Publications by authors named "Hong Ren"

666 Publications

The immunotherapy candidate TNFSF4 may help the induction of a promising immunological response in breast carcinomas.

Sci Rep 2021 Sep 20;11(1):18587. Epub 2021 Sep 20.

Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shaanxi, China.

Immune checkpoint blockade, an immunotherapy, has been applied in multiple systemic malignancies and has improved overall survival to a relatively great extent; whether it can be applied in breast cancer remains unknown. We endeavored to explore possible factors that may influence immunotherapy outcomes in breast cancer using several public databases. The possible treatment target TNF superfamily member 4 (TNFSF4) was selected from many candidates based on its abnormal expression profile, survival-associated status, and ability to predict immune system reactions. For the first time, we identified the oncogenic features of TNFSF4 in breast carcinoma. TNFSF4 was revealed to be closely related to treatment that induced antitumor immunity and to interact with multiple immune effector molecules and T cell signatures, which was independent of endocrine status and has not been reported previously. Moreover, the potential immunotherapeutic approach of TNFSF4 blockade showed underlying effects on stem cell expansion, which more strongly and specifically demonstrated the potential effects of applying TNFSF4 blockade-based immunotherapies in breast carcinomas. We identified potential targets that may contribute to breast cancer therapies through clinical analysis and real-world review and provided one potential but crucial tool for treating breast carcinoma that showed effects across subtypes and long-term effectiveness.
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http://dx.doi.org/10.1038/s41598-021-98131-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452722PMC
September 2021

The inhibition of pectin oligosaccharides on degranulation of RBL-2H3 cells from apple pectin with high hydrostatic pressure assisted enzyme treatment.

Food Chem 2021 Sep 8;371:131097. Epub 2021 Sep 8.

College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

The conditions for the preparation of pectic oligosaccharides (POS) by high hydrostatic pressure-assisted enzymatic (E-HHP) method were explored. The optimal conditions consisted of the pressure of 350 MPa for 20 min, and enzymolysis for 60 min with 0.011 U/mL enzyme. The products were isolated by ion exchange chromatography, galacturonic acid, di- and tri-galacturonides (Tri-GalA) with high purity were obtained. Additionally, the effects of POS on activation and degranulation of RBL-2H3 mast cells were investigated. It was found that Tri-GalA and POS could attenuate the release of β-hexosaminidase and histamine, reduce the production of IL-4 and inhibit the extracellular Ca influx of RBL-2H3 cells. Notably, 150 μg/mL POS significantly alleviated the IgE-mediated allergic reaction of RBL-2H3 cells. These results indicate that POS could be used as an inhibitor in regulating mast cell-mediated allergic inflammatory responses.
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http://dx.doi.org/10.1016/j.foodchem.2021.131097DOI Listing
September 2021

The distribution of hepatitis C virus infection in Shanghai, China: a time-spatial study.

BMC Infect Dis 2021 Sep 18;21(1):974. Epub 2021 Sep 18.

Department of Viral Hepatitis Control and prevention, Division of TB and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

Background: Shanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency.

Methods: Reported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014-2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5'UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1.

Results: A total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value < 0.01). The spatial distribution of acute HCV infection formed one primary cluster (Relative Risk = 2.71), and the chronic formed one primary cluster and three secondary clusters with Relative Risk ranged from 1.94 to 14.42, meanwhile, an overlap of 34 communities between acute and chronic HCV clusters were found with time period spans varied from 6 to 12 years. Genotype 1 (N = 257, 49.71%) was the most prevalent HCV genotype in Shanghai, genotype 3 infections have increased in recent years. Baoshan district presented cluster of acute HCV and the highest proportion of genotype 2, Pudong new area was the cluster of chronic HCV and occupied the highest proportion of genotype 3.

Conclusions: Despite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.
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http://dx.doi.org/10.1186/s12879-021-06577-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449884PMC
September 2021

Clinical value of pediatric sepsis-induced coagulopathy score in diagnosis of sepsis-induced coagulopathy and prognosis in children.

J Thromb Haemost 2021 Aug 18. Epub 2021 Aug 18.

Department of Cardiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: In adults, sepsis-induced coagulopathy (SIC) is diagnosed by the SIC score, known as sepsis-3. There is no pediatric SIC (pSIC) score at present.

Objectives: We proposed a pSIC scoring method and evaluated the diagnostic efficacy of the score in the diagnosis of SIC in children.

Patients/methods: Patient data were retrospectively analyzed from Shanghai Children's Medical Center between February 2014 and January 2015. The pSIC score was modified from the SIC score. The area under ROC curve (AU-ROC) was used to compare the prognostic values of pSIC with other scores for pediatric sepsis-induced disseminated intravascular coagulation (DIC) to arrive at a 28-day outcome.

Results And Conclusions: There were 54 patients in the pSIC group and 37 in the non-pSIC group. The Kaplan-Meier survival curve analysis showed that the 28-day prognosis was better in the non-pSIC than in the pSIC group (p < .001). The AU-ROC of the pSIC score in predicting 28-day mortality in sepsis was 0.716, with the optimal cutoff value of >3 inferior to that of pediatric sequential organ failure (0.716 vs. 0.921, p < .001). The AU-ROC of pSIC in predicting nonovert DIC was 0.845 and the optimal cutoff value was >3. The AU-ROC of pSIC in predicting overt DIC was 0.901, with the best optimal cutoff value of >4. The pSIC score can be used to diagnose SIC in children, screen potential nonovert DIC, and assess the severity of sepsis, organ dysfunction, and 28-day outcome in children.
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http://dx.doi.org/10.1111/jth.15500DOI Listing
August 2021

Fulminant type I cryoglobulinemic glomerulonephritis with unique ultrastructural plugs: a case report.

