV DNA was detected using the SPF10-LiPA25 PCR assay. Baseline prevalence of HPV infection and cervical dysplasia were calculated, stratified by HIV-serostatus. Incidence rate (IR) of infection was calculated as number of new infections from baseline over person-months among 160 HPV-negative participants with complete 12-month follow-up. Baseline HPV prevalence was 23.6% for any HPV and 20.4% for high-risk HPV (hrHPV) types. Most prevalent types were HPV52 (10.1%), HPV35 (2.3%), and HPV51 (2.3%). A quarter (24%) of participants were HIV-positive. HPV prevalence was higher in HIV-positive (32.1%) than HIV-negative (20.8%) participants. hrHPV prevalence was higher in HIV-positive (27.4%) than HIV-negative (18.2%) women. During follow-up, HPV IR was 31.4 (95% CI: 23.8–41.5) for any HPV and 24.2 (95% CI: 17.9–32.8) for hrHPV types. HPV52 had the highest IR (6.0; 95% CI: 6.5–10.3). Overall HPV and hrHPV prevalence were lower than expected, but both prevalence and incidence were higher in HIV-positive than in HIV-negative women.

Background Shoulder function complications are common after treatment for breast cancer. Quite a few survivors still report a limited shoulder range of motion, even though the free range-of-motion upper limb exercise is helpful to restore shoulder function. Mirror therapy (MT) is a classical and effective rehabilitation technique to recover motor and sensory function for the limbs; in addition, studies have reported that MT has an influence on patients with shoulder functional dysfunction including increasing shoulder range of motion, improving shoulder function scores, and decreasing pain scores. Here, we describe a protocol of a randomized controlled trial to explore if free range-of-motion upper limb exercise based on MT has efficacy on shoulder function in survivors after surgery of breast cancer. Methods/design This is a prospective, single-blind, two-arm randomized controlled trial. An estimated 70 participants will be randomly allocated to (1) the MT group or (2) the control group. The participants in the control group receive free range-of-motion upper limb exercise, and participants in the MT group will engage in free range-of-motion upper limb exercise based on MT. The intervention will start on the first day after surgery and be completed at 8 weeks after surgery. The primary outcome in this protocol is shoulder range of motion (ROM), while the Constant-Murley Score (CMS); Disability of the Arm, Shoulder, and Hand Questionnaire (DASH); Tampa Scale of Kinesiophobia (13-item TSK); visual analog scale (VAS); grip strength; arm circumference; and lymphedema are the secondary outcomes. Assessment will be conducted before allocation (baseline) and at 2 weeks, 4 weeks, and 8 weeks after surgery. Discussion Based on the results that MT has an influence on shoulder function immediately after intervention in patients without nerve injury, this randomized controlled trial is to observe the efficacy of MT on shoulder function after a long-term intervention in breast cancer survivors. We look forward to the innovation of this study for both breast cancer rehabilitation and MT. Trial registration Chinese Clinical Trial Registry (ChiCTR) ChiCTR2000033080. Registered on 19 May 2020

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI). Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups. Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.

The aim of this study was to investigate the abnormities in functional connectivity (FC) within each modular network and between modular networks in patients with systemic lupus erythematosus (SLE). Twelve meaningful modular networks were identified via independent component analysis from 41 patients and 40 volunteers. Parametric tests were used to compare the intra- and intermodular FC between the groups. Partial correlation analysis was used to seek the relationships between abnormal FCs and the clinical data. Compared to the controls, SLE patients showed decreased intramodular FC in the anterior default mode network (aDMN), posterior default mode network (pDMN), ventral attention network (VAN), and sensorimotor network (SMN) and increased intramodular FC in the medial visual network (mVN) and left frontoparietal network. In addition, SLE patients showed decreased intermodular FC between the SMN and the lateral visual network (lVN), between the SMN and the VAN, and between the pDMN and the lVN and exhibited increased intermodular FC between the SMN and the salience network (SAN), between the pDMN and the SAN, and between the aDMN and the VAN. Moreover, we found several correlations among the abnormal FCs and the Mini-Mental State Examination in SLE patients. Mild cognitive impairment is compensated by the hyperconnectivity between the aDMN and the VAN, while severe cognitive impairment tends to be compensated by the hyperconnectivity between the SMN and the SAN. The FC value between the SMN and the SAN and between the aDMN and the VAN may serve as neuroimaging markers for monitoring cognitive progression in SLE patients.

