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1.
Medicina (Kaunas) ; 59(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36676738

RESUMO

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.


Assuntos
Quimioterapia de Indução , Leucemia Mieloide Aguda , Humanos , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Resultado do Tratamento , Prognóstico , Indução de Remissão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Medicine (Baltimore) ; 101(47): e31877, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451506

RESUMO

BACKGROUND: At present, apart from lung transplantation, no drugs can effectively treat idiopathic pulmonary fibrosis (IPF). Therefore, it is imperative to explore new drugs to control or treat it. Traditional Chinese medicine (TCM) injections have been widely used in the field of IPF, but there is no comparison of their efficacy in the assisted improvement of IPF. Therefore, the purpose of this study is to network meta-analyze the efficacy and safety of 4 kinds of commonly used TCM injections assisted by conventional treatment to improve the disease. METHODS: Used a computer to find the Randomized Controlled Trials (RCTs) from the 8 major databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, China National Knowledge Infrastructure, WanFang Database and VIP Chinese Science). Cochrane's risk assessment tool was used to evaluate the quality of the literature. The Grading of Recommendations Assessment, Development and Evaluation approach served to assess the certainty in the evidence of direct and indirect estimates. Revman5.3 (Review Manager (RevMan) Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.) and stata14.0 (Stata/SE 14.0 for Windows (64-bit). Revision Apr 22, 2015.Copyright 1985-2015 StataCorp LP). were used for Statistical analysis. Registration number: CRD42020220570. RESULTS: After layer-by-layer screening, 20 RCTs were finally included, which include a total of 1363 patients and 4 kinds of RCT of TCM injection (12 studies on Danhong injection, 5 studies on Ligustrazine injection, 2 studies on Huangqi injection and 1 study on Dazhu hongjingtian injection). The results showed: Clinical effective rate: Danhong Injection (Odds ratio [OR] = 3.94, 95% CI [2.34, 6.64], moderate certainty of evidence), Huangqi injection (OR = 3.40, 95% CI [1.38, 8.41], moderate certainty of evidence) and Ligustrazine injection (OR = 2.74, 95% CI [1.62, 4.64], moderate certainty of evidence) combined with conventional treatment had better curative efficacy than that of the conventional treatment group. SUCRA Ranking: Danhong (80.5) > Huangqi (68.5) > Ligustrazine (52.9) > Dazhu hongjingtian (44.3) > Conventional treatment (3.8); Forced Expiratory Volume In 1s/Forced vital capacity%: SUCRA Ranking: Danhong (80.0) > Ligustrazine (62.9) > Conventional treatment (2.1); Carbon monoxide diffusing capacity%: SUCRA Ranking: Ligustrazine (89.9) > Dazhu hongjingtian (63.4) > Danhong (44.9) > Conventional treatment (1.8); Partial pressure of Oxygen: SUCRA Ranking: Dazhu Hongjingtian (87.1) > Danhong (78.8) > Ligustrazine (34.0) > Conventional treatment (0.0); Partial pressure of carbon dioxide: SUCRA Ranking: Danhong (99.3) > Ligustrazine (50.3) > Conventional treatment (0.4). No obvious adverse reactions were found in all studies. CONCLUSION: The four TCM injections combined with conventional treatment can effectively improve the clinical indicators of patients with IPF, and the improvement effect of Danhong injection was more obvious.


Assuntos
Fibrose Pulmonar Idiopática , Medicina Tradicional Chinesa , Humanos , Metanálise em Rede , Injeções
4.
Chem Biodivers ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469428

RESUMO

Piper longum is a well-known spice and traditional medicine. It was revealed to possess anti-diabetic activity, but few information about its active component and underlying mechanism could be available. In this study, retrofractamides A (1) and C (2) isolated from P. longum showed potent inhibitory activity against PTP1B. Therefore, the potential mechanism was predicted by network pharmacology and molecular docking. PI3K/AKT was obtained as the most remarkable pathway against type 2 diabetes mellitus (T2DM), and AKT1 and GSK3ß were yielded as the top two core targets of retrofractamides A (1) and C (2). Molecular docking of compounds with AKT1 and GSK3ß showed strong binding affinity between them. Additionally, cellular experiments with a L6 cell model was conducted to further verify the above predictions. Results indicated that retrofractamides A (1) and C (2) exerted anti-diabetic effect via activating PI3K/AKT pathway, and they promoted glucose consumption, glucose uptake, glycogen synthesis and glycolysis.