Int J Hematol 2021 Jul 24. Epub 2021 Jul 24.

Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.

Introduction:  Type I cryoglobulinemia is a rare disease which affects the skin, central nervous system and kidneys. It is usually associated with lymphoproliferative disorders such as multiple myeloma, lymphoma and monoclonal gammopathy of renal significance. Proteinuria and membranoproliferative glomerulonephritis are the most common renal manifestations; Case presentation: Here we report the case of a female patient in her late 40 s who had proteinuria accompanied by Raynaud's phenomenon, high blood and plasma viscosity, hearing loss, and cardiac and central nervous system involvement. Monoclonal immunoglobulin G-λ protein was detected and serum was positive for cryoglobulin. Renal biopsy revealed massive cryo-plugs with unique ultrastructural appearance in the glomerular and peritubular capillary lumina. Immunofluorescence showed predominant IgG3/λ deposition in cryo-plugs. As reported, the clinical manifestations of this patient resulted from cryoprecipitate and hyperviscosity syndrome; Conclusion: Cryoglobulinemia should be considered as a possible diagnosis in patients with Raynaud's phenomenon, hyperviscosity syndrome and monoclonal immunoglobulin.
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http://dx.doi.org/10.1007/s12185-021-03194-8DOI Listing
July 2021

Identifying the Key Risk Factors of Mega Infrastructure Projects from an Extended Sustainable Development Perspective.

Int J Environ Res Public Health 2021 07 14;18(14). Epub 2021 Jul 14.

School of Management Science and Real Estate, Chongqing University, Chongqing 400045, China.

Mega infrastructure projects (MIPs) have become increasingly important to the realization of sustainable development in China. Sustainable development is a process of dynamic balance, and coordinating the triple bottom line (the environmental, social, and economic dimensions) will enable more sustainable development of MIPs. However, previous studies have lacked consideration of coordination when applying sustainable development principles to the systematic identification of risks to MIPs. The goals of this study were to clarify the definition and dimensions of the sustainable development of MIPs and to identify the key risks of MIPs. A literature review was performed to extend the definition of sustainable development of MIPs by combining the triple bottom line with a fourth coordination dimension. A conceptual model of MIP risk identification was then proposed from an extended sustainable development perspective, 22 sustainability elements and 75 risk factors were identified, and the key risk factors were determined based on the interview responses and fuzzy set theory. The results show that economic risks have a high probability, social risks have a high loss, environmental risks have an intermediate probability and loss, and coordination risks have the greatest impact. In addition, the three most important key risk factors were found to be construction and installation cost overruns, land acquisition and resettling cost overruns, and information sharing with the public. Identifying key risk factors can provide information to help stakeholders understand the risk factors associated with MIPs and formulate reasonable risk response strategies.
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http://dx.doi.org/10.3390/ijerph18147515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304175PMC
July 2021

Analysis of gut microbiota alteration and application as an auxiliary prognostic marker for sepsis in children: a pilot study.

Transl Pediatr 2021 Jun;10(6):1647-1657

The Laboratory of Pediatric Infectious Diseases, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Emerging evidence suggests that gut microbiota dysbiosis plays a role in sepsis. Recent advances in sequencing technology enable the characterization of the gut microbiota and can provide clues for the pathogenesis of sepsis, which may help develop biomarkers for diagnosis or prognosis prediction in children with sepsis.

Methods: The gut microbiota from 25 children with sepsis and 15 age- and sex-matched healthy controls were extracted and sequenced by high-throughput Illumina Hiseq, targeting the 16S rDNA genes. The differences of gut microbiota between the two groups were analyzed to assess if the gut microbiota can be used as an auxiliary prognostic marker for sepsis.

Results: The diversity of gut microbiota in children with sepsis was significantly lower than that of healthy controls (P<0.001). The overall community structure of gut microbiota was also altered considerably. On the genus level, children with sepsis had more opportunistic pathogens, such as and , while fewer beneficial bacterial, such as , , , , and , were detected. Further analysis of the association between the gut microbiota and clinical features revealed that the pathogens from bacteria culture correlated to the dominant bacteria genus detected in the intestinal flora. Furthermore, the gut microbiota diversity was negatively associated with the antibiotic therapy duration, but did not correlate with type of antibiotics used. Finally, gut microbiota disturbance was correlated with increased mortality rate.

Conclusions: Overall, we confirmed that gut microbiota disturbance occurred in the children with sepsis, and changes in the fecal microbiota were closely related to clinical characteristics. Elucidation of such dysbiosis could improve our understanding of sepsis pathogenesis and help develop microbiota-based diagnosis, monitoring, and therapy for sepsis.
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http://dx.doi.org/10.21037/tp-21-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261590PMC
June 2021

Phylogenetic Analysis of Strains and Identification of Serogroups by Lipopolysaccharide- and O-antigen- based PCR Assay.

Biomed Environ Sci 2021 Jun;34(6):483-488

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102249, China;Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310021, Jiangsu, China.

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http://dx.doi.org/10.3967/bes2021.065DOI Listing
June 2021

Willingness to Donate Remnant Human Biospecimens in the Context of the COVID-19 Pandemic.

Biopreserv Biobank 2021 Jul 16. Epub 2021 Jul 16.

