Publications by authors named "Ru Jia"

133 Publications

Visualizing veins from color images under varying illuminations for medical applications.

J Biomed Opt 2021 Sep;26(9)

Nanjing University of Aeronautics and Astronautics, College of Automation Engineering, Nanjing, Jian, China.

Significance: Effective vein visualization is critically important for several clinical procedures, such as venous blood sampling and intravenous injection. Existing technologies using infrared device or ultrasound rely on professional equipment and are not suitable for daily medical care. A regression-based vein visualization method is proposed.

Aim: We visualize veins from conventional RGB images to provide assistance in venipuncture procedures as well as clinical diagnosis of some venous insufficiency.

Approach: The RGB images taken by digital cameras are first transformed to spectral reflectance images using Wiener estimation. Multiple regression analysis is then applied to derive the relationship between spectral reflectance and the concentrations of pigments. Monte Carlo simulation is adopted to get prior information. Finally, vein patterns are visualized from the spatial distribution of pigments. To minimize the effect of illumination on skin color, light correction and shading removal operations are performed in advance.

Results: Experimental results from inner forearms of 60 subjects show the effectiveness of the regression-based method. Subjective and objective evaluations demonstrate that the clarity and completeness of vein patterns can be improved by light correction and shading removal.

Conclusions: Vein patterns can be successfully visualized from RGB images without any professional equipment. The proposed method can assist in venipuncture procedures. It also shows promising potential to be used in clinical diagnosis and treatment of some venous insufficiency.
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http://dx.doi.org/10.1117/1.JBO.26.9.096006DOI Listing
September 2021

Assessment of PD-L1 Expression on Circulating Tumor Cells for Predicting Clinical Outcomes in Cancer Patients Receiving PD-1/PD-L1 Blockade Therapies.

Oncologist 2021 Sep 13. Epub 2021 Sep 13.

Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.

Background: PD-1/PD-L1 blockade immunotherapies have changed the landscape of cancer therapy. However, the main limitation of these therapies is the lack of definitively predictive biomarkers to predict treatment response. Whether PD-L1 expression on circulating tumor cells (CTCs) is associated with the clinical outcomes of immunotherapy remains to be extensively investigated.

Methods: 155 patients with different advanced cancers were enrolled in this study and treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs). Using the [email protected] method, CTCs were isolated and enumerated. The PD-L1 expression levels were analyzed by an immunofluorescence assay for semiquantitative assessment with four categories (negative, low, medium and high).

Results: Prior to immunotherapy, 81.93% (127/155) of patients had PD-L1-positive CTCs, and 71.61% (111/155) had at least one PD-L1-high CTC. The group with PD-L1-positive CTCs had a higher disease control rate (DCR) (71.56%, 91/127), with a DCR of only 39.29% (11/28) for the remaining individuals (P=0.001). The objective response rate (ORR) and DCR in PD-L1-high patients were higher than those in the other patients (32.44% vs 13.64%, P=0.018 and 75.68% vs 40.91%, P<0.0001, respectively). The reduction in the counts and ratios of PD-L1-positive CTCs and PD-L1-high CTCs reflected a beneficial response to PD-1/PD-L1 inhibitors. Furthermore, patients with PD-L1-high CTCs had significantly longer progression-free survival (PFS) (4.9 vs 2.2 months, P<0.0001) and overall survival (OS) (16.1 vs 9.0 months, P=0.0235) than those without PD-L1-high CTCs.Conclusions The PD-L1 level on CTCs may serve as a clinically actionable biomarker for immunotherapy, and its dynamic changes could predict the therapeutic response.

Implications For Practice: This study was designed to investigate the role of PD-L1 expression on circulating tumor cells in predicting and monitoring response to PD-1/PD-L1 blockade immunotherapies in patients with advanced cancer. The results of the study showed that PD-L1-high expression CTCs were both a predictive biomarker and a prognostic factor in patients with advanced cancer treated with anti-PD-1/PD-L1 mAbs. These observations suggest that PD-L1 level on CTCs is a potential clinical biomarker for immunotherapy.
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http://dx.doi.org/10.1002/onco.13981DOI Listing
September 2021

A method to establish a chronic restraint stress mouse model with colorectal cancer xenografts.

MethodsX 2021 10;8:101304. Epub 2021 Mar 10.

Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Colorectal cancer (CRC) remains one of the most common clinical cancers of digestive tract. Recently, a large number of researches have shown that chronic stress can actively participate in the development of CRC. The proposed method successfully established the model of chronic stress mouse model with colorectal cancer.•Chronic restraint stress (CRS) was used to establish chronic stress model.•CRS was combined with a colorectal cancer xenografts model.•Behavioural tests and tumour growth were used to evaluate model construction.
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http://dx.doi.org/10.1016/j.mex.2021.101304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374275PMC
March 2021

The effect of choice interventions on retention-related, behavioural and mood outcomes: a systematic review with meta-analysis.

Health Psychol Rev 2021 Sep 16:1-37. Epub 2021 Sep 16.

Division of Primary Care, School of Medicine, University of Nottingham, Nottingham, UK.

The provision of choice within interventions has been associated with increased motivation, engagement and interest, as well as improved clinical outcomes. Existing reviews are limited by their wide inclusion criteria or by not assessing behaviour change and mood outcomes. This review examines whether participant-driven choice-based interventions specifically are more likely to be enjoyed and accepted by participants compared to no-choice interventions, and whether this impacts on intervention outcomes in terms of behaviour change or mood. Forty-four randomised controlled trials were identified for inclusion. Random effects meta-analyses were performed for retention-related outcomes (drop-out, adherence and satisfaction), and aggregate behaviour change and mood outcomes. Choice-based interventions resulted in significantly less participant drop-out and increased adherence compared to interventions not offering choice. Results for the behaviour change and mood analyses were mixed. This meta-analytic review demonstrates that choice-based interventions may enhance participant retention and adherence, thus researchers and clinicians alike should consider the provision of choice when designing research and interventions. The evidence for the role of choice in behaviour change and mood is less convincing, and there is a need for more, higher quality research in this area.
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http://dx.doi.org/10.1080/17437199.2021.1962386DOI Listing
September 2021

A single-arm, multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.

