Publications by authors named "Liping Liu"

820 Publications

miR-21 regulates osteogenic and adipogenic differentiation of BMSCs by targeting PTEN.

J Musculoskelet Neuronal Interact 2021 Dec;21(4):568-576

Department of Orthopedic One Ward, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

Objective: To explore the effects and mechanism of miR-21 on the osteogenic/adipogenic differentiation of mouse BMSCs.

Methods: The bilateral ovaries of C57BL/6J mice (n=24) were removed to construct an osteoporosis model. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-21, osteogenic/adipogenic genes, and PTEN. ALP and ARS and ORO staining were used to detect the formation of calcium nodules and lipid droplets in BMSCs. Western blot was used to detect the expression of PTEN.

Results: miR-21 was significantly down-regulated in osteoporotic mice. The expression of miR-21 was significantly up-regulated after the osteogenic induction of BMSCs, and the expression of miR-21 was significantly down-regulated after the adipogenic induction. Overexpression of miR-21 significantly promoted the osteogenic differentiation of BMSCs and inhibits the adipogenic differentiation of BMSCs.

Conclusion: MiR-21 can promote osteogenic differentiation of BMSCs and inhibit their adipogenic differentiation by negatively regulating PTEN.
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December 2021

Generation of duck Tembusu virus using a simple reverse genetic system in duck embryo fibroblast cells.

J Virol Methods 2021 Nov 26:114385. Epub 2021 Nov 26.

Institute of Poultry Science, Shandong Academy of Agricultural Sciences / Shandong Provincial Key Laboratory of Immunity and Diagnosis of Poultry Diseases, No. 1 Jiaoxiao Road, Jinan, Shandong, 250023, China. Electronic address:

Outbreaks of duck Tembusu virus (DTMUV) have caused serious economic losses in China since 2010. In this study, an infectious clone of the DTMUV BZ-2010strain, isolated from layer cherry duck in China, was constructed using the bacterium-free infectious subgenomic-amplicons method. The subgenomic-amplicons of the human cytomegalovirus promoter (pCMV) at the 5' terminus of the first DNA fragment, the entire genome of DTMUV, and the hepatitis delta ribozyme followed by the simian virus 40 polyadenylation signal (HDR/SV40pA) at the 3' terminus of the last DNA fragment were synthesized and amplified by PCR in three DNA fragments. The pCMV and HDR/SV40pA were used to drive the viral RNA transcription and generate a full-length RNA transcript of the virus, and were found to be effective in reassembling DTMUV in duck embryo fibroblast cells. The RNA transcripts from the infection clone were infectious in duck embryo fibroblast cells, generating the reconstituted DTMUV. This study provided a valuable reverse genetic tool for the further study DTMUV pathogenesis.
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http://dx.doi.org/10.1016/j.jviromet.2021.114385DOI Listing
November 2021

Evodiamine induces ROS-Dependent cytotoxicity in human gastric cancer cells via TRPV1/Ca pathway.

Chem Biol Interact 2021 Nov 19;351:109756. Epub 2021 Nov 19.

Institute of Integrated Medicine, Medicine College, Qingdao University, Qingdao, Shandong, 266071, China. Electronic address:

Evodiamine (EVO), a key active ingredient of the fruit of Evodiae fructus, is provided with antitumor effects (mainly cytotoxic effect) including proliferation inhibition, cell cycle arrest, apoptosis, and metastasis inhibition. Our study aims to explain the underlying role of TRPV1/Ca in EVO-induced cytotoxicity in human gastric cancer cells. Human gastric cancer line BGC-823 was used to study EVO-induced cytotoxicity. Cell viability was examined using CCK-8 assay. Apoptosis was examined using Annexin V-FITC/PI staining assay. Intracellular ROS ([ROS]i) levels were examined using DCFH-DA assay. Mitochondrial morphology was examined using Mitotracker Green staining. Mitochondrial membrane potential (Δψm) were examined using JC-1 assay. Intracellular Ca levels ([Ca]i) were examined using Fluo-4 AM assay. Mitochondrial ROS ([ROS]m)levels were examined using Mitotracker Green/MitoSOX Red staining. Mitochondrial Ca ([Ca]m)levels were examined using Mitotracker Green/Rhod-2 Red staining. The protein levels was detected by Western blot. EVO exposure causes significant ROS generation and apoptotic cell death. Pretreatment of EUK134 significantly ameliorated EVO-induced apoptotic cell death. Furthermore, EVO exposure induced [ROS]i generation and mitochondrial dysfunction, including [ROS]m generation and Δψm dissipation, which can be significantly attenuated by pre-incubation of rotenone indicating that [ROS]m is the main source of EVO-induced intracellular ROS generation. Importantly, EVO-induced cytotoxicity was significantly ameliorated by intracellular Ca chelation, confirming that EVO induces cell death through Ca overload. Pharmacological and genetic inhibition of TRPV1 could significantly attenuate Ca influx, ROS generation and apoptotic cell death induced by EVO exposure, while exogenous TRPV1 overexpression could augment the EVO-induced cytotoxicity. Moreover, genetic inhibition of mitochondrial calcium uniporter (MCU) attenuated EVO-induced cell death and mitochondrial dysfunction. EVO exposure induced endoplasmic reticulum (ER) stress demonstrated by the activation of PERK/CHOP in cells exposed to EVO, and PERK/CHOP activation was depleted by EUK134 pre-treatment. Our results support the concept that EVO induces ROS-dependent cytotoxicity via TRPV1/Ca Pathway.
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http://dx.doi.org/10.1016/j.cbi.2021.109756DOI Listing
November 2021

Role of long intergenic non-protein coding RNA 01857 in hepatocellular carcinoma malignancy via the regulation of the microRNA-197-3p/anterior GRadient 2 axis.