Biobank, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Studies using biospecimens can help reveal pathogenic mechanisms and improve prevention, diagnosis, and treatment of diseases. However, there is still a lack of relevant investigation data, which can provide initial evidence for establishing or improving relevant laws and regulations, on people's willingness to donate biospecimens, and whether they agree to waive the right of obtaining informed consent in the special period of sudden outbreak of new infectious diseases. To investigate people's willingness to donate their remnant biospecimens of clinical tests for research in the context of the COVID-19 pandemic and their willingness to sign the informed consent for research using their biospecimens. We conducted a survey using an online questionnaire, which included questions on basic personal information, COVID-19-related information, donation of remnant biospecimens, willingness to sign informed consent, and reasons to do so. Among the 721 valid responses, 620 respondents (86.0%) reported that they would be willing to donate their remnant biospecimens for research, of whom 434 (70.0%) reported that they would donate their remnant biospecimens without signing the informed consent. Of the 11 specified influencing factors, occupation, household income, and degree of concern about the COVID-19 pandemic were associated with willingness to donate remnant biospecimens. Gender and age were associated with willingness to donate remnant biospecimens without signing the informed consent. The main reasons for unwillingness to donate remnant biospecimens and sign the informed consent were a limited knowledge of research and privacy concerns. Most respondents reported that they would be willing to donate their remnant biospecimens for biomedical research without signing an informed consent in the context of the COVID-19 pandemic. Lack of understanding of the proposed research and concerns about personal privacy were the main reasons for unwillingness to donate biospecimens and signing the informed consent.
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http://dx.doi.org/10.1089/bio.2021.0036DOI Listing
July 2021

Prevalence of and risk factors for high-altitude hyperuricaemia in Bai individuals: a cross-sectional study.

J Int Med Res 2021 Jul;49(7):3000605211028140

Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objective: Hyperuricaemia is common in Bai individuals; however, its prevalence remains unclear. This work aimed to investigate high-altitude hyperuricaemia prevalence and risk factors in Bai individuals.

Methods: All eligible participants of Bai ethnicity (aged ≥18 years and undergoing routine medical examination at the People's Hospital of Jianchuan County between January and December 2019) were consecutively enrolled. Demographic and laboratory data were collected to investigate hyperuricaemia prevalence and associated risk factors.

Results: A total of 1393 participants were assessed, comprising 345 (24.8%) with hyperuricaemia showing a male predominance (287/865 [33.2%] males versus 58/528 [11.0%] females). Hyperuricaemia prevalence was significantly higher in participants aged ≥50 years (100/332 [30.1%]) versus those aged 30-40 years (59/308 [19.2%]), and in overweight/obese individuals compared with those showing an underweight or normal body mass index (BMI; 267/885 [30.2%] versus 78/508 [15.4%]). Finally, haemoglobin concentrations and serum uric acid levels were positively correlated.

Conclusion: Besides traditional risk factors, including age, sex and BMI, polycythaemia due to prolonged exposure to high altitude may also cause hyperuricaemia in Bai individuals residing in Yunnan Province.
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http://dx.doi.org/10.1177/03000605211028140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267041PMC
July 2021

A Rapid Pipeline for Pollen- and Anther-Specific Gene Discovery Based on Transcriptome Profiling Analysis of Maize Tissues.

Int J Mol Sci 2021 Jun 26;22(13). Epub 2021 Jun 26.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing 210095, China.

Recently, crop breeders have widely adopted a new biotechnology-based process, termed Seed Production Technology (SPT), to produce hybrid varieties. The SPT does not produce nuclear male-sterile lines, and instead utilizes transgenic SPT maintainer lines to pollinate male-sterile plants for propagation of nuclear-recessive male-sterile lines. A late-stage pollen-specific promoter is an essential component of the pollen-inactivating cassette used by the SPT maintainers. While a number of plant pollen-specific promoters have been reported so far, their usefulness in SPT has remained limited. To increase the repertoire of pollen-specific promoters for the maize community, we conducted a comprehensive comparative analysis of transcriptome profiles of mature pollen and mature anthers against other tissue types. We found that maize pollen has much less expressed genes (>1 FPKM) than other tissue types, but the pollen grain has a large set of distinct genes, called pollen-specific genes, which are exclusively or much higher (100 folds) expressed in pollen than other tissue types. Utilizing transcript abundance and correlation coefficient analysis, 1215 mature pollen-specific (MPS) genes and 1009 mature anther-specific (MAS) genes were identified in B73 transcriptome. These two gene sets had similar GO term and KEGG pathway enrichment patterns, indicating that their members share similar functions in the maize reproductive process. Of the genes, 623 were shared between the two sets, called mature anther- and pollen-specific (MAPS) genes, which represent the late-stage pollen-specific genes of the maize genome. Functional annotation analysis of MAPS showed that 447 MAPS genes (71.7% of MAPS) belonged to genes encoding pollen allergen protein. Their 2-kb promoters were analyzed for -element enrichment and six well-known pollen-specific -elements (AGAAA, TCCACCA, TGTGGTT, [TA]AAAG, AAATGA, and TTTCT) were found highly enriched in the promoters of MAPS. Interestingly, JA-responsive -element GCC box (GCCGCC) and ABA-responsive -element-coupling element1 (ABRE-CE1, CCACC) were also found enriched in the MAPS promoters, indicating that JA and ABA signaling likely regulate pollen-specific MAPS expression. This study describes a robust and straightforward pipeline to discover pollen-specific promotes from publicly available data while providing maize breeders and the maize industry a number of late-stage (mature) pollen-specific promoters for use in SPT for hybrid breeding and seed production.
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http://dx.doi.org/10.3390/ijms22136877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267723PMC
June 2021

Novel biallelic mutations in POLG gene: large deletion and missense variant associated with PEO.

Neurol Sci 2021 Oct 29;42(10):4271-4280. Epub 2021 Jun 29.