Background Herbal and Dietary Supplements (HDS) are capable of causing liver injury, however, the extent of HDS-induced liver injury compared to western medication (WM)-induced liver injury has not been well studied. Methods This was a three-year, retrospective study from 308 centers across Mainland China. 3,877 patients with liver injury due to HDS and 3,796 patients with liver injury due to WM were analyzed. Demographic and clinical characteristics, implicated agents, and severity of liver injury were analyzed using descriptive statistics. Results The HDS group was older (average age 47.65 ± 14.8 years) and had more females (57.92%). The latency to onset of liver injury was greater in the HDS group than in the WM group (41 vs. 35 days, P

The development of new drugs for nonalcoholic steatohepatitis (NASH) is a current focus of research in the management of liver disease. Here we provided an overview of NASH drug pipelines and the challenges faced in conducting phases II and III clinical trials. These challenges include the selection and definition of research populations, rational selection of study end-points, choice of noninvasive diagnostic indicators, accounting for confounding factors and safety assessments. Furthermore, we discussed how to establish guidelines for study design and end-points in complex clinical trials of anti-NASH drugs.

Background Drug-induced liver injury (DILI) is the most common reason for a drug to be withdrawn from the market. Apart from stopping the offending drug, no regimens are available for treating idiosyncratic DILI in clinical practice. Methods We carried out a randomized, double-blind, multidoses, active drug controlled, multicentre phase II trial to assess the safety and efficacy of the study drug, magnesium isoglycyrrhizinate (MgIG), as compared to tiopronin, a standard therapy for DILI in China. The primary outcome was the proportion of alanine aminotransferase (ALT) normalization at week 4 after study drug administration. Logistic regression was used to examine the odds of ALT normalization between low dose (Group A) and high dose (Group B) vs active control (Group C). Results One hundred and seventy-four eligible subjects were randomized and enrolled into three groups: 59 in group A, 56 in group B and 59 in group C. It was shown that group A and group B lowered ALT level even at early stage of study drug administration; when compared with Group C (61.02%), the proportions of ALT normalization at week 4 were significantly greater in Group A (84.75%, P = .0029) and Group B (85.71%, P = .0037) respectively. The results from the univariate logistic model showed that the odds of ALT normalized among subjects in Group A were about 3.6 times greater (OR = 3.55, 95% CI: 1.47-8.57, P = .0049) than subjects in Group C. Similar effect was observed among subjects in Group B (OR = 3.83, 95% CI: 1.54-9.55, P = .0039). Conclusions This trial provided preliminary evidence that MgIG is an effective and safe treatment for patients with acute DILI.

To effectively protect the interface circuit between separated power domains from electrostatic discharge (ESD) damage, a new diode-triggered quad-silicon-controlled rectifier (DTQSCR) is proposed and realized in a 0.18- $ {\mu }\text{m}$ 1.8-V/3.3-V CMOS process. Since the DTQSCR embeds four silicon-controlled rectifier paths and a structure of back-to-back diodes, the silicon area can be efficiently reduced more than 30% as compared to the traditional ESD protection design under the same ESD specification. From the measurement results in silicon chip, an interface circuit (level shifter) with the proposed ESD protection design can successfully sustain a human-body-model of greater than 5.5 kV. The proposed ESD protection device is suitable to protect the interface circuits between different power domains.

Background CMUSE is a rare disease whose diagnosis remains difficult because the lesion is confined to the small bowel. Case presentation Here, we present a case of 43-year-old female patient suffered chronic abdominal pain for 20 years, and finally diagnosed with CMUSE. Capsule endoscopy was performed when general endoscopic investigation failed to find the lesion, but the capsule was stranded in the small intestine. Moreover, capsule retention results in acute intestinal obstruction. Thus, surgery was performed and CMUSE was confirmed. The patient was recovered after partial small intestine resection. Conclusions Capsule retention occurred in nearly 60% of patients with CMUSE. Capsule endoscopy should be avoided when the patient is suspected of CMUSE, especially with severe anemia and radiologic finding in the ileum.

Background Trichomonas vaginalis (TV) is the most common curable sexually transmitted infection (STI) worldwide. Trichomonas vaginalis infection is associated with an increased risk of pelvic inflammatory disease, human immunodeficiency virus transmission, and preterm birth in women. Data on the prevalence and risk factors for TV infection in sub-Saharan African countries remain scarce. Methods A total of 350 Kenyan female sex workers, aged 18 to 50 years, participated in a 2-year longitudinal study of the acquisition of STIs, including TV infection. Every 3 months, cervical and vaginal brush samples were collected for STI testing. At baseline, a sociodemographic and behavior questionnaire was administered. Testing for TV, Chlamydia trachomatis (CT), Neisseria gonorrhoeae, Mycoplasma genitalium, and high-risk human papillomavirus was performed using APTIMA assays. Results The TV baseline prevalence was 9.2% (95% confidence interval [95% CI], 6.3-12.7%) and 2-year cumulative TV incidence was 8.1 per 1000 person months (6.9-9.3). Risk factors for higher TV prevalence at baseline were CT infection (adjusted prevalence ratio [PR], 8.53; 95% CI, 3.35-21.71), human immunodeficiency virus seropositivity (PR, 3.01; 95% CI, 1.45, 6.24) and greater than 4 years of sex work (PR, 2.66; 95% CI, 1.07-6.60). Risk factors for elevated 2-year TV incidence were CT (hazard ratio [HR], 4.28; 95% CI, 1.36-13.50), high-risk human papillomavirus infection (HR, 1.91; 95% CI, 1.06-3.45) and history of smoking (HR, 2.66; 95% CI, 1.24-5.73). Discussion CT infection was positively associated with both prevalent and 2-year incident TV infections.

