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1.
Eur J Anaesthesiol ; Publish Ahead of Print2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33399384

RESUMO

BACKGROUND: Moderate-to-severe pain exists in the early postoperative period after laparoscopic renal surgery. OBJECTIVE: We investigated the analgesic effect of quadratus lumborum block (QLB) via two approaches in patients undergoing laparoscopic renal nephrectomy. DESIGN: A randomised controlled trial. SETTING: An academic tertiary care hospital in Beijing, China. PARTICIPANTS: Ninety-six patients aged 18 to 70 years who were scheduled for elective laparoscopic radical or partial nephrectomy. INTERVENTIONS: Eligible patients were allocated randomly to a control group (no block), lateral QLB group or posterior QLB group. Ultrasound-guided QLB was performed via either the lateral or posterior approach with 30 ml of 0.4% ropivacaine before surgery. MAIN OUTCOME MEASURES: The primary outcome was sufentanil equivalent consumption within 24 h. Among secondary outcomes, somatic and visceral pain intensity at rest and on coughing were assessed with a numerical rating scale (where 0 = no pain and 10 = the worst pain) until 24 h postoperatively. RESULTS: Sufentanil equivalent consumption did not differ among the three groups (118 ±â€Š36 µg in the control group, 115 ±â€Š47 µg in the lateral QLB group and 119 ±â€Š40 µg in the posterior QLB group; P = 0.955). However, both somatic (lateral QLB vs. control, median difference -1, P < 0.001 at rest and -2 to -1, P < 0.001 on coughing; posterior QLB vs. control, -1, P < 0.001 at rest and -2 to -1, P < 0.001 on coughing) and visceral pain scores (lateral QLB vs. control, -1 to 0, P < 0.001 at rest and -1, P < 0.001 on coughing; posterior QLB vs. control, -1 to 0, P < 0.001 at rest and -2 to -1, P < 0.001 on coughing) were significantly lower in the two QLB groups than in the control group. CONCLUSION: For patients undergoing laparoscopic renal surgery, a pre-operative single-shot QLB via the lateral or posterior approach did not decrease opioid consumption, but improved analgesia for up to 24 h after surgery. TRIAL REGISTRATION: www.chictr.org.cn identifier: ChiCTR1800019883.

2.
FASEB J ; 35(2): e21330, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33417289

RESUMO

Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis. Astrocytes polarizing toward neurotoxic A1 phenotype and neurons loss were observed after status epilepticus. Through injecting circIgf1r siRNA into the lateral ventricle, it was found that knocking down circIgf1r in vivo would induce the polarization of astrocytes to phenotype A2 and reduce neuronal loss. The results in vitro further confirmed that inhibiting the expression of circIgf1r in astrocytes could protect neurons by converting reactive astrocytes from A1 to the protective A2. In addition, knocking down circIgf1r in astrocytes could functionally promote astrocyte autophagy and relieve the destruction of 4-AP-induced autophagy flux. In terms of mechanism, circIgf1r promoted the polarization of astrocytes to phenotype A1 by inhibiting autophagy. Taken together, our results reveal circIgf1r may serve as a potential target for the prevention and treatment of neuron damage after epilepsy.

3.
Sci Rep ; 11(1): 664, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33437022

RESUMO

Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX's cardioprotection effect.