PLoS One 2021 18;16(11):e0258312. Epub 2021 Nov 18.

Department of Endocrinology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.

Objective: This study investigates the differential expression and the mechanism of long intergenic non-protein coding RNA (LINC) 01857 in hepatocellular carcinoma (HCC) proliferation and apoptosis.

Methods: LINC01857 expression in HCC tissues and cells was evaluated. In addition, gain-of and loss-of functions were carried out to assess HCC cell proliferation and apoptosis. After that, LINC01857 subcellular localization was predicted and verified. Additionally, the binding relations between LINC01857 and microRNA (miRNA)-197-3p and between miR-197-3p and anterior GRadient 2 (AGR2) were detected and confirmed. Besides, HCC cell proliferation and apoptosis were assessed after silencing LINC01857 or overexpressing AGR2. Next, levels of key factors in the AKT and ERK pathways were measured. Additionally, xenograft transplantation was also conducted to confirm the effect of LINC01857 in HCC.

Results: LINC01857 was overexpressed in HCC. Silencing LINC01857 leads to a blockage in HCC cell proliferation but improved apoptosis. LINC01857 could competitively bind to miR-197-3p and thus upregulate AGR2. miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed. Mechanistically, downregulated miR-197-3p or overexpressed AGR2 were observed to attenuate the effect of the LINC01857 knockdown on suppressing cell proliferation and enhancing apoptosis. Moreover, LINC01857 activated the AKT and ERK pathways through the manipulation of the miR-197-3p/AGR2 axis in HCC.

Conclusion: The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258312PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601473PMC
November 2021

Hospital management of major stroke types in Chinese adults: a population-based study of 20 000 hospitalised stroke cases.

BMJ Open 2021 11 16;11(11):e054265. Epub 2021 Nov 16.

Clinical Trial Service Unit and Epidemiological Studies, NDPH, University of Oxford, Oxford, UK.

Objectives: To compare hospital treatments for major stroke types in Chinese adults by stroke pathological types, sex, age, calendar year, hospital tier, region and other factors.

Design: Cross-sectional analysis of medical records retrieved from 20 229 stroke cases in the China Kadoorie Biobank.

Setting: Ten diverse areas (five urban, five rural) in China.

Participants: First-incident stroke cases who were recruited during an 11-year follow-up of 0.5M participants in the China Kadoorie Biobank.

Methods: Electronic copies of medical records of stroke cases were retrieved for clinical adjudication by local neurologists. Stroke cases were classified as ischaemic stroke (IS) (including lacunar infarction (LACI) and non-LACI (non-LACI)), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) and unspecified stroke types.

Results: Among 20 299 first-ever stroke cases, 17 306 (85%) had IS, 7123 had non-LACI, 6690 had LACI, 3493 had silent LACI, 2623 (13%) had ICH and 370 (2%) had SAH. Among IS cases, antiplatelet treatment was used by 64% (65% non-LACI, 66% LACI, 56% silent LACI), lipid-lowering by 50% (52% non-LACI, 53% LACI, 43% silent LACI) and blood pressure-lowering by ~42% of all IS types, with positive trends in the use of these treatments by calendar year and hospital tier. Among ICH cases, 53% used blood pressure-lowering and 10% used lipid-lowering treatments, respectively. In contrast, traditional Chinese medicines (TCMs) were used by 59% of IS (50% non-LACI, 62% LACI, 74% silent LACI), 38% of ICH and 30% of SAH cases, with positive trends by calendar year and by hospital tier.

Conclusions: Among IS cases, use of antiplatelet and lipid-lowering medications increased in recent years, but use of TCM still exceeded use of blood pressure-lowering treatment. In contrast, blood pressure-lowering treatment was widely used for ICH, but only half of all ICH cases used blood pressure-lowering treatment.
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http://dx.doi.org/10.1136/bmjopen-2021-054265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596044PMC
November 2021

Determining the kinetics of break-induced replication (BIR) by the assay for monitoring BIR elongation rate (AMBER).

Methods Enzymol 2021 29;661:139-154. Epub 2021 Oct 29.

Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA, United States. Electronic address:

A detailed understanding of how homologous recombination proceeds at the molecular level in vivo requires the ability to detect in real time the appearance of specific intermediates of DNA repair. The most detailed analysis of double-strand break (DSB) repair in eukaryotes has come from the study of budding yeast, using an inducible site-specific HO endonuclease to initiate recombination synchronously in nearly all cells of the population. Polymerase chain reaction (PCR) and chromatin immunoprecipitation (ChIP) methods have been used to visualize the timing of the DSB, its resection by 5' to 3' exonucleases, the binding of the Rad51 recombinase and the pairing of the Rad51 filament with a homologous donor sequence. PCR has also been used to identify the next key step: the initiation of new DNA synthesis to extend the invading stand and copy the donor template. In break-induced replication (BIR), there appears to be a very long delay between strand invasion and this primer extension step. Here we describe an alternative method, an assay for monitoring BIR elongation rate (AMBER) based on digital droplet PCR that yields a much earlier time of initial DNA synthesis. We suggest that previous methods have failed to recover the initial long, single-stranded primer extension product that is readily detected by AMBER.
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http://dx.doi.org/10.1016/bs.mie.2021.09.004DOI Listing
October 2021

Individualized airway atomization improves preoperative lung dysfunction in patients with chronic rhinosinusitis with nasal polyps.

Int Forum Allergy Rhinol 2021 Nov 9. Epub 2021 Nov 9.