5.
Materials (Basel) ; 15(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36499940

RESUMO

It has been recognized that the anisotropic structures dominate the deformation and strength properties of laminated rock masses. The resultant strength anisotropy is strongly affected by confining pressures beyond anisotropic structures. Nevertheless, the effects of confinement are inconsistent among existing experiments and not fully understood. This study focuses on the effects of confining pressure on strength anisotropy through theoretical derivation together with experimental results analysis. The variations in the possibility of anisotropic structural plane dominant failure and strength anisotropy degree under different confining pressures are discussed. The different types of anisotropic structural planes, i.e., the fresh contact discontinuity or soft, thick layer, are found as the key factor resulting in different confinement effects. The strength anisotropy weakens gradually and vanishes eventually as confining stress increases for the anisotropic rock mass with the structural plane of fresh contact discontinuity. On the other hand, the strength does not vanish at very high confining stress and the anisotropic strength difference even rises as confining stress increases for the anisotropic rock mass with the anisotropic structural plane of the soft layer. This study improves the understanding of anisotropic rock mass mechanical behavior, especially at high confining stress, and may promote the development of excavation and supporting techniques for underground projects.

6.
J Tissue Viability ; 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36513539

RESUMO

BACKGROUND: This study aims to discuss the expression of matrix metalloproteinase in wound healing of diabetic foot ulcers and further summarize the strategies of targeted matrix metalloproteinase and its inhibitors in the treatment of diabetic foot ulcers. METHODS: Following PRISMA-SCR guidelines, databases (PubMed, Home-PMC-NCBI, CINAHL, Web of Science) were systematically searched from inception to 19 June 2022. Newcastle-Ottawa Scale (NOS) was used to evaluate the bias risk of the included studies. RESULTS: Eight studies are finally eligible for our systematic review. The combined data analysis of 8 studies showed that there were no significant difference in age(p = 0.110), duration of diabetes(p = 0.197), glycosylated hemoglobin content(p = 0.489), size(p = 0.133) and depth(p>0.05) of initial ulcer between the ulcer wound healing group and the non-healing group. MMP-1, 2, 8, 9, and TIMP-1, 2 affected the healing of DFUs. In the DFUs healing group, the concentrations of MMP (MMP-1, 2, 8, 9) decreased, and the concentration of TIMP-1 increased. CONCLUSION: Our study showed that high levels of MMP-1, 2, 9 delayed the healing of diabetic foot ulcers, and high expression of MMP-8 in tissues improved wound healing. This study also summarized the effective intervention strategies for the treatment of diabetic foot ulcers.

7.
Front Pediatr ; 10: 933266, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582513

RESUMO

Psychosocial and stress-related factors (PSFs), defined as internal or external stimuli that induce biological changes, are potentially modifiable factors and accessible targets for interventions that are associated with adverse pregnancy outcomes (APOs). Although individual APOs have been shown to be connected to PSFs, they are biologically interconnected, relatively infrequent, and therefore challenging to model. In this context, multi-task machine learning (MML) is an ideal tool for exploring the interconnectedness of APOs on the one hand and building on joint combinatorial outcomes to increase predictive power on the other hand. Additionally, by integrating single cell immunological profiling of underlying biological processes, the effects of stress-based therapeutics may be measurable, facilitating the development of precision medicine approaches. Objectives: The primary objectives were to jointly model multiple APOs and their connection to stress early in pregnancy, and to explore the underlying biology to guide development of accessible and measurable interventions. Materials and Methods: In a prospective cohort study, PSFs were assessed during the first trimester with an extensive self-filled questionnaire for 200 women. We used MML to simultaneously model, and predict APOs (severe preeclampsia, superimposed preeclampsia, gestational diabetes and early gestational age) as well as several risk factors (BMI, diabetes, hypertension) for these patients based on PSFs. Strongly interrelated stressors were categorized to identify potential therapeutic targets. Furthermore, for a subset of 14 women, we modeled the connection of PSFs to the maternal immune system to APOs by building corresponding ML models based on an extensive single cell immune dataset generated by mass cytometry time of flight (CyTOF). Results: Jointly modeling APOs in a MML setting significantly increased modeling capabilities and yielded a highly predictive integrated model of APOs underscoring their interconnectedness. Most APOs were associated with mental health, life stress, and perceived health risks. Biologically, stressors were associated with specific immune characteristics revolving around CD4/CD8 T cells. Immune characteristics predicted based on stress were in turn found to be associated with APOs. Conclusions: Elucidating connections among stress, multiple APOs simultaneously, and immune characteristics has the potential to facilitate the implementation of ML-based, individualized, integrative models of pregnancy in clinical decision making. The modifiable nature of stressors may enable the development of accessible interventions, with success tracked through immune characteristics.

