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2.
Int J Biol Sci ; 18(2): 599-616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35002512

RESUMO

Lactic acid (LA) metabolism in the tumor microenvironment contributes to the establishment and maintenance of immune tolerance. This pathway is characterized in tumor associated macrophages. However, the role and pathway of LA metabolism at maternal-fetal interface during early pregnancy, especially in decidual macrophage differentiation, are still unclear. Herein, for the first time, we discovered that LA can trigger either M2 or M1 macrophage polarization via oxidative phosphorylation and glycolysis regulation under normoxia or hypoxia, respectively. Also, LA metabolism played a vital role in decidual macrophages-mediated recurrent pregnancy loss (RPL), through HIF-1α/SRC/LDHA pathway. Moreover, blockade of LA intake with AZD3965 (MCT-1 inhibitor) could rescue pregnancy in an abortion-prone mouse model, suggesting a potential therapeutic target in RPL. Collectively, the present study identifies the previously unknown functions of LA metabolism in the differentiation of decidual macrophages in early normal pregnancy and RPL, and provides a potential therapeutic strategy in RPL by manipulating decidual macrophages' functions through LA metabolic pathway.

3.
Sci Total Environ ; 802: 149891, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474296

RESUMO

Animals exposure to polychlorinated biphenyls (PCBs) may result in retention of hydroxylated PCBs (OH-PCBs). OH-PCBs can be accumulated in animals, including humans, through the transmission of food chain. However, there are few studies on the accumulation and metabolism of OH-PCBs exposed to the body through daily diet. Therefore, this study was conducted to investigate the fate of OH-PCBs after being ingested through dietary intake. By adding 3-OH-PCB101 and 4-OH-PCB101 to the edible tissue of crucian carp, which were used as raw materials to prepare mouse feed, with an exposure concentration of 2.5 µg/kg ww. The exposure experiment lasted for a total of 80 days. The blood, feces and 11 tissues of mice at different times were analyzed qualitatively and quantitatively. It was found that major OH-PCB101 were accumulated in intestine or excreted with feces. A small part was accumulated in heart, lung and spleen. For the first time that the conversion from OH-PCB101 to PCB101 in mice was discovered, which shows from another perspective that persistent organic pollutants are difficult to be completely degraded in the environment. 4-MeO-PCB101, 3-MeSO2-PCB101, and 4-MeSO2-PCB101 were also found in various tissues. The results of this study show that after OH-PCBs accumulated in animals re-enter the organism through the food chain, they can be metabolized again and may be reversely transformed into the parent compounds. The present research shed new light on simulating the metabolic transformation process of OH-PCBs exposed to mammals through ingestion of fish. Available data show that second-generation persistent organic pollutants in the environment still need to be continuously concerned.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Animais , Dieta , Peixes , Hidroxilação , Camundongos , Bifenilos Policlorados/análise
4.
Sci Total Environ ; 803: 150009, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492484

RESUMO

The anaerobic ammonium oxidation (anammox) process has been recognized as an efficient nitrogen removal technology. However, anammox bacteria are susceptible to surrounding environments and different pollutants, which limits the extensive application of the anammox process worldwide. Numerous researchers investigate the effects of various pollutants on the anammox process or bacteria, and related findings have also been reviewed with the focused on their inhibitory effects on process performance and microbial community. This review systemically summarized the recent advances in the inhibition, mechanism and recovery process of traditional and emerging pollutants on the anammox process over a decade, such as organics, metals, antibiotics, nanoparticles, etc. Generally, low-concentration pollutants exhibited a promotion on the anammox activity, while high-concentration pollutants showed inhibitory effects. The inhibitory threshold concentration of different pollutants varied. The combined effects of multipollutant also attracts more attentions, including synergistic, antagonistic and independent effects. Additionally, remaining problems and research needs are further proposed. This review provides a foundation for future research on the inhibition in anammox process, and promotes the proper operation of anammox processes treating different types of wastewaters.