Cancer 2021 Aug 6. Epub 2021 Aug 6.

Clinical Development and Regulatory Affairs, Hutchison MediPharma, Shanghai, China.

Background: Several clinical studies of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) therapy as a second-line treatment for biliary tract cancer (BTC) have shown modest efficacy. In this study, surufatinib was evaluated as a second-line VEGFR therapy in patients with BTC.

Methods: This was a single-arm, multicenter, open-label phase 2 study conducted in China. The study enrolled eligible patients with BTC, who had received surufatinib monotherapy as second-line treatment, at a dose of 300 mg, once daily, in 28-day cycles. Tumor assessments were performed every 8 weeks (±7 days) according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Results: As of November 30, 2018, 39 patients with BTC, including 29 (74.4%) with intrahepatic cholangiocarcinoma, 5 (12.8%) with extrahepatic cholangiocarcinoma, and 5 (12.8%) with gallbladder cancer, were enrolled and treated with surufatinib. The 16-week progression-free survival rate was 46.33% (95% CI, 24.38-65.73), with median progression-free survival of 3.7 months and median overall survival of 6.9 months. In addition, results from subgroup and post hoc analyses revealed that patients with the proper tumor locations or appropriate levels of serum biomarkers might receive greater clinical benefits. The top 3 treatment-related adverse events with severity of grade ≥3 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%).

Conclusions: When applied in the treatment of patients with BTC, surufatinib monotherapy has offered moderate clinical efficacy and shown expected tolerability and safety profiles.
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http://dx.doi.org/10.1002/cncr.33803DOI Listing
August 2021

Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR.

J Med Chem 2021 Aug 23;64(15):11219-11228. Epub 2021 Jul 23.

Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.

It is very promising to target the extracellular domain of epidermal growth factor receptor (EGFR) for developing novel and selective anticancer therapies. Herein, we report the discovery of a novel small molecule, , from a one-bead-two-compound (OBTC) cyclic γ-AApeptide library. The molecule was found to bind tightly to the extracellular domain of EGFR. Intriguingly, this molecule could also effectively antagonize EGF-stimulated EGFR phosphorylation and downstream signal transduction. Furthermore, together with its remarkable resistance to proteolytic degradation, was shown to effectively inhibit cell proliferation and migration in vitro and suppresses the growth of tumor in the A549 xenograft model in vivo, highlighting its potential therapeutic application for cancer treatment.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00607DOI Listing
August 2021

Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.

Phytomedicine 2021 Jul 24;88:153606. Epub 2021 May 24.

Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Background: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear.

Purpose: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms.

Methods: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored.

Results: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling.

Conclusions: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.
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http://dx.doi.org/10.1016/j.phymed.2021.153606DOI Listing
July 2021

Doping-Enabled Reconfigurable Strongly Correlated Phase in a Quasi-2D Perovskite.

J Phys Chem Lett 2021 Jun 24;12(21):5091-5098. Epub 2021 May 24.

Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, United States.

Highlighted by the discovery of high-temperature superconductivity, strongly correlated oxides with highly distorted perovskite structures serve as intriguing model systems for pursuing emerging materials physics and testing technological concepts. While 3d correlated oxides with a distorted perovskite structure are not uncommon, their 4d counterparts are unfortunately rare. In this work, we report the tuning of the electrical and optical properties of a quasi-2D perovskite niobate CsBiNbO via hydrogenation. It is observed that hydrogenation induces drastic changes of lattice dynamics, optical transmission, and conductance. It is suggested that changing the orbital occupancy of Nb d orbitals could trigger the on-site Coulomb interaction in the NbO octahedron. The observed hydrogen doping-induced electrical plasticity is implemented for simulating neural synaptic activity. Our finding sheds light on the role of hydrogen in 4d transition metal oxides and suggests a new avenue for the design and development of novel electronic phases.
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http://dx.doi.org/10.1021/acs.jpclett.1c00353DOI Listing
June 2021

PEG-poly(amino acid)s/EpCAM aptamer multifunctional nanoparticles arrest the growth and metastasis of colorectal cancer.

Biomater Sci 2021 May;9(10):3705-3717

Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. and Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Tanshinone II-A (TSIIA) is a derivative of a phenanthrene-quinone extracted from a TCM herb, Salvia miltiorrhiza, and has been widely adopted in the treatment of colorectal cancer (CRC). It is known that TSIIA can lead to the apoptosis and differentiation of certain cell lines and it suppresses the proliferation and metastasis of tumors. However, its poor water solubility and low bioavailability when taken orally have prevented this drug being utilized effectively in the body. A nanoparticle (NP) drug carrier system is a technology that can effectively improve drug utilization and targeting ability. In this study, a new NP drug carrier system is reported: EpCAM targeting TSIIA-encapsulated poly(amino acid)s NPs (EpCAM-TSIIA-NPs). The results show that this new targeted NP drug carrier system has higher cytotoxicity, better water solubility and better targeting ability, and can effectively suppress the proliferation and metastasis of tumors. In addition, the invasion and metastasis mechanism of colorectal cancer (CRC) under β-catenin nuclear meditation suppressed by EpCAM-TSIIA-NPs is also discussed. It is found that the immune-targeted type EpCAM-TSIIA-NPs could effectively enhance the expression of APC and axin when compared to normal NPs. It could improve the stability of β-catenin destruction complex and suppress the occurrence and progression of tumors by stopping the nuclear activities of β-catenin.
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http://dx.doi.org/10.1039/d1bm00160dDOI Listing
May 2021

Depression, anxiety and stress during the COVID-19 pandemic: results from a New Zealand cohort study on mental well-being.

