Publications by authors named "Lin Yan"

1,598 Publications

  • Page 1 of 1

H Long Terminal Repeat-Associating 2 (HHLA2) is a Biomarker of Advanced Stage Hepatocellular Carcinoma and Promotes Tumor Cell Development In Vitro.

Med Sci Monit 2021 May 15;27:e930215. Epub 2021 May 15.

Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China (mainland).

BACKGROUND Several risk factors contribute to the inflammation promoting hepatocellular carcinoma (HCC) development, but the underlying mechanisms are unknown. Human endogenous retrovirus H long terminal repeat-associating 2 (HHLA2), a B7 family member, is highly expressed in various malignant tumor tissues and is related to tumor progression and metastasis. MATERIAL AND METHODS Bioinformatics analysis was used to analyze the gene expression chip GSE33006 of HCC tissue in the GEO database, draw a heat map of differentially expressed genes, and analyze the GO pathway of gene function annotation. Then, we compared HCC tissues with para-carcinoma liver tissues from 55 patients for expression patterns and associations with HHLA2. Effects of HHLA2 knockdown were examined in the human HCC cell line HepG2 to explore effects of HHLA2 on HepG2 cells. RESULTS A significantly higher expression of HHLA2 at the mRNA and protein levels was detected in HCC tissues than in para-carcinoma liver tissues, which was similar to HHLA2 expression in the GSE33006 data. A higher expression of HHLA2 protein was associated with advanced cancer stage, tumor differentiation, and invasion of adjacent structures. In vitro knockdown of HHLA2 expression significantly increased HepG2 cell adhesion, promoted cell apoptosis, induced cell cycle arrest in the G1/S phase, and inhibited cell proliferation, migration, and invasion. CONCLUSIONS Our data indicated there was a higher expression of HHLA2 in HCC tissues than in para-carcinoma liver tissues, and HHLA2 plays a major role in the development and progression of HCC. Owing to its higher expression, HHLA2 is a potential prognostic biomarker for HCC.
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http://dx.doi.org/10.12659/MSM.930215DOI Listing
May 2021

Comparison of Sudden Sensorineural Hearing Loss with Tinnitus and Short-Term Tinnitus.

Neural Plast 2021 20;2021:6654932. Epub 2021 Apr 20.

Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.

Objective: As one of the common symptoms of sudden sensorineural hearing loss (SSH), tinnitus seriously affects the life and work of SSH patients. The present study is aimed at exploring whether SSH can receive acoustic therapy and the factors that affect the efficacy of SSH acoustic therapy.

Methods: A total of 162 patients were outpatients and inpatients, 86 were SSH, and 76 were short-term tinnitus (STT). Both groups received pure tone audiometry, tinnitus matching, and residual inhibition test (RI). The Tinnitus Handicap Inventory (THI), visual analog scale with respect to tinnitus loudness (VAS), and RI in each group were evaluated. The effects of age, degree of hearing loss, and tinnitus course on the efficacy of SSH acoustic therapy were also evaluated.

Results: In the comparison of RI, THI, and VAS, there was no difference between SSH and STT ( > 0.05). SSH patients with mild hearing loss showed better acoustic therapy efficacy compared with SSH patients with severe hearing loss ( < 0.05), but there is no statistical difference in age and the course of tinnitus ( > 0.05).

Conclusion: The present study showed that SSH may improve tinnitus symptom through receiving acoustic therapy and SSH patients with mild hearing loss can get better acoustic therapy effects.
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http://dx.doi.org/10.1155/2021/6654932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079215PMC
April 2021

Cadmium disturbs epigenetic modification and induces DNA damage in mouse preimplantation embryos.

Ecotoxicol Environ Saf 2021 May 11;219:112306. Epub 2021 May 11.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, PR China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China. Electronic address:

Cadmium is an environmental pollutant that has extensive deleterious effects on the reproductive system. However, the mechanisms underlying the effects of cadmium on preimplantation embryos are unclear. Here, we used a mouse model to investigate the effects of maternal cadmium (32 mg/l) exposure in drinking water for 2 days on early embryonic development, and studied the mechanisms associated with epigenetic modifications and DNA damage induced by oxidative stress. We observed that maternal cadmium exposure impaired preimplantation embryo development by inducing embryo death, fragmentation, or developmental blockade. After cadmium exposure, the most survived embryos were at the 8-cell stage, which were used for all measurements. Histone acetylation, not methylation, was disturbed by increasing histone deacetylase 1 (HDAC1) levels after cadmium exposure. Cadmium also disrupted DNA methylation of H19; however genomic DNA methylation can be normally reprogrammed in embryos. Furthermore, cadmium increased reactive oxygen species (ROS) levels and DNA damage, and partly inhibited gene expression related to DNA repair. The distribution and activity of mitochondria was increased; therefore, embryos maintain intracellular homeostasis for survival. Collectively, our findings revealed that maternal cadmium exposure impairs preimplantation embryo development by disturbing the epigenetic modification and inducing DNA damage.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112306DOI Listing
May 2021

The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study.

BMC Cancer 2021 May 11;21(1):536. Epub 2021 May 11.

Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No 41 Damucang Hutong, Xicheng District, Beijing, 100032, China.

Background: At present, the characteristics of mucinous breast carcinoma (MBC) and the factors affecting its prognosis are controversial. We compared the clinical features of MBC with those of infiltrating ductal carcinoma (IDC) and summarized the relevant prognostic factors.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database includes information on 10,593 patients diagnosed with MBC between 2004 and 2016. Chi-square tests and analyses were used to analyze differences in variables between the MBC and IDC groups. Univariate and multivariate Cox proportional hazards models were used to assess the relative impacts of risk factors on cancer-specific survival (CSS) in patients. Kaplan-Meier survival curves were constructed to assess cancer-specific mortality and were compared using the log-rank test.