Assuntos
Compostos de Amônio , Poluentes Ambientais , Anaerobiose , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Águas Residuárias
5.
Sci Total Environ ; 807(Pt 1): 150784, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624282

RESUMO

The effects of multiple antibiotics on the anaerobic ammonia oxidation (anammox) process were investigated. The resistance of the anammox system to high-concentration antibiotics was also demonstrated through gradual acclimation experiments. Inhibition of the anammox process (R1) occurred when the concentrations of erythromycin (ERY), sulfamethoxazole (SMX) and tetracycline (TC) were 0.1, 5.0 and 0.1 mg L-1, respectively. The nitrogen removal efficiency (NRE) of R1 was reduced from 97.2% to 60.7% within 12 days and then recovered to 88.9 ± 9.5% when the nitrogen loading declined from 4.52 ± 0.69 to 2.11 ± 0.58 kg N m-3 d-1. Even when the concentrations of ERY, SMX and TC were as high as 1.0, 15.0 and 1.0 mg L-1, respectively, R1 maintained stable operation. The increases in the abundance of antibiotic resistance genes (ARGs) and in extracellular polymeric substances (EPS) content showed that the anammox process alleviated stress from multiple antibiotics mainly by producing ARGs and secreting EPS. The molecular docking simulation results illustrated the potential binding sites between ammonium transporter and different antibiotics. The upregulation of functional gene expression and the stable abundance of Candidatus Kuenenia in R1 compared with that in the control suggested that the R1 reactor generally maintained more stable long-term operation. This work provides a new understanding of the application of the anammox process to treat wastewater containing multiple antibiotics.


Assuntos
Antibacterianos , Microbiota , Reatores Biológicos , Simulação de Acoplamento Molecular , Nitrogênio , Oxirredução
6.
Bioengineered ; 13(1): 242-252, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34898379

RESUMO

Oxygen therapy and mechanical ventilation are widely used to treat and manage neonatal emergencies in critically ill newborns. However, they are often associated with adverse effects and result in conditions such as chronic lung disease and bronchopulmonary dysplasia. Hence, aclear understanding of the mechanisms underlying hyperoxia-induced lung damage is crucial in order to mitigate the side effects of oxygen-based therapy. Here, we have established an in vitro model of hyperoxia-induced lung damage in type II alveolar epithelial cells (AECIIs) and delineated the molecular basis of oxygen therapy-induced impaired alveolar development. Thus, AECIIs were exposed to a hyperoxic environment and their cell viability, cell cycle progression, apoptosis, mitochondrial integrity and dynamics, and energy metabolism were assessed. The results showed that hyperoxia has no significant effect as an inhibitor of SMAD3 and ERK1/2 in AECIIs, but leads to significant inhibition of cell viability. Further, hyperoxia was found to promote AECII apoptosis and mitochondrial, whereas chemical inhibition of SMAD3 or ERK1/2 further exacerbated the detrimental effects of hyperoxia in AECIIs. Overall, these findings presented herein demonstrate the critical role of SMAD/ERK signaling in the regulation of AECII behavior in varying oxygen environments. Thus, this study offers novel insights for the prevention of neonatal lung dysfunction in premature infants.

