Publications by authors named "Jie Wu"

2,134 Publications

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Chronic restraint stress impairs cognition via modulating HDAC2 expression.

Transl Neurosci 2021 Jan 29;12(1):154-163. Epub 2021 Apr 29.

Comparative Medical Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Panjiayuan Nanli No. 5, Beijing, 100021, People's Republic of China.

Background: To investigate the effects of chronic restraint stress on cognition and the probable molecular mechanism in mice.

Methods: In the current work, a restraining tube was used as a way to induce chronic stress in mice. The protein levels were determined with ELISA and western blot. A series of behavior tests, including the Morris water maze, elevated plus maze, open field test, and novel object recognition test, were also performed to examine the anxiety and the ability of learning and memory. Moreover, murine neuroblastoma N2a cells were used to confirm the findings from mice under chronic stress.

Results: Decreased synaptic functions were impaired in chronic stress with the downregulation of PSD95, GluR-1, the neurotrophic factor BDNF, and immediate-onset genes Arc and Egr. Chronic restraint decreased the histone acetylation level in hippocampal neurons while HDAC2 was increased and was co-localized with glucocorticoid receptors. Moreover, chronic stress inhibited the PI3K/AKT signaling pathway and induced energy metabolism dysfunctions.

Conclusion: This work examining the elevated levels of HDAC2 in the hippocampus may provide new insights and targets for drug development for treating many neurodegenerative diseases.
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http://dx.doi.org/10.1515/tnsci-2020-0168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090798PMC
January 2021

[Research progress and discussion on traditional Chinese medicine properties of Kaempferia parviflora].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(8):1951-1959

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 100029, China.

Kaempferiae Parviflorae Rhizoma is the dried rhizome of Kaempferia parviflora in Zingiberaceae. It is originated and widely distributed in Thailand and other tropical and subtropical regions, where it has been used as food and medicine for thousands of years. K. parviflora is also planted in Yunnan and other places of China, but its traditional Chinese medicine properties are not clear, which greatly limits its compatibility with traditional Chinese medicines. In this article, the English and Chinese literatures of K. parviflora were searched from Web of Science, PubMed, Scopus, CNKI, Wanfang, and VIP databases for research and analysis. The medicinal properties of K. parviflora were preliminarily discussed based on the theory of traditional Chinese medicine under the guidance of clinical application and research literatures. The traditional Chinese medicine properties of K. parviflora were inferred as follows: flat, acrid, sweet. The channel tropisms of K. parviflora included kidney, spleen, stomach, and liver. The function of K. parviflora included tonifying kidney to strengthen essence, tonifying Qi and invigorating spleen, soothing liver and relieving depression. K. parviflora was clinically applied for the diseases such as syndrome of kidney essence deficiency, sex apathy, deficiency of spleen Qi, lassitude and asthenia, a weary spirit, obesity, diabetes, liver Qi stagnation, depression, and restless. The equivalent of dry power is 1.5 g·d~(-1) and the equivalent of decoction is 1.5-6 g·d~(-1). The determination of traditional Chinese medicine properties of K. parviflora has indeed laid a theoretical foundation for its application in the field of traditional Chinese medicine and enriched traditional Chinese medicine resources.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201113.401DOI Listing
April 2021

[Discussion on traditional Chinese medicine properties of Myrtus communis leaves based on literature analysis and Chinese medicine theory].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(8):1935-1942

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 100029, China.

Myrtus communis is a traditional medicinal aromatic plant in the Mediterranean. At present, the plant has been introduced and cultivated in the southern part of China, and it is mostly used for ornamental or cosmetic purposes. Based on literature analysis and the theory of Chinese medicine, we discussed the medicinal parts and properties of M. communis in this paper to provide a theoretical basis for exploring the medicinal value of M. communis and its compatibility with traditional Chinese medicines. Literatures were searched from Web of Science(core collection), PubMed, CNKI, VIP and Wanfang by using the set conditions as key words. Then the obtained literatures were screened and classified. Finally, a total of 376 articles were included, consisting of 44 reviews, 54 germplasm resources, 78 chemical researches, 48 studies on application, extraction, or quality, 18 human trials, 132 pharmacological studies, and 2 safety studies. Based on literature analysis and theories of Chinese medicine, the leaves of M. communis were finally selected as the medicinal part of Chinese medicine, and the traditional Chinese medicine properties of M. communis leaves were deduced as pungent, bitter, and cool. The channel tropisms of M. communis leaves included lung, liver, and large intestine, with functions of detoxifying, resolving a mass, and insecticide. It was used for mouth sores, vaginal itching, hemorrhoids and warts, etc.; appropriate amount shall be applied for external use, and the decoction form shall be used for washing the affected parts; 3-12 g equivalent product shall be used in decoction, and this herb shall be put into the decoction in a later stage. The clarification of the medicinal parts of M. communis, and the determination of the Chinese medicine properties of M. communis leaves would lay a theoretical foundation for its compatibility and application with Chinese medicines, and can do more contribution to the medical and healthcare industry in our country.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201027.405DOI Listing
April 2021

Molecular Epidemiology and Clinical Features of Enteroviruses-Associated Hand, Foot, and Mouth Disease and Herpangina Outbreak in Zunyi, China, 2019.

Front Med (Lausanne) 2021 26;8:656699. Epub 2021 Apr 26.

Department of Clinical Laboratory, Zunyi Medical University Third Affiliated Hospital, Zunyi, China.