Department of Otorhinolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.

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http://dx.doi.org/10.1002/alr.22924DOI Listing
November 2021

SDG2 regulates Arabidopsis inflorescence architecture through SWR1-ERECTA signaling pathway.

iScience 2021 Nov 12;24(11):103236. Epub 2021 Oct 12.

College of Life Science, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Inflorescence architecture is diverse in flowering plants, and two determinants of inflorescence architecture are the inflorescence meristem and pedicel length. Although the ERECTA (ER) signaling pathway, in coordination with the SWR1 chromatin remodeling complex, regulates inflorescence architecture with subsequent effects on pedicel elongation, the mechanism underlying signaling pathway regulation of inflorescence architecture remains unclear. This study determined that SDG2 genetically interacts with the signaling pathways in regulating inflorescence architecture. Transcriptome results showed that auxin might potentially influence inflorescence growth mediated by SDG2 and pathways. SWR1 and ER signaling are required to enrich H2A.Z histone variant and SDG2 regulated SDG2-mediated H3K4me3 histone modification at auxin-related genes and H2A.Z histone variant enrichment. Our study shows how the regulation of inflorescence architecture is mediated by SDG2 and SWR1-ER, which affects auxin hormone signaling pathways.
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http://dx.doi.org/10.1016/j.isci.2021.103236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551540PMC
November 2021

Predictive Value of the ABCD3-I for Short- and Long-Term Stroke after TIA with or without sICAS.

J Atheroscler Thromb 2021 Nov 6. Epub 2021 Nov 6.

China National Clinical Research Center for Neurological Diseases.

Aims: We aimed to validate the predictive value of the ABCD3-I score for short-term and long-term stroke risk after transient ischemic attack (TIA) and to evaluate the influence of symptomatic intracranial artery stenosis (sICAS) on the performance of ABCD3-I.

Methods: We recruited TIA patients from the Third China National Stroke Registry study. Outcome parameters were stroke events during the 14-day, 3-month, 6-month, and 12-month points. The area under the curve (AUC) was calculated as a measure of predictive ability. A multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke.

Results: Among 986 patients, 3.9%, 5.1%, 6.5 %, and 8.2% of participants experienced a stroke event during the 14-day, 3-month, 6-month, and 12-month points post TIA, respectively. The AUCs of ABCD3-I score for the prediction of stroke were 0.786, 0.732, 0.715, and 0.699 at the 14-day, 3-month, 6-month, and 12-month points, respectively. The AUCs were 0.774, 0.690, 0.617, and 0.611 in patients with sICAS, 0.789, 0.748, and 0.758 and 0.734 in those without sICAS. P values of the interaction between ABCD3-I categories and sICAS were 0.0618 for 14-day, 0.0098 for 3-month, 0.0318 for 6-month, and 0.0294 for 12-month.

Conclusions: ABCD3-I score performed well in predicting short-term risk of a stroke after an index TIA in patients with or without sICAS. However, the predictive power decayed with the prolonged period, and the decayed extent was more pronounced among those with sICAS. The assessment of sICAS is a non-ignorable item when using the ABCD3-I score for long-term stroke risk prediction in patients with TIA.
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http://dx.doi.org/10.5551/jat.63050DOI Listing
November 2021

Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3.

Acta Pharm Sin B 2021 Oct 1;11(10):3206-3219. Epub 2021 May 1.

School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC values of 0.61 ± 0.02 and 0.58 ± 0.12 μmol/L against TEAD1 and TEAD3, respectively. Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DC-TEAD3in03 with the IC value of 0.16 ± 0.03 μmol/L, which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling (ABPP) assays. In cells, DC-TEAD3in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD (1-4) reporter assays with the IC value of 1.15 μmol/L. When administered to zebrafish juveniles, experiments showed that DC-TEAD3in03 reduced the growth rate of zebrafish caudal fins, indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages.
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http://dx.doi.org/10.1016/j.apsb.2021.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546857PMC
October 2021

Association Between Gene Polymorphisms and Large-Artery Atherosclerotic Stroke.

Front Neurol 2021 13;12:738148. Epub 2021 Oct 13.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Cystatin C, a marker of atherosclerosis, is encoded by . We aimed to evaluate whether two single-nucleotide polymorphisms (SNPs) of are correlated with large-artery atherosclerotic stroke (LAAS) and prognosis. This subgroup analysis of the Third China National Stroke Registry (CNSR-III) enrolled acute ischemic stroke (AIS) patients within 7 days from August 2015 to March 2018 in China. rs13038305 and rs911119 of were selected based on the strong association with cystatin C concentration. Two loci of (rs13038305 and rs911119) were analyzed in 3,833 ischemic stroke patients. Carriers of T allele in rs13038305 and C allele in rs911119 tend to have lower serum cystatin C levels ( < 0.05). Compared with C/C as a reference in rs13038305, odds ratio (OR) of T/T was 0.486, 95% CI 0.237-0.994, = 0.048. Per C allele of rs13038305 also showed an increased level of low-density lipoprotein cholesterol (LDL-C), β (95% CI) was 1.335 (1.008-1.250), = 0.044. No correlation was found between the selected SNPs and stroke prognosis (functional outcome, recurrence, and mortality). Carriers of the T allele in rs13038305 tend to have a lower proportion of LAAS. rs13038305 and rs911119 polymorphisms were likely to affect cystatin C concentration independently of kidney function.
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http://dx.doi.org/10.3389/fneur.2021.738148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548665PMC
October 2021

Characterization of germline development and identification of genes associated with germline specification in pineapple.

Hortic Res 2021 Nov 1;8(1):239. Epub 2021 Nov 1.