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, 250012, Shandong, China.

Background: Mitochondrial disorders are clinically heterogeneous diseases associated with impaired oxidative phosphorylation (OXPHOS) activity. POLG, which encodes the DNA polymerase-γ (Polγ) catalytic subunit, is the most commonly mutated nuclear gene associated with mitochondrial disorders.

Methods: We carried out whole-exome sequencing (WES) to identify the gene associated with progressive external ophthalmoplegia (PEO). We then performed histopathological analyses, assessed mitochondrial biology, and executed functional studies to evaluate the potential pathogenicity of the identified genetic mutations.

Results: Novel biallelic POLG mutations, including a large deletion mutation (exons 7-21) and a missense variant c.1796C>T (p.Thr599Ile) were detected in the proband. Histopathological analysis of a biopsied muscle sample from this patient revealed the presence of approximately 20% COX-negative fibers. Bioinformatics analyses confirmed that the detected mutations were pathogenic. Furthermore, levels of mitochondrial complex I, II, and IV subunit protein expressions were found to be decreased in the proband, and marked impairment of mitochondrial respiration was evident in cells harboring these mutations.

Conclusion: This study expands the spectrum of known POLG variants associated with PEO and advances current understanding regarding the structural and functional impacts of these mutations.
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http://dx.doi.org/10.1007/s10072-021-05380-2DOI Listing
October 2021

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 08 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

The combination of photodynamic therapy and fractional CO laser for mycobacterium marinum infection.

Photodiagnosis Photodyn Ther 2021 Sep 11;35:102391. Epub 2021 Jun 11.

Department of Dermatology, The Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China. Electronic address:

Mycobacterium marinum (M. marinum) can cause cutaneous infection. Therapy with active antibiotics for 3 to 6 months is one reasonable treatment. However, it is hard to provide an optimal balance with regard to efficacy and tolerability when the patient is complicated with other diseases. We reported two patients with cutaneous M. marinum infections who were successfully treated with 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) combined with fractional CO laser ablation. The results of these two cases indicated that PDT in combination with fractional CO laser ablation of epidermis could be a therapeutic option for the treatment of skin infections caused by M. marinum.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102391DOI Listing
September 2021

A Fast PCR Test for the Simultaneous Identification of Species and Gender in Horses, Donkeys, Mules and Hinnies.

J Equine Vet Sci 2021 07 27;102:103458. Epub 2021 Apr 27.

College of animal science, Inner Mongolia Key Laboratory of Equine Genetics, Breeding and Reproduction, Equine Research Center, Inner Mongolia Agricultural University, Hohhot, China. Electronic address:

Having considered that the current methods are costly and time-consuming, we designed an only 3 pairs primer-based PCR test to accurately identify the species and gender in horses, donkeys, mules and hinnies. Through a thorough sequence comparison between horse and donkey's highly similar genomes, and a vast amount of preliminary confirmation, we found that three fragments, CNGB3 gene on an autosome, displacement loop region on mitochondrial DNA and SRY genes on chromosome Y, within these equine DNA, are enough to enable us achieving our goal. The PCR test described here would be an economical, fast and accurate alternative for the most commonly-used methods, polymerase chain reaction-restriction fragment length polymorphism, microsatellite assay, and sequencing.
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http://dx.doi.org/10.1016/j.jevs.2021.103458DOI Listing
July 2021

Effectiveness of neoadjuvant chemotherapy on the survival outcomes of patients with resectable non-small-cell lung cancer: A meta-analysis of randomized controlled trials.

Surg Oncol 2021 Sep 26;38:101590. Epub 2021 May 26.

Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China. Electronic address:

Purpose: To determine the effectiveness of neoadjuvant chemotherapy (NACT) versus primary surgery on survival outcomes for resectable non-small-cell lung cancer (NSCLC) using an approach based on a meta-analysis.

Methods: The PubMed, EmBase, Cochrane library, and CNKI databases were systematically browsed to identify randomized controlled trials (RCTs) which met a set of predetermined inclusion criteria throughout January 2020. Hazard ratios (HRs) were applied for the pooled overall survival (OS) and progression-free survival (PFS) values, and the pooled survival rates at 1-year and 3-year were used as the relative risk (RR). All the pooled effect estimates with 95% confidence intervals (CIs) were calculated using the random-effects model.

Results: Nineteen RCTs contained a total of 4372 NSCLC at I-III stages was selected for final meta-analysis. We noted NACT was significantly associated with an improvement in OS (HR: 0.87; 95%CI: 0.81-0.94; P < 0.001) and PFS (HR: 0.86; 95%CI: 0.78-0.96; P = 0.005). Moreover, the survival rate at 1-year (RR: 1.07; 95%CI: 1.02-1.12; P = 0.007) and 3-year (RR: 1.16; 95%CI: 1.06-1.27; P = 0.001) in the NACT group was significantly higher than the survival rate for the primary surgery group. Finally, the treatment effects of NACT versus primary surgery on survival outcomes might be different when stratified by the mean age of patients and the tumor stages.

Conclusions: NACT could improve survival outcomes for patients with resectable NSCLC, suggesting its suitable future applicability for clinical practice. However, large-scale RCT should be conducted to assess the chemotherapy regimen on the prognosis of resectable NSCLC.
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http://dx.doi.org/10.1016/j.suronc.2021.101590DOI Listing
September 2021

Source profiles and emission factors of organic and inorganic species in fine particles emitted from the ultra-low emission power plant and typical industries.

Sci Total Environ 2021 Oct 24;789:147966. Epub 2021 May 24.