Results: From 2004 to 2016, 10,593 people were diagnosed with MBC, and 402,797 were diagnosed with IDC. Patients with MBC had significantly higher 5-/10-year CSS rates (96.4%/93.4%) than those with IDC (89%/83.8%). Compared with IDC patients, MBC patients had less lymph node metastasis, an earlier stage, a higher rate of hormone receptor positivity and a lower expression rate of HER2. Univariate and multivariate analyses showed that age ≥ 60 years old (HR = 1.574, 95%CI: 1.238-2.001, P < 0.001), singled status (HR = 1.676, 95%CI: 1.330-2.112, P < 0.001) and advanced TNM/SEER stage were independent prognostic risk factors for MBC. In addition, positive estrogen receptor (HR = 0.577, 95%CI: 0.334-0.997, P = 0.049), positive progesterone receptor (HR = 0.740, 95%CI: 0.552-0.992, P = 0.044), surgical treatment (HR = 0.395, 95%CI: 0.288-0.542, P < 0.001) and radiotherapy (HR = 0.589, 95%CI: 0.459-0.756, P < 0.001) were identified as protective factors.

Conclusion: Compared with IDC, MBC has a better prognosis. For patients with MBC, we identified prognostic factors that can help clinicians better assess patient outcomes and guide individualized treatment.
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http://dx.doi.org/10.1186/s12885-021-08262-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111957PMC
May 2021

The Interaction between Rice Genotype and Magnaporthe oryzae Regulates the Assembly of Rice Root-Associated Microbiota.

Rice (N Y) 2021 May 11;14(1):40. Epub 2021 May 11.

State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, China.

Background: Utilizating the plant microbiome to enhance pathogen resistance in crop production is an emerging alternative to the use of chemical pesticides. However, the diversity and structure of the microbiota, and the assembly mechanisms of root-associated microbial communities of plants are still poorly understood.

Results: We invstigated the microbiota of the root endosphere and rhizosphere soils of the rice cultivar Nipponbare (NPB) and its Piz-t-transgenic line (NPB-Piz-t) when infected with the filamentous fungus Magnaporthe oryzae (M. oryzae) isolate KJ201, using 16S rRNA and internal transcribed spacer 1 (ITS1) amplicon sequencing. The rhizosphere soils showed higher bacterial and fungal richness and diversity than the endosphere except for fungal richness in the rhizosphere soils of the mock treatment. Bacteria richness and diversity increased in the endospheric communities of NPB and Piz-t under inoculation with KJ201 (referred to as 'NPB-KJ201' and 'Piz-t-KJ201', respectively) compared with the corresponding mock treatments, with the NPB-KJ201 showing the highest diversity in the four bacterial endocompartments. In contrast, fungal richness and diversity decreased in the endospheric communities of NPB-KJ201 and Piz-t-KJ201, relative to the corresponding mock treatments, with NPB-KJ201 and Piz-t-KJ201 having the lowest richness and diversity, respectively, across the four fungal endocompartments. Principal component analysis (PCA) indicated that the microbiota of Piz-t-KJ201 of root endophytes were mostly remarkablely distinct from that of NPB-KJ201. Co-occurrence network analysis revealed that the phyla Proteobacteria and Ascomycota were the key contributors to the bacterial and fungal communities, respectively. Furthermore, a comparative metabolic analysis showed that the contents of tryptophan metabolism and indole alkaloid biosynthesis were significantly lower in the Piz-t-KJ201 plants.

Conclusions: In this study, we compared the diversity, composition, and assembly of microbial communities associated with the rhizosphere soils and endosphere of Piz-t-KJ201 and NPB-KJ201. On the basis of the different compositions, diversities, and assemblies of the microbial communities among different compartments, we propose that the host genotype and inoculation pattern of M. oryzae played dominant roles in determining the microbial community assemblage. Further metabolomics analysis revealed that some metabolites may influence changes in bacterial communities. This study improves our understanding of the complex interactions between rice and M. oryzae, which could be useful in developing new strategies to improve rice resistance through the manipulation of soil microorganisms.
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http://dx.doi.org/10.1186/s12284-021-00486-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113375PMC
May 2021

Population genomics study of Vibrio alginolyticus.

Yi Chuan 2021 Apr;43(4):350-361

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.

Vibrio alginolyticus is a Gram-negative bacillus that causes vibriosis to human and aquatic products, including fish, shrimp and shellfish. It poses a threat to public health and causes enormous economic losses to the aquaculture industry. However, research on genetic diversity and pathogenicity-related genetic elements based on whole genome is still lacking. In this study, sixty-eight strains of V. alginolyticus were collected from four provinces of China and the whole genome sequences were obtained. Combined with 113 publicly available genome sequences downloaded from NCBI, we inferred the population structure of V. alginolyticus by using fineSTRUCTURE software, and identified the virulence and antibiotic resistance factors using the VFDB, CARD and ResFinder database. The results indicated that V. alginolyticus included two main lineages, named Lineage 1 and Lineage 2. Both lineages distributed in America and Asia, but all the European genomes were classified into Lineage 1. A single cross-ocean transmission event was inferred from one of the 12 identified clonal groups in our dataset. V. alginolyticus genome contains a variety of virulence factors, such as tlh, OmpU, and IlpA, etc. The distribution of virulence factors revealed no lineage-specificity, but some of which revealed differences in their geographical distribution. A lower frequency of VP1611, vcrD, vopD, fleR/flrC and a higher frequency of IlpA were observed in genomes of Europe than other continents. In China, a lower frequency of fleR/flrC, and no IlpA were observed in genomes from Guangxi province. Among the identified antibiotic resistance genes, TxR and fos are significantly enriched in Lineage 2. In addition, TxR is more common in genomes from Asia, compared with the American and European genomes. But in China, the frequency of TxR in Sichuan genomes is much lower than in other provinces. We also found that large fragments of plasmids or ICEs that carried multiple drug resistance genes were present in five V. alginolyticus genomes (VA24, VA28, 2014V-1011, ZJ-T and Vb1833). Based on population genomics analysis, our study delineated the population structure, distribution of virulence and antibiotic resistance related factors of V. alginolyticus, which lays a foundation for future study of genetic characters and pathogenesis mechanism of this pathogen and will improve the works on monitoring, prevention and control of this pathogen.
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http://dx.doi.org/10.16288/j.yczz.21-061DOI Listing
April 2021

Management and implementation strategies of pre-screening triage in children during coronavirus disease 2019 pandemic in Guangzhou, China.

World J Clin Cases 2021 Apr;9(12):2731-2738

Department of Pediatric Emergency, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China.

Background: Emerging infectious diseases are a constant threat to the public's health and health care systems around the world. Coronavirus disease 2019 (COVID-2019), which was defined by the World Health Organization as pandemic, has rapidly emerged as a global health threat. Outbreak evolution and prevention of international implications require substantial flexibility of frontline health care facilities in their response.