8.
HIV Med ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347514

RESUMO

OBJECTIVE: Although excess mortality, especially suicide, is a critical trait in people living with HIV, consensus about gender differences in these areas is lacking. We conducted meta-analyses to examine gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV. METHODS: We systematically searched PubMed and Web of Science for studies written in English. In this review, suicide among people living with HIV includes suicide death, suicidal ideation, and suicide attempts. Studies reporting the suicide prevalence among males and females living with HIV were eligible for inclusion in our review. Odds ratios (ORs) and 95% confidence intervals (CIs) served as the effect size index. Fixed-effects or random-effects meta-analyses were chosen based on the size of the heterogeneity. RESULTS: A total of 27 studies comprising 801 017 participants from 11 countries were included in the meta-analysis. The overall prevalence of suicidal ideation was 18.0% (95% CI 13.3%-22.8%) in males and 20.8% (95% CI 16.4%-25.1%) in females, and there was a statistically significant higher risk of suicidal ideation in females living with HIV (OR 1.30; 95% CI 1.09-1.56; p < 0.05). The overall prevalence of suicide attempts was 16.8% (95% CI 9.0%-24.5%) in males and 24.7% (95% CI 12.4%-37.1%) in females, and there was a statistically significant higher risk of suicide attempts in females living with HIV (OR 1.34; 95% CI 1.02-1.75; p < 0.05). The pooled prevalence of suicide death was 1.2% (95% CI 0.5%-1.9%) among males and 0.2% (95% CI 0.1%-0.3%) among females, and the risk of suicide death between genders was not statistically significant (OR 0.78; 95% CI 0.50-1.24; p = 0.298). CONCLUSIONS: There were gender differences in suicidal ideation and suicide attempts among people living with HIV. Females living with HIV were more likely to experience suicidal ideation and make suicide attempts, but there were no statistically significant gender differences in suicide death. Appropriate initiatives to optimize the recognition, treatment, and management suicide behaviours of males and females living with HIV may narrow this gender gap.

10.
Ecotoxicol Environ Saf ; 248: 114302, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36399995

RESUMO

Recent investigations have revealed that puerarin (PU) alleviates cadmium (Cd)-caused hepatic damage via inhibiting oxidative stress. Mitochondria are dynamic organelles and play a critical part in regulating the occurrence of oxidative stress, but the role of mitochondria in the protection of PU against hepatocellular damage caused by Cd exposure remains unknown. Thus, this study was aimed to clarify this issue using mouse hepatocyte AML-12 cell line. Transmission electron microscopy analysis firstly showed that PU prevents Cd-induced mitochondrial ultrastructure damage. Mitochondrial network image analysis by confocal microscopy revealed that PU exerts the protection against Cd-induced cytotoxicity via restoring mitochondrial network fragmentation. Also, mitochondrial dynamic protein expression profiles showed that enhanced fission protein levels and inhibited fusion protein levels in Cd-treated cells were significantly reversed by PU, suggesting the protective effect of PU against Cd-induced mitochondrial fission. Moreover, changes of intracellular ATP level and protein levels of key regulators involving in mitochondrial biogenesis indicated that Sirtuin-1(Sirt1) pathway may be involved in the protection of Cd-impaired mitochondrial function by PU. Next, Sirt1 protein levels in treated cells were effectively regulated by genetic knockdown or chemical agonist SRT1720. Accordingly, alleviation of Cd-induced mitochondrial fission assays and cell viability by PU was markedly regulated by SRT1720 or Sirt1 knockdown, suggesting the indispensable role of Sirt1 in this process. Collectively, these findings highlight that PU prevents Cd-induced mitochondrial fission to alleviate cytotoxicity via Sirt1-dependent pathway, which provide novel evidences to fully understand the hepatoprotective action of PU against heavy metal toxicity.