College of Life Science, State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Center for Genomics and Biotechnology, Fujian Agriculture and Forestry University, Fuzhou, China.

Understanding germline specification in plants could be advantageous for agricultural applications. In recent decades, substantial efforts have been made to understand germline specification in several plant species, including Arabidopsis, rice, and maize. However, our knowledge of germline specification in many agronomically important plant species remains obscure. Here, we characterized the female germline specification and subsequent female gametophyte development in pineapple using callose staining, cytological, and whole-mount immunolocalization analyses. We also determined the male germline specification and gametophyte developmental timeline and observed male meiotic behavior using chromosome spreading assays. Furthermore, we identified 229 genes that are preferentially expressed at the megaspore mother cell (MMC) stage during ovule development and 478 genes that are preferentially expressed at the pollen mother cell (PMC) stage of anther development using comparative transcriptomic analysis. The biological functions, associated regulatory pathways and expression patterns of these genes were also analyzed. Our study provides a convenient cytological reference for exploring pineapple germline development and a molecular basis for the future functional analysis of germline specification in related plant species.
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http://dx.doi.org/10.1038/s41438-021-00669-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558326PMC
November 2021

Maintaining stroke care during the COVID-19 pandemic in lower- and middle-income countries: World Stroke Organization Position Statement endorsed by American Stroke Association and American Heart Association.

Int J Stroke 2021 Oct 29:17474930211055878. Epub 2021 Oct 29.

Department of Neurology, Dubai Medical Collage, Dubai.

For more than a year, the SARS-CoV-2 pandemic has had a devastating effect on global health. High-, low-, and middle-income countries are struggling to cope with the spread of newer mutant strains of the virus. Delivery of acute stroke care remains a priority despite the pandemic. In order to maintain the time-dependent processes required to optimize delivery of intravenous thrombolysis and endovascular therapy, most countries have reorganized infrastructure to optimize human resources and critical services. Low-and-middle income countries (LMIC) have strained medical resources at baseline and often face challenges in the delivery of stroke systems of care (SSOC). This position statement aims to produce pragmatic recommendations on methods to preserve the existing SSOC during COVID-19 in LMIC and propose best stroke practices that may be low cost but high impact and commonly shared across the world.
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http://dx.doi.org/10.1177/17474930211055878DOI Listing
October 2021

Ticagrelor versus Clopidogrel in Loss-of-Function Carriers with Stroke or TIA.

N Engl J Med 2021 Oct 28. Epub 2021 Oct 28.

From the China National Clinical Research Center for Neurological Diseases (Yongjun Wang, X.M., A.W., X.X., Y.P., H.L., J.J., J.L., S.N., Yilong Wang, X. Zhao, Z.L., Y.J., W.L., L.L., J.X.), the Department of Neurology (Yongjun Wang, X.M., A.W., X.X., Y.P., H.L., J.J., J.L., S.N., Yilong Wang, X. Zhao, Z.L., Y.J., W.L., L.L., J.X.), and the Advanced Innovation Center for Human Brain Protection (Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, and the Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences (Yongjun Wang), Beijing, the Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai (Q.D.), the Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou (A.X.), the Department of Neurology, Third People's Hospital of Liaocheng (L.C.), and the Department of Neurology, Liaocheng People's Hospital (X. Zhuang), Liaocheng, the Department of Neurology, Second Affiliated Hospital of Harbin Medical University (L.W.), and the Department of Neurology, First Affiliated Hospital of Harbin Medical University (G.L.), Harbin, the Department of Neurology, Weihai Wendeng District People's Hospital (J.Z.), and the Department of Neurology, Weihai Central Hospital (H.M.), Weihai, the Department of Neurology, Second People's Hospital of Huludao, Huludao (Y.F.), and the Department of Neurology, Baotou Central Hospital, Baotou (B.W.) - all in China; Dell Medical School, University of Texas at Austin, Austin (S.C.J.); and the Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom (P.M.B.).

Background: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in loss-of-function carriers have not been extensively performed.

Methods: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days.

Results: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively.

Conclusions: Among Chinese patients with minor ischemic stroke or TIA who were carriers of loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).
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http://dx.doi.org/10.1056/NEJMoa2111749DOI Listing
October 2021

A Scoring System for Assessing the Risk of Malignant Partially Cystic Thyroid Nodules Based on Ultrasound Features.

Front Oncol 2021 6;11:731779. Epub 2021 Oct 6.

Department of Ultrasound, Peking University People's Hospital, Beijing, China.

Objective: To assess the ultrasound (US) features of partially cystic thyroid nodules (PCTNs) and to establish a scoring system to further improve the diagnostic accuracy.

Methods: A total of 262 consecutive nodules from September 2017 to March 2020 were included in a primary cohort to construct a scoring system. Moreover, 83 consecutive nodules were enrolled as an validation cohort from May 2018 to August 2020. All nodules were determined to be benign or malignant according to the pathological results after surgery or ultrasound-guided fine-needle aspiration (US-FNA). The US images and demographic characteristics of the patients were analyzed. The ultrasound features of PCTNs were extracted from primary cohort by two experienced radiologists. The features extracted were used to develop a scoring system using logistic regression analysis. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic efficacy of the scoring system in both the primary cohort and validation cohort. In addition, the radiologists evaluated the benign and malignant PCTNs of the validation cohort according to the ACR TI-RADS guidelines and clinical experience, and the accuracy of their diagnosis were compared with that of the scoring system.