7.
Crit Care ; 25(1): 419, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876193

RESUMO

BACKGROUND: The present study was performed to investigate the impacts of type 2 diabetes mellitus (T2DM) on severe community-acquired pneumonia (SCAP) and to develop a novel prediction model for mortality in SCAP patients with T2DM. METHODS: This was a retrospective observational study conducted in consecutive adult patients with SCAP admitted to the intensive care unit (ICU) of West China Hospital, Sichuan University, China, between September 2011 and September 2019. The primary outcome was hospital mortality. A propensity score matching (PSM) analysis model with a 1:2 ratio was used for the comparisons of clinical characteristics and outcomes between T2DM and nondiabetic patients. The independent risk factors were identified via univariate and then multivariable logistic regression analysis and were then used to establish a nomogram. RESULTS: In total, 1262 SCAP patients with T2DM and 2524 matched patients without T2DM were included after PSM. Patients with T2DM had longer ICU length of stay (LOS) (13 vs. 12 days, P = 0.016) and higher 14-day mortality (15% vs. 10.8%, P < 0.001), 30-day mortality (25.7% vs. 22.7%, P = 0.046), ICU mortality (30.8% vs. 26.5%, P = 0.005), and hospital mortality (35.2% vs. 31.0%, P = 0.009) than those without T2DM. In SCAP patients with T2DM, the independent risk factors for hospital mortality were increased numbers of comorbidities and diabetes-related complications; elevated C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), brain natriuretic peptide (BNP) and blood lactate; as well as decreased blood pressure on admission. The nomogram had a C index of 0.907 (95% CI: 0.888, 0.927) in the training set and 0.873 (95% CI: 0.836, 0.911) in the testing set, which was superior to the pneumonia severity index (PSI, AUC: 0.809, 95% CI: 0.785, 0.833). The calibration curve and decision curve analysis (DCA) also demonstrated its accuracy and applicability. CONCLUSIONS: SCAP patients with T2DM had worse clinical outcomes than nondiabetic patients. The nomogram has good predictive performance for hospital mortality and might be generally applied after more external validations.

8.
Front Oncol ; 11: 769305, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888246

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

9.
J Appl Microbiol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850505

RESUMO

AIM: During several local COVID-19 outbreaks in China in 2020, SARS-CoV-2 or its RNA was isolated or detected from frozen food or packages, revealing the lack of effective disinfection measures in the frozen food chain and risk of transmission. We explored the possibility that disinfectant plus antifreeze could be delivered as thermal fog to realize effective disinfection at subzero temperatures. METHODS AND RESULTS: We selected two disinfectant-antifreeze combinations, didecyl dimethyl ammonium bromide (DDAB) - propylene glycol (PPG) and peracetic acid (PAA) - triethylene glycol (TEG) and each combination is used with a custom-optimized thermal fogging machine. The two fogs were tested in -20 °C freezer warehouses for their disinfection efficacy against a coronavirus porcine epidemic diarrhea virus (PEDV) field strain, a swine influenza virus (SIV) field strain, and three indicator bacteria, Escherichia coli, Staphylococcus aureus and Bacillus subtilis endospores. At -20 °C, the DDAB-PPG or PAA-TEG thermal fogs settle within 3.5 to 4.5 hours, and effectively inactivated PEDV with median tissue culture infective dose of 10-3.5 0.1 ml-1 and SIV-H1N1 with hemagglutination titer of 26 ml-1 within 15-60 min. DDAB-PPG could inactivate S. aureus and E. coli vegetative cells (106 cfu ml-1 ) within 15-60 min but not effective on B. subtilis spores, while PAA-TEG could disinfect B. subtilis spores more effectively than for S. aureus and E. coli. CONCLUSIONS: We showed that a practical subzero temperature disinfection technology was effective in killing enveloped viruses and vegetative bacteria or bacterial spores. DDAB-PPG or PAA-TEG thermal fogging may be a practical technology for cold-chain disinfection. SIGNIFICANCE AND IMPACT OF THE STUDY: This subzero temperature disinfection technology could help to meet the urgent public health need of environmental disinfection in frozen food logistics against pandemic and other potential pathogens and to enhance national and international biosecurity.