Assuntos
Leucemia Mieloide Aguda , Dinâmica Mitocondrial , Animais , Camundongos , Cádmio/toxicidade , Sirtuína 1/genética
11.
Eur Radiol ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36418624

RESUMO

OBJECTIVES: To develop and validate a deep learning (DL) model based on quantitative analysis of contrast-enhanced ultrasound (CEUS) images that predicts early recurrence (ER) after thermal ablation (TA) of colorectal cancer liver metastasis (CRLM). METHODS: Between January 2010 and May 2019, a total of 207 consecutive patients with CRLM with 13,248 slice images at three dynamic phases who received CEUS within 2 weeks before TA were retrospectively enrolled in two centres (153 for the training cohort (TC), 32 for the internal test cohort (ITC), and 22 for the external test cohort (ETC)). Clinical and CEUS data were used to develop and validate the clinical model, DL model, and DL combining with clinical (DL-C) model to predict ER after TA. The performance of these models was compared by the receiver operating characteristic curve (ROC) with the DeLong test. RESULTS: After a median follow-up of 56 months, 49% (99/207) of patients experienced ER. Three key clinical features (preoperative chemotherapy (PC), lymph node metastasis of the primary colorectal cancer (LMPCC), and T stage) were used to develop the clinical model. The DL model yielded better performance than the clinical model in the ETC (AUC: 0.67 for the clinical model, 0.76 for the DL model). The DL-C model significantly outperformed the clinical model and DL model (AUC: 0.78 for the DL-C model in the ETC; both, p < 0.001). CONCLUSIONS: The model based on CEUS can achieve satisfactory prediction and assist physicians during the therapeutic decision-making process in clinical practice. KEY POINTS: • This is an exploratory study in which ablation-related contrast-enhanced ultrasound (CEUS) data from consecutive patients with colorectal cancer liver metastasis (CRLM) were collected simultaneously at multiple institutions. • The deep learning combining with clinical (DL-C) model provided desirable performance for the prediction of early recurrence (ER) after thermal ablation (TA). • The DL-C model based on CEUS provides guidance for TA indication selection and making therapeutic decisions.

13.
Radiat Res ; 198(5): 488-507, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36351324

RESUMO

The intestinal compensatory proliferative potential is a key influencing factor for susceptibility to radiation-induced intestinal injury. Studies indicated that the carnitine palmitoyltransferase 1 (CPT1) mediated fatty acid ß-oxidation (FAO) plays a crucial role in promoting the survival and proliferation of tumor cells. Here, we aimed to explore the effect of 60Co gamma rays on CPT1 mediated FAO in the radiation-induced intestinal injury models, and investigate the role of CPT1 mediated FAO in the survival and proliferation of intestinal cells after irradiation. We detected the changed of FAO in the plasma and small intestine of Sprague Dawley (SD) rats at 24 h after 60Co gamma irradiation (0, 5 and 10 Gy), using target metabolomics, qRT-PCR, immunohistochemistry (IHC), western blot (WB) and related enzymatic activity kits. We then analyzed the FAO changes in radiation-induced intestinal injury models regardless of ex vivo (mice enteroids), or in vitro (normal human intestinal epithelial cell lines, HIEC-6). HIEC-6 cells were transduced with lentivirus vector GV392 and treated with puromycin for obtaining CPT1 stable knockout cell lines, named CPT1 KO. CPT1 enzymatic activities of HIEC-6 cells and mice enteroids were also inhibited by pharmaceutical inhibitor ST1326 and Etomoxir (ETO), to study the function of CPT1 in the survival and proliferation of HIEC-6 cells after 60Co gamma irradiation. We found that CPT1 mediated FAO was altered in the small intestine of the SD rats after irradiation, especially, the expression level and enzymatic activity of CPT1 were significantly increased. Similarly, the expression levels of CPT1 were also remarkably enhanced in mice enteroids and HIEC-6 cells after irradiation. CPT1 inhibition decreased the proliferation of the HIEC-6 cells and mice enteroids after irradiation partially by reducing the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways activation, CPT1 inhibition also reduced the proliferation of mice enteroids after irradiation partially by down-regulating the Wnt/ß-catenin signaling activity. In conclusion, our study indicated that CPT1 plays a crucial role in promoting intestinal epithelial cell proliferation after irradiation.


