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1.
J Thorac Dis ; 16(3): 1777-1786, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38617773

RESUMO

Background: Two-lung ventilation (TLV) with artificial carbon dioxide (CO2) pneumothorax is used during the thoracoscopic phase of minimally invasive esophagectomy (MIE). However, the impact of TLV with artificial pneumothorax on postoperative pulmonary complications (PPCs) after MIE is unclear. This study aimed to compare the incidence of early PPCs between TLV with CO2 pneumothorax and one-lung ventilation (OLV) with bronchial blockade in patients undergoing MIE. Methods: Five hundred ninety-three patients with esophageal cancer who underwent elective MIE with two-field lymph node dissection were analyzed. Patients in the TLV group were intubated using a single-lumen endotracheal tube and underwent surgery using TLV with artificial CO2 pneumothorax. Patients in the OLV group underwent surgery using OLV with a bronchial blocker. Patient characteristics and intraoperative and PPC data were collected and analyzed. Propensity score matching (PSM) was performed to reduce confounding bias. Results: The TLV and OLV group comprised 513 and 80 patients, respectively. PSM matched 197 TLV group and 73 OLV group patients. Incidence of pneumonia within the first 3 days of surgery was higher in the TLV group (11.7% vs. 4.1%) but the difference was not significant (P=0.06). The incidence of infiltrates on chest radiography was 36.0% in the TLV group and 28.8% in the OLV group (P=0.26). Incidence of other major PPCs requiring treatment and major non-pulmonary postoperative complications did not significantly differ between the groups. Length of hospital stay was significantly longer in the TLV group (13.0 vs. 11.0 days; P=0.03). Conclusions: Compared with OLV with bronchial blockade, TLV with CO2 pneumothorax did not reduce the incidence of early PPCs after MIE.

2.
Med ; 5(4): 278-280, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38614071

RESUMO

Immunotherapy has enhanced breast cancer outcomes, but optimizing combination therapies is crucial. Integrating additional treatment modalities, like physical therapies, holds promise for optimizing efficacy. Pan et al. recently reported that combining preoperative immunotherapy with microwave ablation is safe and feasible in early-stage breast cancer, effectively sensitizing peripheral CD8+ T cells.1.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Micro-Ondas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Combinada
3.
Environ Int ; 186: 108626, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38626493

RESUMO

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 µg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 µg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.

4.
PeerJ ; 12: e17173, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560460

RESUMO

Background: Table tennis is an asymmetric sport involving the powerful forward swing of the upper limbs depends on the solid support of the lower limbs. The foot drive really affects the weight balance and stroke accuracy even though the distance and momentum of the lower limb displacement are limited within a limited range. Given that previous research on table tennis has typically focused on the footwork and stroke performance of professional players, the study aimed to investigate the daily static and dynamic plantar load distribution as well as the centers of gravity balance and rearfoot posture among Taiwanese college elite table tennis players. Methods: This is a cross-sectional study of 70 elite male table tennis players (age: 20.0 ± 0.9 years; height: 173.4 ± 5.1 cm, weight: 67.6 ± 5.3 kg, experience: 10.0 ± 1.6 years) and 77 amateur table tennis players of the same gender (age: 20.1 ± 0.8 years, height: 167.4 ± 4.4 cm, weight: 64.3 ± 4.0 kg, experience: 4.4 ± 1.2 years) from Taiwanese universities. The JC Mat optical plantar pressure analyzer was applied to determine the plantar load distribution along with arch index (AI) and centers of gravity balance. Assessment of rearfoot postural alignment was mainly used to contrast the performance of the centers of gravity balance. Results: The static arch indices of both feet in the elite group were symmetrical and considered normal arches (AI: 0.22 ± 0.07) during their non-training and non-competition daily lives. Their static plantar loads were symmetrically concentrated on the bipedal lateral metatarsals (P < 0.05) as well as shifted to the medial and lateral heels (P < 0.05) and the lateral metatarsals (P < 0.05) during the walking midstance phase. Additionally, the plantar loads were mainly applied to the bipedal medial (P < 0.01) and lateral heels (P < 0.05) during the transitional changes between both states. Elite athletes had symmetrical and evenly distributed centers of gravity on both feet (left: 50.03 ± 4.47%; right: 49.97 ± 4.47%) when standing statically, along with symmetrical rearfoot angles and neutral position of the subtalar joint (left: 2.73 ± 2.30°; right: 2.70 ± 2.32°) even though they were statistically lower than those of the amateur athletes (P < 0.05). Conclusions: The daily static and dynamic foot patterns of Taiwanese college elite table tennis players were characterized by plantar load distribution on the lateral metatarsals and the entire calcaneus along with balanced centers of gravity and normal rearfoot posture. This foot and posture layout outlines the excellent athletic performance of the foot and ankle in professional athletes. Portions of this text were previously published as part of a preprint (https://doi.org/10.21203/rs.3.rs-2993403/v1).