Background and purpose — Up to 20% of patients are dissatisfied after total knee arthroplasty (TKA), mainly because of pain and restricted physical function. We developed a prediction model for 6-month knee range of motion, knee pain, and walking limitations in patients undergoing TKA surgery. Patients and methods — We performed a prospective cohort study of 4,026 patients who underwent elective, primary TKA between July 2013 and July 2017. Candidate predictors included demographic, clinical, psychosocial, and preoperative outcome measures. The outcomes of interest were (i) knee extension and flexion range of motion, (ii) knee pain rated on a 5-point ordinal scale, and (iii) self-reported maximum walk time at 6 months post TKA. For each outcome, we fitted a multivariable proportional odds regression model with bootstrap internal validation. Results — At 6 months post TKA, around 5% to 20% of patients had a flexion contracture ³ 10°, range of motion

Objective To investigate the response of the infrapatellar fat pad (IFP) to running at different intensities and further explore the underlying mechanisms of these responses under different running-induced loadings. Methods Animals were randomly assigned into the sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. The rats in the LIR, MIR, and HIR groups were subjected to an 8-week treadmill running protocol. In each group, the IFP was examined at the baseline and at the 8th week to perform histomorphology, immunohistochemistry, and mRNA expression analyses. Results Compared with LIR and MIR, HIR for 8 weeks led to a substantial increase in the surface cellularity (1.67 ± 1.15), fibrosis (1.29 ± 0.36), and vascularity (33.31 ± 8.43) of the IFP but did not increase IFP inflammation or M1 macrophage polarization. Low-to-medium-intensity running resulted in unchanged or decreased fibrosis, vascularity, and surface cellularity in the IFP compared to those of the SED group. Furthermore, serum leptin and visfatin levels were significantly lower in the LIR and MIR groups than in the SED group or the HIR group (P < 0.05). Conclusion The effect of running on IFP remodeling was intensity dependent. In contrast to LIR and MIR, HIR increased the fibrosis and vascularity of the IFP. HIR-induced IFP fibrosis was probably due to mechanical stress, rather than pathological proinflammatory M1/M2 polarization.

Background China has more ascertained cases of diabetes than any other country. Much of the care of people with type 2 diabetes (T2DM) in China is managed by GPs and this will increase with the implementation of health care reforms aimed at strengthening China’s primary health care system. Diabetes care requires effective communication between physicians and patients, yet little is known about this area in China. We aimed to explore the experiences of Chinese GPs in communicating with diabetes patients and how this may relate to communication skills training. Methods Focus groups with Chinese GPs were undertaken. Purposive sampling was used to recruit 15 GPs from Guangzhou city in China. All data were audio-recorded and transcribed. A thematic analysis using the Framework Method was applied to code the data and identify themes. Results Seven males and 8 females from 12 general practices attended 4 focus groups with a mean age of 37.6 years and 7.5 years’ work experience. Four major themes were identified: diversity in diabetic patients, communication with patients, patient-doctor relationship, and communication skills training. GPs reported facing a wide variety of diabetes patients in their daily practice. They believed insufficient knowledge and misunderstanding of diabetes was common among patients. They highlighted several challenges in communicating with diabetes patients, such as insufficient consultation time, poor communication regarding blood glucose monitoring and misunderstanding the risk of complications. They used terms such as “blind spot” or “not on the same channel” to describe gaps in their patients’ understanding of diabetes and its management, and cited this as a cause of ineffective patient-doctor communication. Mutual understanding of diabetes was perceived to be an important factor towards building positive patient-doctor relationships. Although GPs believed communication skills training was necessary, they reported rarely received this. Conclusions Chinese GPs reported facing challenges in communicating with diabetes patients. Some of these were perceived as being due to the patients themselves, others were attributed to system constraints, and some were seen as related to a lack of clinician training. The study identified key issues for the development of primary care-based management of diabetes in China, and for developing appropriate communication skills training programs for the primary care workforce.