BMJ Open 2021 05 3;11(5):e045325. Epub 2021 May 3.

Psychological Medicine, The University of Auckland, Auckland, New Zealand

Objectives: The COVID-19 pandemic has caused unprecedented disruption to daily life. This study investigated depression, anxiety and stress in New Zealand (NZ) during the first 10 weeks of the COVID-19 pandemic, and associated psychological and behavioural factors. It also compares the results with a similar cross-sectional study in the UK.

Design: Cross-sectional study.

Setting: NZ community cohort.

Participants: N=681 adults (≥18 years) in NZ. The cohort was predominantly female (89%) with a mean age of 42 years (range 18-87). Most (74%) identified as NZ European and almost half (46%) were keyworkers. Most were non-smokers (95%) and 20% identified themselves as having clinical risk factors which would put them at increased or greatest risk of COVID-19.

Main Outcome Measures: Depression, anxiety, stress, positive mood and engagement in health behaviours (smoking, exercise, alcohol consumption).

Results: Depression and anxiety significantly exceeded population norms (p<0.0001). Being younger (p<0.0001) and most at risk of COVID-19 (p<0.05) were associated with greater depression, anxiety and stress. Greater positive mood, lower loneliness and greater exercise were protective factors for all outcomes (p<0.0001). Smoking (p=0.037) and alcohol consumption (p<0.05) were associated with increased anxiety. Pet ownership was associated with lower depression (p=0.006) and anxiety (p=0.008). When adjusting for age and gender differences, anxiety (p0.002) and stress (p0.007) were significantly lower in NZ than in the UK. The NZ sample reported lower perceived risk (p<0.0001) and worry about COVID-19 (p<0.0001) than the UK sample.

Conclusions: The NZ population had higher depression and anxiety compared with population norms. Younger people and those most at risk of COVID-19 reported poorer mental health. Interventions should promote frequent exercise, and reduce loneliness and unhealthy behaviours.
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http://dx.doi.org/10.1136/bmjopen-2020-045325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098295PMC
May 2021

Students' Views towards Sars-Cov-2 Mass Asymptomatic Testing, Social Distancing and Self-Isolation in a University Setting during the COVID-19 Pandemic: A Qualitative Study.

Int J Environ Res Public Health 2021 04 15;18(8). Epub 2021 Apr 15.

School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK.

We aimed to explore university students' perceptions and experiences of SARS-CoV-2 mass asymptomatic testing, social distancing and self-isolation, during the COVID-19 pandemic. This qualitative study comprised of four rapid online focus groups conducted at a higher education institution in England, during high alert (tier 2) national COVID-19 restrictions. Participants were purposively sampled university students ( 25) representing a range of gender, age, living circumstances (on/off campus), and SARS-CoV-2 testing/self-isolation experiences. Data were analysed using an inductive thematic approach. Six themes with 16 sub-themes emerged from the analysis of the qualitative data: 'Term-time Experiences', 'Risk Perception and Worry', 'Engagement in Protective Behaviours', 'Openness to Testing', 'Barriers to Testing' and 'General Wellbeing'. Students described feeling safe on campus, believed most of their peers are adherent to protective behaviours and were positive towards asymptomatic testing in university settings. University communications about COVID-19 testing and social behaviours need to be timely and presented in a more inclusive way to reach groups of students who currently feel marginalised. Barriers to engagement with SARS-CoV-2 testing, social distancing and self-isolation were primarily associated with fear of the mental health impacts of self-isolation, including worry about how they will cope, high anxiety, low mood, guilt relating to impact on others and loneliness. Loneliness in students could be mitigated through increased intra-university communications and a focus on establishment of low COVID-risk social activities to help students build and enhance their social support networks. These findings are particularly pertinent in the context of mass asymptomatic testing programmes being implemented in educational settings and high numbers of students being required to self-isolate. Universities need to determine the support needs of students during self-isolation and prepare for the long-term impacts of the pandemic on student mental health and welfare support services.
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http://dx.doi.org/10.3390/ijerph18084182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071290PMC
April 2021

Effect of PRM1201 Combined With Adjuvant Chemotherapy on Preventing Recurrence and Metastasis of Stage III Colon Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Front Oncol 2021 3;11:618793. Epub 2021 Mar 3.

Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Chemotherapy is the standard adjuvant treatment for colon cancer. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting.

Methods: In this parallel-group study, patients who had undergone curative resection for stage III colon cancer were randomly assigned to receive adjuvant chemotherapy (FOLFOX q2w for 6 months, or CapeOx q3w for 6 months) plus PRM1201 (chemo+PRM1201 group) or adjuvant chemotherapy plus placebo (chemo+placebo group). The primary endpoint was disease-free survival (DFS), and the secondary endpoints were quality of life (QOL) and toxicity.

Results: A total of 370 patients were randomly assigned to chemotherapy plus PRM1201 group (n = 184) and chemotherapy plus placebo group (n = 186). Up to October 30, 2019, 96 events of recurrence, metastasis, or death had been reported, of which 38 events were in the group of chemotherapy plus PRM1201 and 58 events in the chemo+placebo group. The 3-year DFS rate was 77.1 and 68.6% in the chemo+PRM1201 and chemo+placebo group, respectively (hazard ratio [HR], 0.63; 95% CI, 0.42 to 0.94). The QOL of patients in the chemo+PRM1201 group were significantly improved in terms of global quality of life, physical functioning, role functioning, emotional functioning, fatigue, and appetite loss. The incidence of grade 3 or 4 treatment-related adverse event (TRAEs) were similar between the two arms.

