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1.
Artigo em Inglês | MEDLINE | ID: mdl-33532866

RESUMO

PURPOSE: We investigated the impact of infusion duration (30 and 60 min) on the pharmacokinetic profile of ramucirumab using a population pharmacokinetic (PopPK) modeling approach. We also assessed the relationship between infusion rate and incidence of immediate infusion-related reactions (IRRs; occurring on the day of administration) using ramucirumab phase II/III study data. METHODS: The impact of different infusion durations (30 vs. 60 min) on the time-course of ramucirumab concentration profiles were evaluated using a PopPK model, established using ramucirumab pharmacokinetic data from 2522 patients. Logistic regression was used to evaluate the association between ramucirumab infusion rate and incidence of immediate IRRs in clinical trials. RESULTS: Ramucirumab time-course concentration profiles were equivalent following a 30- or 60-min infusion. In the pooled clinical study dataset, 254 of 3216 (7.9%) patients receiving ramucirumab experienced at least one immediate IRR (any grade). When grouped according to infusion rate quartile, the incidence of immediate IRRs (any grade or grade ≥ 3) was similar across quartiles; findings were confirmed in sensitivity analyses. The risk of immediate IRRs was not found to be associated with infusion rate based on multivariate logistic analysis. CONCLUSION: Shortening the infusion duration of ramucirumab from 60 to 30 min has no impact on ramucirumab exposure. Analysis of trial data found no relationship between an increased risk of immediate IRRs and a faster infusion rate. Such a change in infusion duration is unlikely to affect the clinical efficacy or overall safety profile of ramucirumab.

2.
Scand J Gastroenterol ; : 1-9, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535004

RESUMO

OBJECTIVE: Obesity and sarcopenia are known to be closely related to nonalcoholic fatty liver disease (NAFLD). We attempted to explore the combined influence of fat and muscle tissue on NAFLD by using visceral fat area to appendicular muscle mass ratio (VAR) as a novel parameter. MATERIAL AND METHODS: In this cross-sectional study, a total of 3255 adults (1399 men and 1856 women) coming for a health examination were enrolled. NAFLD was diagnosed using ultrasound and VAR was measured by bioelectrical impedance analyzer. RESULTS: The prevalence of NAFLD was 46.5% in men and 26.6% in women. VAR differed significantly between subjects with and without NAFLD (4.27 vs. 3.26 in men, 7.89 vs. 5.01 in women, respectively, p < .001). Logistic regression analysis determined VAR as a risk factor for NAFLD, and the multivariable-adjusted odds ratios in the highest VAR quartile was 9.57 (95%CI: 5.98-15.30) for men and 12.37 (95%CI: 6.37-24.05) for women. From the receiver operating characteristic analysis, the area under the curve was 0.767 and 0.834, with the suitable cut-off VAR value of 3.469 and 6.357 for men and women, respectively. To control the influence of obesity, all subjects were stratified according to their BMI. For each BMI group, individuals with VAR above the cut-off value had significant higher prevalence and risk of NAFLD, with odds ratios ranging from 1.76 to 4.75. CONCLUSIONS: Increased VAR is strongly associated with higher risk of NAFLD in both sexes independent of obesity and can serve as a screening reference for NAFLD.

3.
J Immunol Res ; 2021: 4634505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575360

RESUMO

Background: Currently, both clavicular bacterial osteomyelitis (BO) and nonbacterial osteitis (NBO) remain not well understood owing to their much lower incidences. This study is aimed at summarizing similarities and differences between clavicular BO and NBO based on comparisons of literature-reported cases. Methods: We searched the PubMed and Embase databases to identify English published literature between January 1st, 1980, and December 31st, 2018. Inclusion criteria were studies evaluating clinical features, diagnosis, and treatment of clavicular BO and NBO, with eligible data for synthesis analysis. Results: Altogether, 129 studies with 327 patients were included. Compared with BO, clavicular NBO favored females (P < 0.001) and age below 20 years (P < 0.001) and mostly presented in a chronic phase (disease term exceeding 2 months) (P < 0.001). Although local pain and swelling were the top two symptoms for both disorders, fever, erythema, and a sinus tract were more frequently found in BO patients (P < 0.01). Although they both favored the medial side, lesions in the clavicular lateral side mostly occurred in BO patients (P = 0.002). However, no significant differences were identified regarding the serological levels of white blood cell count (P = 0.06), erythrocyte sedimentation rate (P = 0.27), or C-reactive protein (P = 0.33) between BO and NBO patients before therapy. Overall, the BO patients achieved a statistically higher cure rate than that of the NBO patients (P = 0.018). Conclusions: Females, age below 20 years, and a long duration of clavicular pain and swelling may imply NBO. While the occurrence of a sinus tract and lesions in the lateral side may be clues of BO, inflammatory biomarkers revealed limited values for differential diagnosis. BO patients could achieve a better efficacy than the NBO patients based on current evidence.