4.
J Nanosci Nanotechnol ; 21(2): 1202-1211, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33183463

RESUMO

In order to explore the influence of nanoparticle-loaded edaravone on postoperative effects in patients with cerebral hemorrhage, a total of 120 patients who were diagnosed as cerebral hemorrhage and underwent minimally invasive hematoma removal at the designated hospital by the study from December 2014 to December 2018 were selected as research objects and divided into three groups according to the random number table method: edaravone treatment (ET) group, nanoparticle-loaded edaravone treatment (NET) group, and combined treatment (CT) group with 40 patients in each group. Three groups of patients underwent routine treatments based on their conditions, including regulating blood sugar, regulating blood pressure, anti-infection, nutritional support, and managing complications, in which 25 mg edaravone injection and 100 ml saline were added for patients in NET and CT group on the basis of the routine treatment of patients in ET group. The results showed that, after 15 days of standard treatment, the 40 patients in NET group had significantly improved neurological function than that before the treatment; the secretion of inflammatory factors in peripheral serum increased on the 7th day of treatment and decreased on the 14th day of treatment; there was no statistically significant difference in edema volume before treatment and the edema volume in the NET group was (11.56±0.44) mL after treatment, which was significantly smaller than that in ET group of (14.63±1.15) mL and the difference between the three groups was statistically significant (P <0.05). Therefore, it is believed that nanoparticle-loaded edaravone has an important effect on the postoperative effect of patients with cerebral hemorrhage; it can significantly improve the neurological function of patients with cerebral hemorrhage after minimally invasive drainage, and obviously reduce the production and release of interleukin and tumor necrosis factor, which is beneficial to protect healthy brain tissue and other organs throughout the body, and is conducive to the recovery and healing of cerebral hemorrhage. The results of this study provide a reference for further research on the influence of nanoparticle-loaded edaravone on postoperative effects in patients with cerebral hemorrhage.

5.
Food Chem ; 337: 127811, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32799155

RESUMO

This study aimed to evaluate the effects of microwave processing (2.45 GHz, 1000 W, 75-125 °C, and 5-15 min) on the secondary structures, in-vitro protein digestibility, microstructural characteristics, and allergenicity of shrimp. SDS-PAGE analysis showed that the band intensity of tropomyosin reduced with the increase of processing temperatures and durations. The significant reduction in the allergenicity of tropomyosin was up to 75% when treated with microwave at 125 °C for 15 min. A significant reduction by 30-75% in the total soluble protein content, peptide content, and in-vitro protein digestibility of shrimp protein was observed. These changes mentioned above were strongly associated with the modification of the secondary structure of shrimp proteins, including the increase in ß-sheets, and the loss in turns. Also, more microscopic holes, fragments, strips in treated samples were observed by scanning electron microscopy. Therefore, high-intensity microwave treatment showed great potential in reducing the allergenicity of shrimp.

6.
Int J Cancer ; 148(2): 469-480, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33038264

RESUMO

Prostate cancer (PCa) progression is driven by androgen receptor (AR) signaling. Unfortunately, androgen-deprivation therapy and the use of even more potent AR pathway inhibitors (ARPIs) cannot bring about a cure. ARPI resistance (ie, castration-resistant PCa, CRPC) will inevitably develop. Previously, we demonstrated that GRB10 is an AR transcriptionally repressed gene that functionally contributes to CRPC development and ARPI resistance. GRB10 expression is elevated prior to CRPC development in our patient-derived xenograft models and is significantly upregulated in clinical CRPC samples. Here, we analyzed transcriptomic data from GRB10 knockdown in PCa cells and found that AR signaling is downregulated. While the mRNA expression of AR target genes decreased upon GRB10 knockdown, AR expression was not affected at the mRNA or protein level. We further found that phosphorylation of AR serine 81 (S81), which is critical for AR transcriptional activity, is decreased by GRB10 knockdown and increased by its overexpression. Luciferase assay using GRB10-knockdown cells also indicate reduced AR activity. Immunoprecipitation coupled with mass spectrometry revealed an interaction between GRB10 and the PP2A complex, which is a known phosphatase of AR. Further validations and analyses showed that GRB10 binds to the PP2Ac catalytic subunit with its PH domain. Mechanistically, GRB10 knockdown increased PP2Ac protein stability, which in turn decreased AR S81 phosphorylation and reduced AR activity. Our findings indicate a reciprocal feedback between GRB10 and AR signaling, implying the importance of GRB10 in PCa progression.