Conclusions: Chemotherapy in combination with PRM1201 improved the adjuvant treatment of colon cancer. PRM1201 can be recommended as an effective option in clinical practice.

Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR-IOR-16007719.
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http://dx.doi.org/10.3389/fonc.2021.618793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968418PMC
March 2021

A Prospective Randomized, Double-blind Study to Evaluate the Safety, Biodistribution, and Dosimetry of Ga-NODAGA-LM3 and Ga-DOTA-LM3 in Patients with Well-differentiated Neuroendocrine Tumors.

J Nucl Med 2021 Feb 12. Epub 2021 Feb 12.

The First Affiliated Hospital of Fujian Medical University.

Ga-NODAGA-LM3 and Ga-DOTA-LM3 are somatostatin receptor subtype 2 (SSTR2) specific antagonists used for PET/CT imaging. The purpose of this study was to evaluate the safety, biodistribution, and dosimetry of Ga-NODAGA-LM3 and Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors (NETs). Patients were equally randomized into two arms: Arm A, Ga-NODAGA-LM3; Arm B, Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 minutes after Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg total peptide mass) or Ga-DOTA-LM3 (172 MBq ± 21 MBq/40 μg total peptide mass) injection. The biodistribution in normal organs, tumor uptake, and safety were assessed. Radiation dosimetry was calculated using OLINDA/EXM (version 1.0). Sixteen patients, 8 in each arm, were recruited in the study. Both tracers were well tolerated in most patients. Two patients in Arm B had nausea (G2) and one of them had vomiting (G1). The PET images of other fourteen patients were further analyzed. Significantly lower organ uptake was observed in the pituitary, parotids, liver, spleen, pancreas, adrenal, stomach, small intestine, and kidneys with Ga-DOTA-LM3 compared to Ga-NODAGA-LM3. A total of 38 lesions were analyzed, including 18 lesions on Ga-NODAGA-LM3 and 20 lesions on Ga-DOTA-LM3. Both tracers showed good tumor uptake and retention. With Ga-NODAGA-LM3, the tracer accumulation in tumor lesions increased by 138%, from an average SUV of 31.3 ± 19.7 at 5 minutes to 74.6 ± 56.3 at 2h. With Ga-DOTA-LM3, the tumor uptake rapidly reached a high level at 5 minutes after injection, with an average SUV of 36.6 ± 23.6, and continued to increase to 45.3 ± 29.3 until 30 minutes post-injection. Urinary bladder wall is the organ receiving the highest absorbed dose in both arms. The mean effective dose was 0.026 ± 0.003 mSv/MBq for Ga-NODAGA-LM3 and 0.025 ± 0.002 mSv/MBq for Ga-DOTA-LM3. Both Ga-NODAGA-LM3 and Ga-DOTA-LM3 show favorable biodistribution, high tumor uptake, and good tumor retention, resulting in high image contrast. The dosimetric data is comparable to other Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of Ga-NODAGA-LM3 and Ga-DOTA-LM3.
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http://dx.doi.org/10.2967/jnumed.120.253096DOI Listing
February 2021

Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis.

Cancer Cell Int 2021 Jan 7;21(1):29. Epub 2021 Jan 7.

Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.

Background: Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer.

Methods: RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry.

Results: Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo.

Conclusion: Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.
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http://dx.doi.org/10.1186/s12935-020-01682-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792070PMC
January 2021

Protective effects of Bacillus subtilis ASAG 216 on growth performance, antioxidant capacity, gut microbiota and tissues residues of weaned piglets fed deoxynivalenol contaminated diets.

Food Chem Toxicol 2021 Feb 4;148:111962. Epub 2021 Jan 4.

School of Life Science, Shanxi University, 92 Wucheng Road, Taiyuan, 030006, Shanxi, China.

Deoxynivalenol (DON) poses a serious health threat to animals and humans consuming DON-contaminated food and feed. Biological means of detoxification of DON are considered as one of the effective strategies. The aim of the work was to study ameliorative effects of Bacillus subtilis ASAG 216 on DON-induced toxicosis in piglets. A decrease in average daily gain and average daily feed intake was observed in piglets fed DON-contaminated feed. In addition, DON exposure increased the serum concentrations of aspartate aminotransferase, immunoglobulin A, diamine oxidase, endotoxin, and peptide YY. Moreover, DON exposure caused oxidative stress in the serum, liver and jejunum, induced intestinal inflammation, impaired the intestinal barrier, and disturbed the gut microbiota homeostasis. Supplementation of B. subtilis ASAG 216 effectively attenuated the aforementioned effects of DON on piglets. Moreover, DON and de-epoxy-DON (DOM-1) in the serum, liver and kidney were significantly decreased when B. subtilis ASAG 216 was added to DON-contaminated diet. Our results imply that B. subtilis ASAG 216 can protect against DON-induced toxicosis in piglets, and thus this strain has a potential to be used as an animal feed ingredient to counteract harmful effects of DON in animals.
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http://dx.doi.org/10.1016/j.fct.2020.111962DOI Listing
February 2021

Post-radiation circulating tumor DNA as a prognostic factor in locally advanced esophageal squamous cell carcinoma.

Oncol Lett 2021 Jan 25;21(1):68. Epub 2020 Nov 25.