Objective To perform a meta-analysis comparing the structural progression and clinical symptom outcomes as well as adverse events experienced from intra-articular injections of sprifermin compared to a placebo treatment for patients with knee osteoarthritis (KOA). Method We systematically searched the literature for studies that compared long-term outcomes between sprifermin and placebo injections for KOA treatment. Meta-analysis was performed with RevMan5.3 using an inverse variance approach with fixed or random effects models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results Eight studies were included. Overall, there was significantly less improvement of WOMAC total scores in patients receiving sprifermin, compared with the placebo (mean difference (MD) = 3.23, 95% CI 0.76–5.69; I2 = 0%; P = 0.01). Further, sprifermin injection patients gained more, and lost less, cartilage thickness and volume in total femorotibial joint (cartilage thickness: standardized mean differences (SMD) = 0.55, 95% CI 0.26–0.84; I2 = 78%; P = 0.0002; cartilage volume: SMD = 0.39, 95% CI 0.20–0.58; I2 = 49%; P I2 = 0%; P I2 = 0%; P = 0.004) showed a significant difference between the sprifermin and placebo injections. Moreover, there were no significant differences between sprifermin and the placebo in the risk of treatment-emergent adverse events (OR = 1.05; 95% CI 0.52–2.14; I2 = 48%; P = 0.89). Conclusion The data from the included studies provide strong evidence to determine the effect of intra-articular sprifermin on joint structure in individuals with KOA and show no specific adverse effects. Nevertheless, intra-articular sprifermin did not likely have any positive effect on symptom alleviation.

Background More than 50% cognitive impairment was reported by cancer patients before and after medical treatment. However, there are no effective interventions to manage the cognitive problem in women with breast cancer. This pilot study was designed to evaluate the protective effect of Baduanjin exercise on cognitive function and cancer-related symptoms in women with early-stage breast cancer undergoing chemotherapy. Method A single-blinded, randomized control trial was designed. The trial will recruit 70 patients with early-stage breast cancer scheduled to receive chemotherapy from Shanghai in China. All participants will be randomly assigned to (1:1) the supervised Baduanjin group (5 times/week, 30 min each time) or the wait-list control group for 3 months. The effect of Baduanjin exercise intervention will be evaluated by outcome measures including subjective and objective cognitive function, symptoms (fatigue, depression, and anxiety), and health-related quality of life at pre-intervention (T0), 8 weeks (T1), and 12 weeks (T2). The PCI score in the FACT-Cog as the primary cognitive outcome will be reported descriptively, while effect sizes and 95% confidence intervals (CIs) will be calculated. The collected data will be analyzed by using an intention-to-treat principle and linear mixed-effects modeling. Discussion This is the first randomized clinical trial to investigate whether Baduanjin exercise will have a positive role in improving cognitive function in women with breast cancer receiving chemotherapy. If possible, Baduanjin exercise will be a potential non-pharmacological intervention to manage cognitive dysfunction and promote survivorship care among breast cancer survivors. Trial registration Chinese Clinical Trial Registry (ChiCTR) ChiCTR2000033152. Registered on 22 May 2020

Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals.

Gastric cancer is one of the leading causes of cancer death worldwide. Previous studies demonstrated that activation of STAT3 is crucial for the development and progression of gastric cancer. However, the role of STAT3 in neuronal related gene methylation in gastric cancer has never been explored. In this study, by using DNA methylation microarray, we identified a potential STAT3 target, C11orf87, showing promoter hypomethylation in gastric cancer patients with lower STAT3 activation and AGS gastric cancer cell lines depleted with STAT3 activation. Although C11orf87 methylation is independent of its expression, ectopic expression of a constitutive activated STAT3 mutant upregulated its expression in gastric cancer cell line. Further bisulfite pyrosequencing demonstrated a progressive increase in DNA methylation of this target in patient tissues from gastritis, intestinal metaplasia, to gastric cancer. Intriguingly, patients with higher C11orf87 methylation was associated with better survival. Furthermore, hypermethylation of C11orf87 was also frequently observed in other GI cancers, as compared to their adjacent normal tissues. These results suggested that C11orf87 methylation may serve as a biomarker for diagnosis and prognosis of GI cancers, including gastric cancer. We further postulated that constitutive activation of STAT3 might be able to epigenetically silence C11orf87 as a possible negative feedback mechanism to protect the cells from the overactivation of STAT3. Targeted inhibition of STAT3 may not be appropriate in gastric cancer patients with promoter hypermethylation of C11orf87.

Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear “start point” for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.