Results: Based on the eight features of PCTNs, the scoring system showed good differentiation and reproducibility in both cohorts. The scoring system was based on eight features of PCTNs and showed good performance. The area under the curve (AUC) was 0.876 (95% CI, 0.830 - 0.913) in the primary cohort and 0.829(95% CI, 0.730 - 0.903) in the validation cohort. The optimal cutoff value of the scoring system for the diagnosis of malignant PCTNs was 4 points, with a good sensitivity of 71.05% and specificity of 87.63%. The scoring system (AUC=0.829) was superior to radiologists (AUC= 0.736) in diagnosing PCTNs and is a promising method for clinical application.

Conclusions: The scoring system described herein is a convenient and clinically valuable method that can diagnose PCTNs with relatively high accuracy. The use of this method to diagnose PCTNs, which have been previously underestimated, will allow PCTNs to receive reasonable attention, and assist radiologist to confidently diagnose the benignity or malignancy.
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http://dx.doi.org/10.3389/fonc.2021.731779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526936PMC
October 2021

Posterior circulation stroke due to vertebral artery disease in the Chinese population.

Int J Stroke 2021 Oct 17:17474930211052816. Epub 2021 Oct 17.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background And Purpose: Little is known about the distribution of the arteries responsible for noncardiogenic posterior circulation stroke due to vertebral artery disease in the Chinese population. Furthermore, few studies have compared the risk factors, imaging manifestations, and outcomes across different types of vertebral artery disease. Therefore, our aim was to compare the differences in the risk factors, imaging manifestations, and outcome across various types of vertebral artery disease.

Methods: We prospectively enrolled 228 patients from 22 Chinese centers with noncardiogenic posterior circulation stroke due to vertebral artery disease. Vertebral artery disease was classified by the involved segments of the responsible vertebral artery, and basilar artery (BA) involvement or not. Risk factors, clinical-radiologic patterns, and outcomes were compared across different types of vertebral artery disease.

Results: The intracranial vertebral artery (ICVA) was more frequently involved than was the extracranial vertebral artery (ECVA). The ICVA/ICVA + ECVA group more often presented with hypertension and higher systolic blood pressure than did the ECVA group. Compared with the single-segment-of-vertebral-artery group (SSVA), the group with multiple-segments-of-vertebral-artery (MSVA) involvement or SSVA with BA involvement had more serious clinical-radiologic patterns and worse outcomes. Multivariable Cox regression identified MSVA/SSVA + BA involvement as an independent predictor of recurrent ischemic cerebrovascular events.

Conclusions: The risk factors for ICVA/ICVA + ECVA were different from those of ECVA, and the MSVA/SSVA + BA group had more serious clinical-radiologic patterns and worse outcomes.
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http://dx.doi.org/10.1177/17474930211052816DOI Listing
October 2021

Editorial: Antiplatelet Agents in Stroke Prevention.

Front Neurol 2021 28;12:762060. Epub 2021 Sep 28.

Medical School, University of Pécs, Pécs, Hungary.

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http://dx.doi.org/10.3389/fneur.2021.762060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505968PMC
September 2021

Direct N-Glycosylation Profiling of Urine and Prostatic Fluid Glycoproteins and Extracellular Vesicles.

Front Chem 2021 27;9:734280. Epub 2021 Sep 27.

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States.

Expressed prostatic secretions (EPS), also called post digital rectal exam urines, are proximal fluids of the prostate that are widely used for diagnostic and prognostic assays for prostate cancer. These fluids contain an abundant number of glycoproteins and extracellular vesicles secreted by the prostate gland, and the ability to detect changes in their N-glycans composition as a reflection of disease state represents potential new biomarker candidates. Methods to characterize these N-glycan constituents directly from clinical samples in a timely manner and with minimal sample processing requirements are not currently available. In this report, an approach is described to directly profile the N-glycan constituents of EPS urine samples, prostatic fluids and urine using imaging mass spectrometry for detection. An amine reactive slide is used to immobilize glycoproteins from a few microliters of spotted samples, followed by peptide N-glycosidase digestion. Over 100 N-glycan compositions can be detected with this method, and it works with urine, urine EPS, prostatic fluids, and urine EPS-derived extracellular vesicles. A comparison of the N-glycans detected from the fluids with tissue N-glycans from prostate cancer tissues was done, indicating a subset of N-glycans present in fluids derived from the gland lumens. The developed N-glycan profiling is amenable to analysis of larger clinical cohorts and adaptable to other biofluids.
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http://dx.doi.org/10.3389/fchem.2021.734280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503230PMC
September 2021

A Regioselectively Oxidized 2D Bi/BiOx Lateral Nano-Heterostructure for Hypoxic Photodynamic Therapy.

Adv Mater 2021 Oct 13:e2102562. Epub 2021 Oct 13.

Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University, Key Laboratory of Optoelectronic Devices, Systems of Ministry of Education, Guangdong Province Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen, 518060, P. R. China.

Optoelectronic science and 2D nanomaterial technologies are currently at the forefront of multidisciplinary research and have numerous applications in electronics and photonics. The unique energy and optically induced interfacial electron transfer in these nanomaterials, enabled by their relative band alignment characteristics, can provide important therapeutic modalities for healthcare. Given that nano-heterostructures can facilitate photoinduced electron-hole separation and enhance generation of reactive oxygen species (ROS), 2D nano-heterostructure-based photosensitizers can provide a major advancement in photodynamic therapy (PDT), to overcome the current limitations in hypoxic tumor microenvironments. Herein, a bismuthene/bismuth oxide (Bi/BiOx)-based lateral nano-heterostructure synthesized using a regioselective oxidation process is introduced, which, upon irradiation at 660 nm, effectively generates O under normoxia but produces cytotoxic •OH and H under hypoxia, which synergistically enhances PDT. Furthermore, this Bi/BiOx nano-heterostructure is biocompatible and biodegradable, and, with the surface molecular engineering used here, it improves tumor tissue penetration and increases cellular uptake during in vitro and in vivo experiments, yielding excellent oxygen-independent tumor ablation with 660 nm irradiation, when compared with traditional PDT agents.
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http://dx.doi.org/10.1002/adma.202102562DOI Listing
October 2021

Fetal Heart Rate Extraction Based on Wavelet Transform to Prevent Fetal Distress In Utero.