Hand, foot and mouth disease (HFMD) and herpangina (HA), two of the most common childhood infectious diseases, are associated with enteroviruses (EVs) infection. The aim of this study was to identify the molecular epidemiology of enterovirus causing HFMD/HA in Zunyi, China, during 2019, and to describe the clinical features of the cases. We collected the information on demographic and clinical characteristics, laboratory data of laboratory-confirmed EVs associated HFMD/HA cases in Zunyi Medical University Third Affiliated Hospital between March 1 and July 31, 2019. EV types were determined by either one-step real time RT-PCR or partial VP1 gene sequencing and sequence alignment. Phylogenetic analysis of CVA6, CVA2, and CVA5 were established based on the partial VP1 gene sequences by neighbor-joining method. Differences in clinical characteristics and laboratory results of the cases were compared among patients infected with the most prevalent EV types. From 1 March to 31 July 2019, 1,377 EVs associated HFMD/HA inpatients were confirmed. Of them, 4 (0.3%, 4/1,377) were EV-A71-associated cases, 84 (6.1%, 84/1,377) were CVA16-associated cases, and 1,289 (93.6%, 1,289/1,377) were non-EV-A71/CVA16-associated cases. Of the randomly selected 372 non-EV-A71/CVA16 cases, EV types have been successfully determined in 273 cases including 166 HFMD and 107 HA cases. For HFMD cases, the three most common types were CVA6 (80.7%, 134/166), CVA2 (5.4%, 9/166) and CVA5 (3.0%, 5/166); similarly, for HA cases, the three most prevalent serotypes were CVA6 (36.5%, 39/107), CVA2 (21.5%, 23/107) and CVA5 (18.7%, 20/107). Phylogenetic analysis showed that subclade D of CVA5, and subclade E of CVA6 and CVA2 were predominant in Zunyi during the outbreak in 2019. Compared with the cases caused by CVA16, the incidence of high fever and severe infection associated with CVA2, CVA5, and CVA6 was higher. The recent HFMD/HA outbreak in Zunyi is due to a larger incidence of CVA6, CVA2, and CVA5. Novel diagnostic reagents and vaccines against these types would be important to monitor and control EV infections.
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http://dx.doi.org/10.3389/fmed.2021.656699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109248PMC
April 2021

Worldwide trend in human papillomavirus-attributable cancer incidence rates between 1990 and 2012 and Bayesian projection to 2030.

Cancer 2021 May 11. Epub 2021 May 11.

Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: There is a paucity of global comparative trend analyses of all human papillomavirus (HPV)-attributable cancers. In addition, most analyses by international sources only describe past trends; few studies have projected the future trend of HPV-attributable cancers.

Methods: Data were used from the Cancer Incidence in Five Continents (CI5plus) database that contains annual incidence by cancer site, age, and sex, as well as corresponding populations. Age-standardized HPV-attributable cancer incidence rates were calculated and plotted from 1990 through 2012. A Bayesian age-period-cohort model was used to project the HPV-attributable cancer incidence rates of each country up to 2030.

Results: A significant but small decreasing trend worldwide in the HPV-attributable cancer incidence rate was observed with an average annual percent change (AAPC) of -0.3 (95% CI, -0.6 to -0.1). Notably, Uganda had a consistently increasing trend of HPV-attributable cancer incidence rate, with an AAPC of 1.7 (95% CI, 0.6-2.9). U-shaped trends were observed in some high-income countries because of a recent increase in oral cavity and oropharyngeal cancers. Most countries experience a decreasing or stable trend in HPV-attributable cancers incidence rates between 1990 and 2030. However, Japan, the United Kingdom, the Netherlands, Italy, Costa Rica, and Uganda will have an increasing trend during the projection period.

Conclusions: Analyses revealed favorable downward trends in HPV-attributable cancer incidence rates in most of the included countries. However, the persistently increasing trend in HPV-attributable cancer incidence rates in Uganda and the recent increase in oral cavity and oropharyngeal cancer incidence rates in some high-income countries may present a new challenge for global HPV-attributable cancer prevention.

Lay Summary: Analyses revealed favorable downward trends in human papillomavirus (HPV)-attributable cancer incidence rates in most of the included countries. However, the persistently increasing trend in HPV-attributable cancer incidence rates in Uganda and the recent increase in oral cavity and oropharyngeal cancer incidence rates in some high-income countries may present a new challenge for global HPV-attributable cancer prevention.
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http://dx.doi.org/10.1002/cncr.33628DOI Listing
May 2021

An international survey on AI in radiology in 1041 radiologists and radiology residents part 2: expectations, hurdles to implementation, and education.

Eur Radiol 2021 May 11. Epub 2021 May 11.

Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.

Objectives: Currently, hurdles to implementation of artificial intelligence (AI) in radiology are a much-debated topic but have not been investigated in the community at large. Also, controversy exists if and to what extent AI should be incorporated into radiology residency programs.

Methods: Between April and July 2019, an international survey took place on AI regarding its impact on the profession and training. The survey was accessible for radiologists and residents and distributed through several radiological societies. Relationships of independent variables with opinions, hurdles, and education were assessed using multivariable logistic regression.

Results: The survey was completed by 1041 respondents from 54 countries. A majority (n = 855, 82%) expects that AI will cause a change to the radiology field within 10 years. Most frequently, expected roles of AI in clinical practice were second reader (n = 829, 78%) and work-flow optimization (n = 802, 77%). Ethical and legal issues (n = 630, 62%) and lack of knowledge (n = 584, 57%) were mentioned most often as hurdles to implementation. Expert respondents added lack of labelled images and generalizability issues. A majority (n = 819, 79%) indicated that AI should be incorporated in residency programs, while less support for imaging informatics and AI as a subspecialty was found (n = 241, 23%).

Conclusions: Broad community demand exists for incorporation of AI into residency programs. Based on the results of the current study, integration of AI education seems advisable for radiology residents, including issues related to data management, ethics, and legislation.

Key Points: • There is broad demand from the radiological community to incorporate AI into residency programs, but there is less support to recognize imaging informatics as a radiological subspecialty. • Ethical and legal issues and lack of knowledge are recognized as major bottlenecks for AI implementation by the radiological community, while the shortage in labeled data and IT-infrastructure issues are less often recognized as hurdles. • Integrating AI education in radiology curricula including technical aspects of data management, risk of bias, and ethical and legal issues may aid successful integration of AI into diagnostic radiology.
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http://dx.doi.org/10.1007/s00330-021-07782-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111651PMC
May 2021

The application of plan, do, check, act(PDCA) quality management in reducing nosocomial infections in endoscopy rooms: it does work.

Int J Clin Pract 2021 May 10:e14351. Epub 2021 May 10.