Assuntos
Acidente Vascular Cerebral , Tênis , Humanos , Masculino , Adulto Jovem , Adulto , Estudos Transversais , Universidades , Postura
5.
Prev Med Rep ; 41: 102697, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38560595

RESUMO

Background: Healthy lifestyles are effective means to reduce major cardiovascular events. However, little is known about the association of healthy lifestyles with development of carotid atherosclerosis at the early stage of cardiovascular diseases (CVDs). Methods: We enrolled participants from Fujian province in the China PEACE MPP project. We calculated a healthy lifestyle score by adherence to non-smoking, sufficient physical activity, healthy diet and healthy body mass index. Cox proportional hazards regression models and restricted cubic splines (RCS) were used to explore the association between the healthy lifestyles and rapid progression of carotid plaque. Results: 8379 participants were included (mean age: 60.6 ± 8.3 years, 54.6 % female), with a median follow-up of 1.2 years (inter quartile range: 1.0-1.6). RCS showed a significant inverse association between the healthy lifestyle score and progression of carotid plaque. Participants with "intermediate" (HR: 0.72 [95 % confidence interval (CI): 0.65-0.80]) or "ideal" (HR: 0.68 [0.59-0.78]) adherence to healthy lifestyles had a lower risk of progression of carotid plaque compared to those with "poor" adherence. Age, sex, occupation, income, residence type and metabolic status were significant factors influencing the relationship. Farmers benefited more in non-smoking and sufficient physical activity compared to non-farmers, and participants with lower income or without dyslipidaemia benefited more in sufficient physical activity and healthy diet compared to their counterparts (p-for-interaction < 0.05). Conclusions: Healthy lifestyles were associated with lower risk of progression of carotid plaque in populations with atherosclerosis. Promotion of healthy lifestyles from the early stage of carotid atherosclerosis could reduce the burden of CVDs in China.

6.
Am J Transl Res ; 16(3): 768-780, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586086

RESUMO

BACKGROUND: Serum phosphate levels remain insufficiently controlled in chronic kidney disease (CKD) patients, and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate cotransporter type 2b (NPT2b) holds promise as one such strategy. METHODS: The in vitro cellular potency of DZ1462 was evaluated using a radioactive Pi uptake assay on stable Chinese hamster ovary (CHO) cell clones transfected with human NPT2b (hNPT2b) or rat NPT2b (rNPT2b). The ability of DZ1462 to inhibit phosphate absorption was studied in vivo in an acute model after oral bolus challenge with 33PO4 and in an adenine-induced chronic hyperphosphatemia rat model. PK and minitox was also evaluated. RESULTS: The cellular assays with the hNPT2b-CHO and rNPT2b-CHO clones showed that DZ1462 significantly and potently inhibited phosphate uptake. In vivo, in a chronic Pi-fed rat model, DZ1462 effectively inhibited intestinal Pi uptake. In a hyperphosphatemia rat model, DZ1462 significantly inhibited Pi uptake, and DZ1462 in combination with sevelamer had a synergistic effect. The pharmacokinetics (PK) study confirmed that DZ1462 is a gastrointestinal (GI)-restricted compound that can remain in the intestine for a sufficient duration. In addition, DZ1462 also reduced cardiovascular events and ameliorated osteoporosis in a CKD animal model. CONCLUSIONS: This study revealed that a GI-restricted NPT2b inhibitor DZ1462 potently inhibits NPT2b in vitro and blocks intestinal phosphate uptake in multiple animal models with potential to reduce various cardiovascular events in CKD models. Therefore, DZ1462 may be useful to treat renal disease patients who have shown an unsatisfactory response to phosphate binders.

