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1.
Methods Mol Biol ; 2055: 413-431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31502163

RESUMO

Cancer immunotherapies, in particular adoptive T cell therapy and immune-checkpoint blockade therapy have demonstrated a remarkable success in the treatment of cancer. However, due to heterogeneous functionality and complex immune response of immune cells, it remains challenging to identify predictive biomarkers which have the potential to correlate with efficacy and adverse effects of immunotherapies and help selecting patients who might benefit from the therapy, developing more personalized therapeutics as well as reducing clinical trial cost. The single-cell IsoCode chip in conjunction with fluorescent ELISA-based assay enables a simultaneous detection up to 40+ proteins secreted from live single immune cells, providing a large portion of the assayable functions for each immune cell type, and thus precise assessment of multifunctional, or polyfunctional, heterogeneity of each immune cell type.This unique functional detection capability provides a powerful solution to unmet needs in immunotherapy patient profiling today. Recently, the single-cell metric termed polyfunctional strength index (PSI™) by IsoCode chip computed from preinfusion anti-CD19 chimeric antigen receptor (CAR)-T cell products has demonstrated a significant association with clinical response and cytokine release syndrome (CRS) of cancer patient to the therapy after cell product infusion. This chapter elucidates IsoPlexis single-cell highly multiplexed proteomic platform and provides technical details for characterizing cell products and various cell subsets from peripheral blood, bone marrow, or tumor tissues using this assay.

2.
J Nanosci Nanotechnol ; 20(1): 653-657, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383228

RESUMO

This study analytically investigates the picosecond laser ablation of poly(methyl methacrylate) (PMMA) and acrylonitrile butadiene styrene (ABS)/polyvinyl chloride (PVC). Pulsed laser ablation is a well-established tool for polymers. However the ablation mechanism used in laser processing of polymers is not thoroughly understood. This study utilizes a thermal transport model to analyze the relationship between the ablation rate and laser fluence. This model considers the energy balance at the decomposition interface. The calculated variation of the ablation rate with the logarithm of the laser fluence agrees with the measured data. This study also validates that the variation of the ablation rate with the logarithm of the laser fluence obeys Beer's law.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31597496

RESUMO

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer. Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty. Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,737 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters. Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31564411

RESUMO

Arctigenin is the active content of arctium lappa that present anti-cancer abilities in various carcinomas. However, its role and underlying mechanism in drug-resistant colorectal cancer cells has not been addressed. The present study used SW480 and SW620 to established cisplatin-resistant colorectal cancer cell lines, and explored the impact of arctigenin on these cells. Arctigenin at 100 µM significantly inhibited cell proliferation of cisplatin treated R-SW480 and R-SW620 cells as compared with cells treated with cisplatin alone. Arctigenin elevates cell apoptosis, up-regulated pro-apoptotic protein cleaved-caspase-3 and caspase-9 expression level in cisplatin treated R-SW480 and R-SW620 cells. Additionally, arctigenin triggered autophagy and promoted LC3-Ⅱ and p65 expression, while inhibited LC3-Ⅰexpression. Arctigenin impeded the IC50 of not only cisplatin but also oxaliplatin, doxorubicin and Paclitaxel of R-SW480 and R-SW620 cells. More importantly, the mRNA expression of multi drug resistance 1 (MDR1) and protein expression of pgp were significantly inhibited by arctigenin administration. Taken together, arctigenin has the potential in sensitize colorectal cancer cells by activating autophagy, which induced cell apoptosis and inhibited cell growth. Our study revealed that arctigenin has the potential for colorectal cancer treatment and may be useful in adjuvant chemotherapy.

5.
Mol Genet Genomic Med ; : e976, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566921

RESUMO

BACKGROUND: X-linked intellectual disability type Nascimento (XIDTN), caused by mutations in ubiquitin-conjugating enzyme E2A (UBE2A) gene, is characterized by moderate to severe intellectual disability, impaired speech, urogenital anomalies, skin abnormalities, and dysmorphic facial features. METHODS: Whole-exome sequence was carried out in the patients, and the variant of disease-associated gene in the patient and his parents was confirmed by Sanger sequencing. RNA transcript analysis by reverse transcription (RT)-PCR was performed to assess the potential effects of the splice site mutation. RESULTS: A novel splicing mutation (c.331-2A>G) in UBE2A gene, inherited from his mother, was identified in a Chinese boy with intellectual disability and impaired speech. Furthermore, brain magnetic resonance imaging showed multiple patchy hyperintensity in bilateral centrum ovale. RT-PCR demonstrated that this variant generated a novel transcript with a deletion of 29 nucleotides in exon 6 (r.331_359del), resulting in a frameshift mutation (p.L112SfsX17). CONCLUSION: Ultimately, he was diagnosed with XIDTN by genetic analysis. To the best of our knowledge, this is the first case report of this syndrome in China with a confirmed molecular diagnosis. Our case not only expands the mutation spectrum of UBE2A, but also provides additional insights into the genetic and phenotypic heterogeneity of XIDTN as well as phenotype-genotype correlations in this disease.