4.
BMC Med Imaging ; 21(1): 20, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563233

RESUMO

BACKGROUND: To determine the predictive capability of MRI-based radiomics for extrathyroidal extension detection in papillary thyroid cancer (PTC) pre-surgically. METHODS: The present retrospective trial assessed individuals with thyroid nodules examined by multiparametric MRI and subsequently administered thyroid surgery. Diagnosis and extrathyroidal extension (ETE) feature of PTC were based on pathological assessment. The thyroid tumors underwent manual segmentation, for radiomic feature extraction. Participants were randomized to the training and testing cohorts, at a ratio of 7:3. The mRMR (maximum correlation minimum redundancy) algorithm and the least absolute shrinkage and selection operator were utilized for radiomics feature selection. Then, a radiomics predictive model was generated via a linear combination of the features. The model's performance in distinguishing the ETE feature of PTC was assessed by analyzing the receiver operating characteristic curve. RESULTS: Totally 132 patients were assessed in this study, including 92 and 40 in the training and test cohorts, respectively). Next, the 16 top-performing features, including 4, 7 and 5 from diffusion weighted (DWI), T2-weighted (T2 WI), and contrast-enhanced T1-weighted (CE-T1WI) images, respectively, were finally retained to construct the radiomics signature. There were 8 RLM, 5 CM, 2 shape, and 1 SZM features. The radiomics prediction model achieved AUCs of 0.96 and 0.87 in the training and testing sets, respectively. CONCLUSIONS: Our study indicated that MRI radiomics approach had the potential to stratify patients based on ETE in PTCs preoperatively.

5.
Orphanet J Rare Dis ; 16(1): 87, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588903

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a chronic illness involving the central nervous system (CNS) that is characterised by inflammation, demyelination, and degenerative changes. Dalfampridine is one of the available treatments for MS symptoms and comorbidities. This meta-analysis aimed to assess the safety and benefits of dalfampridine versus placebo in MS by summarising data deriving from previously published clinical randomised controlled studies (RCTs). RESULTS: A total of 9 RCTs were included in this meta-analysis, involving 1691 participants. There were significant differences between dalfampridine and placebo in terms of decreased 12-item Multiple Sclerosis Walking Scale score (weighted mean difference [WMD] = - 3.68, 95% confidence interval [CI] [- 5.55, - 1.80], p = 0.0001), improved response to the timed 25-foot walk test (relative risk [RR] = 2.57, 95% CI [1.04, 6.33], p = 0.04), increased 6-min walk test (WMD = 18.40, 95% CI [1.30, 35.51], p = 0.03), increased 9-Hole Peg Test score (WMD = 1.33, 95% CI [0.60, 2.05], p = 0.0004), and increased Symbol Digit Modalities Test score (WMD = 4.47, 95% CI [3.91, 5.02], p < 0.00001). Significant differences in the incidence of side effects were also observed (RR = 1.12, 95% CI [1.04, 1.21], p = 0.002). CONCLUSION: Dalfampridine exerts positive effects on walking ability, finger dexterity, and cognitive function. Treatment should be administered under the guidance of a physician or pharmacist given the higher incidence of adverse events.