Institute of Surface-Earth System Science, School of Earth System Science, Tianjin University, Tianjin 300072, China. Electronic address:

Accurate source markers, source profiles and species-based emission factors (EFs) are currently the key limitations for source apportionment and emission inventory researches. Fine particles (PM) were collected from stack gases of eight types of stationary sources with a dilution sampling system. The mass percentages and EFs of 89 kinds of chemical species in PM including water-soluble ions, elements, carbonaceous species and molecular organic species were obtained. Results showed that water-soluble ions (8%-54%) and elements (5%-45%) were the dominant chemical species. Palmitic acid (0.19%-0.62%) and stearic acid (0.21%-0.59%) were the most abundant organic species. PM source profiles of the eight sources were different from each other with the coefficient of divergence values all higher than 0.4. The addition of organic species could help to further distinguish them. The indicatory chemical components and specific species ratios were obtained by both a statistical equation and randomForest. These indicatory chemical components (e.g. F for glass factory) and species ratios (e.g. K/Mg & OC/Mg for pharmaceutical factory) improved the current knowledges of their indicatory performance in source identification of ambient PM. The EFs of PM from the eight stationary sources ranged from 0.019 to 51.6 kg t of fuel used. The EFs of PM from the pharmaceutical factory were about 70-2600 times higher than other seven types of sources due to the lack of dust-removing devices. Certain EFs measured in this study were about 10-36,000 times lower than corresponding EFs estimated in previous studies which didn't perform field measurements, indicating the necessity for improving emission inventories continuously. This study contributes to identifying emission sources of PM especially for subtypes of stationary sources and to establishing species-based emission inventories.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147966DOI Listing
October 2021

Identifying potential biomarkers in hepatitis B virus infection and its response to the antiviral therapy by integrated bioinformatic analysis.

J Cell Mol Med 2021 Jul 26;25(14):6558-6572. Epub 2021 May 26.

Department of infection, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

The antiviral treatment efficacy varies among chronic hepatitis B (CHB) patients and the underlying mechanism is unclear. An integrated bioinformatics analysis was performed to investigate the host factors that affect the therapeutic responsiveness in CHB patients. Four GEO data sets (GSE54747, GSE27555, GSE66698 and GSE66699) were downloaded from the Gene Expression Omnibus (GEO) database and analysed to identify differentially expressed genes(DEGs). Enrichment analyses of the DEGs were conducted using the DAVID database. Immune cell infiltration characteristics were analysed by CIBERSORT. Upstream miRNAs and lncRNAs of hub DEGs were identified by miRWalk 3.0 and miRNet in combination with the MNDR platform. As a result, seventy-seven overlapping DEGs and 15 hub genes were identified including CCL5, CXCL9, MYH2, CXCR4, CD74, CCL4, HLA-DRB1, ACTA1, CD69, CXCL10, HLA-DRB5, HLA-DQB1, CXCL13, STAT1 and CKM. The enrichment analyses revealed that the DEGs were mainly enriched in immune response and chemokine signalling pathways. Investigation of immune cell infiltration in liver samples suggested significantly different infiltration between responders and non-responders, mainly characterized by higher proportions of CD8+ T cells and activated NK cells in non-responders. The prediction of upstream miRNAs and lncRNAs led to the identification of a potential mRNA-miRNA-lncRNA regulatory network composed of 2 lncRNAs (H19 and GAS5) and 5 miRNAs (hsa-mir-106b-5p, hsa-mir-17-5p, hsa-mir-20a-5p, hsa-mir-6720-5p and hsa-mir-93-5p) targeting CCL5 mRNA. In conclusion, our study suggested that host genetic factors could affect therapeutic responsiveness in CHB patients. The antiviral process might be associated with the chemokine-mediated immune response and immune cell infiltration in the liver microenvironment.
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http://dx.doi.org/10.1111/jcmm.16655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278120PMC
July 2021

Plant derived coumestrol phytochemical targets human skin carcinoma cells by inducing mitochondrial-mediated apoptosis, cell cycle arrest, inhibition of cell migration and invasion and modulation of m-TOR/PI3K/AKT signalling pathway.

Saudi J Biol Sci 2021 May 18;28(5):2739-2746. Epub 2021 Mar 18.

Department of Ophthalmology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222002, China.

The current study was undertaken to investigate anticancer activity of coumestrol phytoestrogen against human skin cancer. MTT assay was performed for cell viability assessment and clonogenic assay for cell colony formation assessment. Apoptosis was analysed by Annexin V/FITC staining, AO/EB staining and western blotting assays. Effects on the m-TOR/PI3K/AKT signalling pathway were investigated by western blotting. Results indicated that coumestrol induced significant toxicity in human skin cancer cells in contrast to mouse skin cancer cells. The proliferation rate in normal skin cells remained almost intact. Annexin V-FITC and AO/EB staining assays indicated coumestrol induced cytotoxicity in skin cancer cells is mediated through apoptosis stimulation. The apoptosis in skin cancer cells was mediated through caspase-activation. Cell migration and invasion was inhibited by coumestrol in human skin cancer cells via inhibition of MMP-2 and MMP-9 expressions. Moreover, m-TOR/PI3K/AKT signalling pathway in SKEM-5 cells was blocked by coumestrol.
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http://dx.doi.org/10.1016/j.sjbs.2021.03.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117110PMC
May 2021

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

J Hepatol 2021 Aug 19;75(2):454-461. Epub 2021 May 19.

Department of Infectious Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, China.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.
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http://dx.doi.org/10.1016/j.jhep.2021.05.003DOI Listing
August 2021

Consolidation Treatment and Long-Term Prognosis of Rituximab in Minimal Change Disease and Focal Segmental Glomerular Sclerosis.