J Healthc Eng 2021 29;2021:7608785. Epub 2021 Sep 29.

Obstetrics Department, Taikang Tongji (Wuhan) Hospital, Wuhan, Hubei 430050, China.

In order to improve the effective extraction of fetal heart rate and prevent fetal distress in utero, a study of fetal heart rate feature extraction based on wavelet transform to prevent fetal distress in utero was proposed. This paper adopts a fetal heart rate detection method based on the maximum value of the binary wavelet transform modulus. The method is simulated by the Doppler fetal heart signal obtained from the clinic. Compared with the original curve, the transformed curve can roughly see the change rule of the original signal and identify the peak point of the signal, but due to the large disturbance of the peak point, the influence on the computer processing is also great. The periodicity of the transformed signal is greatly enhanced, making it easier to deal with the computation. A total of 300 pregnant women with full-term fetal heart monitoring from January 2018 to January 2020 were selected as the research subjects and divided into the observation group and the control group. The observation group consisted of 100 patients with abnormal fetal heart monitoring, and the control group consisted of 200 patients with normal fetal heart monitoring. The uterine contractions and fetal heart rate were recorded, and the incidence of fetal distress, cesarean section, neonatal asphyxia, and amniotic fluid and fecal contamination were observed. The incidence of fetal distress, cesarean section, neonatal asphyxia, and amniotic fluid fecal stain in the observation group were significantly higher than those in the control group. Fetal heart monitoring can accurately judge the situation of the fetus in pregnant women and timely diagnose the abnormal fetal heart rate, which has a better effect on the prognosis of perinatal infants and can reduce their mortality. It can effectively solve the problems existing in the autocorrelation algorithm and extract the fetal heart rate more accurately. It is an effective improved scheme of fetal heart rate extraction. It is very helpful in preventing fetal distress in utero.
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http://dx.doi.org/10.1155/2021/7608785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500751PMC
September 2021

[The effect of Hashimoto's thyroiditis on the diagnostic efficacy of ultrasound-guided fine needle aspiration cytology for thyroid nodules ≥ 1 cm].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Sep;35(9):807-812

Department of Ultrasound,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400012,China.

To explore the diagnostic efficacy of ultrasound-guided fine needle aspiration cytology(US-FNAC) for thyroid nodules ≥1 cm, and the effect of Hashimoto's thyroiditis(HT) on it. The clinical data of 1027 cases of thyroid nodules ≥ 1 cm were retrospectively analyzed. Two-dimensional ultrasound, US-FNAC and BRAFV600E gene testing were performed. The postoperative pathological results were used as the criterion. The two dimensional ultrasound examination, clinical characteristics, follow-up results, and BRAFV600E were used to diagnosis for unoperated patients. The diagnostic efficiency of US-FNAC in HT(+) group and HT(-) group was compared, and the factors affecting the diagnostic efficiency were analyzed. Of the 1027 nodules, the cytological results were nondiagnostic/unsatisfactory in 73 nodules(7.1%), benign in 282(27.5%), atypia of undetermined significance/follicular lesion of undetermined significance in 230(22.4%), follicular neoplasm/suspicious for a follicular neoplasm in 20(1.9%), suspicious for malignancy in 120(11.7%), and malignant in 302(29.4%). 515 cases underwent surgery. Among them, 495 were malignant and 20 were benign. 512 cases continued to be followed up without surgery, and the BRAFV600E of them were wild type. Combined with the two dimensional ultrasound examination, clinical features, and follow-up results, they were judged to be benign. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, false positive rate and the false negative rate the of US-FNAC were 98.7%, 98.4%, 99.3%, 99.5%, 97.5%, 0.7% and 1.6%, respectively. The accuracy, sensitivity and negative predictive value of the HT(+) group were 95.5%, 95.4% and 82.8%, respectively, which were lower than that of HT(-) group (99.5%, 99.4%, 99.2% )(=0.001, 0.018, <0.001). The false negative rate of the HT(+) group was 4.6%, higher than 0.6% of the HT(-) group(=0.018), and HT was an risk factor for increased FNR(=7.596, 95%: 1.452-39.740). US-FNAC is an effective method for the diagnosis of thyroid nodules and it has high sensitivity and specificity in ≥ 1 cm nodules. However, the combination of HT reduces the diagnostic accuracy and HT is a risk factor for increased false negative rate.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.09.008DOI Listing
September 2021

Corrigendum to "Chemotherapy Modulates Endocrine Therapy-Related Resistance Mutations in Metastatic Breast Cancer" [Translational Oncology (2019) 12, 764-774].

Transl Oncol 2021 Dec 3;14(12):101226. Epub 2021 Oct 3.

Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, 410013, China; Department of Breast Cancer Medical Oncology, Hunan, Cancer Hospital, Changsha, 410013, China; Department of Breast Cancer Medical Oncology, the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China. Electronic address:

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http://dx.doi.org/10.1016/j.tranon.2021.101226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498458PMC
December 2021

High-throughput single-cell transcriptomics reveals the female germline differentiation trajectory in Arabidopsis thaliana.