6.
Sex Transm Infect ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397800

RESUMO

OBJECTIVES: To examine the feasibility of non-occupational postexposure prophylaxis (nPEP) as a national strategy for HIV prevention in China, we investigated nPEP usage and related sociodemographic and behavioural factors among five key populations at high risk of contracting HIV. METHODS: We conducted a cross-sectional study among five key populations from November 2018 to September 2019 in China using convenience sampling to recruit participants aged ≥18 years, self-reporting HIV status as either negative or unknown and providing written informed consent. Univariable and multivariable logistic regression models were fitted. RESULTS: Our analysis included data from 2022 participants with a mean age of 35 years (SD=11.62). Only 57 (2.82%) participants had ever used nPEP. Sociodemographic and behavioural factors related to nPEP usage included populations (p<0.0001), age (p<0.05), education (p<0.05), nPEP knowledge (p<0.01), receiving conventional HIV prevention services (p<0.05) and HIV testing (p<0.05). A significant percentage (26%) of nPEP users used nPEP medication more than once. Challenges and concerns, such as multiple use of nPEP and syndemic conditions, were emerging. CONCLUSIONS: Key populations in China had low nPEP usage rates. Female sex workers, people who use drugs, older and illiterate individuals with poor nPEP knowledge, not using HIV prevention services or never tested for HIV should be emphasised. Implementing nPEP services would be an important way to access high-risk individuals for intensive and tailored HIV prevention and intervention. Challenges of providing nPEP services and future study foci are highlighted.

7.
Biol Sex Differ ; 12(1): 17, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514431

RESUMO

BACKGROUND: A significant positive association was found in previous studies among obesity, visceral fat accumulation, and hyperuricemia. The purpose of this study was to explore the association between the ratio of visceral fat area to leg muscle mass (VFA-to-LMM) and hyperuricemia, and verify the role of gender differences in the association. METHODS: A total of 3393 (43.3% are men) participants from Tianjin Union Medical Center-Health Management Center were recruited for this cross-sectional study. The VFA-to-LMM ratio was used as the independent variable. Hyperuricemia, a serum uric acid level ≥ 416 µmol/L in men and in menopausal women and ≥ 357 µmol/L in premenopausal women, was used as the dependent variable. Multiple logistic regression analysis was used to estimate the odds ratio and the 95% confidence interval between the VFA-to-LMM ratio and hyperuricemia. RESULTS: The overall prevalence of hyperuricemia was 14.8% (8.9% in women, and 22.5% in men). After adjustment by age, smoking status (for males), menopause status (for females), drinking status, exercise frequency, blood pressure, alanine aminotransferase, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, creatinine, and history of diseases, a strong positive association was found between the VFA-to-LMM ratio and hyperuricemia in both men (4th vs. 1st quartile 1.60, 95%CI: 1.03-2.49) and women (4th vs. 1st quartile 5.22, 95%CI: 2.44-12.56). After additional adjustment by BMI, there was still a significant positive association in women (4th vs. 1st quartile 2.57, 95%CI: 1.06-6.77). The results of subgroup analysis showed that pre-menopausal women (4th vs. 1st quartile OR: 3.61) have a higher risk of hyperuricemia than postmenopausal women (4th vs. 1st quartile OR: 1.94) with the increase of the VFA-to-LMM ratio. Besides, the interaction analysis results showed the highest risk of hyperuricemia when VFA and LMM were both in the highest quantile (OR: 11.50; 95% CI: 4.86-31.98). CONCLUSION: The VFA-to-LMM ratio was positively associated with the risk of hyperuricemia in women after adjustment by confounders. Pre-menopausal women have a higher risk of hyperuricemia than postmenopausal women with the increase of the VFA-to-LMM ratio. In addition, the highest risk of hyperuricemia was demonstrated when both VFA and LMM were at the highest quartile.