6.
Immunity ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31586542

RESUMO

HIV- and SIV-envelope (Env) trimers are both extensively glycosylated, and antibodies identified to date have been unable to fully neutralize SIVmac239. Here, we report the isolation, structure, and glycan interactions of antibody ITS90.03, a monoclonal antibody that completely neutralized the highly neutralization-resistant isolate, SIVmac239. The co-crystal structure of a fully glycosylated SIVmac239-gp120 core in complex with rhesus CD4 and the antigen-binding fragment of ITS90.03 at 2.5-Å resolution revealed that ITS90 recognized an epitope comprised of 45% glycan. SIV-gp120 core, rhesus CD4, and their complex could each be aligned structurally to their human counterparts. The structure revealed that glycans masked most of the SIV Env protein surface, with ITS90 targeting a glycan hole, which is occupied in ∼83% of SIV strains by glycan N238. Overall, the SIV glycan shield appears to functionally resemble its HIV counterpart in coverage of spike, shielding from antibody, and modulation of receptor accessibility.

7.
IEEE Trans Cybern ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31567110

RESUMO

In this article, we investigate the output consensus tracking problem for a class of high-order nonlinear systems with unknown parameters, uncertain external disturbances, and intermittent actuator faults. Under the directed topology condition, a novel distributed adaptive controller is proposed. The common time-varying trajectory is allowed to be totally unknown by part of the subsystems. Therefore, the assumption on the linearly parameterized trajectory signal in most literature is no longer needed. To achieve the relaxation, extra distributed parameter estimators are introduced in all subsystems. Besides, to handle the actuator faults occurring at possibly infinite times, a new adaptive compensation technique is adopted. It is shown that with the proposed scheme, all closed-loop signals are globally uniformly bounded and asymptotically output consensus tracking can be achieved.

8.
Int J Infect Dis ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580939

RESUMO

BACKGROUND: Few data about healthcare-associated infection (HAI) is available from the developing world, thus we conducted a point prevalence survey (PPS) to determine the prevalence of HAI and antimicrobial use (AMU) in Guangdong province, China. METHODS: A standardized methodology for PPS on HAIs and AMU has been developed by Chinese Nosocomial Infection Control and Quality Improvement Centre. Prevalence of HAI, AMU and baseline hospital-level variables were collected in 189 hospitals from June 2017 to May 2018. RESULTS: Of 5,868,147 patients, 72,976 had one or more HAIs (1.24%) with distinct 82,700 HAIs. The prevalence of device-associated infections, including ventilator-associated pneumonia, catheter-associated urinary tract infection and central-line-associated bloodstream infection were 7.92, 2.06 and 0.63 per 1,000 catheter days, respectively. 10,591(0.18%) HAIs caused by MDROs were identified. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (53.86%) and P. aeruginosa (21.60%). 46.22% (2,712,258/5,868,147) of inpatients were receiving at least one antimicrobial during this survey. CONCLUSIONS: Our survey indicated the relatively lower prevalence of HAI but higher antimicrobial using in Guangdong province compared with other mid-low income and high-income countries. Further studies are warranted to elucidate which HAI-related indicators are the best measures of HAI performance and thus allow improvements leading to better patient outcomes.

9.
Chem Asian J ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584745

RESUMO

The oxidative contraction of α-formal ketone to form continuous all carbon chiral centers promoted by H 2 O 2 is widely used in natural product total synthesis. Typically, using this transformation, the chiral cyclic ketones were obtained as the major products and the ring-opening products as the minor products. Herein, DFT computations have been used to investigate the detailed reaction mechanism and the chemoselectivity. In addition with the widely accepted mechanism of H 2 O 2 -catalyzed transformation, our systematic investigation with various explicit-solvent-model calculations for the first time shows that H 2 O and H 2 O 2 are comparable at catalyzing the rate-determining step of this reaction, which emphasis the importance of solvent effect in such transformations. It is found that both the less ring-constrain and a later transition state in an exothermic reaction account for the origin why the reaction favors ring-contraction pathway rather than ring-opening one. By a comprehensive analysis for the substituted groups, it has been disclosed that the steric effects of the substituted groups on R 2 and R 3 contribute to the selectivity with larger steric hindrance favoring the chiral cyclic products. While the electronic effects on R 1 but not R 3 affect the selectivity with electron-donating groups leading to the cyclic products. Based on our calculations, some predictions for higher selectivity have been made.

