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Response to: 'Clinical features of patients with rheumatic diseases and COVID-19 infection in Sarawak, Malaysia' by Wan et al

Zhong J, Dong L

Ann Rheum Dis, 2020 Jul 24.
PMID: 32709678 DOI: 10.1136/annrheumdis-2020-218441
Effect of different implant configurations on biomechanical behavior of full-arch implant-supported mandibular monolithic zirconia fixed prostheses

Zhong J, Guazzato M, Chen J, Zhang Z, Sun G, Huo X, et al.

J Mech Behav Biomed Mater, 2020 02;102:103490.
PMID: 31877512 DOI: 10.1016/j.jmbbm.2019.103490

Mechanical failure of zirconia-based full-arch implant-supported fixed dental prostheses (FAFDPs) remains a critical issue in prosthetic dentistry. The option of full-arch implant treatment and the biomechanical behaviour within a sophisticated screw-retained prosthetic structure have stimulated considerable interest in fundamental and clinical research. This study aimed to analyse the biomechanical responses of zirconia-based FAFDPs with different implant configurations (numbers and distributions), thereby predicting the possible failure sites and the optimum configuration from biomechanical aspect by using finite element method (FEM). Five 3D finite element (FE) models were constructed with patient-specific heterogeneous material properties of mandibular bone. The results were reported using volume-averaged von-Mises stresses (σVMVA) to eliminate numerical singularities. It was found that wider placement of multi-unit copings was preferred as it reduces the cantilever effect on denture. Within the limited areas of implant insertion, the adoption of angled multi-unit abutments allowed the insertion of oblique implants in the bone and wider distribution of the multi-unit copings in the prosthesis, leading to lower stress concentration on both mandibular bone and prosthetic components. Increasing the number of supporting implants in a FAFDPs reduced loading on each implant, although it may not necessarily reduce the stress concentration in the most posterior locations significantly. Overall, the 6-implant configuration was a preferable configuration as it provided the most balanced mechanical performance in this patient-specific case.
Origin tracing and adulteration identification of bird's nest by high- and low-field NMR combined with pattern recognition

Xing M, Liu F, Lin J, Xu D, Zhong J, Xia F, et al.

Food Res Int, 2024 Jan;175:113780.
PMID: 38129006 DOI: 10.1016/j.foodres.2023.113780

Edible bird's nest (EBN) is a high-value health food with various nutrients and bioactive components. With increasing demand for EBN, they are often adulterated with cheaper ingredients or falsely labeled by the origin information, thus harming consumer interests. In this study, high- and low-field nuclear magnetic resonance (HF/LF-NMR) technology combined with multivariate statistical analysis was used to identify the geographical marker of EBN from different origins and authenticate the adulterated EBN with various adulterants at different adulteration rates. Authentic EBN samples from Malaysia were used to simulate adulteration using gelatin (GL), agar (AG) and starch (ST) at 10 %, 20 %, 40 %, 60 %, 80 %, and 100 % w/w, respectively. The results showed significant differences in composition among EBN from different origins, with isocaproate and citric acid serving as geographical markers for Malaysia and Vietnam, respectively. Leucine, glutamic acid, and N-acetylglycoprotein serving as geographical markers for Indonesia. In addition, PLS model further verified the accuracy of origin identification of EBN. The LF-NMR results of adulteration EBN showed a linear correlation between the transverse relaxation (T2, S2) and the adulterated ratio. The OPLS-DA based on T2 spectra could accurately identify authentic EBN from adulterated with GL, AG and ST at 40 %, 20 %, and 20 %, respectively. Fisher discrimination model was able to differentiate at 20 %, 20 %, and 40 %, respectively. These results show that the 1H NMR combined with multivariate statistical analysis method could be a potential tool for the detection of origin and adulteration of EBN.
A Soft-Tissue Driven Bone Remodeling Algorithm for Mandibular Residual Ridge Resorption Based on Patient CT Image Data

Zhong J, Huang W, Ahmad R, Chen J, Wu C, Hu J, et al.