7.
Commun Biol ; 7(1): 429, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594496

RESUMO

The study aims to explore the effect of PPARγ signaling on ferroptosis and preeclampsia (PE) development. Serum and placental tissue are collected from healthy subjects and PE patients. The PPARγ and Nrf2 decreases in the PE. Rosiglitazone intervention reverses hypoxia-induced trophoblast ferroptosis and decreases lipid synthesis by regulating Nfr2 and SREBP1. Compared to the Hypoxia group, the migratory and invasive abilities enhance after rosiglitazone and ferr1 treatment. Rosiglitazone reduces the effect of hypoxia and erastin. The si-Nrf2 treatment attenuats the effects of rosiglitazone on proliferation, migration, and invasion. The si-Nrf2 does not affect SREBP1 expression. PPARγ agonists alleviates ferroptosis in the placenta of the PE rats. The study confirms that PPARγ signaling and ferroptosis-related indicators were dysregulated in PE. PPARγ/Nrf2 signaling affects ferroptosis by regulating lipid oxidation rather than SREBP1-mediated lipid synthesis. In conclusion, our study find that PPARγ can alleviate PE development by regulating lipid oxidation and ferroptosis.


Assuntos
Ferroptose , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Ratos , Animais , Rosiglitazona/farmacologia , Rosiglitazona/metabolismo , PPAR gama/metabolismo , Metabolismo dos Lipídeos , Placenta/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hipóxia/metabolismo , Lipídeos
8.
Braz J Cardiovasc Surg ; 39(3): e20220424, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629954

RESUMO

OBJECTIVE: To investigate the effect of improving the operative field and postoperative atelectasis of single-lung ventilation (SLV) in the surgical repair of coarctation of the aorta (CoA) in infants without the use of cardiopulmonary bypass (CPB). METHODS: This was a retrospective cohort study. The clinical data of 28 infants (aged 1 to 4 months, weighing between 4.2 and 6 kg) who underwent surgical repair of CoA without CPB from January 2019 to May 2022 were analyzed. Fourteen infants received SLV with a bronchial blocker (Group S), and the other 14 infants received routine endotracheal intubation and bilateral lung ventilation (Group R). RESULTS: In comparison to Group R, Group S exhibited improved exposure of the operative field, a lower postoperative atelectasis score (P<0.001), reduced prevalence of hypoxemia (P=0.01), and shorter durations of operation, mechanical ventilation, and ICU stay (P=0.01, P<0.001, P=0.03). There was no difference in preoperative information or perioperative respiratory and circulatory indicators before SLV, 10 minutes after SLV, and 10 minutes after the end of SLV between the two groups (P>0.05). Intraoperative bleeding, intraoperative positive end-expiratory pressure (PEEP), and systolic pressure gradient across the coarctation after operation were also not different between the two groups (P>0.05). CONCLUSION: This study demonstrates that employing SLV with a bronchial blocker is consistent with enhanced operative field, reduced operation duration, lower prevalence of intraoperative hypoxemia, and fewer postoperative complications during the surgical repair of CoA in infants without the use of CPB.


Assuntos
Coartação Aórtica , Ventilação Monopulmonar , Atelectasia Pulmonar , Lactente , Humanos , Ponte Cardiopulmonar , Coartação Aórtica/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias , Hipóxia , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/prevenção & controle
9.
Artigo em Inglês | MEDLINE | ID: mdl-38643424

