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1.
Apoptosis ; 29(5-6): 920-933, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38625481

RESUMEN

BACKGROUND: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis. METHODS: A mouse model of SAP was established by the retrograde injection of sodium taurocholate (NaTC) solution in the pancreatic duct. For the hP-MSCs group, hP-MSCs were injected via the tail vein and were monitored in vivo. Transmission electron microscopy (TEM) was used to observe the pyroptosis-associated ultramorphology of acinar cells. Immunofluorescence and Western blotting were subsequently used to assess the localization and expression of pyroptosis-associated proteins in acinar cells. Systemic inflammation and local injury-associated parameters were evaluated. RESULTS: Acinar cell pyroptosis was observed during SAP, and the expression of pyroptosis-associated proteins initially increased, peaked at 24 h, and subsequently showed a decreasing trend. hP-MSCs effectively attenuated systemic inflammation and local injury in the SAP model mice. Importantly, hP-MSCs decreased the expression of pyroptosis-associated proteins and the activity of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in acinar cells. CONCLUSIONS: Our study demonstrates the regularity and important role of acinar cell pyroptosis during SAP. hP-MSCs attenuate inflammation and inhibit acinar cell pyroptosis via suppressing NLRP3 inflammasome activation, thereby exerting a protective effect against SAP.


Asunto(s)
Células Acinares , Modelos Animales de Enfermedad , Inflamasomas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Proteína con Dominio Pirina 3 de la Familia NLR , Pancreatitis , Piroptosis , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ratones , Células Acinares/metabolismo , Células Acinares/patología , Inflamasomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Pancreatitis/metabolismo , Pancreatitis/terapia , Pancreatitis/patología , Humanos , Femenino , Trasplante de Células Madre Mesenquimatosas/métodos , Placenta/metabolismo , Embarazo , Masculino , Ratones Endogámicos C57BL
2.
Behav Brain Res ; 465: 114972, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38552744

RESUMEN

The hippocampal salt-inducible kinase 2 (SIK2)-CREB-regulated transcription co-activator 1 (CRTC1) system has been demonstrated to participate in not only the pathogenesis of depression but also the antidepressant mechanisms of several antidepressant medications including fluoxetine, paroxetine, and mirtazapine. Like fluoxetine, paroxetine is also a widely used selective serotonin (5-HT) reuptake inhibitor (SSRI). Recent studies have indicated that paroxetine also modulates several pharmacological targets other than the 5-HT system. Here, we speculate that paroxetine regulates the hippocampal SIK2-CRTC1 system. Chronic stress models of depression, various behavioral tests, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription PCR, and genetic knockdown were used together in the present study. Our results show that the antidepressant actions of paroxetine in mice models of depression were accompanied by its preventing effects against chronic stress on hippocampal SIK2, CRTC1, and CRTC1-CREB binding. In contrast, genetic knockdown of hippocampal CRTC1 notably abrogated the antidepressant effects of paroxetine in mice. In summary, regulating hippocampal SIK2 and CRTC1 participates in the antidepressant mechanism of paroxetine, extending the knowledge of its pharmacological targets.


Asunto(s)
Fluoxetina , Paroxetina , Animales , Ratones , Antidepresivos/farmacología , Fluoxetina/farmacología , Hipocampo/metabolismo , Paroxetina/farmacología , Serotonina/metabolismo
3.
Front Cardiovasc Med ; 11: 1173080, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38312234