7.
Cancer Lett ; 497: 190-201, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33039561

RESUMO

Cancer cells can communicate with the tumor microenvironment and contribute to tumor progression. However, the effects of drug-resistant tumor cells on angiogenesis are unclear. Current anti-angiogenic strategies also have limitations and it would be useful to develop novel targets and treatment strategies. Here, our study showed that the conditioned medium and exosomes from 5-FU-resistant colon cancer cells promoted angiogenesis, and we observed that exosomal dipeptidyl peptidase IV (DPP4) was a potent inducer of this angiogenesis. DPP4-enriched exosomes increased periostin (POSTN) expression in human umbilical vein endothelial cells via Twist1 nuclear translocation or activating Smad signaling pathway, while silencing or inhibition of DPP4 neutralized those effects. The in vivo and clinical data indicated that high DPP4 expression was related to tumor progression. These findings indicate that DPP4 may be a target for inhibiting angiogenesis in 5-FU-resistant colon cancer. Furthermore, exosomal DPP4 concentrations may be a useful prognostic marker for colon cancer.

8.
Water Res ; 188: 116475, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33039833

RESUMO

The focus of infrastructure design and management has turned from a reliability-based approach to a resilience-based one. Resilience is a system's ability to maintain its function and minimize failure consequences when faced with exceptional conditions. This study carries out a large-scale computational experiment to study how resilience is affected by system's structure in a combined sewer system. We build a stochastic generation model, involving a random sampling of facility locations and a graph-based random walk sampling algorithm to generate various layouts of pipelines. The performance of these virtual systems are assessed in the Storm Water Management Model. We apply statistical techniques on these samples to study the relation between resilience and system structure. Results show that the number of combined sewer overflow (CSO) outfalls is a more important factor of resilience compared to the number of wastewater treatment plants (WWTPs). Some locations are found more preferable for WWTP or CSO outfall placement, while adding WWTPs or outfalls at other locations might even lower the system's resilience. Size of the sub-catchments of the CSO outfalls also affects resilience. Although this effect is statistically significant, the extent is not remarkable compared to other factors. We further study the structural features of the cost-effective systems. The highest achievable resilience level increases as the number of CSO outfalls decreases and so does system's cost. This results from the difference in CSO quantity, therefore this dilemma can be cut off by end-of-pipe storage or treatment which specifically tackles CSO. The conclusion of this study provides an insight into the structural factors of combined sewer systems' resilience and can provide guidance for system's planning.


Assuntos
Chuva , Esgotos , Reprodutibilidade dos Testes , Pesos e Medidas
9.
Cancer Med ; 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33314798

RESUMO

BACKGROUND: To estimate the adjusted conditional overall survival (COS) in patients with esophageal cancer after receiving various treatment modalities via a national population-based database, and to investigate the possible time-dependent effects. MATERIALS AND METHODS: Eligible patients diagnosed with esophageal cancer between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. The Kaplan-Meier method was used to calculate conventional survival time. The inverse probability of treatment weighting method was used to estimate the adjusted COS in patients receiving different treatment modalities. Landmark analysis was employed to investigate the possible time-dependent effects of different treatment modalities in patients who had survived a certain period of time. RESULTS: A total of 25,232 patients were included in the final analysis. The conventional 5-year overall survival was 19.3%. The 5-year adjusted COS increased most for the first 3 years, and increased slightly afterwards. In patients with regional esophageal or gastroesophageal junction cancer, stage-specific analysis showed that surgery only and preoperative radiation therapy benefited most for patients with localized disease, preoperative radiation therapy plus surgery benefited regional, and preoperative radiation therapy plus surgery benefited distant disease, with the 5-year adjusted COS given patients had survived 3 years being 67.0% (95% CI 65.2%-68.7%), 59.9% (95% CI 58.3%-61.5%), 58.4% (95% CI 56.3%-60.5%), and 61.8% (95% CI 59.5%-64.1%), respectively. In time-dependent analysis, the benefits of surgery only in localized cases were prominent within 48 months after diagnosis. Preoperative radiation therapy showed long-lasting benefits in patients with regional disease. In patients with distant disease, all treatment modalities showed similar and short-term effects. CONCLUSIONS: The adjusted COS in patients with esophageal cancer increased as time accrued after receiving various treatment modalities. The time-dependent effects in specific tumor stage provided a dynamic view on optimization of treatment strategies.