Department of Gastrointestinal Oncology, The Fifth Medical Centre, Chinese People's Liberation Army General Hospital, Fengtai, Beijing 100071, P.R. China.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant and deadly tumor. Radiation therapy is one of the primary treatments for locally advanced ESCC. However, the biomarkers for prognosis of definitive radiation remain undefined. Peripheral blood circulating tumor (ct)DNA provides information of tumor genetic alterations and has been confirmed as a potential non-invasive biomarker for several types of cancer. The present study investigated the clinical implications of ctDNA detection in patients with ESCC and receiving definitive radiation therapy. Patients with locally advanced ESCC were retrospectively recruited. Plasma samples were collected before, during and following radiation therapy. Next-generation sequencing was performed to identify somatic mutations in 180 genes. A total of 69 baseline and post-radiation plasma samples were collected from 25 patients. A total of 59 non-silent single nucleotide variants were present in 33 genes. All pre-radiation and 58.3% (14/24) of post-radiation samples had at least one mutation. Patients with lymph node metastases (LNM) exhibited a higher number of pre-radiation mutations compared with those without LNM. The variables, progression-free survival (PFS) and overall survival (OS) of the patients with one baseline mutation were not significantly different compared with that in patients with more than one baseline mutation. Patients with initial ctDNA-positive post-radiation samples exhibited significantly reduced PFS (P=0.047) and OS (P=0.005) compared with that in patients with ctDNA-negative samples. The post-radiation plasma ctDNA status was an independent prognostic factor from univariate and multivariate analyses. Dynamic monitoring of ctDNA during follow-up was examined. The results indicated that ctDNA was a predictive and prognostic marker in patients with ESCC and receiving definitive radiation therapy, which may guide subsequent treatment.
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http://dx.doi.org/10.3892/ol.2020.12329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716704PMC
January 2021

Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis.

J Integr Med 2021 03 5;19(2):144-157. Epub 2020 Dec 5.

Department of Acupuncture and Moxibustion, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address:

Objective: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu).

Methods: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing.

Results: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.

Conclusion: Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.
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http://dx.doi.org/10.1016/j.joim.2020.12.004DOI Listing
March 2021

[Effect of Puyu Capsules on behavior,HPA axis and CREB-BDNF pathway expression in hippocampus of depressed mice].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(20):4971-4977

College of Pharmacy, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.

This study aimed to investigate the antidepressant effects of Puyu Capsules and its potential mechanism. The antidepressant activity of Puyu Capsules was evaluated by forced swimming test(FST) and tail suspension test(TST) after subchronic administration in mice. Next, the mice were subjected to a chronic unpredictable stress(CUS) protocol for a period of 28 d to induce depressive-like behaviors. Then, a sucrose preference test, open-field test and novelty-suppressed feeding test were performed to evaluate the antidepressant effect of Puyu Capsules. After the behavioral test, the adrenal index was calculated; the levels of serum corticosterone(CORT) and adrenocorticotropic hormone(ACTH) were detected by enzyme-linked immunosorbent assay(ELISA); the levels of glucocorticoid receptor(GR), protein expression of brain-derived neurotrophic factor(BDNF), and the ratio of phosphorylated cAMP response element binding protein(CREB) to total CREB were detected by Western blot to explore the antidepressant function and mechanism of Puyu Capsules. The results suggested that Puyu Capsules had significant antidepressant effects on both the depression model and CUS model. At the same time, the drug could prevent the change of adrenal index induced by CUS and reverse the abnormal activation of CORT and ACTH in the serum of depressed mice. Finally, Puyu Capsules could also reverse the lower expression of pCREB, BDNF and GR in the hippocampus of CUS mice. In conclusion, Puyu Capsules produced significant antidepressant effects, and the mechanism was closely related to hypothalamic pituitary adrenal(HPA) axis activity, GR and CREB-BDNF pathway expression.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200603.402DOI Listing
October 2020

Rice transcription factor MADS32 regulates floral patterning through interactions with multiple floral homeotic genes.

J Exp Bot 2021 03;72(7):2434-2449

Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University-University of Adelaide Joint Centre for Agriculture and Health, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Floral patterning is regulated by intricate networks of floral identity genes. The peculiar MADS32 subfamily genes, absent in eudicots but prevalent in monocots, control floral organ identity. However, how the MADS32 family genes interact with other floral homeotic genes during flower development is mostly unknown. We show here that the rice homeotic transcription factor OsMADS32 regulates floral patterning by interacting synergistically with E class protein OsMADS6 in a dosage-dependent manner. Furthermore, our results indicate important roles for OsMADS32 in defining stamen, pistil, and ovule development through physical and genetic interactions with OsMADS1, OsMADS58, and OsMADS13, and in specifying floral meristem identity with OsMADS6, OsMADS3, and OsMADS58, respectively. Our findings suggest that OsMADS32 is an important factor for floral meristem identity maintenance and that it integrates the action of other MADS-box homeotic proteins to sustain floral organ specification and development in rice. Given that OsMADS32 is an orphan gene and absent in eudicots, our data substantially expand our understanding of flower development in plants.
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http://dx.doi.org/10.1093/jxb/eraa588DOI Listing
March 2021

Young people, mental health and COVID-19 infection: the canaries we put in the coal mine.

Public Health 2020 Dec 28;189:158-161. Epub 2020 Oct 28.

Division of Primary Care, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. Electronic address:

Objectives: The number of people testing positive for Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in the UK, particularly among young adults, is increasing. We report here on the mental health of young adults and related psychological and behavioural responses to the pandemic and consider the role of these factors in fuelling the increase in coronavirus disease 2019 (COVID-19) in this group.

Methods: An online survey was completed during the first six weeks of the first UK-wide lockdown by 3097 respondents, including data for 364 respondents aged 18-24 years. The survey included measures of mental health and indices capturing related psychological and behavioural responses to the pandemic.