RESUMEN

Aim: Patients with unstable angina pectoris (UAP) usually present anxiety or depression during percutaneous coronary intervention (PCI). This study sought to investigate the instant and short-term effects of acupuncture for anxiety and depression in UAP patients with PCI. Methods: A total of 210 UAP patients who underwent PCI were recruited and randomly assigned (1:1:1) to acupuncture, placebo, or control groups. Enzyme-linked immunosorbent assay was used to detect the levels of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), advanced oxidation protein products (AoPPs), and oxidized low-density lipoprotein (OX-LDL). Serial questionnaires with the Hamilton Anxiety (HAMA) scale and the Pittsburgh Sleep Quality Index were evaluated, and heart rate variability indicators were obtained. Results: Primary end-point: low frequency/high frequency (HF) was lower in the electroacupuncture group (p = 0.014), while standard deviation of normal-to-normal intervals, average standard deviation of normal-to-normal intervals, percentage of successive intervals that differ more than 50 ms, and HF were increased with acupuncture (p = 0.018, p = 0.043, p = 0.016, and p = 0.002, respectively). Secondary end-point: significant improvements in anxiety levels (HAMA) were observed in the three groups (p < 0.001). The fasting insulin and HOMA-IR levels were similar between the control group and the acupuncture group (p = 0.285 and p = 0.165, respectively). The levels of IL-6 and AoPPs differed among the three groups (p = 0.021 and p < 0.001, respectively). However, no significant differences were found in fasting plasma glucose, fasting c-peptide, Hs-CRP, and OX-LDL levels among the three groups (p = 0.585, p = 0.611, p = 0.902, and p = 0.756, respectively). Conclusions: In this study, short-term acupuncture may potentially relieve clinical symptoms before PCI treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03789344).

4.
Bioact Mater ; 34: 221-236, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38235307

RESUMEN

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

5.
BMJ Open ; 13(10): e069742, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880168

RESUMEN

INTRODUCTION: Whether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a randomised controlled trial to investigate the effect of aFXa level monitoring on reducing VTE and to establish a new method for accurately preventing VTE in critically ill patients with low-molecular-weight heparin (LMWH). METHODS AND ANALYSIS: A randomised controlled trial is planned in two centres with a planned sample size of 858 participants. Participants will be randomly assigned to three groups receiving LMWH prophylaxis at a 1:1:1 ratio: in group A, peak aFXa levels will serve as the guide for the LMWH dose; in group B, the trough aFXa levels will serve as the guide for the LMWH dose; and in group C, participants serving as the control group will receive a fixed dose of LMWH. The peak and trough aFXa levels will be monitored after LMWH (enoxaparin, 40 mg, once daily) reaches a steady state for at least 3 days. The monitoring range for group A's aFXa peak value will be 0.3-0.5 IU/mL, between 0.1 and 0.2 IU/mL is the target range for group B's aFXa trough value. In order to reach the peak or trough aFXa levels, groups A and B will be modified in accordance with the monitoring peak and trough aFXa level. The incidence of VTE will serve as the study's primary outcome indicator. An analysis using the intention-to-treat and per-protocol criterion will serve as the main outcome measurement. ETHICS AND DISSEMINATION: The Xuanwu Hospital Ethics Committee of Capital Medical University and Peking University First Hospital Ethics Committee have approved this investigation. It will be released in all available worldwide, open-access, peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05382481.


Asunto(s)
Heparina de Bajo-Peso-Molecular , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapéutico , Enfermedad Crítica/terapia , Enoxaparina/uso terapéutico , Heparina , Heparina de Bajo-Peso-Molecular/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia Venosa/tratamiento farmacológico , Inhibidores del Factor Xa/sangre
6.
Environ Geochem Health ; 45(11): 7829-7839, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37486413

RESUMEN

Environmental persistent free radicals (EPFRs) are receiving growing concerns owing to their potentially adverse impacts on human health. Road dust is one important source of air pollution in most cities and may pose significant health risks. Characteristics of EPFRs in urban road dusts and its formation mechanism(s) are still rarely studied. Here, we evaluated occurrence and size distributions of EPFRs in road dusts from different functional areas of an urban city, and assessed relationship between EPFRs and some transition metals. Strong electron paramagnetic resonance signals of 6.01 × 1016 - 1.3 × 1019 spins/g with the mean g value of 2.0029 ± 0.0019 were observed, indicating that EPFRs consisted of a mixture of C-centered radicals, and C-centered radicals with an adjacent oxygen atom in the urban road dust. Much more EPFRs enriched in finer dust particles. EPFRs significantly correlated with the total Fe, but not water-soluble Fe, suggesting different impacts of water-soluble and insoluble metals in the formation of EFPRs. Health risk assessment results indicated high risk potentials via the ingestion and dermal exposure to EPFRs in road dusts. Future studies are calling to look into formation mechanisms of EPFRs in urban road dusts and to quantitatively evaluate its potential risks on human health.