10.
PLoS One ; 15(12): e0243195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264366

RESUMO

BACKGROUND: The current worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, and the mortality rate of critical ill patients remains high. The purpose of this study was to identify factors that early predict the progression of COVID-19 from severe to critical illness. METHODS: This retrospective cohort study included adult patients with severe or critical ill COVID-19 who were consecutively admitted to the Zhongfaxincheng campus of Tongji Hospital (Wuhan, China) from February 8 to 18, 2020. Baseline variables, data at hospital admission and during hospital stay, as well as clinical outcomes were collected from electronic medical records system. The primary endpoint was the development of critical illness. A multivariable logistic regression model was used to identify independent factors that were associated with the progression from severe to critical illness. RESULTS: A total of 138 patients were included in the analysis; of them 119 were diagnosed as severe cases and 16 as critical ill cases at hospital admission. During hospital stay, 19 more severe cases progressed to critical illness. For all enrolled patients, longer duration from diagnosis to admission (odds ratio [OR] 1.108, 95% CI 1.022-1.202; P = 0.013), pulse oxygen saturation at admission <93% (OR 5.775, 95% CI 1.257-26.535; P = 0.024), higher neutrophil count (OR 1.495, 95% CI 1.177-1.899; P = 0.001) and higher creatine kinase-MB level at admission (OR 2.449, 95% CI 1.089-5.511; P = 0.030) were associated with a higher risk, whereas higher lymphocyte count at admission (OR 0.149, 95% CI 0.026-0.852; P = 0.032) was associated with a lower risk of critical illness development. For the subgroup of severe cases at hospital admission, the above factors except creatine kinase-MB level were also found to have similar correlation with critical illness development. CONCLUSIONS: Higher neutrophil count and lower lymphocyte count at admission were early independent predictors of progression to critical illness in severe COVID-19 patients.

11.
J Affect Disord ; 281: 342-350, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33348177

RESUMO

BACKGROUND: Depression is a common and serious complication in new mothers. We investigated the hypothesis that neuraxial labor analgesia is associated with a decreased risk of postpartum depression. METHODS: In this multicenter prospective cohort study with propensity score matching, 599 nulliparous women with single term cephalic pregnancy who planned vaginal delivery were enrolled and self-selected neuraxial analgesia or not. The primary outcome was 6-week postpartum depression assessed with the Chinese version Edinburgh Postnatal Depression Scale; a score of ≥10 was set as the threshold of postpartum depression. Logistic regression models were established to assess the association between neuraxial labor analgesia and postpartum depression. RESULTS: Of the 577 parturients who completed the study, 417 (72.3%) received neuraxial analgesia and 160 (27.7%) did not. After propensity score matching, 433 parturients were included in the analysis; of whom, 279 (64.4%) received neuraxial analgesia and 154 (35.6%) did not. The incidence of postpartum depression was lower in parturients with neuraxial analgesia than in those without (14.9% [62/417] vs. 23.8% [38/160], P=0.012 before matching; 13.3% [37/279] vs. 23.4% [36/154], P=0.007 after matching). After adjustment for confounding factors, neuraxial analgesia was associated with decreased odds of postpartum depression (odds ratio [OR] 0.50, 95% CI 0.28-0.88, P=0.015 before matching; OR 0.40, 95% CI 0.21-0.77, P=0.006 after matching). LIMITATIONS: As an observational study, unidentified confounders might influence the results. CONCLUSIONS: In nulliparae with single term cephalic pregnancy preparing to give vaginal delivery neuraxial analgesia during labor was associated with a decreased risk of 6-week postpartum depression.

12.
Anesthesiology ; 133(2): 318-331, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33377960

RESUMO

BACKGROUND: Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation-guided intraoperative care reduces postoperative nausea and vomiting. METHODS: This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation-guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality. RESULTS: Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation-guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P < 0.001; forearm, 53 vs. 245% · min, P < 0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation-guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study. CONCLUSIONS: In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation-guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting.