RESUMO

PURPOSE: To evaluate and compare the effect of decentration and tilt on the optical quality of monofocal and trifocal intraocular lenses (IOL). METHODS: Optical quality of a monofocal IOL (AcrySof IQ SN60WF; Alcon Laboratories, Inc., USA) and a trifocal IOL (AcrySof IQ PanOptix; Alcon Laboratories, Inc., USA) was assessed using an in vitro optical bench (OptiSpheric IOL R&D; Trioptics GmbH, Germany). At apertures of 3.0 mm and 4.5 mm, modulation transfer function (MTF) at spatial frequency of 50 lp/mm, MTF curve and the United States Air Force (USAF) resolution test chart of the two IOLs were measured and compared at their focus with different degrees of decentration and tilt. Optical quality at infinity, 60 cm and 40 cm and the through-focus MTF curves were compared when the two IOLs were centered at apertures of 3.0 mm and 4.5 mm. Spectral transmittance of the two IOLs was measured by the UV-visible spectrophotometer (UV 3300 PC; MAPADA, China). RESULTS: The SN60WF and the PanOptix filtered blue light from 400 to 500 nm. Both IOLs at the far focus and the PanOptix at the intermediate focus showed a decrease in optical quality with increasing decentration and tilt. The PanOptix demonstrated enhanced optical quality compared to the previous gradient at the near focus at a decentration range of 0.3-0.7 mm with a 3.0 mm aperture, and 0.5 mm with a 4.5 mm aperture, whereas other conditions exhibited diminished optical quality with increasing decentration and tilt at the focus of both IOLs. When the two IOLs were centered, the SN60WF had better optical quality at infinity, while the PanOptix had better optical quality at 60 cm and 40 cm defocus. The optical quality of the SN60WF exceeded that of the PanOptix at far focus, with a 3 mm aperture decentration up to 0.7 mm and a 4.5 mm aperture decentration up to 0.3 mm; this observation held true for all tilts, irrespective of aperture size. As both decentration and tilt increased, the optical quality of the SN60WF deteriorated more rapidly than that of the PanOptix at the far focal point. CONCLUSIONS: The SN60WF showed a decrease in optical quality with increasing decentration and tilt. Optical quality of the PanOptix at the near focus increased in some decentration conditions and decreased in some conditions, while it showed a decrease at the other focuses with increasing decentration. While tilt only had a negative effect on optical quality. When both IOLs were centered, the PanOptix provided a wider range of vision, while the SN60WF provided better far distance vision. At the far focus, the SN60WF has better resistance to tilt than the PanOptix, but the optical quality degrades more quickly when decentered and tilted.

10.
Environ Pollut ; : 123995, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636840

RESUMO

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n=282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80% of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95%CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95%CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

11.
Int J Orthop Trauma Nurs ; 54: 101095, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38599150

RESUMO

AIMS: In the early stage, we developed an intelligent measurement APP for diabetic foot ulcers, named Diabetic Foot Smart APP. This study aimed to validate the APP in the measurement of ulcer area for diabetic foot ulcer (DFU). METHODS: We selected 150 DFU images to measure the ulcer areas using three assessment tools: the Smart APP software package, the ruler method, and the gold standard Image J software, and compared the measurement results and measurement time of the three tools. The intra-rater and inter-rater reliability were described by Pearson correlation coefficient, intra-group correlation coefficient, and coefficient of variation. RESULTS: The Image J software showed a median ulcer area of 4.02 cm2, with a mean measurement time of 66.37 ± 7.95 s. The ruler method showed a median ulcer area of 5.14 cm2, with a mean measurement time of 171.47 ± 46.43 s. The APP software showed a median ulcer area of 3.70 cm2, with a mean measurement time of 38.25 ± 6.81 s. There were significant differences between the ruler method and the golden standard Image J software (Z = -4.123, p < 0.05), but no significant difference between the APP software and the Image J software (Z = 1.103, p > 0.05). The APP software also showed good inter-rater reliability and intra-rater reliability, with both reaching 0.99. CONCLUSION: The Diabetic Foot Smart APP is a fast and reliable measurement tool with high measurement accuracy that can be easily used in clinical practice for the measurement of ulcer areas of DFU. TRIAL REGISTRATION: Chinese clinical trial registration number: ChiCTR2100047210.

12.
Medicine (Baltimore) ; 103(14): e37681, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579048

RESUMO

OBJECTIVE: To evaluate the relationship between CXCL12/CXCR4 and the progress, prognosis of esophageal squamous cell carcinoma (ESCC), providing evidence for potential early diagnosis, clinical treatment, prognosis evaluation, and therapeutic target of ESCC. METHODS: Databases of PubMed, the Cochrane Library, Embase, and Web of Science were searched for the relationship between CXCL12/CXCR4 and clinicopathological characteristics and survival time of ESCC. Stata16.0 software was used to conduct meta-analysis. RESULTS: A total of 10 studies involving 1216 cases of patients with ESCC were included in our study. The results indicated that high-level expression of CXCR4 was significantly correlated with tumor differentiation [OR = 0.69, 95% confidence interval (CI): (0.50, 0.97)], tumor infiltration [OR = 0.39, 95% CI: (0.25, 0.61)], lymph node metastasis [OR = 0.36, 95% CI: (0.21, 0.61)], clinical stage [OR = 0.33, 95% CI: (0.24, 0.45)] of ESCC. The expression of CXCR4 was also significantly correlated with OS [HR = 2.00, 95% CI: (1.63, 2.45)] and disease-free survival [HR = 1.76, 95% CI: (1.44, 2.15)] in patients of ESCC after surgical resection. No significant relationship was observed between the expression of CXCL12 and the clinicopathological characteristics of ESCC. CONCLUSION: CXCR4 might be a potential biomarker for the progress and prognosis evaluation, and therapeutic target for ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Prognóstico , Biomarcadores Tumorais/metabolismo , Receptores CXCR4
13.
Heart Fail Rev ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498262