Aim: To explore the effect of the implementation and management strategy of pre-screening triage in children during COVID-19.

Methods: The standardized triage screening procedures included a standardized triage screening questionnaire, setup of pre-screening triage station, multi-point temperature monitoring, extensive screenings, and two-way protection. In order to ensure the implementation of the pre-screening triage, the prevention and control management strategies included training, emergency exercise, and staff protection. Statistical analysis was performed on the data from all the children hospitalized from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. Data were obtained from questionnaires and electronic medical record systems.

Results: A total of 17561 children, including 2652 who met the criteria for screening, 192 suspected cases, and two confirmed cases without omission, were screened from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. There was zero transmission of the infection to any medical staff.

Conclusion: The effective strategies for pre-screening triage have an essential role in the prevention and control of hospital infection.
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http://dx.doi.org/10.12998/wjcc.v9.i12.2731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058678PMC
April 2021

Molecular mechanism of apelin-13 regulation of colonic motility in rats.

Eur J Pharmacol 2021 May 5;904:174149. Epub 2021 May 5.

Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, China. Electronic address:

Apelin is a novel neuropeptide identified as the endogenous ligand for the apelin receptor. Apelin and its receptor are widely distributed in the gastrointestinal tract. Studies have reported that apelin-13 is involved in modulating gastrointestinal motility; however, the evidence is insufficient and the relevant mechanism is still not fully clear. Consequently, our study designed to explore the effect induced by exogenous apelin-13, to analyze the mechanism of action in isolated rat colons and colonic smooth muscle cells. The spontaneous contractions of colonic smooth muscle strips from rat were measured in an organ bath system. L-type calcium currents and large conductance Ca-activated K (BK) currents in rat colonic smooth muscle cells were investigated using the electrophysiological patch-clamp technique. Apelin-13 decreased the spontaneous contractile activity of colonic smooth muscle strips in a dose-dependent manner, and the inhibitory effect was not abolished by tetrodotoxin. The electrophysiological recordings revealed that apelin-13 reduced the crest currents of L-type calcium in a concentration-dependent manner in colonic smooth muscle cells at the test potential of 0 mV. Moreover, apelin-13 moved the current-voltage (I-V) curves of L-type calcium channels upward, but did not change their contour. Furthermore, the characteristics of L-type calcium channels with steady-state activation and steady-state inactivation were not significantly changed. Similarly, application of apelin-13 also significantly decreased BK currents in a concentration-dependent manner. In conclusion, apelin-13 inhibited the spontaneous contractile activity of isolated rat colons via the suppression of L-type calcium channels and BK channels in colonic smooth muscle cells.
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http://dx.doi.org/10.1016/j.ejphar.2021.174149DOI Listing
May 2021

Enhanced Sinks of Polycyclic Aromatic Hydrocarbons Due to Kuroshio Intrusion: Implications on Biogeochemical Processes in the Ocean-Dominated Marginal Seas.

Environ Sci Technol 2021 May 4. Epub 2021 May 4.

State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361102, China.

The biogeochemical processes of polycyclic aromatic hydrocarbons (PAHs) in the South China Sea (SCS) are influenced by the exchanges of water masses, energies, and materials between this marginal sea and the Pacific Ocean. To investigate the impact of oceanic water intrusion on semivolatile compounds, we collected seawater samples in the Western Pacific, northern, and central SCS in 2017 and analyzed for dissolved PAHs. PAH concentrations in the water columns of the Pacific Ocean and SCS were 1.7-11 and 1.1-7.3 ng L, respectively, showing spatial distinctions in terms of the composition and source characteristics. A common depletion for three-ring PAHs was found in the northern SCS by comparing the modeling results of conservative mixing by Kuroshio intrusion. Kuroshio water increased the levels of temperature, dissolved oxygen, and nutrients when intruding into the northern SCS and was likely to enhance the bioavailability of PAHs and stimulate their biodegradation process. In the water column, the most effective layer under the Kuroshio intrusion impact is different for three- and four-ring PAHs, where the three-ring PAHs' depletion was most significant at the surface; however, for four-ring PAHs, that was at the deep chlorophyll maximum layer. This study highlighted the effect of ocean currents on PAHs for their water-column processes both from physical and biogeochemical perspectives.
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http://dx.doi.org/10.1021/acs.est.1c01009DOI Listing
May 2021

CircRNA ZNF609 promotes angiogenesis in nasopharyngeal carcinoma by regulating miR-145/STMN1 axis.

Kaohsiung J Med Sci 2021 May 4. Epub 2021 May 4.

The Second Department of Otolaryngology, Head and Neck Surgery of The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Nasopharyngeal carcinoma (NPC) is the most common type of human malignant tumor in the head and neck, and tumor angiogenesis is essential for its development. Here, we showed that the circRNA ZNF609/microRNA (miR)-145/Stathmin 1 (STMN1) axis regulated angiogenesis in NPC.Circ-ZNF609, miR-145, and STMN1 expression in NPC cells and NPC samples were examined using qRT-PCR. The protein levels of STMN1, VEGFR1, and VEGFR2 were evaluated using western blotting. VEGF level was determined by ELISA. The proliferation of NPC cells and HUVECs was examined using a CCK-8 assay. Transwell assays and wound-healing assays were applied to assess the migration of NPC cells and HUVECs, respectively. Angiogenesis of HUVECs was evaluated by an angiogenesis assay. In addition, a dual-luciferase reporter assay and RNA pull-down assays were employed to verify the binding relationship between circ-ZNF609 and miR-145 as well as between miR-145 and STMN1. Here, we showed that circ-ZNF609 and STMN1 expression was increased, while miR-145 expression was decreased in NPC cells and NPC samples. Circ-ZNF609 may negatively regulate miR-145 expression by acting as a ceRNA. Silencing circ-ZNF609 suppressed cell proliferation, migration, and angiogenesis in NPC, while knockdown of miR-145 reversed these effects. In addition, we found that STMN1 was the downstream target of miR-145. MiR-145 overexpression suppressed cell proliferation, migration, and angiogenesis in NPC, which was abolished by STMN1 overexpression. Our data suggested that circ-ZNF609 promotes cell proliferation, migration, and angiogenesis in NPC by upregulating the expression of STMN1 by sponging miR-145 in NPC.
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http://dx.doi.org/10.1002/kjm2.12381DOI Listing
May 2021

Tailoring PTV expansion to improve the dosimetry of post modified radical mastectomy intensity-modulated radiotherapy for left-sided breast cancer patients by using 4D CT combined with cone beam CT.