Asunto(s)
Contaminación del Aire , Elementos de Transición , Humanos , Polvo/análisis , Radicales Libres , Ciudades , Monitoreo del Ambiente
7.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3664-3677, 2023 Jul.
Artículo en Chino | MEDLINE | ID: mdl-37474998

RESUMEN

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).


Asunto(s)
Reserva Ovárica , Deficiencia Yin , Humanos , Deficiencia Yin/tratamiento farmacológico , Deficiencia Yang/tratamiento farmacológico , Síndrome , Proteinuria , Biomarcadores
8.
Medicine (Baltimore) ; 102(24): e33977, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37327264

RESUMEN

RATIONALE: In most cases, uterine rupture occurs during the third trimester of pregnancy or during labor. Even fewer reports have been published about the occurrence of this condition without a gynecologic history of any surgical procedure. Due to their scarcity and variable clinical presentation, early diagnosis of uterine rupture may be difficult, and if the diagnosis is not timely, the condition may be life-threatening. PATIENT CONCERNS: Herein, 3 cases of uterine rupture from a single institution are described. Three patients are at different gestational weeks and all have no history of uterine surgery. They came to the hospital due to acute abdominal pain, which is characterized by severe and persistent pain in the abdomen, with no apparent vaginal bleeding. DIAGNOSES: All 3 patients were diagnosed with uterine rupture during the operation. INTERVENTIONS: One patient underwent uterine repair surgery; while the other 2 underwent subtotal hysterectomy due to persistent bleeding and pathological examination after surgery confirmed placenta implantation. OUTCOMES: The patients recovered well after the operation, and no discomfort occurred in the follow-up. LESSONS: Acute abdominal pain during pregnancy can pose both diagnostic and therapeutic challenges. It is important to consider the possibility of uterine rupture, even in cases where there is no history of prior uterine surgery. The key to the treatment of uterine rupture is to shorten the diagnosis time as much as possible, this potential complication should be carefully monitored for and promptly addressed to ensure the best possible outcomes for both the mother and the developing fetus.


Asunto(s)
Abdomen Agudo , Rotura Uterina , Embarazo , Humanos , Femenino , Rotura Uterina/diagnóstico , Rotura Uterina/etiología , Rotura Uterina/cirugía , Rotura Espontánea/cirugía , Rotura Espontánea/etiología , Útero/cirugía , Histerectomía/efectos adversos , Dolor Abdominal/etiología , Dolor Abdominal/cirugía , Abdomen Agudo/diagnóstico , Abdomen Agudo/etiología , Abdomen Agudo/cirugía
9.
J Infect Public Health ; 16(6): 884-892, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37058869

RESUMEN

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has affected a large number of countries. Informing the public and decision makers of the COVID-19's economic burdens is essential for understanding the real pandemic impact. METHODS: COVID-19 premature mortality and disability impact in Taiwan was analyzed using the Taiwan National Infectious Disease Statistics System (TNIDSS) by estimating the sex/age-specific years of life lost through death (YLLs), the number of years lived with disability (YLDs), and the disability-adjusted life years (DALYs) from January 2020 to November 2021. RESULTS: Taiwan recorded 1004.13 DALYs (95% CI: 1002.75-1005.61) per 100,000 population for COVID-19, with YLLs accounting for 99.5% (95% CI: 99.3%99.6%) of all DALYs, with males suffering more from the disease than females. For population aged ≥ 70 years, the disease burdens of YLDs and YLLs were 0.1% and 99.9%, respectively. Furthermore, we found that duration of disease in critical state contributed 63.9% of the variance in DALY estimations. CONCLUSIONS: The nationwide estimation of DALYs in Taiwan provides insights into the demographic distributions and key epidemiological parameter for DALYs. The essentiality of enforcing protective precautions when needed is also implicated. The higher YLLs percentage in DALYs also revealed the fact of high confirmed death rates in Taiwan. To reduce infection risks and disease, it is crucial to maintain moderate social distancing, border control, hygiene measures, and increase vaccine coverage levels.