RESUMO

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

14.
Inorg Chem ; 63(11): 5151-5157, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38446757

RESUMO

Adsorption separation of the Xe/Kr mixture remains a tough issue since Xe and Kr have an inert nature and similar sizes. Here we present a chlorinated metal-organic framework (MOF) [JXNU-19(Cl)] and its nonchlorinated analogue (JXNU-19) for Xe/Kr separation. The two isostructural MOFs constructed from the heptanuclear cobalt-hydroxyl clusters bridged by organic ligands are three-dimensional structures. Detailed contrast of the Xe/Kr adsorption separation properties of the MOF shows that significantly enhanced Xe uptakes and Xe/Kr adsorption selectivity (17.1) are observed for JXNU-19 as compared to JXNU-19(Cl). The main binding sites for Xe in the MOF revealed by computational simulations are far away from the chlorine sites, suggesting that the introduction of the chlorine groups results in the unfavorable Xe adsorption for JXNU-19(Cl). The optimal pores, high surface area, and multiple strong Xe-framework interactions facilitate the effective Xe/Kr separation for JXNU-19.

15.
J Virol ; 98(4): e0125823, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38546211

RESUMO

Dengue fever, an infectious disease prevalent in subtropical and tropical regions, currently lacks effective small-molecule drugs as treatment. In this study, we used a fluorescence peptide cleavage assay to screen seven compounds to assess their inhibition of the dengue virus (DENV) NS2B-NS3 protease. DV-B-120 demonstrated superior inhibition of NS2B-NS3 protease activity and lower toxicity compared to ARDP0006. The selectivity index of DV-B-120 was higher than that of ARDP0006. In vivo assessments of the antiviral efficacy of DV-B-120 against DENV replication demonstrated delayed mortality of suckling mice treated with the compound, with 60-80% protection against life-threatening effects, compared to the outcomes of DENV-infected mice treated with saline. The lower clinical scores of DENV-infected mice treated with DV-B-120 indicated a reduction in acute-progressive illness symptoms, underscoring the potential therapeutic impact of DV-B-120. Investigations of DV-B-120's ability to restore the antiviral type I IFN response in the brain tissue of DENV-infected ICR suckling mice demonstrated its capacity to stimulate IFN and antiviral IFN-stimulated gene expression. DV-B-120 not only significantly delayed DENV-2-induced mortality and illness symptoms but also reduced viral numbers in the brain, ultimately restoring the innate antiviral response. These findings strongly suggest that DV-B-120 holds promise as a therapeutic agent against DENV infection and highlight its potential contribution in addressing the current lack of effective treatments for this infectious disease.IMPORTANCEThe prevalence of dengue virus (DENV) infection in tropical and subtropical regions is escalating due to factors like climate change and mosquito vector expansion. With over 300 million annual infections and potentially fatal outcomes, the urgent need for effective treatments is evident. While the approved Dengvaxia vaccine has variable efficacy, there are currently no antiviral drugs for DENV. This study explores seven compounds targeting the NS2B-NS3 protease, a crucial protein in DENV replication. These compounds exhibit inhibitory effects on DENV-2 NS2B-NS3, holding promise for disrupting viral replication and preventing severe manifestations. However, further research, including animal testing, is imperative to assess therapeutic efficacy and potential toxicity. Developing safe and potent treatments for DENV infection is critical in addressing the rising global health threat posed by this virus.