J Appl Clin Med Phys 2021 May 2. Epub 2021 May 2.

Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China.

Purpose: Our study aimed to improve the dosimetry of post modified radical mastectomy intensity-modulated radiotherapy (PMRM-IMRT) for left-sided breast cancer patients by tailoring and minimizing PTV expansion three-dimensionally utilizing 4D CT combined with on-board cone beam CT (CBCT).

Methods: We enrolled a total of 10 consecutive left-sided breast cancer patients to undergo PMRM-IMRT. We measured the intra-fractional CTV displacement attributed to respiratory movement by defining 9 points on the left chest wall and quantifying their displacement by using the 4D CT, and measured the inter-fractional CTV displacement resulting from the integrated effect of respiratory movement, thoracic deformation and set up errors by using CBCT. We created 3 different PMRM-IMRT plans for each of the patients using PTV (tailored PTV expansion three-dimensionally), PTV and PTV (isotropic 0.5- cm and isotropic 0.7- cm expanding margin of CTV), respectively. We performed paired samples t test to establish a hierarchy in terms of plan quality and dosimetric benefits. P < 0.05 was considered statistically significant.

Results: The inter-fractional CTV displacement (2.6 ± 2.2 mm vertically, 2.8 ± 2.3 mm longitudinally, and 1.7 ± 1.2 mm laterally) measured by CBCT was much larger than the intra-fractional one (0.5 ± 0.5 mm vertically, 0.5 ± 1.0 mm longitudinally, and 0.3 ± 0.3 mm laterally, respectively) measured by 4D CT. Intensity-modulated radiotherapy with tailored PTV expansion based on inter-fractional CTV displacement had dosimetrical advantages over those with PTV or those with PTV owing to its perfect PTV dose coverage and better OARs sparing(especially of heart and left lung).

Conclusion: The CTV displacement in PMRM-IMRT predominantly arises from inter-fraction rather than from intra-fraction during natural respiration and differs in 3 coordinate axes either inter-fractionally or intra-fractionally. Tailoring and minimizing PTV expansion three-dimensionally significantly improves the dosimetry of PMRM-IMRT for left-sided breast cancer patients.
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http://dx.doi.org/10.1002/acm2.13244DOI Listing
May 2021

Optical Coherence Tomography of Plaque Erosion and Thrombus in Severe Vertebral Artery Stenosis.

Diagnostics (Basel) 2021 Apr 1;11(4). Epub 2021 Apr 1.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, China International Neuroscience Institute (China-INI), Beijing 100053, China.

A 69-year-old male presented with medically refractory vertebrobasilar insufficiency and paroxysmal subjective dizziness for six months. Severe stenosis of a dominant left V2 vertebral artery segment was identified on digital subtraction angiography (DSA) with an irregular intraluminal filling defect immediately above the stenosis. Optical coherence tomography (OCT) demonstrated a normal lumen at the distal end, with red thrombus detected distal to the stenosis. Atherosclerotic plaque containing fibro-lipid was also identified and treated with a drug-eluting stent. Distal red thrombi were not covered by stenting, indicating embolization risk in the future. Clear posterior fossa symptoms occurred after intervention, and treatment with a standard dual antiplatelet regimen and statin therapy was prescribed for one year. Six months after treatment, the symptoms improved, and six-minute walking distances were successful with no gait impairment. To our knowledge, this is the first V2 segment stenosis assessed by OCT imaging before and after stenting, indicating an intact fibrous cap with thrombus formation, as well as plaque erosion. Understanding the role and careful use of OCT may improve the identification of red thrombus and plaque erosion when clinically indicated.
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http://dx.doi.org/10.3390/diagnostics11040638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065715PMC
April 2021

A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment.

Ren Fail 2021 Dec;43(1):766-773

Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: This study aimed to explore the effectiveness of thiamin and folic acid supplementation on the improvement of the cognitive function in patients with maintenance hemodialysis.

Method: In the present study, we randomly assigned patients undergoing hemodialysis who had the Montreal Cognitive Assessment (MoCA) score lower than 26 to treatment group ( = 25, thiamin 90 mg/day combined with folic acid 30 mg/day) or control group ( = 25, nonintervention). All subjects were followed up for 96 weeks. The primary outcome was the improvement of the MoCA score. The secondary outcomes included homocysteine level, survival and safety.

Results: Patients in treatment group had an increase of the MoCA score from 21.95 ± 3.81 at baseline to 25.68 ± 1.96 at week 96 ( < 0.001, primary outcome), as compared with the MoCA score from 20.69 ± 3.40 to 19.62 ± 3.58 in control group. Thiamin combined with folic acid treatment also resulted in lower level of serum homocysteine in treatment group compare with control group at week 96 ( < 0.05, secondary outcome). 3 patients and 9 patients died during follow-up period in treatment and control group respectively ( = 0.048). The proportion of adverse events in treatment group was significantly lower than that in control group.

Conclusion: Hemodialysis patients with cognitive impairment treated with thiamin and folic acid had a significant improvement in MoCA score.
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http://dx.doi.org/10.1080/0886022X.2021.1914656DOI Listing
December 2021

Rs2686344 and serum squamous cell carcinoma antigen could predict clinical efficacy of neoadjuvant chemotherapy for cervical cancer.

Curr Probl Cancer 2021 Apr 18:100755. Epub 2021 Apr 18.

Department of Gynecology & Obstetrics, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. Electronic address:

Objective: To evaluate the predictive value of a single nucleotide polymorphism (SNP) rs2686344 and squamous cell carcinoma antigen (SCCAg) levels in the clinical efficacy of neoadjuvant chemotherapy (NACT) for cervical cancer.

Methods: A total of 92 patients with stage IB2-IIIB carcinoma of the uterine cervix who received NACT treatment were enrolled. The relationship between the genotypes of SNP rs2686344 which is located on CAMKK2 on chromosome 12, SCCAg levels and the response to NACT was analyzed. The relationship between the SNP rs2686344 genotypes, SCCAg levels, the response to NACT and the five-year survival rate was evaluated.