10.
Ann Bot ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34871356

RESUMO

BACKGROUND AND AIMS: We conducted a comprehensive analysis of the functional traits of leaves (leaflets) of cycads. This study was aimed to clarify the functional divergence between the earlier-origin Cycadaceae and the later-differentiated Zamiaceae, and the differences in trait associations between cycads and angiosperms. METHODS: We selected 20 Cycadaceae species and 21 Zamiaceae species from the same cycad garden in South China, and measured their leaf structure, economic traits, mechanical resistance (Fp), and leaf water potential at the turgor loss point (πtlp). In addition, we compiled a dataset of geographical distribution along with climatic variables for these cycad species, and some leaf traits of tropical-subtropical angiosperm woody species from literature for comparison. KEY RESULTS: The results showed significantly contrasting leaf trait syndromes between the two families, with Zamiaceae species exhibiting thicker leaves, higher carbon investments, and greater Fp than Cycadaceae species. Leaf thickness (LT) and πtlp were correlated with mean climatic variables in their native distribution ranges, indicating their evolutionary adaptation to environmental conditions. Compared to the leaves of angiosperms, the cycad leaves were thicker and tougher, and more tolerant to desiccation. Greater Fp was associated with a higher structural investment in both angiosperms and cycads; however, cycads showed lower Fp at a given leaf mass per area or LT than angiosperms. Enhancement of Fp led to more negative πtlp in angiosperms, but the opposite trend was observed in cycads. CONCLUSIONS: Our results reveal that variations in leaf traits of cycads are mainly influenced by taxonomy and the environment of their native range. We also demonstrate similar leaf functional associations in terms of economics, but different relationships with regard to mechanics and drought tolerance between cycads and angiosperms. This study expands our understanding of the ecological strategies and likely responses of cycads to future climate change.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34872484

RESUMO

BACKGROUND: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. OBJECTIVE: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. METHODS: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. RESULTS: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. CONCLUSION: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34890839

RESUMO

Large-scale genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies have identified multiple noncoding variants associated with genetic diseases by affecting gene expression. However, pinpointing causal variants effectively and efficiently remains a serious challenge. Here, we developed CARMEN, a novel algorithm to identify functional noncoding expression-modulating variants. Multiple evaluations demonstrated CARMEN's superior performance over state-of-the-art tools. Applying CARMEN to GWAS and eQTLs datasets further pinpoints several causal variants other than reported lead single-nucleotide polymorphisms (SNPs). CARMEN scales well with the massive datasets and is available online as a web server at http://carmen.gao-lab.org.

13.
Biomater Sci ; 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34927632

RESUMO

Liver fibrosis therapy remains limited due to the inefficiency of drug delivery and inflammation induced by Kupffer cells. In this study, an exosome-liposome hybrid drug delivery system (LIEV) was developed to increase the efficacy of clodronate (CLD)-inhibition of Kupffer cells and to effectively deliver nintedanib (NIN) to liver fibroblasts to ensure enhanced anti-fibrosis therapy. CLD and NIN co-loaded LIEV (CLD/NIN@LIEV) exerted non-specific inhibition of phagocytosis by Kupffer cells, reduced inflammatory cytokines, and showed homologous homing properties mediated by fibroblast-derived exosomes, thereby achieving superior antifibrotic effects in a CCl4-induced fibrosis mouse model by inhibiting the proliferation of fibroblasts. Furthermore, the inhibited Kupffer cells regenerated within 10 days after dosage withdrawal. Unlike carrier-free NIN treatment, CLD/NIN@LIEV induced a marked decrease in liver enzymes, indicating improved safety and anti-fibrosis efficacy. These results indicate its great potential for treatment with the combined anti-fibrosis agent and Kupffer cell inhibition strategies to enhance the liver fibrosis therapy.