8.
JAMA Netw Open ; 4(1): e2031661, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33416884

RESUMO

Importance: Radiotherapy is a common treatment for rectal cancer, yet the risk of second gynecological malignant neoplasms (SGMNs) in patients with rectal cancer undergoing radiotherapy have not been adequately studied. Objective: To investigate the association between radiotherapy and the risk of individual types of SGMN in patients with rectal cancer and assess survival outcomes. Design, Setting, and Participants: A large population-based cohort study was designed to identify the risk of SGMNs in patients with rectal cancer diagnosed from January 1973 to December 2015. The statistical analysis was conducted from September 2019 to April 2020. The study was based on the 9 cancer registries of Surveillance, Epidemiology, and End Results database. A total of 20 142 female patients with rectal cancer in localized and regional stage were included. Exposure: Receipt of neoadjuvant radiotherapy for rectal cancer. Main Outcomes and Measures: The development of an SGMN defined as any type of GMN occurring more than 5 years after the diagnosis of rectal cancer. The cumulative incidence of SGMNs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the radiotherapy-associated risk for SGMNs in patients undergoing radiotherapy vs patients not undergoing radiotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SGMNs. Results: Of 20 142 patients, 16 802 patients (83.4%) were White and the median age was 65 years (interquartile range, 54-74 years). A total of 5310 (34.3%) patients were treated with surgery and radiotherapy, and 14 832 (65.7%) patients were treated with surgery alone. The cumulative incidence of SGMNs during 30 years of follow-up was 4.53% among patients who received radiotherapy and 1.53% among patients who did not. In competing risk regression analysis, undergoing radiotherapy was associated with a higher risk of developing cancer of the uterine corpus (adjusted hazard ratio, 3.06; 95% CI, 2.14-4.37; P < .001) and ovarian cancer (adjusted hazard ratio, 2.08; 95% CI, 1.22-3.56; P = .007) compared with those who did not receive radiotherapy. The dynamic radiotherapy-associated risks (RR) for cancer of the uterine corpus significantly increased with increasing age at rectal cancer diagnosis (aged 20-49 years: adjusted RR, 0.79; 95% CI, 0.35-1.79; P = .57; aged 50-69 years: adjusted RR, 3.74; 95% CI, 2.63-5.32; P < .001; aged ≥70 years: adjusted RR, 5.13; 95% CI, 2.64-9.97; P < .001) and decreased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 3.22; 95% CI, 2.12-4.87; P < .001; 120-239 months: adjusted RR, 2.72; 95% CI, 1.75-4.24; P < .001; 240-360 months: adjusted RR, 1.95; 95% CI, 0.67-5.66; P = .22), but the dynamic RR for ovarian cancer increased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 0.70; 95% CI, 0.26-1.89; P = .48; 120-239 months: adjusted RR, 2.26; 95% CI, 1.09-4.70; P = .03; 240-360 months: adjusted RR, 11.84; 95% CI, 2.18-64.33; P = .004). The 10-year overall survival among patients with radiotherapy-associated cancer of the uterine corpus was significantly lower than that among matched patients with primary cancer of the uterine corpus (21.5% vs 33.6%; P = .01). Conclusions and Relevance: Radiotherapy for rectal cancer was associated with an increased risk of cancer of the uterine corpus and ovarian cancer. Special attention should be paid to reduce radiotherapy-associated SGMNs and improve their prognosis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33503493

RESUMO

BACKGROUND: Previous studies have shown that gaming-related cues could induce gaming cravings and bring about changes in brain activities in subjects with Internet gaming disorder (IGD). However, little is known about the brain network organizations in IGD subjects during a cue-craving task and the relationship between this network organization and IGD severity. METHODS: Sixty-one IGD subjects and 61 matched recreational game users (RGUs) were scanned while performing a cue-craving task. We calculated and compared the participation coefficient (PC) among brain network modules between IGD subjects and RGUs. Based on the results, further group comparison analyses were performed to explain the PC changes and to explore the relationship between PCs and IGD severity. RESULTS: While performing a cue-craving task, compared with RGUs, IGD subjects showed significantly decreased PCs in the default-mode network (DMN) and the frontal-parietal network (FPN). Specifically, the number of connections between nodes in the ventromedial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex and other nodes in the DMN of IGD subjects was much larger than that in RGUs. Correlation results showed that the number of DMN intra-modular connections was positively correlated with addiction severity and craving degree. CONCLUSIONS: These results provide neural evidence that can explain why cognitive control, emotion, attention and other functions are impaired in IGD subjects in the face of gaming cues, which leads to compulsive behavior toward games. These findings extend our understanding of the neural mechanism of IGD and have important implications for developing effective interventions to treat IGD subjects.

