Objective: To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. Methods: Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. Results: A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( ): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% : -1.60, -1.09), -1.10 kg/m (95% : -1.42, -0.78), and -1.28 cm (95% : -1.69, -0.86), respectively. Conclusion GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

OBJECTIVE: To investigate the distribution of peripheral blood lymphocytes and natural killer (NK) cells, and its influence on the prognosis of patients with myelodysplastic syndromes (MDS). METHODS: The lymphocytes proportion, absolute lymphocyte counts (ALC), NK cell proportion and absolute NK cell counts (ANKC) as well as the related data of 95 MDS patients diagnosed between 2013 and 2017 analyzed retrospectively. The correlation of ALC and ANKC with prognosis was also analyzed. RESULTS: As compared with low ALC patients, MDS patients with ALC≥0.885×10/L had a higher overall response rate (66.7% vs 35.8%) (P＜0.01). The ALC of effective patients after treatment significatitly increased in compaison of ALC at diagnosis. Multivariate analysis indicated that patients with ALC≥0.885×10/L had long overall survival (OS) time in comparison with patients with low level (16.4 vs 12.4 months) (P＜0.05). The OS time of patients with ANKC≥0.110×10/L was shorter in comparison with patients with low level (10.9 vs 16.3 months) (P＜0.01). Otherwise, blast, cytogenetic risks and treatment response were also independent risk factors of MDS (P＜0.05). Revised International Prognostic Scoring System (IPSS-R) combined with ANKC could improve predictive accuracy of IPSS-R alone (AUC 0.718 vs 0.674) (P＜0.05). CONCLUSION Lymphocytes and NK cells are important for the prognosis evaluation of MDS patients.

PURPOSE: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. RESULTS: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). CONCLUSION: Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.
Adult ; Bone Marrow ; Comorbidity ; Dermatitis ; Drug Therapy ; Humans ; Methods ; Mucositis ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Intensity-Modulated* ; Temporal Lobe

Purpose To assess the frequency of discordances in ER, PR and HER-2 status between primary and recurrent cancer and the impact of the discordance on breast cancer patient survival. Method Immunohistochemistry and/or fluorescent in situ hybridization was used to evaluate ER, PR and HER-2 status of primary and recurrent cancer in 62 breast cancer patients. The correlation between discordances in ER, PR and HER-2 receptors and clinicopathologic characteristics and patient survival was analyzed. Results Among 62 patients with breast recurrent cancer, discordance rate for ER, PR, and HER-2 was found in 6 (9.7％), 9 (14.5％) and 3 (4.8％) patients, respectively. During the follow-up period the ER-discordant cases had a poorer overall survival (median 29 months vs 44 months, P=0.021) and post-recurrence survival (median 6 months vs 15 months, P=0.027), compared with the concordant cases. No impact on overall survival or post-recurrence survival was observed for PR and HER-2 discordance when compared with the respective concordant cases (P> 0.05 for all).Conclusion Our results demonstrate an evident change regarding ER, PR and HER-2 between breast primary and recurrent cancer, and the ER unstable status in breast cancer suggust a worse prognosis.