Commun Biol 2021 10 1;4(1):1149. Epub 2021 Oct 1.

College of Life Sciences, State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, College of Plant Protection, Fujian Agriculture and Forestry University, 350002, Fuzhou, China.

Female germline cells in flowering plants differentiate from somatic cells to produce specialized reproductive organs, called ovules, embedded deep inside the flowers. We investigated the molecular basis of this distinctive developmental program by performing single-cell RNA sequencing (scRNA-seq) of 16,872 single cells of Arabidopsis thaliana ovule primordia at three developmental time points during female germline differentiation. This allowed us to identify the characteristic expression patterns of the main cell types, including the female germline and its surrounding nucellus. We then reconstructed the continuous trajectory of female germline differentiation and observed dynamic waves of gene expression along the developmental trajectory. A focused analysis revealed transcriptional cascades and identified key transcriptional factors that showed distinct expression patterns along the germline differentiation trajectory. Our study provides a valuable reference dataset of the transcriptional process during female germline differentiation at single-cell resolution, shedding light on the mechanisms underlying germline cell fate determination.
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http://dx.doi.org/10.1038/s42003-021-02676-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486858PMC
October 2021

Polarization-insensitive ultra-short waveguide taper.

Opt Lett 2021 Oct;46(19):5027-5030

Waveguide taper, a key component in the photonic integrated circuit (PIC), enables on-chip mode conversion, but large-footprint tapers are detrimental to the PIC, which desires compact and efficient devices. Polarization sensitivity also limits the tapers in the applications involving orthogonal modes. In this work, we design an efficient polarization-insensitive ultra-short MMI-based waveguide taper, through the mode spreading principle and the self-image principle. The proposed taper is 26.3 µm long, one order of magnitude shorter than the standard linear taper. We fabricate the taper, and experimentally demonstrate that it exhibits a high transmission efficiency of ∼70 and a wide 1 dB bandwidth of >54, for both TE and TM polarizations.
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http://dx.doi.org/10.1364/OL.436223DOI Listing
October 2021

Gasotransmitters: Potential Therapeutic Molecules of Fibrotic Diseases.

Oxid Med Cell Longev 2021 20;2021:3206982. Epub 2021 Sep 20.

Chronic Disease Research Center, Medical College, Dalian University, Dalian, 116622 Liaoning, China.

Fibrosis is defined as the pathological progress of excessive extracellular matrix (ECM), such as collagen, fibronectin, and elastin deposition, as the regenerative capacity of cells cannot satisfy the dynamic repair of chronic damage. The well-known features of tissue fibrosis are characterized as the presence of excessive activated and proliferated fibroblasts and the differentiation of fibroblasts into myofibroblasts, and epithelial cells undergo the epithelial-mesenchymal transition (EMT) to expand the number of fibroblasts and myofibroblasts thereby driving fibrogenesis. In terms of mechanism, during the process of fibrosis, the activations of the TGF- signaling pathway, oxidative stress, cellular senescence, and inflammatory response play crucial roles in the activation and proliferation of fibroblasts to generate ECM. The deaths due to severe fibrosis account for almost half of the total deaths from various diseases, and few treatment strategies are available for the prevention of fibrosis as yet. Recently, numerous studies demonstrated that three well-defined bioactive gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS), generally exhibited anti-inflammatory, antioxidative, antiapoptotic, and antiproliferative properties. Besides these effects, a number of studies have reported that low-dose exogenous and endogenous gasotransmitters can delay and interfere with the occurrence and development of fibrotic diseases, including myocardial fibrosis, idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, diabetic diaphragm fibrosis, and peritoneal fibrosis. Furthermore, in animal and clinical experiments, the inhalation of low-dose exogenous gas and intraperitoneal injection of gaseous donors, such as SNAP, CINOD, CORM, SAC, and NaHS, showed a significant therapeutic effect on the inhibition of fibrosis through modulating the TGF- signaling pathway, attenuating oxidative stress and inflammatory response, and delaying the cellular senescence, while promoting the process of autophagy. In this review, we first demonstrate and summarize the therapeutic effects of gasotransmitters on diverse fibrotic diseases and highlight their molecular mechanisms in the process and development of fibrosis.
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http://dx.doi.org/10.1155/2021/3206982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478550PMC
September 2021

Risk Assessment of Hazmat Road Transportation Considering Environmental Risk under Time-Varying Conditions.

Int J Environ Res Public Health 2021 09 17;18(18). Epub 2021 Sep 17.

School of Business, East China University of Science and Technology, Shanghai 200237, China.

Hazardous materials shipments are integral to the development of industrial countries. Significant casualties and severe environmental pollution quickly ensue when accidents occur. Currently, relevant research on risk assessment of hazardous materials' road transportation remains limited when both the population exposure risk and environmental risk are considered, especially in regard to analyzing the differences of accident impacts in different populations and environments. This paper adopts a Gaussian plume model to simulate dynamic areas at three levels of population exposure and assesses the pollution scope of air, groundwater, lakes, and rivers with a variety of diffusion models. Then, we utilize various costs to analyze the differences of accident impacts in population exposure and environmental pollution. Finally, a risk assessment model of hazardous materials road transportation under time-varying conditions is presented by considering the bearing capacity of the assessed area. Furthermore, this model is applied to a case study involving a risk assessment of hazardous materials transportation of a highly populated metropolitan area of Shanghai, China. The resulting analyses reveal that the safety of hazardous materials transportation could be effectively improved by controlling certain model parameters and avoiding road segments with a high risk of catastrophic accident consequences.
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http://dx.doi.org/10.3390/ijerph18189780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467851PMC
September 2021

NUAK2 silencing inhibits the proliferation, migration and epithelial‑to‑mesenchymal transition of cervical cancer cells via upregulating CYFIP2.