Using resting-state functional magnetic resonance imaging and graph theory approaches to investigate the topological characteristics of functional networks and their potential correlations with clinical information in patients with systemic lupus erythematosus (SLE). A total of 41 patients and 35 volunteers were consecutively recruited. Detailed clinical data of all participants were recorded. All participants underwent a resting-state functional magnetic resonance imaging examination. Functional networks were constructed by a Pearson correlation matrix of 116 brain regions. The topological properties were analyzed by graph theory. Parametric tests were used to compare the topological properties between the groups. Partial correlation analysis was used to identify relationships between the abnormal topological properties and the clinical data. The nodal network metrics were abnormal in the SLE patients compared to the controls. Decreased nodal efficiency was identified in the right insula, bilateral putamen, and bilateral Heschl's gyrus in the SLE patients. Decreased degree centrality was also found in the right amygdala and bilateral Heschl's gyrus. In addition, the SLE patients showed decreased network functional connectivity (FC) between several regions, particularly between the basal ganglia and the cerebellum. Moreover, FC values between the right putamen and vermis 6 were positively correlated with Mini-Mental State Examination scores. The nodal efficiency and the degree centrality values in the left Heschl's gyrus were both positively correlated with the course of the disease. The topological structure of the functional network was apparently abnormal in SLE patients. FC values between the right putamen and vermis 6 may serve as a neuroimaging marker for evaluating the progressive cognitive decline in SLE patients. Decreased synergy between the basal ganglia region and the cerebellum in the extrapyramidal system may be one cause of cognitive dysfunction in SLE patients.

On-chip electrostatic discharge (ESD) protection device with large dimension can sustain high-ESD current, but the parasitic capacitance of the ESD protection device will increase the difficulty of impedance matching and degrade the bandwidth for broadband radio frequency (RF) applications. The traditional distributed ESD protection circuit can achieve good impedance matching, but it has a worse ESD robustness because of larger resistance caused by the input inductor. In this paper, a new distributed ESD protection structure with the stacked diodes with embedded silicon-controlled rectifier is proposed to attain good ESD robustness without degrading the RF performance. The proposed ESD protection circuit has been successfully verified in a 40-nm, 2.5-V CMOS process to sustain a human-metal model of 5 kV. The proposed ESD protection circuit is suitable to protect the broadband RF circuits in advanced nanoscale CMOS technology.

OBJECTIVE To evaluate tolvaptan as a novel therapeutic option for Chinese patients with liver cirrhosis-associated ascites in a phase 2 clinical trial. METHODS This randomized, double-blind, placebo-controlled, multicenter trial was conducted in patients with insufficient responses to combination therapies of an oral loop diuretic and an aldosterone antagonist. Reduction in body weight and abdominal circumference, increase in 24-h cumulative urine volume and improvement in serum sodium level from baseline to the end of treatment in the tolvaptan groups (15 mg/day or 30 mg/day orally) were compared with those in the placebo group. Drug safety was also assessed. RESULTS Sixty-two patients were allocated to the placebo group, 56 to the tolvaptan 15-mg group and 63 to the tolvaptan 30-mg group. Their mean changes in body weight were -0.5 ± 1.6 kg, -2.1 ± 2.0 kg and -1.9 ± 2.0 kg, respectively. Body weight reductions in both tolvaptan groups were significantly greater than that in the placebo group (difference -1.6, 95% confidence interval [CI] -2.5 to -0.8, and difference -1.4, 95% CI, -2.2 to -0.7, both P

The RC -based power-rail electrostatic discharge (ESD) clamp with nMOS of large size has been widely utilized to enhance the ESD robustness of CMOS integrated circuits. However, such circuit design that only detects the rising time of ESD pulse may be accidentally triggered in some conditions, such as fast power-ON, hot-plug, and envelope tracking applications. In this paper, a new power-rail ESD clamp circuit with transient and voltage detection function has been proposed and implemented in a 0.18- $\mu \text{m}$ 1.8-V CMOS technology. The measurement results from the silicon chip have demonstrated that the new proposed power-rail ESD clamp circuit with adjustable minimum starting voltage ( ${V}_{\text {starting}}$ ) can achieve good ESD robustness and avoid triggering under fast power-ON condition. In addition, the proposed circuit has a low standby leakage current of 270 nA at 125 °C under normal power-ON condition.

Pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) has not yet been approved by the US Food and Drug Administration. Over the past decade, a large number of clinical studies have explored the safety and efficacy of different drugs in treating nonalcoholic steatohepatitis (NASH), including diet pills, antioxidants, insulin sensitizers, lipid-lowering agents, anti-inflammatory cytokines, cytoprotective agents and intestinal probiotics. Based on the evidence from randomized controlled trials a number of academic groups have developed guidelines for the diagnosis and management of NAFLD and NASH. In this article, we discussed the current situation of NASH pharmacotherapy.