Asunto(s)
COVID-19 , Años de Vida Ajustados por Discapacidad , Masculino , Femenino , Humanos , Esperanza de Vida , Años de Vida Ajustados por Calidad de Vida , Método de Montecarlo , Taiwán/epidemiología , COVID-19/epidemiología , Salud Global , Costo de Enfermedad
10.
Front Oncol ; 13: 860711, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36910668

RESUMEN

Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

11.
Int J Ophthalmol ; 16(2): 251-259, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36816210

RESUMEN

AIM: To evaluate the trend of glaucoma internal filtration surgeries for inpatients between 2015 and 2021 at the Eye Hospital of Wenzhou Medical University. METHODS: A review of the medical records of inpatients who had been diagnosed with glaucoma and received anti-glaucoma surgery between January 1, 2015 and December 31, 2021 was conducted. The glaucoma diagnosis in this study included primary open angle glaucoma, primary angle-closure glaucoma, secondary glaucoma, and paediatric glaucoma. The types of surgeries were categorised as internal filtration, external filtration, and cyclodestruction surgery based on the pathway of aqueous humor outflow. The trend of these glaucoma surgeries in the sample of patients with different types of glaucoma was then analysed. RESULTS: The number of patients hospitalised for glaucoma surgery increased yearly, from 752 in 2015 to 1373 in 2021, at the Eye Hospital of Wenzhou Medical University. Regarding the patients diagnosed with primary open angle glaucoma, internal filtration surgery increased from 27.40% of the sample to 54.40% of the sample, while external filtration surgery decreased from 71.50% to 44.20% between 2015 and 2021. For paediatric glaucoma, internal filtration surgery increased from 37.50% in 2015 to 88.20% in 2021. Whilst different types of surgeries were performed on the sample of patients with secondary glaucoma, the proportion of internal filtration surgery also showed an increase from 18.20% in 2015 to 40.90% in 2021. Meanwhile, internal filtration surgery in the patient sample with primary angle-closure glaucoma already accounted for over 70.00% in 2015, and showed a small increase by 2021. CONCLUSION: As surgical technology and surgical experience continue to elevate and improve, the range of glaucoma surgeries are correspondingly evolving. This study find that internal filtration surgeries accounted for an increasing proportion of treatments in the surgical management of glaucoma between 2015 and 2021.

12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-981496

RESUMEN

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

13.
PLoS One ; 17(12): e0278711, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36477459

RESUMEN

Breast cancer is heterogenous in development and cell population with prognoses being highly dependent on numerous factors from driving mutations, biomarker expression and variation in extracellular environment, all affecting response to therapies. Recently, much attention has been given to the role of metabolic alteration in cancers, expanding from the Warburg effect to highlight unique patterns in different cancer cell populations for improving diagnostic and therapeutic approaches. We recently reported on modulation of mannosylation of α-dystroglycan with the metabolite ribitol in breast cancer lines. Here we investigate the effects of pentose sugars ribitol, ribose, and xylitol media supplementation in breast cancer cells by metabolomics and differential gene expression profiling. This combined approach revealed distinctive patterns of alterations in metabolic pathways by ribitol, contrasted with the closely related pentose ribose and pentitol xylitol. Significantly, ribitol supplementation enhances utilization of glucose by glycolysis, whereas ribose improves oxidative phosphorylation and fatty acid synthesis. Ribitol supplementation also increased levels of reduced glutathione (associated with a decrease in oxidative phosphorylation, gluconeogenesis), where ribose supplementation elevated levels of oxidized glutathione (GSSG) indicating an increase in oxidative stress. Treatment with ribitol also enhanced nucleotide biosynthesis. The apparent TCA cycle dysregulation, with distinctive pattern in response to the individual pentitol and pentose, such as ribitol increasing succinate and fumarate while decreasing citrate, demonstrate the adaptive capability of cancer cells to nutritional environment. This metabolic reprogramming presents new avenues for developing targeted therapies to cancers with metabolites, especially in combination with other drug treatments.