Adv Healthc Mater, 2024 Sep;13(22):e2400091.
PMID: 38722148 DOI: 10.1002/adhm.202400091

The role of the biomechanical stimulation generated from soft tissue has not been well quantified or separated from the self-regulated hard tissue remodeling governed by Wolff's Law. Prosthodontic overdentures, commonly used to restore masticatory functions, can cause localized ischemia and inflammation as they often compress patients' oral mucosa and impede local circulation. This biomechanical stimulus in mucosa is found to accelerate the self-regulated residual ridge resorption (RRR), posing ongoing clinical challenges. Based on the dedicated long-term clinical datasets, this work develops an in-silico framework with a combination of techniques, including advanced image post-processing, patient-specific finite element models and unsupervised machine learning Self-Organizing map algorithm, to identify the soft tissue induced RRR and quantitatively elucidate the governing relationship between the RRR and hydrostatic pressure in mucosa. The proposed governing equation has not only enabled a predictive simulation for RRR as showcased in this study, providing a biomechanical basis for optimizing prosthodontic treatments, but also extended the understanding of the mechanobiological responses in the soft-hard tissue interfaces and the role in bone remodeling.
A review of dietary phytochemicals and their relation to oxidative stress and human diseases

Guan R, Van Le Q, Yang H, Zhang D, Gu H, Yang Y, et al.

Chemosphere, 2021 May;271:129499.
PMID: 33445014 DOI: 10.1016/j.chemosphere.2020.129499

Phytochemicals refer to active substances in plant-based diets. Phytochemicals found in for example fruits, vegetables, grains and seed oils are considered relatively safe for consumption due to mammal-plant co-evolution and adaptation. A number of human diseases are related to oxidative stress caused by for example chemical environmental contaminants in air, water and food; while also lifestyle including smoking and lack of exercise and dietary preferences are important factors for disease development in humans. Here we explore the dietary sources of antioxidant phytochemicals that have beneficial effects on oxidative stress, cardiovascular and neurological diseases as well as cancer. Plant-based diets usually contain phenolic acids, flavonoids and carotenoids, which have strong antioxidant properties, and therefore remove the excess of active oxygen in the body, and protect cells from damage, reducing the risk of cardiovascular and Alzheimer's disease. In most cases, obesity is related to diet and inactivity and plant-based diets change lipid composition and metabolism, which reduce obesity related hazards. Cruciferous and Allium vegetables are rich in organic sulphides that can act on the metabolism of carcinogens and therefore used as anti-cancer and suppressing agents while dietary fibres and plant sterols may improve intestinal health and prevent intestinal diseases. Thus, we recommend a diet rich in fruits, vegetables, and grains as its content of phytochemicals may have the potential to prevent or improve a broad sweep of various diseases.
Fulltext Ancient forest plants possess cytotoxic properties causing liver cancer HepG2 cell apoptosis

Yue X, Ling Ma N, Zhong J, Yang H, Chen H, Yang Y, et al.

Environ Res, 2024 Jan 15;241:117474.
PMID: 37879390 DOI: 10.1016/j.envres.2023.117474

Here, we collected 154 plant species in China ancient forests looking for novel efficient bioactive compounds for cancer treatments. We found 600 bioactive phyto-chemicals that induce apoptosis of liver cancer cell in vitro. First, we screen the plant extract's in vitro cytotoxicity inhibition of cancer cell growth using in vitro HepG2 cell lines and MTT cytotoxicity. The results from these initial MTT in vitro cytotoxicity tests show that the most efficient plants towards hepatoma cytoxicity is Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus). We then used in cell-counting kit-8 (CCK-8) to further understand in vivo tumor growth using nude mice and GC-MS and LC-QTOF-MS to analyze the composition of compounds in the extracts. Extracted chemically active molecules analyzed by network pharmacology showed inhibition on the growth of liver cancer cells by acting on multiple gene targets, which is different from the currently used traditional drugs acting on only one target of liver cancer cells. Extracts from Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus) induce apoptosis in hepatoma cancer cell line HepG2 with a killing rate of more than 83% and a tumor size decrease by 62-67% and a killing rate of only 6% of normal hepatocyte LO2. This study highlight efficient candidate species for cancer treatment providing a basis for future development of novel plant-based drugs to help meeting several of the UN SDGs and planetary health.
Corrigendum to "High-throughput screening of ancient forest plant extracts shows cytotoxicity towards triple-negative breast cancer" [Environ. Int. 181 (2023) 108279]

Li Y, Ma NL, Chen H, Zhong J, Zhang D, Peng W, et al.

Environ Int, 2024 Apr 25.
PMID: 38670876 DOI: 10.1016/j.envint.2024.108695
Fulltext High-throughput screening of ancient forest plant extracts shows cytotoxicity towards triple-negative breast cancer

Li Y, Ling Ma N, Chen H, Zhong J, Zhang D, Peng W, et al.