10.
J Hazard Mater ; 384: 121285, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31577969

RESUMO

Despite the global importance of atmospheric heavy metal input into agricultural soils, research has primarily focused on the amount of the depositions with limited attention given to the risk of the newly deposited heavy metals. To understand the remobilization of the newly deposited copper (Cu) and lead (Pb) from the atmosphere and explore the metals' mobility and bioavailability to rice (Oryza sativa L.), a soil transplant experiment was conducted in three areas along a gradient of atmospheric depositions. Approximately 61% of the Cu and 76% of the Pb depositions tended to be present in potentially mobile fractions. The soil retention of newly deposited Cu and Pb presented as higher mobile fractions than these in the original soil. The newly deposited Cu and Pb in soils only accounted for 0.34-8.7% and 0.07-0.29% of the total soil Cu and Pb pools, but they contributed 30-84% and 6-41% in rice tissues, respectively. A major implication of these findings is that once the heavy metal is deposited, it may be reactivated in soils and transported to aerial parts or foliar uptake into plant tissues, emphasizing the important role of the newly deposited Cu and Pb in contributing to the edible parts of crops.

11.
BMJ Open ; 9(10): e031043, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601592

RESUMO

INTRODUCTION: Migraine is a primary cause of disability worldwide, particularly affecting young adults and middle-aged women. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating acute migraine attacks, the methodologies in academic studies and commonly applied practices vary greatly. This study protocol outlines a plan to assess and rank the effectiveness of the different acupuncture methods in order to develop a prioritised acupuncture-based treatment regimen for acute migraine attacks. OBJECTIVE: To compare the efficacy of different acupuncture methods and conventional medicinal methods in the treatment of acute migraine attacks. METHODS AND ANALYSIS: Six databases will be searched, including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database and Wanfang Database from inception to 31 August 2019. The primary outcomes will be assessed using metrics for intensity and duration (in hours) of pain post-treatment. Bayesian network meta-analysis will be conducted using WinBUGS V.1.4.3. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation System to assess the quality of evidence. ETHICS AND DISSEMINATION: The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol. PROSPERO REGISTRATION NUMBER: CRD42019126472.

12.
Org Biomol Chem ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596301

RESUMO

A highly efficient domino aza-MIRC (Michael Induced Ring Closure) reaction between barbiturate-derived alkenes and N-alkoxy α-haloamides has been achieved in moderate to excellent yields. This reaction proceeds smoothly under mild conditions via a domino aza-Michael addition/intramolecular SN2 sequence, providing a practical tool in the synthesis of bioactive molecules spirobarbiturate-3-pyrrolidinones.

14.
J Periodontol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489644

RESUMO

BACKGROUD: The present study was to determine the role of Toll-like receptor 4 (TLR4) signaling in inflammation and alveolar bone resorption using a murine model of Porphyromonas gingivalis (P. gingivalis) associated ligature-induced peri-implantitis. METHODS: Smooth surface titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in Wild-type (WT) and TLR4-/- (TLR4 KO) mice. Silk ligatures immersed with P. gingivalis were tied around the implants 4 weeks after the implant placement and confirmation of osteointegration. Two weeks after the ligation, bone resorption, osteoclastogenesis, cellular inflammatory responses and gingival mRNA expression levels of cytokines were assessed by micro-computed tomography, Tartrate-resistant acid phosphatase (TRAP) staining, immunobiological examination and Real-time quantitative PCR respectively. RESULTS: In both WT and TLR4 KO mice, the bone resorption around implants was significantly increased in the P. gingivalis/ligation group compared to control group. In P. gingivalis/ligation group, the levels of bone resorption, TRAP+ cell formation, and gingival CD3+ and CD45+ cell infiltration were significantly decreased in TLR4 KO mice compared to that in WT mice. RANKL/OPG ratio was significantly increased after P. gingivalis/ligation treatment in WT mice not in TLR4 KO mice. When comparing the P. gingivalis/ligation group with the respective control group, gingival mRNA expressions of IL-1ß, IFN-γ and 1L-17 were significantly increased in TLR4 KO mice. CONCLUSIONS: This study suggests that TLR4 mediates alveolar bone resorption in P. gingivalis associated ligature-induced peri-implantitis through regulation of immune B cell infiltration, RANKL/OPG expression ratio, and differential inflammatory cytokine production. This article is protected by copyright. All rights reserved.