14.
Immunol Lett ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34968530

RESUMO

Chlamydia trachomatis (C. trachomatis) is the most commonly diagnosed bacterial sexually transmitted infection (STI) worldwide. Marrow derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes, which are effective inhibitors for T cell activation. This study explores the role of MDSCs in the immune escape mechanism of C. trachomatis. We established a vaginal infection model of a BALB/c-Chlamydia trachomatis mouse pneumonia strain (MoPn), and compared the percentages of MDSCs, CD4+T, and CD8+T cells in the spleen and cervix of mice before and after infection. The expression levels of arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) in MDSCs, and the expression level of transcriptional co-activator yes-associated protein 1 (YAP1) in the cervix were also compared. The results show that the proportion of MDSCs increases, while the proportion of CD4+T and CD8+T cells decreases after C. trachomatis-infection. The expression of Arg-1 and iNOS in MDSCs and YAP1 in host cells is up-regulated. C. trachomatis growth is inhibited after the inhibition of YAP1 in host cells. The proportion of MDSCs decreases after in vivo pharmacological inhibition of YAP1 in the C. trachomatis-infected mouse model. These results demonstrate, for the first time, the participation of MDSC in the immune escape of C. trachomatis under the action of YAP1.

15.
Acta Pharmacol Sin ; 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34931017

RESUMO

Cholestasis is a major cause of a series of bile flow malfunction-related liver diseases. Pregnane X receptor (PXR) is a key regulator in endo- and xeno-biotics metabolism, which has been considered as a promising therapeutic target for cholestasis. In this study we conducted human PXR (hPXR) agonistic screening using dual-luciferase reporter gene assays, which led to discovering a series of potent hPXR agonists from a small Euphorbiaceae diterpenoid library, containing 35 structurally diverse diterpenoids with eight different skeleton types. The most active compound 6, a lathyrane diterpenoid (5/11/3 ring system), dose-dependently activated hPXR with a high selectivity, and significantly upregulated the expression of hPXR downstream genes CYP3A4 and UGT1A1. In LCA-induced cholestasis mouse model, administration of compound 6 (50 mg· kg-1. d-1, ip) for 7 days significantly suppressed liver necrosis and decreased serum levels of AST, ALT, Tbili, ALP, and TBA, ameliorating LCA-induced cholestatic liver injury. We further revealed that compound 6 exerted its anti-cholestatic efficacy via activation of PXR pathway, accelerating the detoxification of toxic BAs and promoting liver regeneration. These results suggest that lathyrane diterpenoids may serve as a promising scaffold for future development of anti-cholestasis drugs.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34844547

RESUMO

BACKGROUND: Human adipose-derived stem cells (hASCs) play an important role in regenerative medicine. OBJECTIVE: Exploring the mechanism of Rg1 in the promotion of the proliferation and adipogenic differentiation of hASCs is important in regenerative medicine research. METHODS: In order to observe ginsenoside Rg1 in promoting the proliferation and adipogenic differentiation of hASCs, Rg1 medium at different concentrations was established and tested using the cell counting kit-8 (CCK-8) assay, oil red O staining, alizarin red, and alcian blue. Compared to the control, differentially expressed genes (DEGs) were screened via DEG analysis, which were carried out in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To explore the relationship among mRNA, long non-coding RNA (lncRNA) and microRNA (miRNA), we constructed a competing endogenous RNA (ceRNA) network. RESULTS: In this study, Rg1 was observed to promote the proliferation and adipogenic differentiation of hASCs. Additionally, enriched BPs and KEGG pathways may be involved in the promotion process, where FXR1 and Lnc-GAS5-AS1 were found to be regulatory factors. The regulatory network suggested that Rg1 could regulate the adipocytokine signaling pathway and IL-17 signaling pathway via FXR1 and Lnc-GAS5-AS1, which served as the mechanism encompassing the promotion of Rg1 on the proliferation and adipogenic differentiation of hASCs. CONCLUSION: A comprehensive transcriptional regulatory network related to the promotion ability of Rg1 was constructed, revealing mechanisms regarding Rg1's promotion of the proliferation and adipogenic differentiation of hASCs. The present study provides a theoretical basis in optimizing the function of hASCs.