Drug Des Devel Ther 2021 10;15:1945-1953. Epub 2021 May 10.

Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

Purpose: There is currently a lack of studies investigating long-term prognosis and the necessity of further rituximab (RTX) consolidation treatment for minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The aim of this study was to evaluate the efficacy of RTX for these diseases and to investigate whether a consolidation treatment can lower risks of relapse and reinforce long-term remission.

Patients And Methods: A retrospective study was conducted. The relapse and remission of 70 patients treated with 1 course of RTX treatment (4 infusions of 375 mg/m2) over a median follow-up time of 27 months (12-60 months) were analyzed. The rates of patients that were able to achieve non-relapse for a duration of 24 months between RTX consolidation therapy and non-consolidation therapy were compared.

Results: There were 67 cases (95.71%) of remission and 3 cases (4.29%) of non-remission. The average number of relapses decreased from 3.7±2.5 times before the treatment to 0.8±1.8 times after treatment (P <0.001). The average avannual number of relapses decreased from 1.3±1.2 times/year to 0.2±0.3 times/year (P <0.001). The results from the Cox proportional-hazards model showed that the risk of relapse in patients who received RTX non-consolidation treatment was significantly higher than those with consolidation treatment (odds ratios (OR) 20.9, 95% confidence intervals (CI) OR 5.7-75.7, p<0.001). The 24-month relapse-free rate was also significantly higher in patients with consolidation therapy compared with non-consolidation therapy (86.36% vs 25%, p<0.001). No adverse events were recorded.

Conclusion: RTX is highly effective in treating MCD and FSGS, and RTX consolidation therapy may be recommended to reinforce long-term remissions.
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http://dx.doi.org/10.2147/DDDT.S302257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121273PMC
May 2021

TaxonKit: A practical and efficient NCBI taxonomy toolkit.

Authors:
Wei Shen Hong Ren

J Genet Genomics 2021 Apr 15. Epub 2021 Apr 15.

Institute for Viral Hepatitis, Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address:

The National Center for Biotechnology Information (NCBI) Taxonomy is widely applied in biomedical and ecological studies. Typical demands include querying taxonomy identifier (TaxIds) by taxonomy names, querying complete taxonomic lineages by TaxIds, listing descendants of given TaxIds, and others. However, existed tools are either limited in functionalities or inefficient in terms of runtime. In this work, we present TaxonKit, a command-line toolkit for comprehensive and efficient manipulation of NCBI Taxonomy data. TaxonKit comprises seven core subcommands providing functions, including TaxIds querying, listing, filtering, lineage retrieving and reformatting, lowest common ancestor computation, and TaxIds change tracking. The practical functions, competitive processing performance, scalability with different scales of datasets and good accessibility could facilitate taxonomy data manipulations. TaxonKit provides free access under the permissive MIT license on GitHub, Brewsci, and Bioconda. The documents are also available at https://bioinf.shenwei.me/taxonkit/.
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http://dx.doi.org/10.1016/j.jgg.2021.03.006DOI Listing
April 2021

The clinical outcomes and biomarker features of severe sepsis/septic shock with severe neutropenia: a retrospective cohort study.

Transl Pediatr 2021 Mar;10(3):464-473

Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Severe sepsis/septic shock with severe neutropenia often leads to poor prognosis. However, it is unknown if severe neutropenia is associated with different clinical outcomes and biomarker features in severe sepsis/septic patients.

Methods: This retrospective cohort study enrolled 141 severe sepsis/septic shock patients admitted to intensive care unit of Shanghai Children's Medical Center between January 2015 and November 2019. Patients were followed up for the development of ventilation support, the use of vasoactive drugs, continuous renal replacement therapy (CRRT) procedure, and mortality. Biomarkers that reflect the level of inflammation in severe sepsis/septic shock patients with neutropenia were compared to that in patients without neutropenia.

Results: Of 141 patients enrolled, 54 patients suffered from severe sepsis/septic shock with severe neutropenia. In patients with severe sepsis/septic shock, severe neutropenia as a complication was an independent risk factor for the use of vasoactive drugs (RR 9.796; 95% CI: 3.774, 25.429; P<0.001), but not for ventilation support (RR 0.157; 95% CI: 0.06, 0.414; P<0.001), CRRT procedure (RR 1.032; 95% CI: 0.359, 2.969; P=0.953) or 28-day mortality (RR 1.405; 95% CI: 0.533, 3.708; P=0.492). Severe sepsis/septic patients with severe neutropenia had a higher plasma level of the following biomarkers: c-reaction protein (CRP) (180.5 121 mg/mL, P<0.001), procalcitonin (PCT) (12.15 2.7 ng/mL; P=0.005), interleukin (IL)-6 (316.83 55.77 pg/mL, P<0.001), IL-10 (39.165 10.09 pg/mL, P<0.001), interferon (IFN)-γ (6.155 3.71 pg/mL, P=0.016), and the percentage of regulatory T cells (Tregs) (2.7% 2.09%, P=0.003). Based on the receiver operating characteristic curves, IL-10 exhibited high specificity (79.4%) in evaluating the prognosis of septic patients with neutropenia.

Conclusions: In patients with severe sepsis/septic shock, being complicated with severe neutropenia is associated with higher proportion of using vasoactive drugs, and those patients tend to have higher plasma levels of IL-6, IL-10, IFN-γ and percentage of Treg.
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http://dx.doi.org/10.21037/tp-20-230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039791PMC
March 2021

circCCDC66 promotes thyroid cancer cell proliferation, migratory and invasive abilities and glycolysis through the miR-211-5p/PDK4 axis.