Asunto(s)
Neoplasias , Ribitol , Carbono , Ribosa , Redes y Vías Metabólicas , Perfilación de la Expresión Génica
14.
PLoS One ; 17(12): e0278482, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36454905

RESUMEN

Limb Girdle Muscular Dystrophy 2I (LGMDR9) is one of the most common LGMD characterized by defects in glycosylation of α-dystroglycan (matriglycan) resulting from mutations of Fukutin-related protein (FKRP). There is no effective therapy currently available. We recently demonstrated that ribitol supplement increases levels of matriglycan in cells in vitro and in FKRP-P448L (P448L) mutant mouse model through drinking water administration. To be clinically relevant, we have now conducted a dose-escalating efficacy study by gavage in P448L mutant mice. Six months of ribitol treatment daily significantly rescued functions of skeletal, respiratory, and cardiac muscles dose-dependently. This was associated with a dose dependent increase in matriglycan and improvement in muscle pathology with reductions in muscle degeneration, inflammatory infiltration and fibrosis. Importantly, ribitol significantly increased life span and muscle functions of the female animals receiving treatment from 10 months of age. The only observed side effect was gastrointestinal tract bloating with loose stool and this effect is also dose dependent. The results validate the mechanism that ribitol as a pre-substrate of glycosyltransferase is able to compensate for the decreased function of mutant FKRP with restoration of matriglycan expression and provide a guidance for future clinical trial design.


Asunto(s)
Distrofia Muscular de Cinturas , Fenómenos Fisiológicos Musculoesqueléticos , Femenino , Ratones , Animales , Ribitol , Longevidad , Modelos Animales de Enfermedad , Músculos , Pentosiltransferasa/genética
15.
Psychol Res Behav Manag ; 15: 3663-3671, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36544911

RESUMEN

Purpose: To investigate the relationship among patients' stereotypes of doctors, effectiveness of doctors' communication skills evaluated by patients, and patients' trust in doctors. Patients and Methods: A cross-sectional survey with a total of 3289 patients from 103 hospitals in eastern, central and western China was conducted. Results: There were strong correlations among patients' stereotypes, patients' evaluation on doctors' communication skills, and patients' trust (r = 0.50-0.67, p < 0.01 for all). Patients' trust was predicted by patients' stereotypes directly (ß = 0.32, 95% CI: 0.27-0.37) and indirectly (ß = 0.19, 95% CI: 0.16-0.23) through patients' evaluation on doctors' communication skills. Conclusion: Both patients' stereotypes and patients' evaluation on doctors' communication skills have predictive effects on patients' trust. Patients' stereotypes are not only a direct predictor of patients' trust but also an indirect predictor via doctors' communication skills as a mediator. This national survey underlines the significance of patients' stereotypes, and emphasizes the importance of developing doctors' communication skills on patients' trust. In order to build a more trustful doctor-patient relationship, there should be a joint effort at social and individual level to reinforce positive impression and suppress negative stereotypes of doctors. As far as communication skills are concerned, doctors are encouraged to use helpful verbal and nonverbal techniques that benefit their profession impression management.