17.
Curr Med Sci ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846699

RESUMO

OBJECTIVE: To investigate the effectiveness of molding custom-made insoles for female patients with foot pain. METHODS: The study included 20 patients whose insoles were prescribed according to biomechanical evaluations and molded by repositioning the subtalar joint in its neutral position using a simple set of tools. Plantar biomechanics were measured under the following conditions: static stand, walking at self-comfortable walking speed (CWS) barefoot, walking in patient owned running shoes, and walking in running shoes plus insoles. Each patient's upper arm isometric muscle strength and subjective feelings before and after the insole intervention were assessed. RESULTS: The molded insoles increased plantar contact area both during static standing and walking at CWS compared to the barefoot condition. The insoles also had more evenly distributed plantar contact area and loading rate, with the changes in the medial arch area being most significant. Moreover, the custom-made insole intervention immediately increased maximum resistance and duration of bilateral upper arms, as well as improved foot comfort, especially at the medial arch area during single leg squat tests. CONCLUSION: Molding custom-made insoles by repositioning the subtalar joint in its neutral position can be accomplished with a simple set of tools, making this method highly applicable for a majority of less developed regions. Insoles molded using this method are effective in immediately improving plantar biomechanics disorders and enhancing isometric upper muscle performance in female patients with foot pain.

18.
Brain Sci ; 11(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34827494

RESUMO

BACKGROUND: The efficacy of interlimb-coordinated training on gait and upper limb functional improvement remains unclear. The latest published randomized controlled trials have supported the potential benefits of interlimb-coordinated training to enhance gait function. Upper limb functional recovery may also benefit from interlimb-coordinated training since most everyday activities require the coordinated use of both hands to complete a task. This study investigates the efficacy of interlimb-coordinated training on gait and upper limb functional recovery over a short-medium term period. METHODS: A total of 226 acute stroke patients will be recruited from four centres over four years. Patients will be randomly allocated to either conventional therapy or conventional therapy plus interlimb-coordinated training. Outcomes will be recorded at baseline, after 2 weeks of intervention, and at 3- and 6-months post-intervention. Gait speed is the primary outcome measure. Secondary outcome measures include Fugl-Meyer Assessment of Motor Recovery, Berg Balance Scale, Timed Up and Go test, Action Research Arm Test, electroencephalography, and magnetic resonance imaging. CONCLUSION: The results of this trial will provide an in-depth understanding of the efficacy of early interlimb-coordinated intervention on gait and upper functional rehabilitation and how it may relate to the neural plasticity process.

19.
Eur J Surg Oncol ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34838392

RESUMO

PURPOSE: Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). PATIENTS AND METHODS: From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). RESULTS: Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P= 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P= 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001). CONCLUSION: Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

20.
Am Heart J ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34785173

RESUMO

BACKGROUND: The efficacy and safety of intravenous infusion of nicorandil during primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) remain uncertain. OBJECTIVES: The primary objective of the CLinical Efficacy and sAfety of intravenous Nicorandil (CLEAN) trial is to evaluate the long-term efficacy and safety of intravenous administration of nicorandil as adjuncts to reperfusion therapy in patients with STEMI undergoing primary PCI. DESIGN: The CLEAN trial is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,500 patients from 40 centers across China. Patients were randomly (1:1) assigned to receive intravenous nicorandil (6 mg as a bolus before reperfusion, followed by 48 hours of continuous infusion at a dose of 6 mg/h after coronary intervention) or the same dose of placebo according to randomization. The primary efficacy outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, target vessel revascularization, and unplanned hospitalization for heart failure within 12 months. The secondary efficacy outcomes included the individual components of the combined efficacy endpoint, incidence of slow coronary flow after PCI, and incidence of complete ST-segment resolution at 2 hours after PCI. The safety outcomes included the incidence of hypotension after drug infusion and other adverse events during medication. SUMMARY: CLEAN will determine whether the addition of intravenous nicorandil as adjuncts to reperfusion therapy reduces the major adverse cardiovascular events in STEMI patients undergoing primary PCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04665648.

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