Department of Infection Management, People's Hospital of Liyang, China.

Background: The role of plan, do, check, act(PDCA) cycle quality management in reducing nosocomial infections in endoscopy rooms remains unclear, we aimed to evaluate the effects of PDCA in the nosocomial infections control of endoscopy rooms.

Methods: This present study was a before and after design. The patients treated in our endoscopy room from January 1, 2019 to December 31, 2019 were included in the control group, which were managed according to current department practice. The patients from January 1, 2020 to December 31, 2020 were included in the PDCA group, which were managed according to PDCA cycle quality management including formulation of cleaning and disinfection process. establishment of an infection control team and improvement of inspection standards. The nosocomial infections of patients, the pass rate of medical staff's knowledge on the nosocomial infection and hand hygiene, the pass rate of disinfection of endoscope cavity and surface, the incidence of sharp injury and biological pollution were compared between two groups.

Results: A total of 1020 patients were included, with 512 patients in PDCA group and 508 patients in the control group. The incidence of nosocomial infections in PDCA group was significantly lower than that of control group(0.98% vs. 2.76%, P=0.002). The pass rate of medical staff's knowledge on the nosocomial infection and hand hygiene were significantly higher than that of control group (all P<0.05). The pass rate of disinfection of endoscope cavity in PDCA group was significantly higher than that of control group(P=0.037). The incidence of sharp injury and biological pollution in PDCA group were significantly lower than that of control group (all P<0.05).

Conclusions: PDCA cycle management is beneficial to reduce the risk of nosocomial infection, enhance the awareness of infection control and reduce the risk of occupational exposure of medical staff in the endoscopy room.
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http://dx.doi.org/10.1111/ijcp.14351DOI Listing
May 2021

Analysis of pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence.

Transl Androl Urol 2021 Apr;10(4):1620-1626

The State Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, Women's Rehabilitation Medical Center, Jiangsu Province People's Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210036, China.

Background: To investigate the changes in pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence (SUI).

Methods: A retrospective survey was conducted on 922 women aged 20-40 years who received health examinations at the First Affiliated Hospital of Nanjing Medical University between July 2017 and December 2019. The women were split into two groups: those who had SUI (n=87) and those that did not (n=835). Questionnaires and pelvic floor electrical physiological indexes were collected.

Results: The mean age of the group of women with SUI was 29.77 years, while the mean age of the group of women with no SUI was 24.49 years. The body mass indexes (BMI) of the women with SUI were significantly higher than those of the women with no SUI. Importantly, the normal rates of type I and II fibers in the women with SUI were obviously lower than those in the women with no SUI. Moreover, the vaginal dynamic pressure in the women with SUI was significantly lower than in the women with no SUI. The study also found that the incidence of SUI in nulliparous women was higher in those aged 30-40 and that both low-weight and obese women had an increased risk of SUI. Type I and type II muscle fibers were more abnormal in the women with SUI than in those with no SUI. In multivariate logistic regression, the ages, BMIs, and type I fiber indexes of nulliparous women were related to SUI.

Conclusions: Nulliparous women have a higher rate of SUI. Compared to women with no SUI, the possible potential risk factors are age (>30 years), higher BMI, and abnormal type I muscle fiber of the pelvic floor.
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http://dx.doi.org/10.21037/tau-20-1235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100828PMC
April 2021

Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs.

BMC Genomics 2021 May 8;22(1):332. Epub 2021 May 8.

College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, Guangdong, 510642, People's Republic of China.

Background: In the process of pig breeding, the average daily gain (ADG), days to 100 kg (AGE), and backfat thickness (BFT) are directly related to growth rate and fatness. However, the genetic mechanisms involved are not well understood. Copy number variation (CNV), an important source of genetic diversity, can affect a variety of complex traits and diseases and has gradually been thrust into the limelight. In this study, we reported the genome-wide CNVs of Duroc pigs using SNP genotyping data from 6627 animals. We also performed a copy number variation region (CNVR)-based genome-wide association studies (GWAS) for growth and fatness traits in two Duroc populations.

Results: Our study identified 953 nonredundant CNVRs in U.S. and Canadian Duroc pigs, covering 246.89 Mb (~ 10.90%) of the pig autosomal genome. Of these, 802 CNVRs were in U.S. Duroc pigs with 499 CNVRs were in Canadian Duroc pigs, indicating 348 CNVRs were shared by the two populations. Experimentally, 77.8% of nine randomly selected CNVRs were validated through quantitative PCR (qPCR). We also identified 35 CNVRs with significant association with growth and fatness traits using CNVR-based GWAS. Ten of these CNVRs were associated with both ADG and AGE traits in U.S. Duroc pigs. Notably, four CNVRs showed significant associations with ADG, AGE, and BFT, indicating that these CNVRs may play a pleiotropic role in regulating pig growth and fat deposition. In Canadian Duroc pigs, nine CNVRs were significantly associated with both ADG and AGE traits. Further bioinformatic analysis identified a subset of potential candidate genes, including PDGFA, GPER1, PNPLA2 and BSCL2.

Conclusions: The present study provides a necessary supplement to the CNV map of the Duroc genome through large-scale population genotyping. In addition, the CNVR-based GWAS results provide a meaningful way to elucidate the genetic mechanisms underlying complex traits. The identified CNVRs can be used as molecular markers for genetic improvement in the molecular-guided breeding of modern commercial pigs.
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http://dx.doi.org/10.1186/s12864-021-07654-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106131PMC
May 2021

Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4.

Aging Cell 2021 May 6:e13370. Epub 2021 May 6.

Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.

Research on ageing-associated genes is important for investigating ageing and anti-ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3-HDAC complex and inhibits its deacetylated activity, leads to hyper-acetylation of the histones at the promoters of mTOR-related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing-associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.
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http://dx.doi.org/10.1111/acel.13370DOI Listing
May 2021

Long-term Diet Quality and Gut Microbiome Functionality: A Prospective, Shotgun Metagenomic Study among Urban Chinese Adults.