Oncol Lett 2021 May 26;21(5):416. Epub 2021 Mar 26.

Department of General Surgery, Qingdao Municipal Hospital, Qingdao University School of Medicine, Shandong, Qingdao 266000, P.R. China.

Cancer metastasis is the main cause of death in cancer patients, including patients with thyroid cancer (TC). TC is the most common malignant endocrine tumour. In the recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) serve a significant role in the development of many types of human cancer. However, the function and underlying mechanism of circCCDC66 in TC remain unclear. The present study aimed to explore the role of circCCDC66 in TC. To do so, reverse transcription quantitative PCR was used to detect the expression level of circCCDC66. Cell viability, migratory and invasive abilities, and glucose consumption were evaluated by cell counting kit 8, Transwell and glucose consumption assays, respectively. The association between circCCDC66 or pyruvate dehydrogenase kinase 4 (PDK4) and miR-211-5p was verified by dual-luciferase reporter assay. The results demonstrated that circCCDC66 expression was significantly increased in TC tissues and cell lines. Furthermore, silencing circCCDC66 inhibited TC cell proliferation, migratory and invasive abilities and glycolysis . Further validation demonstrated that circCCDC66 directly interacted with the microRNA (miR) miR-211-5p. Subsequently, the activity of circCCDC66 was attenuated by miR-211-5p. In addition, the results demonstrated that circCCDC66 may promote papillary thyroid cancer progression by sponging miR-211-5p and increasing expression of PDK4. In conclusion, the present study demonstrated that circCCDC66 could promote TC cell proliferation, migratory and invasive abilities and invasion and glycolysis through the miR-211-5p/PDK4 axis. These findings suggested that targeting circCCDC66 may be considered as a promising therapeutic strategy for TC.
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http://dx.doi.org/10.3892/ol.2021.12677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020395PMC
May 2021

Sinonasal manifestations and dynamic profile of RT-PCR results for SARS-CoV-2 in COVID-19 patients.

Ann Palliat Med 2021 Apr 23;10(4):4174-4183. Epub 2021 Mar 23.

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Key Laboratory of Otorhinolaryngology-Head & Neck Surgery Ministry of Education, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Key Laboratory of Nasal Diseases, Beijing, China.

Background: Sinonasal symptoms were usually reported to appear initially, yielding the symptoms important for the early detection of coronavirus disease 2019 (COVID-19). This study was conducted retrospectively to investigate the detailed sinonasal manifestations and dynamic profile of real-time reverse transcription polymerase chain reaction (RT-PCR) results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients longitudinally.

Methods: This retrospective study included 11 consecutive patients. The prevalence, timing and severity of sinonasal manifestations were analyzed. Oropharyngeal, nasal, sputum and stool specimens were collected to detect RT-PCR for SARS-CoV-2 over COVID-19 period.

Results: Among the 11 patients, 6 (54.5%) were female, and the median age was 51 (IQR, 36-62) years. Seven patients (63.6%) experienced sinonasal symptoms, with 6 (54.5%) exhibiting sinonasal symptoms on the onset day. Seven patients (63.6%) demonstrated nasal obstruction, 5 (45.5%) had rhinorrhea, and 4 (36.4%) exhibited olfactory dysfunction. All six patients with sinonasal symptoms on the onset day had non-severe infections. Most patients (85.7%) with sinonasal symptoms had non-severe infections. Sinonasal symptoms commonly appeared early. The positive RT-PCR rate for SARS-CoV-2 in various specimens was highest in the first week (73.3%), then gradually decreased over the disease course, but 3 patients (27.3%) had experienced a long-lasting fluctuated positive RT-PCR results since 29 days of illness in both groups, especially for two patients with airway comorbidities.

Conclusions: Sinonasal symptoms were more prevalent in patients with mild or moderate COVID-19 and usually appeared early. In addition, regular nucleic acid testing for SARS-CoV-2 should be considered for COVID-19 patients with certain airway comorbidities.
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http://dx.doi.org/10.21037/apm-20-2493DOI Listing
April 2021

Normal tissue adjacent to tumor expression profile analysis developed and validated a prognostic model based on Hippo-related genes in hepatocellular carcinoma.

Cancer Med 2021 05 4;10(9):3139-3152. Epub 2021 Apr 4.

Department of Infectious Diseases, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Hepatocellular carcinoma (HCC) is the most common malignant disease worldwide. Although the diagnosis and treatment of HCC have greatly improved in the recent years, there is still a lack of accurate methods to predict the prognosis of patients. Evidence has shown that Hippo signaling in tissues adjacent to HCC plays a significant role in HCC development. In the present study, we aimed to construct a model based on the expression of Hippo-related genes (HRGs) in tissues adjacent to HCC to predict the prognosis of HCC patients.

Methods: Gene expression data of paired normal tissues adjacent to HCC (PNTAH) and clinical information were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The HRG signature was constructed using four canonical Hippo-related pathways. Univariate Cox regression analysis was used to screen survival-related HRGs. LASSO and multivariate Cox regression analyses were used to construct the prognostic model. The true and false positive rates of the model were confirmed using receiver operating characteristic (ROC) analysis.

Results: The prognostic model was constructed based on the expression levels of five HRGs (NF2, MYC, BIRC3, CSNK1E, and MINK1) in PNTAH. The mortality rate of HCC patients increased as the risk score determined by the model increased. Furthermore, the risk score was found to be an independent risk factor for the survival of patients. ROC analysis showed that the prognostic model had a better predictive value than the other conventional clinical parameters. Moreover, the reliability of the prognostic model was confirmed in TCGA-LIHC cohort. A nomogram was generated to predict patient survival. An exploration of the predictive value of the model in HCC tissues indicated that the model is PNTAH-specific.