Results: The effective group accounted for 84.85% in patients with low level (≤3.5 ng/mL) of post-treatment SCCAg (post-SCCAg), while the ineffective group accounted for 15.15%. The post-SCCAg levels and the genotypes of rs2686344 were significantly correlated with NACT response (P = 0.003, and P = 0.006). In patients with CC or CT genotype of SNP rs2686344, effective group accounted for 81.18%, while ineffective group accounted for 18.82%; For patients with TT genotype, effective response group accounted for 28.57%, ineffective group accounted for 71.43%. Post-SCCAg level >3.5 ng/mL and TT genotype of SNP rs2686344 showed as independent risk factors for NACT response in the multivariate analysis (P = 0.002, and P = 0.048). There was no significant difference in 5-year overall survival and 5-year disease-free survival between patients with different levels of post-SCCAg, or among different rs2686344 genotypes.

Conclusion: The high level of post-SCCAg (>3.5 ng/mL) and TT genotype of rs2686344 may suggest a higher risk of poor response to NACT.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100755DOI Listing
April 2021

Radiofrequency ablation versus total thyroidectomy in patients with papillary thyroid microcarcinoma located in the isthmus: a retrospective cohort study.

Int J Hyperthermia 2021 ;38(1):708-714

Department of Ultrasound, First Medical Center of General Hospital of Chinese PLA, Beijing, China.

Objective: This retrospective study aimed to examine the benefits and complications of radiofrequency ablation (RFA) in patients with papillary thyroid microcarcinoma (PTMC) in the isthmus.

Methods: This retrospective study included patients with PTMC in the isthmus and treated at the Chinese People's Liberation Army hospital from 05/2014 to 05/2018. The patients were divided into the RFA and total thyroidectomy (TT) groups. The outcomes were operation-related complications, rate of recurrence, metastasis rate, and thyroid carcinoma-specific questionnaire of quality of life (THYCA-QOL).

Results: Among 218 patients, 115 patients underwent RFA, and 103 underwent TT. The rates of disappearance of the ablation zone at 1, 3, 6, 12, and 18 months after RFA were 0.8% (1/115), 10.4% (12/115), 51.3% (59/115), 90.4% (104/115), and 100% (115/115), respectively. Surgical time, blood loss, hospital stays, and treatment costs were higher with TT than with RFA (all  < 0.001). The final THYCA-QOL score of the RFA group was significantly higher than in the TT group ( < 0.001). Minor pain at the operation site was seen in all patients in the RFA group. No distant metastasis was detected in all patients, but one patient in the RFA group had a recurrence after 6 months. The final THYCA-QOL score of the RFA group was significantly lower than in the TT group ( < 0.001).

Conclusion: These results suggest that RFA for PTMC in the isthmus had similar outcomes than TT. It will have to be confirmed in future studies.
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http://dx.doi.org/10.1080/02656736.2021.1916625DOI Listing
January 2021

Cellular microRNAs influence replication of H3N2 canine influenza virus in infected cells.

Vet Microbiol 2021 Apr 20;257:109083. Epub 2021 Apr 20.

Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

MicroRNAs (miRNAs) are known to play important regulatory roles in host-virus interactions. Avian-origin H3N2 canine influenza virus (CIV) has emerged as the most prevalent subtype among dogs in Asia since 2007. To evaluate the roles of host miRNAs in H3N2 CIV infection, here, miRNA profiles obtained from primary canine bronchiolar epithelial cells (CBECs) and canine alveolar macrophages (CAMCs) were compared between infected and mock-infected cells with the H3N2 CIV JS/10. It was found that the expressions of cfa-miR-125b and cfa-miR-151, which have been reported to be associated with innate immunity and inflammatory response, were significantly decreased in CIV-infected canine primary cells. Bioinformatics prediction indicated that 5' seed regions of the two miRNAs are partially complementary to the mRNAs of nucleoprotein (NP) and non-structural protein 1 (NS1) of JS/10. As determined by virus titration, quantitative real-time PCR (qRT-PCR) and western blotting, overexpression of the two miRNAs inhibited CIV replication in cell culture, while their inhibition facilitated this replication, suggesting that the two miRNAs could act as negative regulators of CIV replication. Our findings support the notion that some cellular miRNAs can influence the outcome of virus infection, which helps to elucidate the resistance of host cells to viral infection and to clarify the pathogenesis of H3N2 CIV.
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http://dx.doi.org/10.1016/j.vetmic.2021.109083DOI Listing
April 2021

Maternal nicotine exposure aggravates metabolic associated fatty liver disease via PI3K/Akt signaling in adult offspring mice.

Liver Int 2021 Apr 24. Epub 2021 Apr 24.

Department of Ultrasound, The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.

Aim: The aim of this study is to investigate the effect of maternal nicotine exposure (MNE) on the development of metabolic associated fatty liver disease (MAFLD) in adulthood offspring and the underlying mechanism.

Methods: Pregnant mice (n = 22) were subcutaneously injected with either saline vehicle (n = 11) or nicotine (n = 11) twice a day on gestational days 11-21. Offspring mice (n = 176) from both groups were weaned at postnatal day 21, and for 6 months after postnatal day 21, 96 mice were fed either a standard chow diet (n = 48) or a high-fat diet (n = 48). Serum lipid indicators, liver function indicators, insulin, and liver mitochondrial respiration were analyzed. The expression levels of fibrosis-related proteins, phosphorylated PI3K, phosphorylated Akt, sterol regulatory element-binding transcription factor 1 (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPAR-α) were detected in the liver by immunohistochemistry and Western blotting.

Results: MNE significantly decreased the weight of both maternal and offspring mice (~30%) and inhibited organ growth in offspring mice (P < .05). MNE also significantly increased serum levels of total bile acid, triglycerides, total cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, and insulin while decreasing serum high-density lipoprotein levels and mitochondrial respiration activity in mice fed either the normal diet or high-fat diet (all P < .05). These effects of MNE on lipid metabolism and insulin resistance were mediated via PI3K and Akt phosphorylation and down-regulation of SREBP1c and PPAR-α.

Conclusion: Our data indicate MNE induces lipid metabolism disorder and insulin resistance to promote MAFLD progression in adult offspring through activation of PI3K/Akt signaling and suppression of SREBP1c and PPARα protein expression.
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http://dx.doi.org/10.1111/liv.14902DOI Listing
April 2021

Efficacy and safety of intermittent vs continuous furosemide for heart failure concomitant renal dysfunction: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(16):e25669

Department of Nephrology, The Affiliated People's Hospital, Ningbo University, Ningbo, China.