Curr Dev Nutr 2021 Apr 2;5(4):nzab026. Epub 2021 Apr 2.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Diet is known to affect human gut microbiome composition; yet, how diet affects gut microbiome functionality remains unclear.

Objective: We compared the diversity and abundance/presence of fecal microbiome metabolic pathways among individuals according to their long-term diet quality.

Methods: In 2 longitudinal cohorts, we assessed participants' usual diets via repeated surveys during 1996-2011 and collected a stool sample in 2015-2018. Participants who maintained a healthy or unhealthy diet (i.e., stayed in the highest or lowest quintile of a healthy diet score throughout follow-up) were selected. Participants were excluded if they reported a history of cancer, cardiovascular disease, diabetes, or hypertension; had diarrhea or constipation in the last 7 d; or used antibiotics in the last 6 mo before stool collection. Functional profiling of shotgun metagenomics was performed using HUMAnN2. Associations of dietary variables and 420 microbial metabolic pathways were evaluated via multivariable-adjusted linear or logistic regression models.

Results: We included 144 adults (mean age = 64 y; 55% female); 66 had an unhealthy diet and 78 maintained a healthy diet. The healthy diet group had higher Shannon α-diversity indexes of microbial gene families and metabolic pathways (both < 0.02), whereas β-diversity, as evaluated by Bray-Curtis distance, did not differ between groups (both > 0.50). At < 0.01 [false discovery rate (FDR) <0.15], the healthy diet group showed enriched pathways for vitamin and carrier biosynthesis (e.g., tetrahydrofolate, acetyl-CoA, and l-methionine) and tricarboxylic acid (TCA) cycle, and increased degradation (or reduced biosynthesis) of certain sugars [e.g., cytidine monophosphate (CMP)-legionaminate, deoxythymidine diphosphate (dTDP)-l-rhamnose, and sucrose], nucleotides, 4-aminobutanoate, methylglyoxal, sulfate, and aromatic compounds (e.g., catechol and toluene). Meanwhile, several food groups were associated with the CMP-legionaminate biosynthesis pathway at FDR <0.05.

Conclusions: In a small longitudinal study of generally healthy, older Chinese adults, we found long-term healthy eating was associated with increased α-diversity of microbial gene families and metabolic pathways and altered symbiotic functions relevant to human nutrition and health.
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http://dx.doi.org/10.1093/cdn/nzab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068758PMC
April 2021

A ten N6-methyladenosine-related long non-coding RNAs signature predicts prognosis of triple-negative breast cancer.

J Clin Lab Anal 2021 May 2:e23779. Epub 2021 May 2.

Shanghai Research Center of Biliary Tract Disease, Shanghai, China.

Background: Patients with triple-negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6-methyladenosine-(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A-related long non-coding RNAs (LncRNAs) in TNBC.

Methods: Clinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A-related LncRNAs to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous RNA (ceRNA) network was established for the functional analysis on targeted mRNAs.

Results: We identified 10 independent prognostic m6A-related LncRNAs (SAMD12-AS1, BVES-AS1, LINC00593, MIR205HG, LINC00571, ANKRD10-IT1, CIRBP-AS1, SUCLG2-AS1, BLACAT1, and HOXB-AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.997 and 0.864 in TCGA and GSE76250 datasets, respectively. Recurrence and PS model status were defined as independent prognostic factors of TNBC. These ten LncRNAs were all differentially expressed in high-risk TNBC compared with controls. The ceRNA network revealed the regulatory axes for nine key LncRNAs, and mRNAs in the network were identified to function in pathways of cell communication, signaling transduction and cancer.

Conclusion: Our findings proposed a ten-m6A-related LncRNAs as potential biomarkers to predict the prognostic risk of TNBC.
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http://dx.doi.org/10.1002/jcla.23779DOI Listing
May 2021

An Optimized Transformation System and Functional Test of -Like TCP Gene in (Gesneriaceae).

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.

The development of an ideal model plant located at a key phylogenetic node is critically important to advance functional and regulatory studies of key regulatory genes in the evolutionary developmental (evo-devo) biology field. In this study, we selected in the family Gesneriaceae, a basal group in Lamiales, as a model plant to optimize its genetic transformation system established previously by us through investigating a series of factors and further conduct functional test of the -like floral symmetry gene . By transforming a RNAi:CpCYC vector, we successfully achieved the desired phenotypes of upright actinomorphic flowers, which suggest that actually determines the establishment of floral zygomorphy and the horizontal orientation of flowers in . . We also confirmed the activities of promoter in dorsal petals, dorsal/lateral staminodes, as well as the pedicel by transferring a promoter:GUS vector into . . Furthermore, we testified the availability of a transient gene expression system using . mesophyll protoplasts. The improved transformation system together with the inherent biological features would make an attractive new model in functional and regulatory studies for a broad range of evo-devo issues.
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http://dx.doi.org/10.3390/ijms22094544DOI Listing
April 2021

Effect of Waste Glass on the Properties and Microstructure of Magnesium Potassium Phosphate Cement.

Materials (Basel) 2021 Apr 20;14(8). Epub 2021 Apr 20.

State Key Laboratory of Environmental-Friendly Energy Materials, School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, Sichuan, China.

Waste glass is a bulk solid waste, and its utilization is of great consequence for environmental protection; the application of waste glass to magnesium phosphate cement can also play a prominent role in its recycling. The purpose of this study is to evaluate the effect of glass powder (GP) on the mechanical and working properties of magnesium potassium phosphate cement (MKPC). Moreover, a 40mm × 40mm × 40mm mold was used in this experiment, the workability, setting time, strength, hydration heat release, porosity, and microstructure of the specimens were evaluated. The results indicated that the addition of glass powder prolonged the setting time of MKPC, reduced the workability of the matrix, and effectively lowered the hydration heat of the MKPC. Compared to an M/P ratio (MgO/KHPO mass ratio) of 1:1, the workability of the MKPC with M/P ratios of 2:1 and 3:1 was reduced by 1% and 2.1%, respectively, and the peak hydration temperatures were reduced by 0.5% and 14.6%, respectively. The compressive strength of MKPC increased with an increase in the glass powder content at the M/P ratio of 1:1, and the addition of glass powder reduced the porosity of the matrix, effectively increased the yield of struvite-K, and affected the morphology of the hydration products. With an increase in the M/P ratio, the struvite-K content decreased, many tiny pores were more prevalent on the surface of the matrix, and the bonding integrity between the MKPC was weakened, thereby reducing the compressive strength of the matrix. At less than 40 wt.% glass powder content, the performance of MKPC improved at an M/P ratio of 1:1. In general, the addition of glass powders improved the mechanical properties of MKPC and reduced the heat of hydration.
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http://dx.doi.org/10.3390/ma14082073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074337PMC
April 2021

Functional Genomic Analyses of the 21q22.3 Locus Identifying Functional Variants and Candidate Gene for Breast Cancer Risk.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Department of Medicine, Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.