Lenvatinib (LenvimaA Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC. The probabilities and survival rates were obtained from two Phase III trials: the SELECT trial comparing lenvatinib to placebo, and the DECISION trial comparing sorafenib to placebo. A bimonthly cycle length and half-cycle correction were used for a lifetime time horizon. Medical costs and utility data were obtained from RedBook, Healthcare Cost and Utilization Project, and the published literature. All costs were adjusted to US$2015, discounted at 3% annually. Then second-order Monte Carlo simulation with distributions was conducted to obtain the acceptability curve to address the uncertainty around model inputs.In the base case, lenvatinib was the most cost-effective treatment compared to sorafenib (incremental cost-effectiveness ratio [ICER] = $25,275/quality-adjusted life year [QALY]) and placebo (ICER = $40,869). Sorafenib is also cost-effective compared to placebo (ICER = $64,067/QALY). The treatment decisions were found to be sensitive to the treatment costs and the health utility associated with lenvatinib and its side effects. The acceptability curve showed lenvatinib optimal 80% of time at WTP of $100,000/QALY.This study suggests that lenvatinib is the optimally cost-effective treatment for RR-DTC, although both lenvatinib and sorafenib are cost-effective compared to placebo.

Summary Background Rehabilitation is widely advocated and provided as a standard of care for patients with total knee arthroplasty (TKA) but its effects on intermediate- to longer-term physical function is unclear. Also unknown is the relationship between the number of rehabilitation sessions attended and functional outcomes. Methods We conducted a prospective cohort study of 1540 patients who had undergone TKA and were referred for rehabilitation. Physical function was indexed by the Short-Form 36 (SF-36) physical function score at 6 months post-TKA. We used multivariable linear regression to assess the association between rehabilitation attendance and Month-6 physical function. Among patients who attended rehabilitation, multivariable linear regression was used to examine the dose–response association between the number of sessions attended and Month-6 physical function. Results Of the 1540 patients, 68 patients did not attend rehabilitation, 86 patients attended one session, and 1386 patients attended two or more sessions. Adjusted for the propensity to attend rehabilitation, rehabilitation attendance was independently associated with better Month-6 SF-36 physical function (point estimate, 5.0 points; 95% CI, 0.5–9.5; P = 0.028 compared with patients with no rehabilitation). Among patients who attended rehabilitation, attending five sessions was associated with a 3.6-point increase in SF-36 scores (95% CI, 0.8–6.5; P = 0.01) relative to patients who attended one session. Conclusions Rehabilitation attendance post-TKA is associated with an increase in self-report physical function. Among patients who attended rehabilitation, a modest dose–response relationship was observed between the number of sessions and functional outcomes.

Coccidioidomycosis (CM) is a fungal infection endemic in the southwestern United States (US). In California, CM incidence increased more than 213% (from 6.0/100,000 (2014) to 18.8/100,000 (2017)) and continues to increase as rates in the first half of 2018 are double that of 2017 during the same period. This cost-of-illness study provides essential information to be used in health planning and funding as CM infections continue to surge. We used a &ldquo, bottom-up&rdquo, approach to determine lifetime costs of 2017 reported incident CM cases in California. We defined CM natural history and used a societal approach to determine direct and discounted indirect costs using literature, national datasets, and expert interviews. The total lifetime cost burden of CM cases reported in 2017 in California is just under $700 million US dollars, with $429 million in direct costs and $271 million in indirect costs. Per person direct costs were highest for disseminated disease ($1,023,730), while per person direct costs were lowest for uncomplicated CM pneumonia ($22,039). Cost burden varied by county. This is the first study to estimate total costs of CM, demonstrating its huge cost burden for California.

Objective To develop a prediction model for postoperative day 3 mobility limitations in patients undergoing total knee arthroplasty (TKA). Design Prospective cohort study. Setting Inpatients in a tertiary care hospital. Participants A sample of patients (N=2300) who underwent primary TKA in 2016-2017. Interventions Not applicable. Main Outcome Measure Candidate predictors included demographic variables and preoperative clinical and psychosocial measures. The outcome of interest was mobility limitations on post-TKA day 3, and this was determined a priori by an ordinal mobility outcome hierarchy based on the type of the gait aids prescribed and the level of physiotherapist assistance provided. To develop the model, we fitted a multivariable proportional odds regression model with bootstrap internal validation. We used a model approximation approach to create a simplified model that approximated predictions from the full model with 95% accuracy. Results On post-TKA day 3, 11% of patients required both walkers and therapist assistance to ambulate safely. Our prediction model had a concordance index of 0.72 (95% confidence interval, 0.68-0.75) when evaluating these patients. In the simplified model, predictors of greater mobility limitations included older age, greater walking aid support required preoperatively, less preoperative knee flexion range of movement, low-volume surgeon, contralateral knee pain, higher body mass index, non-Chinese race, and greater self-reported walking limitations preoperatively. Conclusion We have developed a prediction model to identify patients who are at risk for mobility limitations in the inpatient setting. When used preoperatively as part of a shared-decision making process, it can potentially influence rehabilitation strategies and facilitate discharge planning.