Background: Currently, there are no meta-analyses evaluating the efficacy and safety of intermittent vs continuous furosemide for heart failure concomitant renal dysfunction. Our protocol is conceived to evaluate the efficacy and safety of intermittent vs continuous furosemide for heart failure concomitant renal dysfunction.

Methods: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. The systematic review protocol has been registered in Open Science Framework registries. The following databases including PubMed, Cochrane Library, Web of Science, and EMBASE will be searched using the key phrases "loop diuretics," "furosemide," "heart failure," and "renal dysfunction" for all randomized clinical trials (RCTs) published up to May 2021. Revman 5.3 (Nordic Cochrane Centre, Denmark) will be used to complete the meta-analysis and generate forest plots. We will choose between a fixed effects and random effects model based upon the heterogeneity of included studies. Significance will be set at P < .05.

Results: Our protocol is conceived to test the hypothesis that continuous furosemide could lead to better outcomes in patients presenting with heart failure concomitant renal dysfunction.

Registration Number: 10.17605/OSF.IO/CQZRS.
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http://dx.doi.org/10.1097/MD.0000000000025669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078240PMC
April 2021

Prospective assessment of breast cancer risk from multimodal multiview ultrasound images via clinically applicable deep learning.

Nat Biomed Eng 2021 Apr 19. Epub 2021 Apr 19.

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.

The clinical application of breast ultrasound for the assessment of cancer risk and of deep learning for the classification of breast-ultrasound images has been hindered by inter-grader variability and high false positive rates and by deep-learning models that do not follow Breast Imaging Reporting and Data System (BI-RADS) standards, lack explainability features and have not been tested prospectively. Here, we show that an explainable deep-learning system trained on 10,815 multimodal breast-ultrasound images of 721 biopsy-confirmed lesions from 634 patients across two hospitals and prospectively tested on 912 additional images of 152 lesions from 141 patients predicts BI-RADS scores for breast cancer as accurately as experienced radiologists, with areas under the receiver operating curve of 0.922 (95% confidence interval (CI) = 0.868-0.959) for bimodal images and 0.955 (95% CI = 0.909-0.982) for multimodal images. Multimodal multiview breast-ultrasound images augmented with heatmaps for malignancy risk predicted via deep learning may facilitate the adoption of ultrasound imaging in screening mammography workflows.
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http://dx.doi.org/10.1038/s41551-021-00711-2DOI Listing
April 2021

Dietary fiber in a low-protein diet during gestation affects nitrogen excretion in primiparous gilts, with possible influences from the gut microbiota.

J Anim Sci 2021 Apr 19. Epub 2021 Apr 19.

Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, and Animal Nutrition Institute, Sichuan Agricultural University, Wenjiang, Chengdu, People's Republic of China.

We investigated the effects of dietary fiber (DF) supplementation in normal or low crude protein (CP) diets on reproductive performance and nitrogen (N) utilization in primiparous gilts. In total, 77 Landrace × Yorkshire (LY) pregnant gilts were randomly allocated to four dietary treatments in a 2 × 2 factorial design. The groups comprised 1) equal intake of normal CP (12.82% and 0.61% total lysine), 2) low CP (10.53% and 0.61% total lysine), and 3) with or 4) without DF supplementation (cellulose, inulin, and pectin in a 34:10:1 ratio). A low-protein diet during gestation significantly reduced daily weight gain from days 91-110 of pregnancy (-162.5 g/d, P = 0.004). From N balance trials conducted at days 35-38, 65-68, and 95-98 of pregnancy, DF addition increased fecal N excretion at days 65-68 (+24.1%) and 95-98 (+13.8%) of pregnancy (P < 0.05), but reduced urinary N excretion (P < 0.05), resulting in greater N retention at each gestational stage. DF increased fecal microbial protein levels and excretion during gestation. A low CP diet also reduced urinary N excretion at different gestational stages. An in vitro fermentation trial on culture media with non-protein N urea and ammonium bicarbonate (NH4HCO3) as the only N sources revealed that microbiota derived from feces of gestating gilts fed the high DF diet exhibited a greater capacity to convert non-protein N to microbial protein. Microbial fecal diversity, as measured by 16S rRNA sequencing, revealed significant changes from DF, but not CP diets. Gilts fed a low CP diet had a higher number of stillbirths (+ 0.83 per litter, P = 0.046) and a lower piglet birth weight (1.52 kg vs. 1.37 kg, P = 0.006), regardless of DF levels. Collectively, DF supplementation to gestation diets shifted N excretion from urine to feces in the form of microbial protein, suggesting that the microbiota had a putative role in controlling N utilization from DF. Additionally, a low-protein diet during gestation negatively affected the litter performance of gilts.
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http://dx.doi.org/10.1093/jas/skab121DOI Listing
April 2021

Telitacicept Following Plasma Exchange in the Treatment of Subjects With Recurrent NMOSD: Study Protocol for a Single-Center, Single-Arm, Open-Label Study.

Front Neurol 2021 18;12:596791. Epub 2021 Mar 18.

Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease that recurrently relapses and leads to severe disability. The available choices for disease prevention are few or intolerable. Previous studies suggested that telitacicept may provide a promising therapeutic strategy for autoimmune diseases involving B cells. Therefore, this study aims to assess the effectiveness and safety of telitacicept for recurrent NMOSD. We will perform a single-arm, single-center, open-label, specialist study with a total enrollment of eight participants. The treatment regimen includes plasma exchange three times and subcutaneous injection of telitacicept for 46 cycles, with a total period of 48 weeks. The primary endpoint is the time to first recurrence after enrollment. Secondary endpoints are Expanded Disability Status Scale (EDSS) score, Opticospinal Impairment Scale (OSIS) score, Hauser Ambulation Index, number of lesions on MRI, and changes in visual evoked potential (VEP), optical coherence tomography (OCT) and immunologic status. All adverse events after medication will be documented and investigated. This study will explore the safety and effectiveness of telitacicept following plasma exchange regarding the time to recurrence in neuromyelitis optica spectrum disorder (NMOSD) for the first time. Chictr.org.cn, identifier ChiCTR1800019427.
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http://dx.doi.org/10.3389/fneur.2021.596791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044936PMC
March 2021

A scoping review on the influencing factors and development process of professional identity among nursing students and nurses.