Results: The mental health of 18- to 24-years-olds in the first 6 weeks of lockdown was significantly poorer than that of older respondents and previously published norms: with 84% reporting symptoms of depression and 72% reporting symptoms of anxiety. Young adults also reported significantly greater loneliness and reduced positive mood, both of which were also associated with greater mental health difficulties.

Conclusions: We contend that the combination of mental health, social and economic considerations may have contributed to the rise of COVID-19 infections in young adults, and ascribing blame to this group will not aid our efforts to regain control of the disease.
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http://dx.doi.org/10.1016/j.puhe.2020.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598559PMC
December 2020

Determination of the iron bioavailability, conformation, and rheology of iron-binding proteins from Tegillarca granosa.

J Food Biochem 2021 01 28;45(1):e13517. Epub 2020 Oct 28.

College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.

The increased interest in achieving, solely through diet, the same effect on iron levels with supplementation, leads to numerous studies on iron absorption of iron binding proteins (IBPs). The characteristics of IBPs from Tegillarca granosa (T. granosa) and its iron utilization were determined to analyze their relationship. The results showed in T. granosa, Fe(ӀӀ) was main iron form in hemoglobin (TH) and that Fe(ӀӀ) and Fe(ӀӀӀ) coexisted in ferritin (TF). After in vitro digestion, TH was easier to be digested than TF, bovine hemoglobin, and bovine ferritin. In caco-2 cells model, iron bioavailability of TH also was the best, which related to TH's superior fluid properties, higher ratios of α-helix to β-sheet and amide I to amide II. These suggest TH could be used as a good source of organic iron and provide references for application of T. granosa in human nutrition. PRACTICAL APPLICATIONS: This research investigated the iron bioavailability and structural properties of iron-binding proteins from Tegillarca granosa (T. granosa). Moreover, the effects of iron absorption in bovine hemoglobin and ferritin were compared with those from T. granosa. The results showed the hemoglobin in T. granosa had better iron bioavailability and it could be a good source of iron. These data could provide a basic instruction of the application of T. granosa in functional food production.
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http://dx.doi.org/10.1111/jfbc.13517DOI Listing
January 2021

Xiaoyaosan slows cancer progression and ameliorates gut dysbiosis in mice with chronic restraint stress and colorectal cancer xenografts.

Biomed Pharmacother 2020 Dec 28;132:110916. Epub 2020 Oct 28.

Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Depression is a risk factor for colorectal cancer (CRC) progression. Xiaoyaosan (XYS) is a traditional Chinese medicine prescription for treating depression. Our present study aimed to investigate the effect of XYS on chronic restraint stress (CRS) in mice with CRC xenografts and explore its underlying mechanisms. XYS treatment for 21 consecutive days successfully reduced the tumour volume and tumour weight in mice and prolonged the overall survival time. In addition, the intestinal permeability in the XYS group was significantly improved after administration. The 16S rRNA high-throughput sequencing method was used to sequence stool samples to check the structure and changes of gut bacteria. XYS mainly regulated the abundance of Bacteroides, Lactobacillus, Desulfovibrio and Rikenellaceae. Taken together, these results provide direct strong evidence that XYS effectively improves the progression of CRC in CRS-handled mice, and its efficacy is associated with the modulation of gut dysbiosis. The application of XYS can be a novel therapeutic strategy for CRC patients with depression.
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http://dx.doi.org/10.1016/j.biopha.2020.110916DOI Listing
December 2020

CD47 Enhances Cell Viability and Migration Ability but Inhibits Apoptosis in Endometrial Carcinoma Cells via the PI3K/Akt/mTOR Signaling Pathway.

Front Oncol 2020 26;10:1525. Epub 2020 Aug 26.

Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.

To measure expression levels of CD47 during endometrial carcinoma development, and to determine specific modulatory effects. CD47 expression levels in endometrial carcinoma tissues and adjacent tissues were analyzed using qRT-PCR. CD47-overexpressed or downregulated cell models were established using CD47 plasmid or CD47 shRNA. The effects of CD47 on HEC-1A and Ishikawa cell growth were evaluated using CCK-8 assays. Migration ability of transfected HEC-1A and Ishikawa cells were examined using wound healing assays. Flow cytometry was used to measure the effects of CD47 on apoptosis and the cell cycle in HEC-1A and Ishikawa cells. Western blot was used to analyze the correlation between CD47 expression level and PI3K/Akt/mTOR signaling pathway. Highly expressed CD47 was observed in endometrial carcinoma tissues, with higher levels in more advanced tissues than in early tissues. Upregulation of CD47 enhanced cell viability and migration ability in HEC-1A and Ishikawa cells, while silencing CD47 caused the opposite results. CD47 overexpression suppressed apoptosis and inhibited cell cycle arrest in HEC-1A and Ishikawa cells. CD47 upregulation contributes to the activation of PI3K/Akt/mTOR signaling pathway in endometrial carcinoma cells. CD47 exerts oncogenic functions in endometrial carcinoma by activating PI3K/Akt/mTOR signaling, suggesting it may be a novel immunotherapeutic target for therapeutic interventions.
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http://dx.doi.org/10.3389/fonc.2020.01525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479237PMC
August 2020

Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study.

Lancet Oncol 2020 11 20;21(11):1500-1512. Epub 2020 Sep 20.

Department of Clinical Development and Regulatory Affairs, Hutchison MediPharma, Shanghai, China.

Background: Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs.

Methods: SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov, NCT02588170. Follow-up is ongoing.