13.
Front Pharmacol ; 11: 581991, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178024

RESUMO

Post-menopausal osteoporosis (PMOP) is associated with estrogen deficiency and worldwide, is becoming increasingly more prevalent in aging women. Various anti-PMOP drugs have been developed to reduce the burden of PMOP; generally, these drugs are efficacious, but with some adverse side effects. Tubson-2 decoction (TBD), a popular traditional Mongolian medicine, has been used to treat PMOP for centuries. However, the precise mechanisms underlying the action of TBD on PMOP have yet to be fully elucidated. Herein, we combined network pharmacology with untargeted metabolomics to identify the key targets and metabolic pathways associated with the interventional effects of TBD on ovariectomized (OVX) rats. Furthermore, we investigated the bone histomorphometry of eight different groups of rats to evaluate the therapeutic effect of TBD. First, we established a TBD-target/PMOP network via network pharmacology; this network identified three key protein targets-vitamin D receptor (VDR), cytochrome P450 19A1 (CYP19A1), and 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1). Morphological analysis showed that severe impairment of the bone micro-architecture in OVX rats could be improved by TBD administration. The TBD-treated rats had a significantly lower bone surface-to-tissue volume (BS/TV) and a significantly smaller trabecular separation (Tb·Sp.) (P<0.05) than the OVX rats; in contrast, bone volume fraction (BVF), trabecular thickness (Tb·Th.), trabecular number (Tb·N.), and bone mineral density (BMD) were significantly higher in the TBD-treated rats (P<0.05). Multivariate and univariate analysis showed that OVX resulted in significant alterations in the concentrations of 105 metabolites and 11 metabolic pathways (P<0.05); in addition, 26 potential biomarkers were identified to investigate the progression of PMOP. Network pharmacology showed that major alterations in vitamin B6 metabolism were associated with the VDR target. Next, we validated the three crucial targets (VDR [P<0.01], HSD11B1 [P<0.01], and CYP19A1 [P<0.05]) by enzyme-linked immunosorbent assays (ELISAs) and demonstrated that the levels of these targets were elevated in the OVX group but reduced in the TBD-treatment group. Collectively, our results suggest that the interventional effects of TBD on OVX rats are likely to be associated with the down regulation of VDR. Our findings enhance our molecular understanding of the interventional effects of TBD on PMOP and will allow us to develop further TBD studies.

14.
Nucleic Acids Res ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179754

RESUMO

Cancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors but posed computational challenges on integrating and utilizing the massive published datasets to inform immunotherapy. Here, we present Tumor Immune Single Cell Hub (TISCH, http://tisch.comp-genomics.org), a large-scale curated database that integrates single-cell transcriptomic profiles of nearly 2 million cells from 76 high-quality tumor datasets across 27 cancer types. All the data were uniformly processed with a standardized workflow, including quality control, batch effect removal, clustering, cell-type annotation, malignant cell classification, differential expression analysis and functional enrichment analysis. TISCH provides interactive gene expression visualization across multiple datasets at the single-cell level or cluster level, allowing systematic comparison between different cell-types, patients, tissue origins, treatment and response groups, and even different cancer-types. In summary, TISCH provides a user-friendly interface for systematically visualizing, searching and downloading gene expression atlas in the TME from multiple cancer types, enabling fast, flexible and comprehensive exploration of the TME.