To assess the value of endorectal ultrasonography ( ERUS ) in predicting the pathological response to neoadjuvant chemoradiotherapy( NCRT ) for locally advanced rectal cancer( LARC) . Methods Ninety‐nine patients with LARC received NCRT and total mesorectal excision in our hospital were retrospectively analyzed . T he maximum length and thickness of rectal tumor were measured by ERUS both before NCRT ( ERUS1 ) and after NCRT following sugery ( ERUS2 ) ,and the length and thickness reduction rate were calculated . T he patients were classified into good responder group ( n ＝ 47 ) and poor responder group( n ＝ 52 ) ,or pathological complete response ( pCR) group ( n ＝ 25 ) and non‐pCR group ( n＝74) according to pathological tumor regression grade ( T RG ) . T he differences of various parameters were compared between groups . T he correlations between these parameters and T RG grading were analyzed by Spearman correlation analysis . T he ROC curve was used to evaluate the diagnostic efficacy of the parameter . Results T he length and thickness of ERUS2 were significantly shorter than that of ERUS1( all P ＜0 .05) . T he length and thickness of ERUS2 in good responder group were shorter than those in poor responder group ,while the length and thickness reduction rate were higher than those in poor responder group with significant difference ( all P ＜ 0 .05 ) . T he length and thickness of ERUS2 in pCR group were shorter than those in non‐pCR group ,w hile the length and thickness reduction rate were higher than those in non‐pCR group with significant difference ( all P ＜ 0 .05 ) . T he length and thickness of ERUS2 were positively correlated with T RG grading ( r ＝ 0 .577 ,0 .605 ; all P ＜ 0 .01 ) and the length and thickness reduction rate were negatively correlated with T RG grading ( r ＝ －0 .681 ,－0 .598 ; all P ＜0 .01 ) . ROC curve showed the cut‐off value of the length and thickness reduction rate to predict good responder were 41 .34% ,46 .46% , with corresponding AUC areas of 0 .843 ,0 .796 , sensitivity of 74 .5% ,70 .2% , and specificity of 76 .9% ,80 .8% ,respectively . ROC curve showed the cut‐off value of the length and thickness reduction rate to predict pCR were 57 .36% ,58 .52% ,with corresponding AUC areas of 0 .851 and 0 .895 , sensitivity of 68 .0% ,76 .0% ,and specificity of 94 .6% ,93 .2% ,respectively . Conclusions T he changes of length and thickness of tumor after NCRT are well correlated with treatment response . T he length and thickness reduction rate measured on ERUS present high accuracy in prediction of good response and pCR in LARC patients .

BACKGROUND: Blood purification (BP) is one of the most important rescue measures for patients with critical illness in the intensive care unit (ICU), especially for those with acute kidney injury. The purpose of this nationwide survey was to reveal the real world of current BP practice in different ICUs all over China. This study was designed to be a multi-center cross-sectional study. METHODS: All adult patients (over 18 years of age), who were admitted to ICU and required BP in 35 sub-centers across China were included during 30-day survey period in 2018. Demographic characteristics and clinical data were recorded including the timing of treatment initiation, indications, modality, relative contraindication, establishment of vascular access, selection of filter/membrane, settings, anti-coagulation, executive department, complication, intake, and output. DISCUSSION: This nationwide survey may contribute to reveal the real world of current BP practice in different ICUs all over China. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-EOC-17013119; http://www.chictr.org.cn/showproj.aspx?proj=22487.

BACKGROUND: Renal artery stenosis (RAS) is always associated with abnormalities in renal microvascular perfusion (RMP). However, few imaging methods can simultaneously evaluate the degree of luminal stenosis and RMP. Thus, this study will aim to evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) for assessing both RAS and RMP to achieve a one-stop assessment of patients with suspected renovascular hypertension. METHODS: This will be a single-center diagnostic study with a sample size of 440. Patients with chronic kidney disease (CKD) and suspected of having resistant hypertension will be eligible. Patients with Stages 1-3 CKD will undergo CEUS and computed tomography (CT) angiography (CTA). Values obtained by CEUS and CTA for diagnosing low-grade (lumen reduced by <60%) and high-grade (lumen reduced by ≥60%) RAS will be compared. Moreover, all patients will also undergo radionuclide imaging. The diagnostic value for RAS will be assessed by the receiver operating characteristic curve, including the accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and area under the ROC. Pearson correlation analysis will be performed to assess the association between CEUS findings for RMP and glomerular filtration rate measured by a radionuclide imaging method. CONCLUSION: The data gathered from this study will be used to evaluate the feasibility of expanding clinical applications of CEUS for evaluation of patients with suspected renovascular hypertension. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR1800016252; https://www.chictr.org.cn.
Contrast Media ; Glomerular Filtration Rate ; physiology ; Humans ; Hypertension, Renovascular ; physiopathology ; ROC Curve ; Renal Artery ; physiopathology ; Renal Artery Obstruction ; physiopathology

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
Adult ; Antigens, CD19 ; metabolism ; Bone Marrow ; metabolism ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Gene Expression Regulation, Leukemic ; Gene Regulatory Networks ; Humans ; Immunotherapy, Adoptive ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; therapy ; RNA, Long Noncoding ; genetics ; metabolism ; Receptors, Antigen, T-Cell ; Transcription Factors ; metabolism ; Transcriptome ; genetics