J Prof Nurs 2021 Mar-Apr;37(2):391-398. Epub 2020 May 6.

Kiang Wu Hospital, 85-87 Estr. de Coelho do Amaral, Macau, China.

Background: Professional identity (PI) is culturally shaped. It is associated with a sufficient and stable workforce of professionals. China has a relatively low ratio of nursing professionals to its population.

Aim: This scoping review aims to obtain comprehensive knowledge of the influencing factors and PI development process among nursing students and nurses in China.

Methods: A scoping review was conducted. The most common Chinese databases, China National Knowledge Infrastructure and Wanfang Data were searched for publications in Chinese. The databases of EBSCOhost and ProQuest Dissertation & Thesis Global (Full Text) were searched for publications in English. After screening the title and abstract of the articles and further assessing the full text of the articles identified after the initial screening, 53 articles were included for analysis.

Results: The influencing factors to PI development in nursing were grouped into four dimensions: personal, family, institutional, and social factors. The social factors tended to negatively affect professional identity whereas the factors of the three other dimensions exerted influence in different directions. A framework was established based on PI levels in different career stages of nurses to depict the continuum and dynamic nature of the development process.

Conclusions: The PI development in nursing is a dynamic process shaped by multidimensional factors. Changes in policy should be made to reverse the nursing profession stereotype of being an assistant role to medicine.
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http://dx.doi.org/10.1016/j.profnurs.2020.04.018DOI Listing
May 2020

Canine Parvovirus Infections in Taiwanese Pangolins ().

Vet Pathol 2021 Apr 19:3009858211002198. Epub 2021 Apr 19.

National Chung Hsing University, Taichung.

Canine parvovirus type 2 (CPV-2) is among the most important and highly contagious pathogens that cause enteric or systemic infections in domestic and nondomestic carnivores. However, the spillover of CPV-2 to noncarnivores is rarely mentioned. Taiwanese pangolins () are threatened due to habitat fragmentation and prevalent animal trafficking. Interactions between Taiwanese pangolins, humans, and domestic animals have become more frequent in recent years. However, information about the susceptibility of pangolins to common infectious agents of domestic animals has been lacking. From October 2017 to June 2019, 4 pangolins that were rescued and treated in wildlife rescue centers in central and northern Taiwan presented with gastrointestinal signs. Gross and histopathological examination revealed the main pathologic changes to be necrotic enteritis with involvement of the crypts in all intestinal segments in 2 pangolins. By immunohistochemistry for CPV-2, there was positive labeling of cryptal epithelium throughout the intestine, and immunolabeling was also present in epidermal cells adjacent to a surgical amputation site, and in mononuclear cells in lymphoid tissue. The other 2 pangolins had mild enteritis without crypt involvement, and no immunolabeling was detected. The nucleic acid sequences of polymerase chain reaction (PCR) amplicons from these 4 pangolins were identical to a Chinese CPV-2c strain from domestic dogs. Quantitative PCR revealed a higher ratio of CPV-2 nucleic acid to internal control gene in the 2 pangolins with severe intestinal lesions and positive immunoreactivity. Herein, we present evidence of CPV-2 infections in pangolins.
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http://dx.doi.org/10.1177/03009858211002198DOI Listing
April 2021

A novel nonsense variant in MT-CO3 causes MELAS syndrome.

Neuromuscul Disord 2021 Mar 3. Epub 2021 Mar 3.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 West Wenhua Road Jinan, Jinan, Shandong 250012 China; Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong 266035 China; Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong 266035 China; Brain Science Research Institute, Shandong University, Jinan, Shandong 250000, China. Electronic address:

Both mitochondrial and nuclear gene mutations can cause cytochrome c oxidase (COX, complex Ⅳ) dysfunction, leading to mitochondrial diseases. Although numerous diseases caused by defects of the COX subunits or COX assembly factors have been documented, clinical cases directly related to mitochondrial cytochrome c oxidase subunit 3 gene (MT-CO3) mutations are relatively rare. Here, we report a 47-year-old female patient presented with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Muscle pathology revealed ragged-red fibres and remarkable COX-deficient muscle fibres. Muscle mitochondrial DNA sequencing analysis identified a novel MT-CO3 variant (m.9553G>A) that changed a highly conserved amino acid to a stop codon (p.Trp116*). This variant was heteroplasmic in multiple tissues, where the mutation load was 13% in oral epithelial cells, 89% in muscle samples, and not detectable in the peripheral blood lymphocytes. Single muscle fiber PCR analysis showed clear segregation of the mutation load with COX deficient fibres. Western blot analysis of the muscle samples revealed a significant decrease in the levels of COX1, COX2, COX3, COX4 and UQCRC2. COX respiration activity was remarkably reduced (58.84%) relative to the controls according to spectrophotometric assays. Taken together, our results indicated that this m.9553G>A variant may be responsible for the MELAS symdrome in the proband by affecting the stability and function of COX. The study expands the clinical and molecular spectrum of COX3-specific mitochondrial diseases.
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http://dx.doi.org/10.1016/j.nmd.2021.02.020DOI Listing
March 2021

Recent Advances in Macrophage-Mediated Drug Delivery Systems.

Int J Nanomedicine 2021 7;16:2703-2714. Epub 2021 Apr 7.

Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Macrophages have been extensively used in the development of drug delivery systems, as they can prolong the circulation and release of drugs, extend their half-life, increase their stability and targeting ability, and reduce immunogenicity. Moreover, they have good biocompatibility and degradability and offer abundant surface receptors for targeted delivery of a wide variety of drugs. Macrophage-mediated drug delivery systems can be prepared by loading drugs or drug-loaded nanoparticles into macrophages, macrophage membranes or macrophage-derived vesicles. Although such systems can be used to treat inflammation, cancer, HIV infection and other diseases, they require further research and optimization since they have been assembled from diverse sources and therefore can have quite different physical and chemical properties. Moreover, potential cell-drug interactions can limit their application, and the biological activity of membrane proteins might be lost during membrane extraction and storage. In this review, we summarize the recent advances in this field and discuss the preparation of macrophage-mediated drug delivery systems, their advantages over other delivery systems, their potential applications and future lines of research.
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http://dx.doi.org/10.2147/IJN.S298159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039204PMC
May 2021

Efficacy and safety of ultrasound-guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma in patients aged 55 years or older: a retrospective study.