We previously identified a locus at 21q22.3, tagged by the single nucleotide polymorphism (SNP) rs35418111, being associated with breast cancer risk at a genome-wide significance level; however, the underlying causal functional variants and gene(s) responsible for this association are unknown. We performed functional genomic analyses to identify potential functional variants and target genes that may mediate this association. Functional annotation for SNPs in high linkage disequilibrium (LD, r > 0.8) with rs35418111 in Asians showed evidence of promoter and/or enhancer activities, including rs35418111, rs2078203, rs8134832, rs57385578, and rs8126917. These five variants were assessed for interactions with nuclear proteins by electrophoretic mobility shift assays. Our results showed that the risk alleles for rs2078203 and rs35418111 altered DNA-protein interaction patterns. Cis-expression quantitative loci (cis-eQTL) analysis, using data from the Genotype-Tissue Expression database (GTEx) European-ancestry female normal breast tissue, indicated that the risk allele of rs35418111 was associated with a decreased expression of the gene, a relatively uncharacterized endoribonuclease in humans. We investigated the biological effects of on breast cancer cell lines by transient knock-down of expression in MCF-7, T47D, and MDA-MB-231 cell lines. Knockdown of mRNA in breast cancer cell lines consistently decreased cell proliferation, colony formation, and migration/invasion, regardless of estrogen receptor status. We performed RNA sequencing in MDA-MB-231 cells transfected with siRNA targeting and subsequent gene set enrichment analysis to identify gene networks associated with knockdown. These data indicated was involved in networks associated with inflammation and metabolism. Finally, we showed trends in expression patterns in breast tissues from The Cancer Genome Atlas (TCGA); early-stage breast cancers had elevated expression compared with normal tissue, but significantly decreased expression in late-stage disease. Our study provides evidence of a significant role for the human gene in breast cancer pathogenesis and the association between the rs35418111/21q22.3 locus and breast cancer risk, which may be mediated through functional SNPs, rs35418111 and rs2078203, that regulate expression of .
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http://dx.doi.org/10.3390/cancers13092037DOI Listing
April 2021

MLL3 Inhibits Apoptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Promotes Secretion of Inflammatory Factors by Activating CCL2 and the NF-κB Pathway.

Inflammation 2021 Apr 29. Epub 2021 Apr 29.

Department of Rheumatology and Immunology, Xinxiang Central Hospital, NO.56 Jinsui Avenue, Xinxiang, 453000, Henan, China.

Rheumatoid arthritis (RA) remains the most common inflammatory arthritis and a major cause of disability. This study investigated the mechanism of MLL3 in fibroblast-like synoviocyte (FLS) apoptosis and inflammatory factor secretion in RA. Expression of MLL3 in synovial tissue of RA patients and patients with bone trauma was detected. FLS was isolated and identified by flow cytometry. Expressions of TNF-α, IL-1β, IL-8, and IL-10 and apoptosis were measured by MTT, flow cytometry, and ELISA. Western blot and qRT-PCR were performed to detect MLL3 and CCL2 expressions, H3K4me3 level, and NF-κB pathway-related proteins in rat joints. MLL3 was highly expressed in the synovial tissue of RA patients, and silencing MLL3 in FLS-RA promoted apoptosis, inhibited pro-inflammatory factors TNF-α, IL-1β, and IL-8 secretion, and promoted anti-inflammatory factor IL-10 secretion. Inhibition of MLL3 suppressed intracellular H3K4me3 and CCL2 expressions. CCL2 activated the NF-κB pathway to promote pro-inflammatory factors TNF-α, IL-1β, and IL-8, inhibit anti-inflammatory factor IL-10, and inhibit apoptosis in FLS-RA. Inhibition of MLL3 expression in RA rats reduced joint redness, swelling, and intra-articular inflammation, but increasing H3K4me3 level reversed the ameliorative effects of sh-MLL3 on RA rats. Collectively, MLL3 activated the NF-κB pathway by increasing H3K4me3 modification in the CCL2 promoter region in FLS-RA, thereby inhibiting apoptosis and promoting pro-inflammatory factors of FLS-RA.
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http://dx.doi.org/10.1007/s10753-021-01459-2DOI Listing
April 2021

Gastrointestinal-type chemotherapy prolongs survival in an atypical primary ovarian mucinous carcinoma: A case report.

World J Clin Cases 2021 Apr;9(11):2533-2541

Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China.

Background: Primary ovarian mucinous carcinoma is a rare histologic subtype of epithelial ovarian carcinoma and exhibits considerable morphologic overlap with secondary tumour. It is hard to differentiate primary from metastatic ovarian mucinous carcinoma by morphological and immunohistochemical features. Because of the histologic similarity between primary ovarian mucinous carcinoma and metastatic gastrointestinal carcinoma, it has been hypothesized that ovarian mucinous carcinomas might respond better to non-gynecologic regimens. However, the standard treatment of advanced ovarian mucinous carcinoma has not reached a consensus.