10.
Cell Death Dis ; 12(1): 101, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473116

RESUMO

Leukemia arises from blockage of the differentiation/maturation of hematopoietic progenitor cells at different stages with uncontrolled proliferation of leukemic cells. However, the signal pathways that block cell differentiation remain unclear. Herein we found that SUMOylation of the M2 isoform of pyruvate kinase (PKM2), a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis. SUMOylation of PKM2 lysine 270 (K270) triggered conformation change from tetrameric to dimeric of PKM2, reduced PK activity, and led to nuclear translocation of PKM2. SUMO1 modification of PKM2 recruits and promotes degradation of RUNX1 via a SUMO-interacting motif, resulting in blockage of myeloid differentiation of NB4 and U937 leukemia cells. Replacement of wild type PKM2 with a SUMOylation-deficient mutant (K270R) abrogated the interaction with RUNX1, and the blockage of myeloid differentiation in vitro and in xenograft model. Our results establish PKM2 as an essential modulator of leukemia cell differentiation and a potential therapeutic target, which may offer synergistic effect with differentiation therapy in the treatment of leukemia.

11.
BMC Public Health ; 21(1): 221, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499839

RESUMO

BACKGROUND: In China, non-occupational post-exposure prophylaxis (nPEP) is not a conventional service yet and nPEP related studies are very few. Recently, China's 13th Five Year Action Plan for HIV/AIDS Containment and Prevention examines the feasibility of including nPEP as one of the national strategies for HIV prevention. However, there is a concern that nPEP use might exacerbate high-risk sexual activities. In order to facilitate a research-based policy making of routinizing nPEP services, the current study examined potential effects of nPEP use on condom use and number of sexual partners among Chinese men who have sex with men (MSM) . METHODS: A cross-sectional survey was conducted in two cities of China in November and December 2018. Descriptive analyses of participants' sociodemographic and behavioral characteristics were conducted using SPSS 24.0. Mplus 7.4 was used to conduct confirmatory factor analysis and structural equation modeling. RESULTS: The sample included 419 Chinese MSM with a mean age of 28.04 (SD = 9.71). Participants reported more positive anticipation of their own behaviors than other MSM's behaviors regarding condom use and number of sexual partners if nPEP were to be routinized in China. About 60% of participants reported discrepancies between anticipated individual and population behaviors as a potential result of routinization of nPEP services. Anticipated individual behavioral change was positively related to age and duration of residence in the current city, and negatively related to education. Anticipated population behavioral change was positively related to age. Anticipated behavioral discrepancy was positively related to being ethnic minority and never married. CONCLUSIONS: These findings identify a high-risk subgroup of MSM, who reported they would use condoms less and/or have more sexual partners when nPEP becomes available. This subgroup of MSM might benefit from targeted health interventions. Moreover, there is a clear discrepancy between anticipated individual and population behavioral changes regarding future routinization of nPEP services, suggesting incorporating nPEP services as a means of community development for MSM.

12.
Eur J Med Chem ; 211: 113114, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33360793

RESUMO

Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of hit compound 7 and conduct further structure-activity relationship (SAR) studies that result in the development of compound 19 with a novel indole-2-carboxamide hinge scaffold. Compound 19 displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, compound 19 also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 19 shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, compound 19 represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC.

13.
Biomed Pharmacother ; 133: 110921, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378991

RESUMO

Dendritic cells (DCs) play a critical immuno-modulating role in pregnancy, which requires the maternal immune system to tolerate semiallogeneic fetus and at the same time to maintain adequate defense against pathogens. DCs interact closely with other immune components such as T cells, natural killer cells and macrophages, as well as the endocrine system to keep a pregnancy-friendly environment. Aberrant DC activities have been related to various pregnancy-associated diseases such as recurrent spontaneous abortion, preterm birth, pre-eclampsia, peripartum cardiomyopathy and infectious pregnancy complications. These findings make DCs an attractive candidate for prevention or therapy on the pregnancy-associated diseases. Here, we review recent findings that provide new insights into the roles of DCs in pregnancy and the related diseases. We also discuss the medical potentials to manipulate DCs in clinics. Whereas this is an emerging area with much work remaining, we anticipate that a better understanding of the role of DCs in maternal-fetal immunotolerance and a therapeutic manipulation of DCs will help women suffering from the pregnancy-associated diseases.