15.
J Cell Physiol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490023

RESUMO

This study aimed to examine whether lung tissue extracellular matrix (ECM) hydrogels have protective effects on radiation-induced lung injury (RILI). The cytocompatibility and histocompatibility were tested for the obtained ECM-derived hydrogel. Sprague-Dawley rats were randomly divided into three groups (n = 18): control group (control); rats receiving irradiation and intratracheal injection of normal saline (IR + NS); and rats receiving irradiation and intratracheal injection of lung ECM-derived hydrogel (IR + ECM). The wet/dry weight ratio was used to evaluate the congestion and edema of the lungs. Histopathological analysis of lung tissues was performed using hemotoxylin and eosin staining and Masson's trichrome staining. Immunohistochemical staining and western blot analyses were carried out to determine the expression of epithelial-mesenchymal transition (EMT)-related proteins in lung tissues (E-cadherin, α-smooth muscle actin [α-SMA], and vimentin). In addition, tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1) and interleukin-6 (IL-6), hydroxyproline, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were also evaluated. The ECM-derived hydrogels had good cytocompatibility and histocompatibility. ECM-derived hydrogel treatment improved lung histopathology injury and pulmonary edema. Higher expression of E-cadherin and lower expression of vimentin and α-SMA were found in the IR + ECM group compared with those in the IR + NS group. Hydroxyproline levels were reduced by ECM-derived hydrogel treatment compared with those in the IR + NS group. Obvious increases of TNF-α, IL-6, and TGF-ß1 were identified following irradiation. Marked reductions in MDA content and increases in SOD were induced by ECM-derived hydrogel treatment in rats after radiation. ECM-derived hydrogels were shown to protect against RILI, potentially by reducing EMT, inflammation, and oxidative damage.

16.
J Synchrotron Radiat ; 26(Pt 5): 1733-1741, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31490165

RESUMO

The microscopic structures of ThF4-LiF and ThF4-LiF-BeF2 molten salts have been systematically investigated by in situ high-temperature X-ray absorption fine-structure (XAFS) spectroscopy combined with molecular-dynamics (MD) simulations. The results reveal that the local structure of thorium ions was much more disordered in the molten state of the ThF4-LiF-BeF2 salt than that in ThF4-LiF, implying that the Th and F ions were exchanged more frequently in the presence of Be ions. The structures of medium-range-ordered coordination shells (such as Th-F2nd and Th-Th) have been emphasized by experimental and theoretical XAFS analysis, and they play a significant role in transport properties. Using MD simulations, the bonding properties in the molten ThF4-LiF and ThF4-LiF-BeF2 mixtures were evaluated, confirming the above conclusion. This research is, to the best of our knowledge, the first systematic study on the ThF4-LiF-BeF2 molten salt via quantitative in situ XAFS analysis and MD simulations.

17.
Mol Cancer Ther ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515296

RESUMO

Increased activity of PI3K/AKT/mTOR pathway has been observed in chronic myeloid leukemia (CML). Morin, a kind of flavonoid, exhibits a significant anticancer activity by suppressing the PI3K/AKT signaling pathway. However, the effect of morin on CML and its underlying mechanisms are poorly understood. Here, we found that morin dose-dependently inhibited the proliferation of CML cell lines K562 and KCL22 and induced their apoptosis, with a significant increase in cell apoptosis upon exposure of cells to 50 µM morin. Moreover, morin significantly reduced CML xenograft growth in nude mice. Mechanically, morin attenuated phosphorylated AKT level by upregulating PTEN expression, thus leading to the inhibition of AKT signaling. Knockdown of PTEN by its si-RNA completely abrogated morin-induced cell apoptosis, indicating that PTEN mediates the inductive effect of morin on CML cell apoptosis. More importantly, we found that miR-188-5p was significantly upregulated in CML patients and CML cell lines. Treating CML cells with morin markedly downregulated miR-188-5p expression level. Further, we demonstrated that miR-188-5p repressed PTEN expression by directly targeting its 3'-UTR. miR-188-5p downregulation induced by morin enhanced CML cell apoptosis by relieving miR-188-5p repression of PTEN expression. In summary, morin exerts significant anticancer efficacy in CML by regulating miR-188-5p/PTEN axis and thus repressing the PI3K/AKT signaling.