Case Summary: A 56-year-old postmenopausal woman presented with repeated pain attacks in the right lower quadrant abdomen, accompanied by diarrhoea, anorexia, and weight loss for about 3 mo. The patient initially misdiagnosed as having gastrointestinal carcinoma because of similar pathological features. Based on the physical examination, tumour markers, imaging tests, and genetic tests, the patient was clinically diagnosed with ovary mucinous adenocarcinoma. Whether gastrointestinal-type chemotherapy or gynecologic chemotherapy was a favourable choice for patients with advanced ovarian mucinous cancer had not been determined. The patient received a chemotherapy regimen based on the histologic characteristics rather than the tumour origin. The patient received nine cycles of FOLFOX and bevacizumab. This was followed by seven cycles of bevacizumab maintenance therapy for 9 mo. Satisfactory therapeutic efficacy was achieved.

Conclusion: The genetic analysis might be used in the differential diagnosis of primary ovarian mucinous carcinoma and non-gynecologic mucinous carcinoma. Moreover, primary ovarian mucinous carcinoma patients could benefit from gastrointestinal-type chemotherapy.
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http://dx.doi.org/10.12998/wjcc.v9.i11.2533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040163PMC
April 2021

sp. nov., isolated from mangrove sediments.

Int J Syst Evol Microbiol 2021 Apr;71(4)

Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, PR China.

A novel Gram-staining-negative, catalase- and oxidase-positive, facultatively anaerobic and rod-shaped motile bacterial strain, designated as ZWAL4003, was isolated from mangrove sediments of the Zini Mangrove Forest, Zhangzhou City, PR China. Phylogenetic analysis based on its 16S rRNA gene sequence indicated that ZWAL4003 was grouped into a separated branch with MSSRF60 (97.38% nucleotide sequence identity) and NBRC 103148 (97.27%). The major cellular fatty acids were C (12.6%), C (17.6%), and summed feature 3 (Cω6 /C ω7, 45.6%). Its genome had a length of 4650556 bp with 42.8% DNA G+C content, and contained genes involved in the biosynthesis of bacteriocin, β-lactone, resorcinol, -acyl amino acid, and arylpolyene. The DNA-DNA hybridization and average nucleotide identity values for whole-genome sequence comparisons between ZWAL4003 and LMG 24470 were clearly below the thresholds used for the delineation of a novel species. The morphological and chemotaxonomic characteristics and the genotypic data of ZWAL4003 indicated that it represented a novel species of the genus . Its proposed name is sp. nov., and the type strain is ZWAL4003 (=KCTC 72971=MCCC 1A17474).
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http://dx.doi.org/10.1099/ijsem.0.004777DOI Listing
April 2021

Clinical significance of blood platelets and mean platelet volume in patients with ulcerative colitis.

J Int Med Res 2021 Apr;49(4):3000605211009715

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, Hubei, China.

Objectives: This retrospective study aimed to investigate and analyze the clinical significance of blood platelets (PLTs) and mean platelet volume (MPV) in patients with ulcerative colitis (UC).

Methods: A total of 132 patients with UC and 208 healthy subjects were enrolled. PLTs, MPV, platelet-large cell rate (P-LCR), C-reactive protein (CRP), fibrinogen (FIB) and D-dimer were analyzed. Correlations were calculated between disease activity/extent of disease and MPV, PLT, and CRP levels in patients with UC.

Results: PLT levels were significantly higher while MPV and P-LCR were lower in patients with UC compared with controls. Disease activity was positive correlated with CRP (r = 0.564) and PLT (r = 0.307) but negatively correlated with MPV (r = -0.351). Extent of disease was positively correlated with CRP (r = 0.312) but showed no correlation with PLTs and MPV. FIB and D-dimer were higher in patients with UC, but the difference in FIB levels was not statistically significant.

Conclusions: PLTs and MPV are potential biomarkers for UC disease activity. These data may help clinicians to attain a more comprehensive judgment of the general condition of patients with UC.
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http://dx.doi.org/10.1177/03000605211009715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072101PMC
April 2021

Toxicological evaluation of aqueous extract of the traditional Chinese formula Qing Hao Gan Cao.

Toxicol Res (Camb) 2021 Mar 15;10(2):183-191. Epub 2021 Feb 15.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.

(QHGC), a Chinese medicinal formula containing and , has been used to treat sunstroke and as an antiviral agent for more than 800 years. It has not previously been subject to a toxicological safety evaluation in acute and subacute (28 days) studies. Therefore, the acute and subacute toxicity of an aqueous extract of QHGC were evaluated . For the QHGC preparation, the botanical raw materials were crushed into pieces and mixed in the ratio of 10:1 in distilled water for 12 h, then boiling three times for 2 h each time. The three decoctions were mixed and filtered, then spray-dried with hot air at 160°C for 30 min, and stored at room temperature. For the acute toxicity test, 72.0 g/kg of QHGC extract was administered by gavage to male and female mice. Body weight, general observations, and autopsy results were recorded. No mortality or toxicity signs were observed during the studies. For the subacute toxicity test, 4.0, 8.0, or 16.0 g/kg/day of QHGC extract was administered to rats for 28 days. General observations and mortality, body weight, biochemical and hematological parameters, organ weight, and pathological morphology were analyzed. The acute and subacute toxicity studies did not show significant changes in body weight, general observations, hematology and biochemical parameters, organ weight, and liver, spleen, stomach, duodenum, testis, ovary, lung, heart, and kidney histopathological analyses. The consumption of QHGC aqueous extract can be considered safe within the conditions of this study.
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http://dx.doi.org/10.1093/toxres/tfaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045583PMC
March 2021

Genomic Evolution and Variation of SARS-CoV-2 in the Early Phase of COVID-19 Pandemic in Guangdong Province, China.

Curr Med Sci 2021 Apr 20;41(2):228-235. Epub 2021 Apr 20.

Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 510000, China.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) with unknown origin spread rapidly to 222 countries, areas or territories. To investigate the genomic evolution and variation in the early phase of COVID-19 pandemic in Guangdong, 60 specimens of SARS-CoV-2 were used to perform whole genome sequencing, and genomics, amino acid variation and Spike protein structure modeling analyses. Phylogenetic analysis suggested that the early variation in the SARS-CoV-2 genome was still intra-species, with no evolution to other coronaviruses. There were one to seven nucleotide variations (SNVs) in each genome and all SNVs were distributed in various fragments of the genome. The Spike protein bound with human receptor, an amino acid salt bridge and a potential furin cleavage site were found in the SARS-CoV-2 using molecular modeling. Our study clarified the characteristics of SARS-CoV-2 genomic evolution, variation and Spike protein structure in the early phase of local cases in Guangdong, which provided reference for generating prevention and control strategies and tracing the source of new outbreaks.
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http://dx.doi.org/10.1007/s11596-021-2340-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056187PMC
April 2021

Automated synthesis of prexasertib and derivatives enabled by continuous-flow solid-phase synthesis.

Nat Chem 2021 May 19;13(5):451-457. Epub 2021 Apr 19.

Department of Chemistry, National University of Singapore, Singapore, Republic of Singapore.

Recent advances in end-to-end continuous-flow synthesis are rapidly expanding the capabilities of automated customized syntheses of small-molecule pharmacophores, resulting in considerable industrial and societal impacts; however, many hurdles persist that limit the number of sequential steps that can be achieved in such systems, including solvent and reagent incompatibility between individual steps, cumulated by-product formation, risk of clogging and mismatch of timescales between steps in a processing chain. To address these limitations, herein we report a strategy that merges solid-phase synthesis and continuous-flow operation, enabling push-button automated multistep syntheses of active pharmaceutical ingredients. We demonstrate our platform with a six-step synthesis of prexasertib in 65% isolated yield after 32 h of continuous execution. As there are no interactions between individual synthetic steps in the sequence, the established chemical recipe file was directly adopted or slightly modified for the synthesis of twenty-three prexasertib derivatives, enabling both automated early and late-stage diversification.
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http://dx.doi.org/10.1038/s41557-021-00662-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054510PMC
May 2021

MTM1 plays an important role in the regulation of zinc tolerance in Saccharomyces cerevisiae.

J Trace Elem Med Biol 2021 Jul 14;66:126759. Epub 2021 Apr 14.

College of Life Sciences, Shanghai Normal University, Shanghai, 200234, China. Electronic address:

Background: Acquisition and distribution of zinc supports a number of biological processes. Various molecular factors are involved in zinc metabolism but not fully explored.

Basic Procedures: Spontaneous mutants were generated in yeast with excess zinc culture followed by whole genome DNA sequencing to discover zinc metabolism related genes by bioinformatics. An identified mutant was characterized through metallomic and molecular biology methods.

Main Findings: Here we reported that MTM1 knockout cells displayed much stronger zinc tolerance than wild type cells on SC medium when exposed to excess zinc. Zn accumulation of mtm1Δ cells was dramatically decreased compared to wild type cells under excessive zinc condition due to MTM1 deletion reduced zinc uptake. ZRC1 mRNA level of mtm1Δ cells was significantly higher than that in the wild-type strain leading to increased vacuolar zinc accumulations in mtm1Δ cells. The mRNA levels of ZRT1 and ZAP1 decreased in mtm1Δ cells contributing to less Zn uptake. The zrc1Δmtm1Δ double knockout strain exhibited Zn sensitivity. MTM1 knockout did not afford resistance to excess zinc through an effect mediated through an influence on levels of ROS. Superoxide dismutase 2 (Sod2p) activity in mtm1Δ cells was severely impaired and not restored through Zn supplementation. Meanwhile, additional Zn showed no significant effect on the localization and expression of Mtm1p.

Principal Conclusions: Our study reveals the MTM1 gene plays an important role in the regulation of zinc homeostasis in yeast cells via changing zinc uptake and distribution. This discovery provides new insights for better understanding biochemical communication between vacuole and mitochondrial in relation to zinc-metabolism.
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http://dx.doi.org/10.1016/j.jtemb.2021.126759DOI Listing
July 2021

Theoretical Exploration of Electrochemical Nitrate Reduction Reaction Activities on Transition-Metal-Doped -BP.

J Phys Chem Lett 2021 Apr 19;12(16):3968-3975. Epub 2021 Apr 19.

Laboratory of Chemical Engineering Thermodynamics, Department of Chemical Engineering, Tsinghua University, Beijing 100084, People's Republic of China.

Electrocatalytic conversion of nitrate (NO) into ammonia can not only eliminate harmful pollutant but also provide a green method for a low-temperature ammonia synthesis. The electrochemical NO reduction reactions (NORRs) of a series of transition-metal-doped hexagonal boron phosphide (-BP) monolayers were comprehensively evaluated using density functional theory. The V-doped -BP monolayer was found to stand near the top of the volcano plot with the limiting potential of -0.22 V versus a reversible hydrogen electrode, exhibiting the lowest overpotential among the investigated systems in this work. Besides, the competing hydrogen evolution reaction is significantly suppressed due to the weak adsorption of the H atom. Importantly, the structure of the V-doped -BP monolayer can be retained very well until 900 K, illustrating the initial indication of high thermal stability and great promise for synthesis. This study not only offers an eligible NORR electrocatalyst but also provides an atomic understanding of the behind mechanisms of the NORR process.
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http://dx.doi.org/10.1021/acs.jpclett.1c00855DOI Listing
April 2021

Correction to: LncRNA APCDD1L-AS1 induces icotinib resistance by inhibition of EGFR autophagic degradation via the miR-1322/miR-1972/ miR-324-3p-SIRT5 axis in lung adenocarcinoma.

Biomark Res 2021 Apr 14;9(1):25. Epub 2021 Apr 14.

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China.

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http://dx.doi.org/10.1186/s40364-021-00279-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048049PMC
April 2021

Network meta-analysis of triazole, polyene, and echinocandin antifungal agents in invasive fungal infection prophylaxis in patients with hematological malignancies.

BMC Cancer 2021 Apr 14;21(1):404. Epub 2021 Apr 14.

Department of Urology Surgery, the First Affiliated Hospital of Jinan University, No.613 West Huangpu street, Guangzhou, 510630, P. R. China.