Int J Hyperthermia 2021 ;38(1):604-610

School of Medicine, Nankai University, Tianjin, China.

Purpose: To evaluate the efficacy and safety of radiofrequency ablation for low-risk papillary thyroid microcarcinoma (PTMC) in patients aged 55 years or older.

Methods: This retrospective study included 95 patients aged 55 years or older who underwent radiofrequency ablation (RFA) for PTMCs between June 2014 and January 2019. Incidence and duration of postoperative complications were recorded and evaluated. Tumor volume and volume reduction rate (VRR) changes were calculated. Patients were also closely monitored for tumor recurrence, regrowth, and lymph node metastasis.

Results: All nodules were completely ablated. The mean initial volume of the ablated thyroid nodules was 107.27 ± 99.10 mm, and the volume decreased significantly during the follow-up time. The VRR in 1st, 3rd, 6th, 12th, 18th, 24th and 36th month were -591.64 ± 623.65%, -170.89 ± 319.51%, 9.74 ± 128.43%, 77.99 ± 45.26%, 99.35 ± 3.61%, 99.45 ± 3.05% and 99.78 ± 1.54%, respectively. No patient had any life-threatening complications. One patient had lymph node metastasis and one had a recurrence; both underwent a second radiofrequency ablation treatment and achieved satisfactory treatment results.

Conclusions: Our study suggests that radiofrequency ablation is a safe and effective option for low-risk PTMC in patients aged 55 years or older who are at a high risk of general anesthesia and postoperative complications or those who refuse surgery.
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http://dx.doi.org/10.1080/02656736.2021.1912416DOI Listing
January 2021

Association of genetic variants in TPMT, ITPA, and NUDT15 with azathioprine-induced myelosuppression in southwest china patients with autoimmune hepatitis.

Sci Rep 2021 Apr 12;11(1):7984. Epub 2021 Apr 12.

Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital of Sichuan University, No.37, Guoxue Xiang, Wuhou District, Chengdu, 610041, China.

This study aimed to investigate the influence of TPMT*3C, ITPA, NUDT15, and 6-thioguanine nucleotides (6-TGN) on azathioprine (AZA)-induced myelosuppression in Southwest China patients with autoimmune hepatitis (AIH). A total of 113 Chinese patients with AIH receiving AZA maintenance treatment were evaluated. The relevant clinical data of the patients were collected from the hospital information system. Genotyping of TPMT*3C(rs1142345), ITPA (rs1127354) and NUDT15(rs116855232) was conducted using a TaqMan double fluorescent probe. The concentration of 6-TGN was determined using UPLC-MS/MS. Among AIH patients treated with AZA, 40 (35.4%) exhibited different degrees of myelosuppression. The NUDT15 variant was associated with leukopenia (P = 8.26 × 10; OR = 7.5; 95% CI 3.08-18.3) and neutropenia (P = 3.54 × 10; OR = 8.05; 95% CI 2.96-21.9); however, no significant association with myelosuppression was observed for TPMT*3C and ITPA variants (P > 0.05). There was no significant difference in 6-TGN concentration between AIH patients with or without myelosuppression (P = 0.556), nor was there a significant difference between patients with variant alleles of TPMT*3C, ITPA, or NUDT15 and wild-type patients (P > 0.05). Interestingly, it was found that patients with a lower BMI had higher adjusted 6-TGN levels and a higher incidence of myelosuppression (P = 0.026 and 0.003). This study confirmed that NUDT15 variants are a potential independent risk predictor for AZA-induced leukopenia and neutropenia. BMI may be a crucial non-genetic factor that affects the concentration of AZA metabolites and myelosuppression. In addition, the 6-TGN concentration in red blood cells does not reflect the toxicity of AZA treatment, and new biomarkers for AZA therapeutic drug monitoring need further research.
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http://dx.doi.org/10.1038/s41598-021-87095-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042108PMC
April 2021

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS.

BMC Complement Med Ther 2021 Apr 12;21(1):120. Epub 2021 Apr 12.

College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China.

Background: The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.

Methods: Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites.

Results: The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism.

Conclusions: These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.
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http://dx.doi.org/10.1186/s12906-021-03276-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043067PMC
April 2021

T1a triple negative breast cancer has the worst prognosis among all the small tumor (<1 cm) of TNBC and HER2-rich subtypes.

Gland Surg 2021 Mar;10(3):943-952

Department of Breast Surgery, Peking Union Medical College Hospital, Beijing, China.

Background: Triple negative breast cancer (TNBC), accounting for 15% of all breast cancer cases, was usually considered as the most aggressive subtype. The present study evaluated the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival in large-scale population.

Methods: This retrospective study enrolled T1a/T1b/T1c TNBC and HER2/hormone receptor (HoR) patients diagnosed between 2010 to 2012 from the Surveillance, Epidemiology, and End Results database. The following information was extracted for further analyses: demographic variables including age at diagnosis, race, marital status, laterality, histological grade, T/N stage, American Joint Committee on Cancer (AJCC) stage, radiation therapy, survival and cause of death. Kaplan-Meier method and Cox regression were engaged for breast cancer specific survival (BCSS) and overall survival (OS) analyses.

Results: In all, the present study enrolled 6,953 TNBC and 2,648 HER2/HoR patients. T1a TNBC which generally omitted adjuvant chemotherapy had worse prognosis than T1a HER2/HoR [BCSS: hazard ratio (HR) 3.23, 95% confidence interval (CI): 1.05-9.09, P=0.03; OS: HR 2.63, 95% CI: 1.25-5.56, P=0.01] and T1b HER2/HoR (BCSS: HR 5.26, 95% CI: 1.61-16.7, P=0.006; OS: HR 3.03, 95% CI: 1.27-7.14, P=0.013) tumors which both were recommended by the National Comprehensive Cancer Network (NCCN) guideline to have chemotherapy. T1a TNBC also showed a trend with poorer prognosis than T1b TNBC, but did not reach statistical significance.

Conclusions: T1a TNBC had the worst prognosis among all small tumors (<1 cm) of TNBC and HER2/HoR subtypes, indicating the necessity of more intensive adjuvant treatment.
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http://dx.doi.org/10.21037/gs-20-762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033067PMC
March 2021