18.
Int J Cancer ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498891

RESUMO

Metastasis is the leading cause of death for non-small cell lung cancer (NSCLC) patients. However, how lung cancer cells invade blood vessels during metastasis remains unclear. Here, based on bioinformatics analyses, we found that PLEK2 might regulate NSCLC migration and vascular invasion. As little is known about the function of PLEK2 in NSCLC, we aimed to clarify this. We demonstrated that PLEK2 was significantly upregulated in TGFß1-treated NSCLC cells through ELK1 transcriptional activation, highly expressed in NSCLC tissues, and negatively correlated with NSCLC overall survival. Meanwhile, PLEK2 overexpression significantly promoted NSCLC epithelial-to-mesenchymal transition (EMT) and migration, HMVEC-L endothelial-to-mesenchymal transition (EndoMT), and the destruction of vascular endothelial barriers. Moreover, PLEK2 knockdown inhibited TGFß1-induced EMT and EndoMT. Furthermore, PLEK2 was found to directly interact with SHIP2 and target it for ubiquitination and degradation in NSCLC cells. Next, we confirmed that SHIP2 overexpression inhibits NSCLC EMT, migration, and invasion and showed that PLEK2 overexpression can activate SHIP2-associated TGF-ß/PI3K/Akt signaling. Our results suggest that PLEK2 could be a novel prognostic marker and potential therapeutic target for NSCLC metastasis and vascular invasion. This article is protected by copyright. All rights reserved.

19.
Theranostics ; 9(19): 5577-5594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534504

RESUMO

Rationale: Colorectal cancer (CRC) is one of the most common cancers worldwide. Ciclopirox olamine (CPX) has recently been identified to be a promising anticancer candidate; however, novel activities and detailed mechanisms remain to be uncovered. Methods: The cytotoxic potential of CPX towards CRC cells was examined in vitro and in vivo. The global gene expression pattern, ROS levels, mitochondrial function, autophagy, apoptosis, etc. were determined between control and CPX-treated CRC cells. Results: We found that CPX inhibited CRC growth by inhibiting proliferation and inducing apoptosis both in vitro and in vivo. The anti-cancer effects of CPX involved the downregulation of DJ-1, and overexpression of DJ-1 could reverse the cytotoxic effect of CPX on CRC cells. The loss of DJ-1 resulted in mitochondrial dysfunction and ROS accumulation, thus leading to CRC growth inhibition. The cytoprotective autophagy was provoked simultaneously, and blocking autophagy pharmacologically or genetically could further enhance the anti-cancer efficacy of CPX. Conclusion: Our study demonstrates that DJ-1 loss-induced ROS accumulation plays a pivotal role in CPX-mediated CRC inhibition, providing a further understanding for CRC treatment via modulating compensatory protective autophagy.

20.
Sci Rep ; 9(1): 13069, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506454

RESUMO

Platelet-leukocyte aggregate (PLA) is implicated in the etiology of both vascular lesions and cardiovascular events. This prospective cohort study aimed to examine the prognostic value of PLA for major adverse cardiac and cerebrovascular events (MACCE) and perioperative adverse events (AEs) in patients with rheumatic heart disease undergoing surgical intervention by Cox proportional hazard regression and logistic regression. A total of 244 patients were included, of whom 7 were lost to follow-up. Among the analyzed 237 subjects who completed 3-year follow-up, 30 experienced MACCE and 38 experienced perioperative AEs. Preoperative PLA was higher in subjects who developed MACCE (13.32%) than in those who did not (8.69%, p = 0.040). In multivariate regression, elevated PLA was associated with increased MACCE (hazard ratio 1.51 for each quartile, 95% CI 1.07-2.13; p = 0.020), and perioperative AEs (odds ratio 1.61, 95% CI 1.14-2.26; p = 0.007). The optimal PLA cut-off for predicting MACCE was 6.8%. Subjects with PLA > 6.8% had a higher prevalence of MACCE (17.1% vs. 5.5%, p = 0.009) and perioperative AEs (19.9% vs. 8.6%, p = 0.018). Kaplan-Meier analysis showed shorter MACCE-free survival in patients with PLA > 6.8% (p = 0.007, log rank). Elevated preoperative PLA is associated with increased MACCE and perioperative AEs in patients with rheumatic valve disease undergoing surgical intervention.

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