Findings: Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1-16·7) in the surufatinib group and 16·6 months (9·2-not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4-11·1) in the surufatinib group versus 3·8 months (3·7-5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22-0·50; p<0·0001). As the trial met the predefined criteria for early discontinuation of the study at the interim analysis, the study was terminated early, as recommended by the independent data monitoring committee. The most common treatment-related adverse events of grade 3 or worse were hypertension (47 [36%] of 129 patients in the surufatinib group vs nine [13%] of 68 patients in the placebo group) and proteinuria (25 [19%] vs zero). Treatment-related serious adverse events were reported in 32 (25%) of 129 patients in the surufatinib group and nine (13%) of 68 patients in the placebo group. Treatment-related deaths occurred in three patients in the surufatinib group (disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown reason) and one patient in the placebo group (cachexia and respiratory failure).

Interpretation: Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population.

Funding: Hutchison MediPharma.
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http://dx.doi.org/10.1016/S1470-2045(20)30496-4DOI Listing
November 2020

Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study.

Lancet Oncol 2020 11 20;21(11):1489-1499. Epub 2020 Sep 20.

Department of Clinical and Regulatory Affairs, Hutchison MediPharma, Shanghai, China.

Background: Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients with advanced pancreatic NETs.

Methods: SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient's best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821.

Findings: Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3-19·4) in the surufatinib group and 11·1 months (5·7-35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5-13·8) for surufatinib versus 3·7 months (2·8-5·6) for placebo (hazard ratio 0·49, 95% CI 0·32-0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 [38%] of 113 with surufatinib vs four [7%] of 59 with placebo), proteinuria (11 [10%] vs one [2%]), and hypertriglyceridaemia (eight [7%] vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage [possibly treatment-related] and cerebral haemorrhage [unlikely to be treatment-related]), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression.

Interpretation: Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population.

Funding: Hutchison MediPharma.
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http://dx.doi.org/10.1016/S1470-2045(20)30493-9DOI Listing
November 2020

Effect of sodium butyrate on ABC transporters in lung cancer A549 and colorectal cancer HCT116 cells.

Oncol Lett 2020 Nov 24;20(5):148. Epub 2020 Aug 24.

Department of Anorectal Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230000, P.R. China.

Histone deacetylase (HDAC) inhibitors and DNA alkylators are effective components of combination chemotherapy. The aim of the present study was to investigate the possible mechanism of their synergism by detecting the effect of HDAC inhibitors on the expression levels of drug transporters that export DNA alkylators. It was demonstrated that the HDAC inhibitor sodium butyrate (NaB) induced the differential expression of multidrug resistant ATP-binding cassette (ABC) transporters in lung cancer and colorectal cancer cells. Specifically, NaB increased the mRNA expression levels of and , and protein expression levels of multidrug resistance-1 (MDR1), multidrug resistance-associated protein 7 (MRP7) and MRP9. Moreover, NaB decreased the expression levels of and mRNAs, as well as those of MRP1, MRP2 and MRP3 proteins. The molecular mechanism underlying this process was subsequently investigated. NaB decreased the expression of HDAC4, but not HDAC1, HDAC2 or HDAC3. In addition, NaB promoted histone H3 acetylation and methylation at lysine 9, as well as MDR1 acetylation, suggesting that acetylation and methylation may be involved in NaB-mediated ABC transporter expression. Thus, the present results indicated that the synergism of the HDAC inhibitors with the DNA alkylating agents may due to the inhibitory effect of MRPs by HDAC inhibitors. The findings also suggested the possibility of antagonistic effects following the combined treatment of HDAC inhibitors with MDR1 ligands.
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http://dx.doi.org/10.3892/ol.2020.12011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471751PMC
November 2020

Mental health in the UK during the COVID-19 pandemic: cross-sectional analyses from a community cohort study.

BMJ Open 2020 09 15;10(9):e040620. Epub 2020 Sep 15.

Division of Primary Care, University of Nottingham, Nottingham, UK

Objectives: Previous pandemics have resulted in significant consequences for mental health. Here, we report the mental health sequelae of the COVID-19 pandemic in a UK cohort and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the first wave of data collection, which examined short-term consequences for mental health, as reported during the first 4-6 weeks of social distancing measures being introduced.

Design: Cross-sectional online survey.

Setting: Community cohort study.

Participants: N=3097 adults aged ≥18 years were recruited through a mainstream and social media campaign between 3 April 2020 and 30 April 2020. The cohort was predominantly female (n=2618); mean age 44 years; 10% (n=296) from minority ethnic groups; 50% (n=1559) described themselves as key workers and 20% (n=649) identified as having clinical risk factors putting them at increased risk of COVID-19.

Main Outcome Measures: Depression, anxiety and stress scores.

Results: Mean scores for depression ([Formula: see text] =7.69, SD=6.0), stress ([Formula: see text] =6.48, SD=3.3) and anxiety ([Formula: see text] = 6.48, SD=3.3) significantly exceeded population norms (all p<0.0001). Analysis of non-modifiable factors hypothesised to be associated with mental health outcomes indicated that being younger, female and in a recognised COVID-19 risk group were associated with increased stress, anxiety and depression, with the final multivariable models accounting for 7%-14% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54%-57% of total variance.

Conclusions: Increased psychological morbidity was evident in this UK sample and found to be more common in younger people, women and in individuals who identified as being in recognised COVID-19 risk groups. Public health and mental health interventions able to ameliorate perceptions of risk of COVID-19, worry about COVID-19 loneliness and boost positive mood may be effective.
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http://dx.doi.org/10.1136/bmjopen-2020-040620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493070PMC
September 2020

[Rural environmental sanitation in the central, southern and northern regions of Shaanxi Province in 2018].

Wei Sheng Yan Jiu 2020 Jul;49(4):540-545

Shaanxi Provincial Center for Disease Control and Prevention, Xi'an 710054, China.

Objective: To understand the rural sanitary conditions in different geographical areas of Shaanxi Province.