Mol Med Rep 2021 Nov 24;24(5). Epub 2021 Sep 24.

Department of Obstetrics and Gynecology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430010, P.R. China.

NUAK family kinase 2 (NUAK2) has been reported to be involved in various cancer cell processes, including proliferation, apoptosis and invasion, by targeting multiple genes. However, to the best of our knowledge, its biological function in cervical cancer (CC) has not yet been elucidated. Therefore, the present study aimed to measure the expression of NUAK2 and to evaluate its functions in CC. The expression levels of NUAK2 and cytoplasmic FMRP‑interacting protein 2 (CYFIP2) were detected in CC tissues and cell lines. In addition, the effects of NUAK2 and CYFIP2 knockdown on CC cell proliferation, migration, invasion and epithelial‑to‑mesenchymal transition (EMT) were evaluated using Cell Counting Kit‑8, immunofluorescence, wound healing assay, Transwell assay and western blotting, respectively. Furthermore, co‑immunoprecipitation was performed to determine the interaction between NUAK2 and CYFIP2. The results revealed that the expression levels of NUAK2 were upregulated in CC tissues and cells, whereas CYFIP2 expression was reduced. In addition, knockdown of NUAK2 reduced cell proliferation, migration, invasion and EMT. Notably, NUAK2 was found to bind directly to CYFIP2. Furthermore, CYFIP2 inhibition reversed the effects of NUAK2 on CC cells. In summary, NUAK2 may regulate CYFIP2 expression to promote CC cell proliferation, migration, invasion and EMT.
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http://dx.doi.org/10.3892/mmr.2021.12457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477169PMC
November 2021

Physiologic Regulation of Systemic Klotho Levels by Renal CaSR Signaling in Response to CaSR Ligands and pH.

J Am Soc Nephrol 2021 Sep 22. Epub 2021 Sep 22.

Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas

Background: The kidney is the source of sKlotho and kidney-specific loss of Klotho leads to a phenotype resembling the premature multiorgan failure phenotype in Klotho-hypomorphic mice ( mice). Klotho and the Ca-sensing receptor (CaSR) are highly expressed in the distal convoluted tubule (DCT). The physiologic mechanisms that regulate sKlotho levels are unknown.

Methods: We measured sKlotho in WT and tubule-specific CaSR (TS-CaSR) mice treated with calcimimetics, alkali, or acid, and Klotho shed from minced mouse kidneys, and from HEK-293 cells expressing the CaSR and Klotho, in response to calcimimetics, calcilytics, alkalotic and acidic pH, and ADAM protease inhibitors. The CaSR, Klotho, and ADAM10 were imaged in mouse kidneys and cell expression systems using confocal microscopy.

Results: The CaSR, Klotho, and ADAM10 colocalize on the basolateral membrane of the DCT. Calcimimetics and HCO increase serum sKlotho levels in WT but not in CaSR mice, and acidic pH suppresses sKlotho levels in WT mice. In minced kidneys and cultured cells, CaSR activation with high Ca, calcimimetics, or alkali increase shed Klotho levels ADAM10, as demonstrated using the ADAM10 inhibitor GI254023X and siRNA. In cultured cells, the CaSR, Klotho, and ADAM10 form cell surface aggregates that disperse after CaSR activation.

Conclusions: We identify a novel physiologic mechanism for regulation of sKlotho levels by the renal CaSR-ADAM10-Klotho pathway. We show that CaSR activators, including alkali, increase renal CaSR-stimulated Klotho shedding and predict that this mechanism is relevant to the effects of acidosis and alkali therapy on CKD progression.
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http://dx.doi.org/10.1681/ASN.2021020276DOI Listing
September 2021

Cross-Cultural Adaptation and Validation of the Emotional Inhibition Scale in a Chinese Cancer Sample.

Front Psychol 2021 3;12:654777. Epub 2021 Sep 3.

Department of Nursing, Nanfang Hospital, Southern Medical University, Guangzhou, China.

The Emotional Inhibition Scale (EIS) is a brief measure based on a four-factor model with documented validity in a mood disorder sample that may be useful for assessing emotional inhibition in patient populations, such as individuals with cancer. The present study adapted the EIS to Chinese conditions and examined the psychometric characteristics of the EIS in patients with cancer. The recruited participants comprised a sample of 100 patients (sample 1) and a sample of 202 patients (sample 2) with cancer. The two samples (sample 1 and sample 2) with cancer completed surveys including the EIS. The Toronto Alexithymia Scale-20 was completed by the two sample groups to assess criterion validity. Statistical analyses included internal consistency (sample 1), exploratory factor analyses (EFAs; sample 1), and confirmatory factor analyses (CFAs; sample 2). The results showed that EFA and CFA confirmed the four-factor solution proposed by the original authors (verbal inhibition, self-control, disguise of feelings, and timidity). The internal consistency and test-retest reliability of the EIS were satisfactory. In conclusion, the EIS demonstrated acceptable reliability and validity for assessing emotional inhibition in Chinese-speaking patients with cancer and may be a useful measure for assessing the level of emotional inhibition and the effect of emotional disclosure interventions.
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http://dx.doi.org/10.3389/fpsyg.2021.654777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446548PMC
September 2021

A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes.

Nat Commun 2021 09 17;12(1):5503. Epub 2021 Sep 17.

Hightide Therapeutics, Rockville, MD, USA.

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease -4.8% vs. -2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.
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http://dx.doi.org/10.1038/s41467-021-25701-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448729PMC
September 2021
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