To study the correlation between ultra high performance liquid chromatography( UPLC) fingerprint of Smilax china and its anti-pelvic inflammatory effect,and to explore the pharmacodynamic material basis of S. china against pelvic inflammatory disease.UPLC fingerprints of 10 batches of S. china from different habitats were established,and the values of SOD,MDA,TNF-α,and IL-6 in rats with pelvic inflammation were measured. The weight of each single pharmacodynamics index to the total efficacy was determined by analytic hierarchy process,and the contribution of each peak in fingerprints to the each single pharmacodynamics index and total efficacy was analyzed by the grey relational analysis. Then the structures of chemical constituents at the identified peaks were confirmed by comparing with the reference substance. The 27 common characteristic peaks of UPLC fingerprints were all related to the anti-pelvic inflammation effect of S. china,of which 13 peaks were identified as peak 2( 3,5-dihydroxy-2-methylbenzoic acid-3-O-glucoside),peak 3( chlorogenic acid),peak 5( 2,7,4-trihydroxydihydroflavone-5-O-glucoside),peak 6( 7,4-dihydroxydihydroflavonol-5-O-glucoside),peak 7( taxifolin-7-O-glucoside),peak 9( taxifolin),peak 10( polydatin),peak 11( oxyresveratrol),peak 12( astilbin),peak15( resveratrol),peak 16( quercitrin),peak 18( engeletin) and peak 24( kaempferol). The correlation degree of 21 peaks and the total efficacy was greater than 0. 8,and the top 10 ranked by correlation degree were as follows: peak 1,3,7,19,18,17,4,11,16,and 21. The results showed that the anti-pelvic inflammation effect of S. china was achieved by the combined action of pharmacodynamic substances. In order to control the quality of S. china and its prepared slices more effectively,the index components of content detection should be selected reasonably.
Animals ; China ; Chromatography, High Pressure Liquid ; Female ; Pelvic Inflammatory Disease ; drug therapy ; Phytochemicals ; pharmacology ; Plant Extracts ; pharmacology ; Rats ; Smilax ; chemistry

OBJECTIVE: To explore expression of β-catenin and NF-κB signaling pathway in synovial tissue of rats with different degrees of knee osteoarthritis (KOA). METHODS: Forty-eight SPF male rats weighed (200±20) g were randomly divided into three groups, namely model group (32 rats), sham operation group (8 rats) and control group (8 rats). KOA model rats were established by Hulth method, and 8 rats were killed at 2, 4, 8, 12 weeks respectively after modeling, in order to establish KOA model rats with moderate, early, mild and severe degree. Sham operation group was only cut off capsule of knee joint and suture to exclude interference factor, control group was untreated. Behavior, synovial hyperplasia and cartilage degeneration of rats among each group were observed. Expression of NF-κB and signaling pathway and β-catenin in synovial tissue of rats were detected by real-time PCR. RESULTS: KOA rat model was successfully established, and synovial hyperplasia was observed in KOA model at mild and early degree, and then gradually decreased; while cartilage degeneration in the early moderate and severe KOA model was significantly expressed, and gradually aggravated with time. The results of PCR showed that expression of β-catenin in 4-week group (8.57±0.46) and 8-week group (4.23±0.09) were higher than those in control group (<0.05); expression of TLR-2 in 2-week group (12.04±4.02) and 4-week group (8.54±2.13) were higher than those in control group(<0.05), and TLR-4 in 2-week group(5.04±0.93), 4-week group (3.29±0.58) and 8-week group (1.63±0.12) were higher than those in control group; expression of NF-κB was significantly higher in 2-week group (10.15±2.04), 4-week group (15.97±4.17), 8-week group (7.69±1.48) and 12-week group (6.70±1.58) than that in control group (<0.05), and expression of IL-1β was significantly higher in 4-week group (2.79±0.25) and 8-week group (2.46±0.32) than that of control group (<0.05). CONCLUSIONS On the RNA expression level, both of β-catenin and NF-κB signaling pathways are involved in synovial inflammation in KOA model rats, and they play a regulatory role in expression of IL-1β, degeneration of KOA.
Animals ; Inflammation ; Male ; NF-kappa B ; Osteoarthritis, Knee ; Rats ; Signal Transduction ; beta Catenin