16.
BMC Palliat Care ; 21(1): 130, 2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35854257

RESUMEN

BACKGROUND AND AIM: Patient deaths are common in the intensive care unit, and a nurse's perception of barriers to and supportive behaviors in end-of-life care varies widely depending upon their cultural background. The aim of this study was to describe the perceptions of intensive care nurses regarding barriers to and supportive behaviors in providing end-of-life care in a Chinese cultural context. METHODS: A cross-sectional survey was conducted among intensive care nurses in 20 intensive care units in 11 general hospitals in central and eastern China. Instruments used in this study were general survey and Beckstrand's questionnaire. Data were collected via online survey platform. Descriptive analysis was used to describe general characteristics of participants and mean and standard deviations of the barriers and supportive behaviors. The mean and standard deviation were used to describe the intensity and frequency of each barrier or supportive behavior following Beckstrand's method to calculate the score of barriers and supportive behaviors. Content analysis was used to analyze the responses to open-ended questions. RESULTS: The response rate was 53% (n = 368/700). Five of the top six barriers related to families and the other was the nurse's lack of time. Supportive behaviors included three related to families and three related to healthcare providers. Nurses in the intensive care unit felt that families should be present at the bedside of a dying patient, there is a need to provide a quiet, independent environment and psychological support should be provided to the patient and family. Nurses believe that if possible, families can be given flexibility to visit dying patients, such as increasing the number of visits, rather than limiting visiting hours altogether. Families need to be given enough time to perform the final rites on the dying patient. Moreover, it is remarkable that nurses' supportive behaviors almost all concern care after death. CONCLUSIONS: According to ICU-nurses family-related factors, such as accompany of the dying patients and acceptence of patient's imminent death, were found the major factors affecting the quality of end-of-life care. These findings identify the most prominent current barriers and supportive behaviors, which may provide a basis for addressing these issues in the future to improve the quality of end-of-life care.


Asunto(s)
Enfermeras y Enfermeros , Cuidado Terminal , Actitud del Personal de Salud , Cuidados Críticos/psicología , Estudios Transversales , Humanos , Unidades de Cuidados Intensivos , Encuestas y Cuestionarios , Cuidado Terminal/métodos
17.
Cell Rep ; 38(12): 110488, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35320730

RESUMEN

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which acts through various mechanisms to reduce ER stress. While the UPR has been well studied for its effects on the ER, its impact on the Golgi is less understood. The Golgi complex receives transport vesicles from the endosome through two types of tethering factors: long coiled-coil golgin and the multisubunit Golgi-associated retrograde protein (GARP) complex. Here, we report that ER stress increases the phosphorylation of golgin Imh1 to maintain the GARP-mediated recycling of the SNAREs Snc1 and Tlg1. We also identify a specific function of the Golgi affected by ER stress and elucidate a homeostatic response to restore this function, which involves both an Ire1-dependent and a MAP kinase Slt2/ERK2-dependent mechanism. Furthermore, our findings advance a general understanding of how two different types of tethers act cooperatively to mediate a transport pathway.


Asunto(s)
Aparato de Golgi , Proteínas SNARE , Endosomas/metabolismo , Aparato de Golgi/metabolismo , Proteínas de la Matriz de Golgi/metabolismo , Fusión de Membrana , Proteínas SNARE/metabolismo
18.
J Plast Reconstr Aesthet Surg ; 75(3): 1094-1099, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34903491

RESUMEN

BACKGROUND: Soft tissue expansion is a common technique for the regeneration of extra skin to repair skin defects. However, some warning signs like skin thinning and telangiectasia are often found during the expansion process, which indicates the skin flaps cannot be further expanded. These signs may result in the suspension of expansion or ultimately jeopardize the final outcome. Fat grafting is used to treat these potential complications and enable the continuation of the expansion procedure in some cases. In this study, we aimed to investigate the efficiency and safety of fat grafting in this process. METHODS: The study was conducted on patients from January 2012 to December 2017 with warning signs of expansion treated with fat grafting (treatment group) or pause expansion (control group). Follow-up data, such as expansion status, dermal thickness, telangiectasia, skin texture using volume assessment, B-mode ultrasound, and semiquantitative scoring, were collected. RESULTS: A total of 67 expanded skin regions with warning signs were enrolled. The expansion fold increased 2.14-fold at 12 weeks after treatment compared with 0.74-fold in control (P=0.02). The semiquantitative score was significant improved at 4 weeks (9.03 ± 0.73 vs. 7.45 ± 0.55; p=0.033). Meanwhile, the skin thickness in the experimental group did not show decreasing trend even in the continued expansion process. CONCLUSIONS: Autologous fat grafting represents an effective and safe method to rescue expanded skin from limited skin regeneration. This technique also represents a valuable tool to increase the chances for further expansion.