Background And Aim: Triazole, polyene, and echinocandin antifungal agents are extensively used to treat invasive fungal infections (IFIs); however, the optimal prophylaxis option is not clear. This study aimed to determine the optimal agent against IFIs for patients with hematological malignancies.

Methods: Randomized controlled trials (RCTs) comparing the effectiveness of triazole, polyene, and echinocandin antifungal agents with each other or placebo for IFIs in patients with hematological malignancies were searched. This Bayesian network meta-analysis was performed for all agents.

Results: The network meta-analyses showed that all triazoles, amphotericin B, and caspofungin, but not micafungin, reduced IFIs. Posaconazole was superior to fluconazole [odds ratio (OR), 0.30; 95% credible interval (CrI), 0.12-0.60], itraconazole (OR, 0.40; 95% CrI, 0.15-0.85), and amphotericin B (OR, 4.97; 95% CrI, 1.73-11.35). It also reduced all-cause mortality compared with fluconazole (OR, 0.35; 95% CrI, 0.08-0.96) and itraconazole (OR, 0.33; 95% CrI, 0.07-0.94), and reduced the risk of adverse events compared with fluconazole (OR, 0.02; 95% CrI, 0.00-0.03), itraconazole (OR, 0.01; 95% CrI, 0.00-0.02), posaconazole (OR, 0.02; 95% CrI, 0.00-0.03), voriconazole (OR, 0.005; 95% CrI, 0.00 to 0.01), amphotericin B (OR, 0.004; 95% CrI, 0.00-0.01), and caspofungin (OR, 0.05; 95% CrI, 0.00-0.42) despite no significant difference in the need for empirical treatment and the proportion of successful treatment.

Conclusions: Posaconazole might be an optimal prophylaxis agent because it reduced IFIs, all-cause mortality, and adverse events, despite no difference in the need for empirical treatment and the proportion of successful treatment.
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http://dx.doi.org/10.1186/s12885-021-07973-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048157PMC
April 2021

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data.

Horm Metab Res 2021 Apr 14;53(4):272-279. Epub 2021 Apr 14.

Department of Obstetrics and Gynecology, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China.

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052-3.393 μIU/ml, 1.01-1.54 ng/dl, and 2.51-3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.
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http://dx.doi.org/10.1055/a-1402-0290DOI Listing
April 2021

Amyloid-β: A double agent in Alzheimer's disease?

Authors:
Hao Yu Jie Wu

Biomed Pharmacother 2021 Apr 10;139:111575. Epub 2021 Apr 10.

Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China. Electronic address:

Amyloid-β (Aβ) accumulation is one of the cardinal pathological hallmarks of Alzheimer's disease and plays an important role in its pathogenesis. Although the neurotoxic effects of Aβ has been extensively studied, recent studies have revealed that it may also have protective effects. Here, we review novel findings that have shifted our understanding of the role of Aβ in the pathogenesis of Alzheimer's disease. An in-depth and comprehensive understanding of Aβ will provide us with a broader perspective on the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.biopha.2021.111575DOI Listing
April 2021

Prognostic Value of an Immunohistochemical Signature in Patients With Bladder Cancer Undergoing Radical Cystectomy.

Front Oncol 2021 25;11:641385. Epub 2021 Mar 25.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: This study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy.

Methods: IHC was performed on tumor specimens from 366 patients with transitional cell bladder cancer. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with bladder cancer. The Kaplan-Meier estimate was performed to assess DFS, and unadjusted and adjusted Cox regression models were used to identify independent risk factors to predict DFS of patients with bladder cancer.

Results: Based on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the high-risk group (p < 0.001). Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the classifier and clinicopathological factors was developed for clinical application.

Conclusion: The nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of bladder cancer.
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http://dx.doi.org/10.3389/fonc.2021.641385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027317PMC
March 2021

Neoadjuvant pembrolizumab with chemotherapy for the treatment of stage IIB-IIIB resectable lung squamous cell carcinoma.

J Thorac Dis 2021 Mar;13(3):1760-1768

Department of Thoracic Surgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Background: Researches on programmed cell death (PD-1) as neoadjuvant immunotherapy for resectable non-small cell lung cancer is underway, which brings hope for individuals with the disease. However, a study dedicated to lung squamous cell carcinoma (LUSC) specifically has yet to be conducted. Now, data from our pilot prospective research neoadjuvant study provide new insights in the field of neoadjuvant regimen for LUSC.

Methods: Between June 2019 and July 2020, 37 adults with untreated, surgically resectable stage IIB-IIIB LUSC were enrolled into this prospective study. Patients received 2 cycles of pembrolizumab (2 mg/kg) with chemotherapy (albumin-bound paclitaxel 100 mg/m on days 1 and 8 + carboplatin AUC 5) via intravenous administration every 3 weeks, and underwent surgical treatment 3-4 weeks after the second cycle. The primary endpoint of the study was the tumor pathologic complete response (pCR) rate. The toxicity profile, tumor major pathological remission, complete resection rate, response rate, and operative and postoperative complications were also evaluated.

Results: The postoperative pathological specimens of 17 (45.9%) patients suggested pCR. Neoadjuvant pembrolizumab with chemotherapy had an acceptable side-effect profile, and no patients withdrew from the study preoperatively due to disease progression or toxicity. A major pathological response occurred in 24 (64.9%) resected tumors. All tumors were completely resected (R0, 100%). According to the Response Evaluation Criteria in Solid Tumors (RESIST), a response was evaluated before surgery in 32 (86.5%) patients by computed tomography. Twenty-five (67.6%) patients underwent thoracoscopic surgery. No deaths or postoperative major complications requiring reoperation occurred. Recurrence or metastasis was found in 2 patients during follow-up of 2-14 months.

Conclusions: The early outcomes of pembrolizumab with chemotherapy in the neoadjuvant setting as a novel treatment for resectable stage IIB-IIIB LUSC showed a high pCR rate that has not been seen previously, as well as a high R0 resection rate and a low toxicity profile. The long-term efficacy of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.
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http://dx.doi.org/10.21037/jtd-21-103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024839PMC
March 2021