14.
Oncologist ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33274542

RESUMO

BACKGROUND: In the intent-to-treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation. Clinicaltrials.gov NCT01170663 MATERIALS AND METHODS: Tumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the EORTC QLQ-C30 v3.0. Pre-specified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR. RESULTS: In both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved/stable QoL, with more tumor shrinkage associated with greater symptom palliation. CONCLUSIONS: Treatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric/gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. IMPLICATIONS FOR PRACTICE: Ramucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first-line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with non-measurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.

15.
Complement Ther Clin Pract ; 42: 101278, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33276227

RESUMO

OBJECTIVE: To assess the efficacy and safety of retention enema with traditional Chinese medicine (TCM) for ulcerative colitis (UC) through a meta-analysis of published studies. METHODS: Literatures were retrieved from five electronic databases. Quality evaluation and meta-analysis were respectively conducted using the Cochrane collaboration and RevMan5.3. Overall quality of evidence was evaluated using GRADE system. Effect sizes were pooled using random effect models. RESULTS: Seventeen RCTs were included. Compared with routine pharmacotherapies (RPs), TCM enema exhibited a statistically significant difference in clinical efficacy and reduction of the recurrence rate. The results of qualitative description for other endpoints, such as improvements in anabrosis, ulcer, diarrhea, and hematochezia, suggested that TCM enema had better efficacy than RPs. Furthermore, the incidence of side effects in TCM was lower than that in RPs. CONCLUSION: This meta-analysis confirmed the efficacy and safety of TCM enema for improving UC symptoms. However, further well-designed researches are needed.

16.
Front Oncol ; 10: 596330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282745

RESUMO

Purpose: Chordomas are rare, slow-growing sarcomas without any accepted prognostic biomarkers. Owing to their proximity to critical neurovascular structures, discovering predictive biomarkers in chordoma has been a significant research effort because it may potentially reduce risky therapies in patients with less aggressive tumors. In response, because cyclin E1 overexpression correlates with patient prognosis in several malignancies, we investigated its expression in chordoma and whether it informs patient prognosis. Methods: Seventy-five chordoma patient specimens were enrolled in a tissue microarray (TMA) to evaluate cyclin E1 expression via immunohistochemical staining. Western blot was used to assess cyclin E1 expression in chordoma cell lines and fresh tissues. We then correlated cyclin E1 staining intensity in the TMA to clinicopathological features and chordoma patient outcomes. Results: Sixty-three percent of the chordoma patient specimens in the TMA, fifty-six percent of the fresh chordoma tissues, and all chordoma cell lines showed high cyclin E1 expression. In TMA analysis, cyclin E1 expression positively correlated to chordoma patient disease status. By survival analysis, high cyclin E1 expression was an independent prognostic risk factor for chordoma patients along with advanced disease status and positive surgical margin. Conclusion: Cyclin E1 is a promising biomarker predicting chordoma patient prognosis.

17.
BMC Infect Dis ; 20(1): 950, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308173

RESUMO

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Fluoroquinolonas/uso terapêutico , Macrolídeos/uso terapêutico , Mutação , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/genética , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , China/epidemiologia , DNA Girase/genética , DNA Topoisomerase IV/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/isolamento & purificação , Prevalência , RNA Ribossômico 23S/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia
18.
Gland Surg ; 9(5): 1214-1226, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224796