15.
EBioMedicine ; 62: 103111, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186808

RESUMO

BACKGROUND: Osteoporosis is a common metabolic bone disease, which always leads to osteoporotic fractures. Biomarkers of bone mineral density (BMD) are helpful for prevention and early diagnosis of osteoporosis. This study aims to identify metabolomic biomarkers of low BMD. METHODS: We included 701 participants who had BMD measures by dual-energy X-ray absorptiometry scans and donated fasting plasma samples from three clinical centres as a discovery set and another 278 participants from the fourth centre as an independent replication set. We used a liquid chromatography-mass spectrometry-based metabolomics approach to profile the global metabolites of fasting plasma. FINDINGS: Among the 265 named metabolites identified in our study, six were associated with low BMD (FDR-adjusted P<0.05) in the discovery set and were successfully validated in the independent replication set. The circulating levels of five metabolites, i.e., inosine, hypoxanthine, PC (O-18:0/22:6), SM (d18:1/21:0) and isoleucyl-proline were associated with decreased odds of low BMD, and PC (16:0/18:3) level was associated with increased odds of low BMD. Per 1-SD increase in a composite metabolite score of these six metabolites was associated with about half decreased odds of low BMD (odds ratio 0.59, 95% confidence interval: 0.52-0.68). Furthermore, introduction of a panel of metabolites selected by elastic net regression to a prediction model of classical risk factors and plasma biomarker of bone resorption substantially improved the prediction performance for low BMD (AUCs: 0.782 vs. 0.698, P=0.002). INTERPRETATION: Metabolomics profiling may help identify novel biomarkers of low BMD and be helpful for early diagnosis of osteoporosis beyond the current clinical index. FUNDING: This study was supported by the National Key R&D Program of China [2018YFC2001500 to J.S.], Shanghai Municipal Science and Technology Major Project [2017SHZDZX01], the National Natural Science Foundation of China [Key Program, 91749204 to J.S.], the National Natural Science Foundation of China [General Program, 81771491 to J.S.], the Project of Shanghai Subject Chief Scientist [2017BR011 to J.S.], Grants from the TCM Supported Project [18431902300 to J.S.] from the Science and Technology Commission of Shanghai Municipality, and the National Natural Science Foundation of China [General Program, 81972089 to Z.X.]. Y.Z. was supported by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, and the National Natural Science Foundation of China [81973032].

16.
ACS Chem Neurosci ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225685

RESUMO

Cerebral ischemia is accompanied by mitochondrial integrity destruction. Thus, reversion of mitochondrial damage holds great potential for cerebral ischemia therapy. As a crucial Bcl-2 family member, pro-apoptotic Bax protein is a main effector of mitochondrial permeabilization and plays an important role in mitochondrial homeostasis. However, there is still a lack of an effective cerebral protective strategy through selectively targeting Bax. In this study, we reported that natural small-molecule protosappanin A (PTA) showed a significant mitochondrial protective effect on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cells injury through increasing ATP production and maintaining mitochondrial DNA (mtDNA) content. The mechanism study revealed that PTA selectively induced pro-apoptotic protein Bax degradation, without affecting other Bcl-2 family members such as Bcl-2, Bcl-xl, Bad, Puma, Bid, Bim, and Bik. In addition, we found that PTA promoted the association of autophagosomal marker LC3B to Bax for its degradation via an autophagy-dependent manner but not the ubiquitin-proteasome pathway. Collectively, our findings offered a new pharmacological strategy for maintaining mitochondrial function by inducing autophagic degradation of Bax and also provided a novel drug candidate against ischemic neuronal injury.

17.
Int J Rheum Dis ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226736

RESUMO

OBJECTIVE: This study explored differences between primary Sjögren's syndrome-associated interstitial lung disease (pSS-ILD) patients with and without ILD progression, and analyzed the factors affecting the progression and prognosis of pSS-ILD. METHODS: This study is a retrospective cohort study which enrolled 113 pSS-ILD patients hospitalized between 2011 and 2017. RESULTS: The 3-year survival rate of the pSS-ILD patients was 91.15%, and the 5-year survival rate was 84.07%. Univariate analysis showed that Raynaud's syndrome, hypoproteinemia, extensive lung involvement, possible usual interstitial pneumonia pattern were risk factors for the progression of ILD in patients with pSS-ILD, and cyclophosphamide was a protective factor for the progression of ILD in patients with pSS-ILD. Multiple logistic regression analysis showed that extensive lung involvement (odds ratio 4.143, 95% CI: 1.203-14.267, P < .05) was an independent risk factor for the progression of pSS-ILD. Cox hazard analysis showed that pSS-ILD with hypoproteinemia (hazard ratio [HR] 17.758, 95% CI: 4.753-66.340, P <- .05) and extensive lung involvement (HR 3.450, 95% CI: 1.419-8.390, P < .05) were associated with worse survival of patients. CONCLUSION: Extensive lung involvement is an independent risk factor for the progression of ILD in patients with pSS-ILD. Hypoproteinemia and extensive lung involvement are independent risk factors for mortality in patients with pSS-ILD, after controlling for potentially influential variables.