Assuntos
Carnitina O-Palmitoiltransferase , Sistema de Sinalização das MAP Quinases , Animais , Humanos , Camundongos , Ratos , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Proliferação de Células , Raios gama , Ratos Sprague-Dawley , Oxirredução
16.
J Environ Public Health ; 2022: 3938915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238825

RESUMO

In the 21st century with the popularization of digital technology, as a printmaking born out of industrial printing, it has undergone a revolutionary evolution. Silkscreen printmaking is a type of print with high technology content, strong dependence on media, and no traditional load. Thirty years ago, as soon as silkscreen prints settled in China, they began artistic exploration and experimentation with a brand-new attitude. Several generations of screen print workers have achieved it, expanded it, and made it independent in the fusion of modern language methods and oriental cultural spirit, and in the exploration of screen vocabulary, characteristics and character, it has an independent status and ranks among the international elite qualifications. This paper analyzes the root problems of high-tech printmaking tools, materials, technical principles, and causes of aesthetics. Starting from the background of the concept of green development, it expounds its related concepts, analyzes the theoretical origin of green development, and clearly recognizes the high-tech. The limitation of printmaking in the development space-that is, the expression language of digital plate making, is relatively correct in theory, so as to carry out step-by-step exploration and practice.


Assuntos
Indústrias , China , Estudos de Viabilidade , Humanos
17.
MedComm (2020) ; 3(4): e181, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36254250

RESUMO

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

18.
Proc Natl Acad Sci U S A ; 119(42): e2202133119, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36215479

RESUMO

Unfolded protein response (UPR) is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. ER proteostasis is essential to adapt to cell proliferation and regeneration in development and tumorigenesis, but mechanisms linking UPR, growth control, and cancer progression remain unclear. Here, we report that the Ire1/Xbp1s pathway has surprisingly oncogenic and tumor-suppressive roles in a context-dependent manner. Activation of Ire1/Xbp1s up-regulates their downstream target Bip, which sequesters Yorkie (Yki), a Hippo pathway transducer, in the cytoplasm to restrict Yki transcriptional output. This regulation provides an endogenous defensive mechanism in organ size control, intestinal homeostasis, and regeneration. Unexpectedly, Xbp1 ablation promotes tumor overgrowth but suppresses invasiveness in a Drosophila cancer model. Mechanistically, hyperactivated Ire1/Xbp1s signaling in turn induces JNK-dependent developmental and oncogenic cell migration and epithelial-mesenchymal transition (EMT) via repression of Yki. In humans, a negative correlation between XBP1 and YAP (Yki ortholog) target gene expression specifically exists in triple-negative breast cancers (TNBCs), and those with high XBP1 or HSPA5 (Bip ortholog) expression have better clinical outcomes. In human TNBC cell lines and xenograft models, ectopic XBP1s or HSPA5 expression alleviates tumor growth but aggravates cell migration and invasion. These findings uncover a conserved crosstalk between the Ire1/Xbp1s and Hippo signaling pathways under physiological settings, as well as a crucial role of Bip-Yki interaction in tumorigenesis that is shared from Drosophila to humans.


Assuntos
Proteínas de Drosophila , Proteínas Serina-Treonina Quinases , Animais , Carcinogênese/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Retículo Endoplasmático/metabolismo , Endorribonucleases , Via de Sinalização Hippo , Humanos , Proteínas Serina-Treonina Quinases/genética , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-36183274