ObjectiveTo evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database.MethodsWe retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified.ResultsThe analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups.ConclusionsBicyclol is a potential candidate for DILI.

// Ziwei Tu 1, 6 , Qu Chen 1 , Jie Ting Zhang 3 , Xiaohua Jiang 3, 4 , Yunfei Xia 1, 2 , Hsiao Chang Chan 3, 4, 5 1 Department of Radiation Oncology, Sun Yat-sen University, Cancer Center, Guangzhou, Guangdong, China 2 State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Guangzhou, Guangdong, China 3 Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China 4 School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China 5 Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, PR China 6 Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China Correspondence to: Xia Yunfei, email: xiayf@sysucc.org.cn Jiang Xiaohua, email: xjiang@cuhk.edu.hk Hsiao Chang Chan, email: hsiaocchan@cuhk.edu.hk Keywords: CFTR, nasopharyngeal carcinoma, prognosis, metastasis Received: May 26, 2016 Accepted: October 14, 2016 Published: October 19, 2016 ABSTRACT While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage ( p = 0.026), distant metastasis ( p < 0.001) and poor prognosis ( p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor ( p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.

// Kaisheng Liu 1, * , Xiaohu Zhang 1, 3, * , Jie Ting Zhang 1 , Lai Ling Tsang 1 , Xiaohua Jiang 1, 2 , Hsiao Chang Chan 1, 2, 3 1 Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China 2 School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China 3 Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, PR China * These authors contributed equally to this work Correspondence to: Hsiao Chang Chan, email: hsiaocchan@cuhk.edu.hk Xiaohua Jiang, email: xjiang@cuhk.edu.hk Keywords: CFTR, β-catenin, NF-κB, small intestine, inflammation Received: March 29, 2016 Accepted: August 24, 2016 Published: August 31, 2016 ABSTRACT While inflammation with aberrant activation of NF-κB pathway is a hallmark of cystic fibrosis (CF), the molecular mechanisms underlying the link between CFTR defect and activation of NF-κB-mediated pro-inflammatory response remain elusive. Here, we investigated the link between CFTR defect and NF-κB activation in ΔF508 cftr −/− mouse intestine and human intestinal epithelial cell lines. Our results show that the NF-κB/COX-2/PGE 2 pathway is activated whereas the β-catenin pathway is suppressed in CF mouse intestine and CFTR-knockdown cells. Activation of β-catenin pathway by GSK3 inhibitors suppresses CFTR mutation/knockdown-induced NF-κB/COX-2/PGE 2 pathway in ΔF508 mouse intestine and CFTR-knockdown cells. In contrast, suppression of β-catenin signaling induces the nuclear translocation of NF-κB. In addition, CFTR co-localizes and interacts with β-catenin while CFTR mutation disrupts the interaction between NF-κB and β-catenin in mouse intestine. Treatment with proteasome inhibitor MG132 completely reverses the reduced expression of β-catenin in Caco-2 cells. Collectively, these results indicate that CFTR stabilizes β-catenin and prevents its degradation, defect of which results in the activation of NF-κB-mediated inflammatory cascade. The present study has demonstrated a previously unsuspected interaction between CFTR and β-catenin that regulates NF-κB nuclear translocation in mouse intestine. Therefore, our study provides novel insights into the physiological function of CFTR and pathogenesis of CF-related diseases in addition to the NF-κB-mediated intestinal inflammation seen in CF.

In this paper, the wireless sensor network (WSN) with the ZigBee standard is integrated with the flexible arrayed potentiometric sensor, such as flexible arrayed pH sensor and flexible arrayed glucose biosensor that achieve a wireless sensing system. The wireless sensing system is accomplished by the graphical language laboratory virtual instrumentation engineering workbench and the detection signals are displayed in real time in the computer. A potentiometric electrochemical method is used to measure the output signal of potential difference between the silver/silver chloride (Ag/AgCl) reference electrode and the flexible arrayed potentiometric sensor. We provide a wireless sensing system of XBee module, which has the advantages of low cost, easy operation, portable device, high accuracy, real-time monitoring, and rapid detection. According to the experimental results of flexible arrayed pH sensor and flexible arrayed glucose biosensor, the range of pH values from pH 1 to pH 13 has a good average sensitivity of 51.38 mV/pH and a linearity of 0.995, and the range of glucose solution concentration from 100 to 500 mg/dL has a good average sensitivity of 0.179 mV(mg/dL) -1 and a linearity of 0.999. The actual target in this paper is to provide a wireless sensing system for ion sensing and monitoring of human physiological data.

A new power-rail ESD clamp circuit with both timing and voltage-level detection is proposed against false trigger events. A RC stage is used for dv/dt detection and a diode string is used to detect the over-stress voltage level during ESD events. By using fully isolated polysilicon diodes, the standby leakage current of the proposed power-rail ESD clamp can be effectively reduced.