Methods: According to the stratified random sampling method, 30 agriculture-related counties were selected(The central area includes 13 counties in Xi'an, Tongchuan, Weinan, Xianyang and Baoji cities. The southern area includes 10 counties in Hanzhong, Ankang, Shangluo cities. The northern area includes 7 counties in Yulin, Yan'an cities. ). Five townships were selected randomly in each county(excluding Chengguan Town), and 4 administrative villages were selected randomly in each township as survey villages, which were collected the soil samples for testing lead, cadmium and chromium in each subject village, and 5 households were randomly selected in each villages as survey households. The data was obtained through data reading, interviews, on-site observations, and laboratory testing, etc. The detection of soil lead and cadmium was carried out according to the Measurement of Soil Quality Lead and Cadmium by Graphite Furnace Atomic Absorption Spectrophotometry(GB/T 17141-1997), and the detection of chromium was carried out according to the Determination of Total Chromium in Soil by Flame Atomic Absorption Spectrometry(HJ 491). The data was statistically analyzed and evaluated according to the central, southern and northern regions.

Results: The population coverage of rural centralized water supply in the three regions(central、southern and northern area) was 92. 86%, 75. 49% and 70. 41%, respectively. The penetration rate of sanitary toilets was 28. 18%, 45. 38% and 9. 90%, respectively. The proportion of villages where domestic garbage was randomly stacked was 0. 38%, 4. 00% and 32. 86%, respectively. The proportion of villages where domestic sewage was randomly discharged was 30. 38%, 40. 00% and 60. 00%, respectively. The heavy metals exceeding the standard in the soil were mainly cadmium. The over-standard rates were 4. 62%, 21. 50% and 0. 71%, respectively. The three regional differences of the above result were statistically significant(χ~2=57 676. 74, 18 143. 94, 124. 86, 33. 15 and 54. 12, P<0. 01).

Conclusion: There was still some decentralized water supply population in the province. The coverage rate of the centralized water supply population and the proportion of drinking water after complete treatment projects were both higher in the central area than in the southern area and northern area. Sanitation toilets have a low penetration rate in the province, which was higher in the southern area than in the central area and the northern area. The domestic garbage was randomly discarded, and domestic sewage was randomly discharged, which was more in the northern area than in the central area and the southern area. Soil cadmium pollution was relatively heavy, mainly in the southern area.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2020.04.003DOI Listing
July 2020

Effect of laver powder on textual, rheological properties and water distribution of squid (Dosidicus gigas) surimi gel.

J Texture Stud 2020 12 11;51(6):968-978. Epub 2020 Sep 11.

College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.

In order to ameliorate the gel quality of Dosidicus gigas surimi, the effects of laver powder on gel properties, rheological properties, and water-holding capacity (WHC) were investigated. Results indicated that the addition of laver powder could significantly increase the hardness, chewiness, and breaking force of surimi gels. However, the texture indexes and gel strength began to decline when additional amount exceeded 0.6%. Rheological results demonstrated that the addition of laver powder increased the storage modulus (G') and viscosity of surimi, prolonged protein denaturation temperature in surimi gels. Moreover, the WHC of surimi gel was improved with the increase of laver powder. Further analyses in low-field nuclear magnetic resonance revealed that laver powder could shorten the transverse relaxation time, enhanced the combination with water, and altered the distribution of different water categories. The proportion of bound water and immobilized water reached its maximum and minimum at 0.6% of laver powder, respectively. Correlation analyses showed that WHC of surimi gel was negatively correlated well with the proportion of loose-bound water, but positively correlated with the strong-bound water and free water. In conclusion, the results supported that 0.6% was the optimal additional amount of laver powder for the squid-based surimi production based on the current ingredients of surimi products.
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http://dx.doi.org/10.1111/jtxs.12556DOI Listing
December 2020

Pharmacological evidence for the involvement of ryanodine receptors in halothane-induced liver injury in mice.

Toxicology 2020 10 11;443:152560. Epub 2020 Aug 11.

Department of Drug Safety Sciences, Division of Clinical Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan. Electronic address:

Drug-induced liver injury (DILI) is a major safety concern in drug development. Halothane (HAL), an inhaled anesthetic, induces severe and idiosyncratic liver injury. Ryanodine receptors (RyR) are major intracellular calcium release channels found on the plasma membrane of the endoplasmic reticulum (ER). It has been reported that disordered hepatic calcium homeostasis is a feature of HAL-induced liver injury (HILI) in guinea pigs. However, there are no reports on whether RyR could mediate the pathogenesis of HILI. The aim of the present study was to investigate the effect of RyR on HILI. Ryanodine (RYA, RyR agonist, 50 μg/kg, i.p.) was administered to BALB/c female mice 1 h before HAL administration (15 mmol/kg, i.p.), which significantly elevated plasma transaminase levels and induced severe hepatic inflammation and necrosis. In contrast, dantrolene sodium (DAN, RyR antagonist) treatment significantly suppressed HILI in a dose- and time-dependent manner and alleviated liver damage. The number of infiltrated neutrophils in the liver were higher in the group treated with HAL + RYA than in the group treated with HAL alone, while DAN treatment decreased neutrophil infiltration in HILI. The hepatic mRNA levels of proinflammatory cytokines; chemokines; and factors related to danger signals, neutrophils, oxidative and ER stress, pro-apoptosis, and RyR were significantly increased with RYA pretreatment, whereas these levels were decreased with DAN treatment. These results suggest that RYA exacerbates HILI, and DAN exerts a protective effect against HILI. Hence, our study provides a novel insight regarding the effect of RyR in the mechanism underlying HILI.
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http://dx.doi.org/10.1016/j.tox.2020.152560DOI Listing
October 2020
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