Asunto(s)
Colgajos Quirúrgicos , Expansión de Tejido , Pueblo Asiatico , Humanos , Estudios Retrospectivos , Trasplante de Piel , Expansión de Tejido/métodos , Trasplante Autólogo , Resultado del Tratamiento
19.
Age Ageing ; 51(1)2022 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-34850812

RESUMEN

Long-term care (LTC) facilities, in which older adults are institutionalised, have the responsibility to address their residents' rights, privacy and comfort in expressing themselves sexually in an acceptable manner. However, many older adults have reported barriers in their sexual expression, which is often a result of the care staff's attitudes in the facilities. This review synthesis evidence from qualitative studies on the challenges faced by care staff when supporting sexual expression of older residents in LTC facilities. The systematic review and meta-synthesis is reported according to the Enhanced Transparency in Reporting the Synthesis of Qualitative Research Statement. A systematic literature search for peer-reviewed studies was conducted on PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, PsycINFO, CINAHL and ProQuest Theses and Dissertations from inception until December 2020. Sandelowski and Barroso's two-step approach was used to synthesise the evidence. Seventeen qualitative studies published between 2004 and 2020 were included. This review encapsulated the experiences and challenges of 4,387 care staff whose age ranged from 18 to 69 years. Through the meta-synthesis, four themes were identified: varying manifestations of sexual expression and situations encountered, a spectrum of care staff's attitudes, setting boundaries in dementia care and workplace support. Managing sexual expression can be challenging for the care staff, given the complex interplay between personal beliefs, social contexts, moral dilemmas, practical barriers and the lack of clear policies. This review highlighted the need to equip them with knowledge, skills and confidence in managing sexuality in LTC facilities.


Asunto(s)
Personal de Salud , Cuidados a Largo Plazo , Anciano , Humanos , Investigación Cualitativa , Conducta Sexual , Instituciones de Cuidados Especializados de Enfermería
20.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4165-4176, 2021 Dec.
Artículo en Chino | MEDLINE | ID: mdl-34951257

RESUMEN

Understanding the relationship between soil erosion and the changes in landscape patterns is important for guiding the management and development of watersheds. The Nangou watershed in Ansai County, Shaanxi on the Loess Plateau, is an area with the implement of "Grain for Green", ecological agriculture, ecological tourism and the demonstration of science and technology for landscape management. We quantified the spatial and temporal variations of landscape pattern and soil erosion from 1981 to 2018 using the GIS and the universal soil loss equation (USLE). The relationship between the soil erosion modulus and nine landscape pattern indices in three categories was analyzed using the principal component analysis at both plot and landscape levels. The results showed that, among the five landscape types, the spatial and temporal changes of cultivated land and woodland dominated the evolution of landscape patterns, which affected the concentration and distribution degree of the whole watershed. Soil erosion in the Nangou watershed decreased annually, with erosion area, erosion modulus and soil erosion intensity decreasing by 29.7%, 61.2%, and 73.4% from 1981 to 2018, respectively. The variation of cultivated land and forest land areas determined the changes of soil erosion modulus of the whole watershed. The change trend of landscape pattern index was consistent with that of soil erosion. "Grain for Green" Project was the major dri-ving force for the changes in the landscape pattern and for the reduction of soil erosion. The characteristic development and management could weaken soil erosion intensity in parts of the study area. The rational configuration of landscape types could effectively control soil erosion in a watershed. The combination of rational configuration and characteristic management could help achieve the goals for sustainable and high quality development of the watershed.


Asunto(s)
Conservación de los Recursos Naturales , Erosión del Suelo , Agricultura , China , Monitoreo del Ambiente , Suelo
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