Background: Early quadriceps muscle strength assessment after a total knee arthroplasty (TKA) provides timely information on progress, but little is known about the pain profile and predictive validity associated with common clinical muscle strength tests. This study aimed to, in patients with a recent TKA, examine the associations of isometric and isotonic quadriceps strength with gait speed, accounting for knee pain experienced during testing. Methods: A sample of 76 patients (mean age 68 years; 46 women) with a recent TKA (median, 1.5 months) participated. Quadriceps strength was measured on both limbs using a knee extension machine. Isotonic strength was assessed with a one-repetition maximum test. Isometric strength was measured at 40° and 70° of knee flexion using a custom-built load cell. To allow for valid comparisons between the tests, quadriceps strength symmetry ratios were calculated. Knee pain during testing was measured using an 11-point pain scale. Fast gait speed was measured using the 10-m walk test. Results: Compared with isotonic test, quadriceps strength ratio was higher for the 40° flexion isometric test (P = 0.01), and this difference may be explained by the lower knee pain intensity elicited during the isometric tests (P's

Nowadays the mass incidents have become one of the factors that affect the stability of society. The research on their evolutionary process is of great significance to find out the new theories and methods of public safety. Based on the methods of system dynamics and multi-agent, we establishes a model that apply to the evolutionary mechanism of mass events and puts forward four related subjects that influence mass incidents. The subjects are public, government, media and community. The model can reflect the evolutionary mechanism of mass incidents and provide the theoretical support for emergency management of government.

Background This study aimed to examine the agreement between sexually transmitted infection (STI) screening using self-collected specimens and physician-collected specimens, and to investigate the acceptability of self-collection for screening in an 18-month study of female sex workers in a high-risk, low-resource setting. Methods A total of 350 female sex workers in Nairobi, Kenya, participated in a prospective study from 2009 to 2011. Women self-collected a cervicovaginal specimen. Next, a physician conducted a pelvic examination to obtain a cervical specimen. Physician- and self-collected specimens were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium (MG) using Aptima nucleic acid amplification assays (Hologic). Specimens were collected at 3-month intervals over 18-month follow-up. κ Statistics measured agreement of positivity between self-collection and physician collection. Results Baseline STI prevalence was 2.9% for N. gonorrhoeae, 5.2% for C. trachomatis, 9.2% for T. vaginalis, and 20.1% for MG in self-collected samples, and 2.3%, 3.7%, 7.2%, and 12.9%, respectively, in physician-collected samples. κ Agreement was consistently strong (range, 0.66-1.00) for all STIs over the 18-month study period, except for MG, which had moderate agreement (range, 0.50-0.75). Most participants found self-collection easy (94%) and comfortable (89%) at baseline, with responses becoming modestly more favorable over time. Conclusions Self-collected specimen screening results showed strong agreement to clinical-collected specimens, except for MG, which was consistently detected more commonly in self-collected than in physician-collected specimens. Acceptability of the self-collection procedure was high at baseline and increased modestly over time. In high-risk, low-resource settings, STI screening with self-collected specimens provides a reliable and acceptable alternative to screening with physician-collected specimens.

OBJECTIVE To compare accuracy of detecting high-grade cervical lesions (squamous intraepithelial lesions or greater, HSIL+) by high-risk HPV messenger RNA (hrHPV-RNA) testing between physician- and self-collected specimens, and by conventional cytology. METHODS The present prospective longitudinal study included data collected among female sex workers (FSWs) in Nairobi, Kenya, between December 2, 2009, and February 15, 2013. Participants self-collected cervico-vaginal specimens for hrHPV-RNA testing, and a physician collected cervical specimens for hrHPV-RNA testing and conventional cytology. hrHPV-RNA testing was conducted every 3 months, and conventional cytology every 6 months. RESULTS Overall, 350 FSWs aged 18-50 years participated. hrHPV-RNA prevalence decreased slightly from 29.9% (103/344) at baseline to 24.3% (53/218) at 24 months for physician-collected, and 28.5% (98/344) to 24.3% (53/218) for self-collected specimens. Agreement between the sampling methods appeared to increase over time (baseline κ 0.55, 95% confidence interval [CI] 0.45-0.65; 24 months κ 0.83, 95% CI 0.74-0.91). Among 21 patients with HSIL+ over 24 months, 18 (86%) and 17 (81%) had hrHPV-RNA-positive results at baseline in physician- and self-collected specimens, respectively; and 20 (95%) had baseline hrHPV-RNA-positive results or cytology anomalies. CONCLUSION Overall agreement between physician- and self-collected hrHPV-RNA results was moderate and appeared to increase over time. Baseline physician- and self-collected hrHPV-RNA tests were similarly strong indicators of cumulative HSIL+ over 24 months.