Conclusions: We developed and validated a prognostic model based on the expression levels of five HRGs in PNTAH, and this model should be helpful in predicting the prognosis of patients with HCC.
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http://dx.doi.org/10.1002/cam4.3890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085948PMC
May 2021

"Reading Pictures Instead of Looking": RGB-D Image-Based Action Recognition via Capsule Network and Kalman Filter.

Sensors (Basel) 2021 Mar 22;21(6). Epub 2021 Mar 22.

Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

This paper proposes an action recognition algorithm based on the capsule network and Kalman filter called "Reading Pictures Instead of Looking" (RPIL). This method resolves the convolutional neural network's over sensitivity to rotation and scaling and increases the interpretability of the model as per the spatial coordinates in graphics. The capsule network is first used to obtain the components of the target human body. The detected parts and their attribute parameters (e.g., spatial coordinates, color) are then analyzed by Bert. A Kalman filter analyzes the predicted capsules and filters out any misinformation to prevent the action recognition results from being affected by incorrectly predicted capsules. The parameters between neuron layers are evaluated, then the structure is pruned into a dendritic network to enhance the computational efficiency of the algorithm. This minimizes the dependence of in-depth learning on the random features extracted by the CNN without sacrificing the model's accuracy. The association between hidden layers of the neural network is also explained. With a 90% observation rate, the OAD dataset test precision is 83.3%, the ChaLearn Gesture dataset test precision is 72.2%, and the G3D dataset test precision is 86.5%. The RPILNet also satisfies real-time operation requirements (>30 fps).
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http://dx.doi.org/10.3390/s21062217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005215PMC
March 2021

Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

Lancet Infect Dis 2021 08 24;21(8):1107-1119. Epub 2021 Mar 24.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Electronic address:

Background: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study.

Methods: We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing.

Findings: Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90%] of 20 in the 50 μg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 μg group, 50 [33%] of 150 in the two-dose 50 μg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 μg group, and 65 [43%] of 150 in the three-dose 50 μg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 μg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 μg vaccine group, two [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 μg vaccine group, and six [4%] in the three-dose 50 μg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 μg vaccine group, and five [3%] in the three-dose 50 μg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 μg vaccine group, and two [1%] in the three-dose 50 μg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 μg group and 72% (108 of 150) in the 50 μg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6-23·1) in the 25 μg group and 14·1 (10·8-18·3) in the 50 μg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8-128·5) in the 25 μg group and 69·1 (53·0-90·0) in the 50 μg group.

Interpretation: The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy.

Funding: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00127-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990482PMC
August 2021

Effect of continuous nursing on nursing quality and patient quality of life and satisfaction among children with pneumonia.

J Int Med Res 2021 Mar;49(3):300060521993691

Department of Pediatric Internal Medicine, Hebei Hengshui People's Hospital, Hebei Hengshui, China.

Objective: In this study, we aimed to explore the effect of continuous nursing care on children with pneumonia, including patient survival and quality of life.

Methods: We included 90 children with pneumonia who were admitted to our hospital from May 2017 to June 20, 2017. We established two patient groups (45 children per group); the routine group received general care and the continuous group received continuous nursing care. We observed the correlation among nursing effectiveness, clinical symptom improvement, quality of life, satisfaction, and complications.

Results: Our results showed that effectiveness in the continuous care group was 95.55%, significantly higher than that in the routine group (75.55%). Duration of hypothermia (1.75 ± 0.65 days), time to cough remission (4.24 ± 1.12 days), time to rale remission (4.15 ± 0.89 days), and time to remission of shortness of breath (2.65 ± 0.65 days) in the continuous group was shorter than those in the routine group. The incidence of total complications in the continuous group was 8.89%, which was significantly lower than that in the routine group (26.67%). The continuous care group showed greater improvement after intervention.

Conclusion: Continuous care in children with pneumonia can help to reduce illness severity, pain, heart and lung failure, and serve to avoid medical disputes.
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http://dx.doi.org/10.1177/0300060521993691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165847PMC
March 2021

NOD1 Agonist Protects Against Lipopolysaccharide and D-Galactosamine-Induced Fatal Hepatitis Through the Upregulation of A20 Expression in Hepatocytes.

Front Immunol 2021 4;12:603192. Epub 2021 Mar 4.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Increasing evidence suggests that NODs are involved in liver diseases; however, the underlying mechanisms remain obscure. In the present study, we analyzed the effect of NOD1 agonist pretreatment on acute liver failure induced by lipopolysaccharide (LPS) in D-galactosamine (D-GalN)-sensitized mice. We found that pretreatment with the NOD1 agonist markedly reduced LPS/D-GalN-induced mortality, elevation of serum ALT levels, and hepatocyte apoptosis. The protective effect of NOD1 agonist was independent of tumor necrosis factor (TNF)-α inhibition. NOD1 agonist pretreatment also attenuated TNF-α/D-GalN-induced apoptotic liver damage. The anti-apoptotic protein A20 expression was more pronounced in NOD1 agonist pretreated mice than in controls, and knockdown of A20 abrogated the protective effect of NOD1 agonist on LPS/D-GalN-induced liver injury and hepatocyte apoptosis. Further experiments showed that NOD1 agonist-induced A20 upregulation required the presence of kupffer cells and TNF-α. Taken together, our data strongly indicate that NOD1 is involved in the regulation of liver injury and could be a potential therapeutic target for liver diseases.
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http://dx.doi.org/10.3389/fimmu.2021.603192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969647PMC
June 2021
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