RESUMO

Background: The aim of the present study was to develop a magnetic resonance imaging (MRI) radiomics model and evaluate its clinical value in predicting preoperative lymph node metastasis (LNM) in patients with papillary thyroid carcinoma (PTC). Methods: Data of 129 patients with histopathologically confirmed PTC were retrospectively reviewed in our study (90 in training group and 39 in testing group). 395 radiomics features were extracted from T2 weighted imaging (T2WI), diffusion weighted imaging (DWI) and T1 weighted multiphase contrast enhancement imaging (T1C+) respectively. Minimum redundancy maximum relevance (mRMR) was used to eliminate irrelevant and redundant features and least absolute shrinkage and selection operator (LASSO), to additionally select an optimized features' subset to construct the radiomics signature. Predictive performance was validated using receiver operating characteristic curve (ROC) analysis, while decision curve analyses (DCA) were conducted to evaluate the clinical worth of the four models according to different sequences. A radiomics nomogram was built using multivariate logistic regression model. The nomogram's performance was assessed and validated in the training and validation cohorts, respectively. Results: Seven key features were selected from T2WI, five from DWI, ten from T1C+ and seven from the combined images. The scores (Rad-scores) of patients with LNM were significantly higher than patients with non-LNM in both the training cohort and the validation cohort. The combined model performed better than the T2WI, DWI, and T1C+ models alone in both cohorts. In the training cohort, the area under the ROC (AUC) values of T2WI, DWI, T1C+ and combined features were 0.819, 0.826, 0.808, and 0.835, respectively; corresponding values in the validation cohort were 0.798, 0.798, 0.789, and 0.830. The clinical utility of the combined model was confirmed using the radiomics nomogram and DCA. Conclusions: MRI radiomic model based on anatomical and functional MRI images could be used as a non-invasive biomarker to identify PTC patients at high risk of LNM, which could help to develop individualized treatment strategies in clinical practice.

19.
Phys Chem Chem Phys ; 22(44): 25930-25935, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33164002

RESUMO

The physicochemical properties of TiO2 are largely dependent on the defects. Here, using first-principles calculations, we report a systematic investigation of the magnetic properties of Ti-defected rutile TiO2 systems. The results of our calculations show that the VTi concentration can significantly affect the size of the magnetism, and that the magnetism weakens with decreasing VTi concentration. Studies of phonon dispersion curves show that systems with lower VTi concentrations of 8.33% and 6.25% are kinetically stable. Further detailed calculations on the Ti11O24 system indicate that the magnetism mainly originates from four of the six nearest-neighbor O atoms to the Ti vacancy, but much less from the other two. The magnetic ground states are discussed, and the results show that for the Ti11O24 system, the ferromagnetic (FM) state of the four nearest-neighbor O atoms to the Ti vacancy is the magnetic ground state, and for the Ti22O48 system, the FM state of the two vacancies is the magnetic ground state. In addition, our calculations also indicate that the magnetic properties of Ti-defected TiO2 can be tuned via strain engineering. In general, this metal-defected TiO2 represents a novel kind of semiconductor. Research into the magnetic properties reported in this paper can enrich theoretical knowledge in this area and provide more potential candidates for TiO2-based materials.

20.
Front Oncol ; 10: 584072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194727

RESUMO

Background: The relationship between pelvic radiation therapy (RT) and second primary rectal cancer (SPRC) is unclear. The aim of this study was to assess the risk and prognosis of SPRC after pelvic RT. Materials and Methods: Data for patients who had primary pelvic cancer (PPC) between 1973 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SPRC. Five-year overall survival (OS) and rectal cancer-specific survival (RCSS) were calculated using Kaplan-Meier curves. Results: A total of 573,306 PPC patients were included, 141,225 of whom had been treated with RT. Primary cancers were located in the prostate (50.83%), bladder (24.18%), corpus uterus (16.26%), cervix (5.83%), and ovary (2.91%). A total of 1,491 patients developed SPRC. Overall, the patients who received RT were at increased risk of developing SPRC (SIR = 1.39, 95% confidence interval [CI]: 1.27-1.52). The risk of SPRC decreased in patients who did not undergo RT (SIR = 0.85, 95% CI: 0.80-0.91). The SIR for SPRC in patients who underwent external beam radiation therapy (EBRT) was 1.22 (95% CI: 1.09-1.36). The SIR for SPRC in patients who underwent a combination of EBRT and brachytherapy (EBRT-BRT) was 1.85 (95% CI: 1.60-2.14). For patients who received RT, the SIR for SPRC increased with time after a 5-year latency period from PPC diagnosis. The survival of RT-treated SPRC patients was significantly worse than that of patients with primary rectal cancer only (PRCO). Conclusions: Patients receiving pelvic RT were at an increased risk of developing SPRC. Different pelvic RT treatment modalities had different effects on the risk of SPRC. We suggest that long-term surveillance of SPRC risk is required for patients who have undergone pelvic RT, especially young patients.

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