RESUMO

INTRODUCTION: Posterolateral approach has been advocated for the treatment of ankle fractures involving the posterior malleolus and satisfactory results were demonstrated in several studies. The Bartonicek classification based on 3-dimensional CT scanning was commonly used for treatment recommendation of posterior malleolar fracture (PMF). The aim of this retrospective study was to evaluate the clinical effect of the posterolateral approach for the treatment of PMF and present outcomes of patients with different types of Bartonicek classification. METHOD: We retrospectively reviewed the clinical outcomes of 72 patients with ankle fractures involving posterior malleolus (PM) from January 2016 to December 2018. Posterior malleolus fractures (PMFs) were all directly reduced and fixed by a posterolateral approach using lag screws and/or buttress plates. AOFAS score and VAS pain score were used as the primary functional outcome measures. The radiographic evaluation included the quality of the reduction and Kellgren-Lawrence (KL) osteoarthritis classification. According to the CT-based Bartonicek classification, all patients were classified into three groups: 42 type II, 18 type III and 12 type IV. Bartonicek type II patients were further divided into subtype IIa 19 cases, subtype IIb 16 cases and subtype IIc 7 cases. The radiological and functional outcomes were analyzed among different types and subtypes of Bartonicek classification. RESULTS: Sixty-eight patients (94.5%) achieved good or excellent reduction of PMF after surgery. The mean AOFAS score was 81.35 ± 6.15 at 6 months and 90.56 ± 4.98 at the final follow-up, respectively. The VAS score was 6.62 ± 1.03 one week after surgery, and 1.20 ± 0.92 at the final follow-up. Radiological evaluation at the final follow-up showed that primary bone union was achieved in all patients and 65 patients (88.9%) got no (KL grade 0) or just doubtable (KL grade 1) post-traumatic osteoarthritis. AOFAS scores decreased significantly with the severity of Bartonicek classification at 6 month (p < 0.001) and final follow-up (p < 0.05), while there was no statistical difference of VAS pain score among different types of Bartonicek classification. Reduction quality and the presence of osteoarthritis was not correlated to Bartonicek classification either. Besides, AOFAS scores at the final follow-up were statistically different among three subtypes of Bartonicek type II fractures (p < 0.05), and Bartonicek subtype IIa fractures had the highest AOFAS scores as 93 ± 4.99. Presence and severity of osteoarthritis was lower in patients with subtype IIa PMF compared to other subtype groups, this finding was statistically significant (p < 0.05). CONCLUSION: The posterolateral approach could achieve good clinical outcomes in the treatment of posterior malleolus fracture. Patients with a Bartonicek type II fracture had a better functional outcome measured by the AOFAS score compared to other types. Bartonicek type IIa fractures got a higher AOFAS score and a lower incidence of osteoarthritis at the final follow-up than the other two subtypes. Classification of PMFs according to the Bartonicek classification was reliable.

20.
Front Plant Sci ; 13: 998985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36226286

RESUMO

Glycosylation was catalyzed by UDP-glycosyltransferase (UGT) and was important for enriching diversity of flavonoids. Chinese bayberry (Morella rubra) has significant nutritional and medical values because of diverse natural flavonoid glycosides. However, information of UGT gene family was quite limited in M. rubra. In the present study, a total of 152 MrUGT genes clustered into 13 groups were identified in M. rubra genome. Among them, 139 MrUGT genes were marked on eight chromosomes and 13 members located on unmapped scaffolds. Gene duplication analysis indicated that expansion of MrUGT gene family was mainly forced by tandem and proximal duplication events. Gene expression patterns in different tissues and under UV-B treatment were analyzed by transcriptome. Cyanidin 3-O-glucoside (C3Glc) and quercetin 3-O-glucoside (Q3Glc) were two main flavonoid glucosides accumulated in M. rubra. UV-B treatment significantly induced C3Glc and Q3Glc accumulation in fruit. Based on comprehensively analysis of transcriptomic data and phylogenetic homology together with flavonoid accumulation patterns, MrUFGT (MrUGT78A26) and MrUGT72B67 were identified as UDP-glucosyltransferases. MrUFGT was mainly involved in C3Glc and Q3Glc accumulation in fruit, while MrUGT72B67 was mainly involved in Q3Glc accumulation in leaves and flowers. Gln375 and Gln391 were identified as important amino acids for glucosyl transfer activity of MrUFGT and MrUGT72B67 by site-directed mutagenesis, respectively. Transient expression in Nicotiana benthamiana tested the function of MrUFGT and MrUGT72B67 as glucosyltransferases. The present study provided valuable source for identification of functional UGTs involved in secondary metabolites biosynthesis in M. rubra.

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