Environ Int, 2023 Nov;181:108279.
PMID: 37924601 DOI: 10.1016/j.envint.2023.108279

According to the World Health Organization, women's breast cancer is among the most common cancers with 7.8 million diagnosed cases during 2016-2020 and encompasses 15 % of all female cancer-related mortalities. These mortality events from triple-negative breast cancer are a significant health issue worldwide calling for a continuous search of bioactive compounds for better cancer treatments. Historically, plants are important sources for identifying such new bioactive chemicals for treatments. Here we use high-throughput screening and mass spectrometry analyses of extracts from 100 plant species collected in Chinese ancient forests to detect novel bioactive breast cancer phytochemicals. First, to study the effects on viability of the plant extracts, we used a MTT and CCK-8 cytotoxicity assay employing triple-negative breast cancer (TNBC) MDA-MB-231 and normal epithelial MCF-10A cell lines and cell cycle arrest to estimate apoptosis using flow cytometry for the most potent three speices. Based on these analyses, the final most potent extracts were from the Amur honeysuckle (Lonicera maackii) wood/root bark and Nigaki (Picrasma quassioides) wood/root bark. Then, 5 × 106 MDA-MB-231 cells were injected subcutaneously into the right hind leg of nude mice and a tumour was allowed to grow before treatment for seven days. Subsequently, the four exposed groups received gavage extracts from Amur honeysuckle and Nigaki (Amur honeysuckle wood distilled water, Amur honeysuckle root bark ethanol, Nigaki wood ethanol or Nigaki root bark distilled water/ethanol (1:1) extracts) in phosphate-buffered saline (PBS), while the control group received only PBS. The tumour weight of treated nude mice was reduced significantly by 60.5 % within 2 weeks, while on average killing 70 % of the MDA-MB-231 breast cancer cells after 48 h treatment (MTT test). In addition, screening of target genes using the Swiss Target Prediction, STITCH, STRING and NCBI-gene database showed that the four plant extracts possess desirable activity towards several known breast cancer genes. This reflects that the extracts may kill MBD-MB-231 breast cancer cells. This is the first screening of plant extracts with high efficiency in 2 decades, showing promising results for future development of novel cancer treatments.
European Association of Urology Section of Urolithiasis and International Alliance of Urolithiasis Joint Consensus on Retrograde Intrarenal Surgery for the Management of Renal Stones

Zeng G, Zhao Z, Mazzon G, Pearle M, Choong S, Skolarikos A, et al.

Eur Urol Focus, 2022 Sep;8(5):1461-1468.
PMID: 34836838 DOI: 10.1016/j.euf.2021.10.011

BACKGROUND: Retrograde intrarenal surgery (RIRS) has become the preferred treatment modality for nephrolithiasis. However, because of ongoing uncertainties regarding the optimal perioperative management, operative technique, and postoperative follow-up, as well as a lack of standardization for outcome reporting, consensus is needed to achieve more uniform clinical practice worldwide.
OBJECTIVE: To develop recommendations for RIRS on the basis of existing data and expert consensus.
DESIGN, SETTING, AND PARTICIPANTS: A protocol-driven, three-phase study was conducted by the European Association of Urology Section of Urolithiasis (EULIS) and the International Alliance of Urolithiasis (IAU). The process included: (1) a nonsystematic review of the literature to define domains for discussion; (2) a two-round modified Delphi survey involving experts in this field; and (3) an additional group meeting and third-round survey involving 64 senior representative members to formulate the final conclusions.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The results from each previous round were returned to the participants for re-evaluation of their decisions during the next round. The agreement threshold was set at 70%.
RESULTS AND LIMITATIONS: The panel included 209 participants who developed 29 consensus statements on the following topics of interest: (1) perioperative infection management; (2) perioperative antithrombotic therapy; (3) fundamentals of the operative technique; and (4) standardized outcome reporting. Although this consensus can be considered as a useful reference for more clinically oriented daily practice, we also acknowledge that a higher level of evidence from further clinical trials is needed.
CONCLUSIONS: The consensus statements aim to guide and standardize clinical practice and research on RIRS and to recommend standardized outcome reporting.
PATIENT SUMMARY: An international consensus on the best practice for minimally invasive surgery for kidney stones was organized and developed by two international societies. It is anticipated that this consensus will provide further guidance to urologists and may help to improve clinical outcomes for patients.
Fulltext Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Klein AP, Wolpin BM, Risch HA, Stolzenberg-Solomon RZ, Mocci E, Zhang M, et al.

Nat Commun, 2018 02 08;9(1):556.
PMID: 29422604 DOI: 10.1038/s41467-018-02942-5

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
Fulltext A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, et al.

J Natl Cancer Inst, 2020 Oct 01;112(10):1003-1012.
PMID: 31917448 DOI: 10.1093/jnci/djz246

BACKGROUND: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown.
METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).
RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.
CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

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