18.
Virol J ; 17(1): 171, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168022

RESUMO

BACKGROUND: The SureX HPV genotyping test (SureX HPV test), which targets the human papillomavirus (HPV) E6/E7 genes was compared with the Cobas 4800 and Venus HPV tests for detecting 14 high-risk HPV (HR-HPV) types in clinical referral and follow-up patients to evaluate its value for cervical cancer screening. METHODS: Two different populations were enrolled in the study. The first population comprised 185 cases and was used for comparing the SureX HPV test (Health, China) with the Cobas 4800 test (Roche, USA). The second population comprised 290 cases and was used for comparing the SureX HPV test (Health, China) with the Venus HPV test (Zhijiang, China). Polymerase chain reaction (PCR) sequencing was performed for further confirmation of discordant results. RESULTS: In the first population, the overall agreement rate was 95.6% for 14 high-risk HPV types. Eight discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 75.0% between the SureX HPV test and PCR sequencing and 25.0% between the Cobas 4800 test and PCR sequencing (P < 0.01). In the second population, the overall agreement rate was 95.5%. Thirteen discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 76.9% between the SureX HPV test and PCR sequencing and 23.1% between the Venus HPV test and PCR sequencing (P < 0.01). With cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the sensitivity values of the SureX HPV test and the Venus HPV test were 93.5% and 92.0%, (P > 0.05), while the specificity values were 43.3% and 46.7%, respectively (P > 0.05). CONCLUSION: The SureX HPV test had good consistency with both the Cobas 4800 and Venus HPV tests for 14 HR-HPV types. In addition, it avoided some false negatives and false positives. Therefore, the SureX HPV test can be used for cervical cancer screening.

19.
Can Assoc Radiol J ; : 846537120968782, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151087

RESUMO

BACKGROUND: Radiomic features in pancreatic ductal adenocarcinoma (PDAC) often lack validation in independent test sets or are limited to early or late stage disease. Given the lethal nature of PDAC it is possible that there are similarities in radiomic features of both early and advanced disease reflective of aggressive biology. PURPOSE: To assess the performance of prognostic radiomic features previously published in patients with resectable PDAC in a test set of patients with unresectable PDAC undergoing chemotherapy. METHODS: The pre-treatment CT of 108 patients enrolled in a prospective chemotherapy trial were used as a test cohort for 2 previously published prognostic radiomic features in resectable PDAC (Sum Entropy and Cluster Tendency with square-root filter[Sqrt]). We assessed the performance of these 2 radiomic features for the prediction of overall survival (OS) and time to progression (TTP) using Cox proportional-hazard models. RESULTS: Sqrt Cluster Tendency was significantly associated with outcome with a hazard ratio (HR) of 1.27(for primary pancreatic tumor plus local nodes), (Confidence Interval(CI):1.01 -1.6, P-value = 0.039) for OS and a HR of 1.25(CI:1.00 -1.55, P-value = 0.047) for TTP. Sum entropy was not associated with outcomes. Sqrt Cluster Tendency remained significant in multivariate analysis. CONCLUSION: The CT radiomic feature Sqrt Cluster Tendency, previously demonstrated to be prognostic in resectable PDAC, remained a significant prognostic factor for OS and TTP in a test set of unresectable PDAC patients. This radiomic feature warrants further investigation to understand its biologic correlates and CT applicability in PDAC patients.

20.
Pharm Biol ; 58(1): 1115-1122, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33191819

RESUMO

CONTEXT: Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown. OBJECTIVE: This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury. MATERIALS AND METHODS: 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor ß (TGF-ß)/Smad pathway were conducted on renal tissues. RESULTS: Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II. CONCLUSION: FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-ß/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.

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