Assuntos
Doenças Transmissíveis , Vírus da Dengue , Dengue , Piperidinas , Viroses , Animais , Camundongos , Vírus da Dengue/fisiologia , Camundongos Endogâmicos ICR , Endopeptidases/farmacologia , Dengue/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Viroses/tratamento farmacológico , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/química
16.
J Clin Med ; 13(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38541914

RESUMO

(1) Background: Either pre-operative physical status or unstable hemodynamic changes has been reported to play a potential role in causing vital organ dysfunction. Therefore, we intended to investigate the impact of the American Society of Anesthesiologist (ASA) classification and intraoperative hemodynamic instability on non-surgical complications following orthopedic surgery. (2) Methods: We collected data on 6478 patients, with a mean age of 57.3 ± 16, who underwent orthopedic surgeries between 2018 and 2020. The ASA classification and hemodynamic data were obtained from an anesthesia database. Non-surgical complications were defined as a dysfunction of the vital organs. (3) Results: ASA III/IV caused significantly higher odds ratios (OR) of 17.49 and 40.96, respectively, than ASA I for developing non-surgical complications (p < 0.001). Non-surgical complications were correlated with a 20% reduction in systolic blood pressure (SBP), which was intraoperatively compared to the pre-operative baseline ((OR) = 1.38, p = 0.02). The risk of postoperative complications increased with longer durations of SBP < 100 mmHg, peaking at over 20 min ((OR) = 1.33, p = 0.34). (4) Conclusions: Extended intraoperative hypotension and ASA III/IV caused a significantly higher risk of adverse events occurring within the major organs. The maintenance of hemodynamic stability prevents non-surgical complications after orthopedic surgeries.

17.
Phytomedicine ; 128: 155355, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38555773

RESUMO

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

18.
Stem Cell Reports ; 19(3): 399-413, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38428414

RESUMO

Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1+ mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1+ cells, where a distinct PDGFRAlow subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1+PDGFRAlow limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1+PDGFRAlow LML cells might be a prominent stem cell source for human cartilage regeneration.


Assuntos
Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Células-Tronco , Terapia Baseada em Transplante de Células e Tecidos , Mesoderma , Transplante de Células-Tronco Mesenquimais/métodos , Diferenciação Celular , Fator de Transcrição MSX1/genética
19.
J Multidiscip Healthc ; 17: 983-990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476252

RESUMO

Objective: To analyze the relevant research publications on infectious disease nursing in China to understand the current research status of infectious disease in nursing. Methods: Retrieve relevant literature on infectious disease in nursing from the establishment of the Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang Database until May 10, 2021. Conduct bibliometric analysis using CiteSpace software. Key words were analyzed using cluster analysis. Results: A total of 4693 relevant literature on infectious disease research in nursing care were included in this study. The overall number of publications on infectious disease research in nursing showed an increasing trend, with a peak in 2010. There were 324 papers funded by scientific research funds, mainly from provincial-level fund projects. The core journal with the most published articles was Nursing Research. The research on infectious disease in nursing mainly focused on various aspects of infectious disease in nursing and infection control. CiteSpace cluster analysis of keywords showed that a total of six clusters were formed: infectious diseases, infectious disease care, health education, mental health, infectious disease nurses, and etiology. After 2015, high-mutation keywords included "quality nursing" and "infection control". Conclusion: Chinese research on infectious disease research in nursing closely follows clinical reality and has developed rapidly. Currently, research focuses on infectious disease research in nursing and infection control. Future research trends will further broaden the depth and breadth of the research, enhance research on infection control and quality nursing, and improve the breadth and depth of the research.

20.
Signal Transduct Target Ther ; 9(1): 59, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462638

RESUMO

Diet, serving as a vital source of nutrients, exerts a profound influence on human health and disease progression. Recently, dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, and metabolic disorders. These interventions have demonstrated substantial potential in modulating metabolism, disease trajectory, and therapeutic responses. Metabolic reprogramming is a hallmark of malignant progression, and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication. Dietary intake, as a key environmental factor, can influence tumor metabolism. Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors, thereby increasing the efficacy of cancer treatments. However, the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex. Despite encouraging results, the mechanisms underlying diet-based therapeutic strategies remain largely unexplored, often resulting in underutilization in disease management. In this review, we aim to illuminate the potential effects of various dietary interventions, including calorie restriction, fasting-mimicking diet, ketogenic diet, protein restriction diet, high-salt diet, high-fat diet, and high-fiber diet, on cancer and the aforementioned diseases. We explore the multifaceted impacts of these dietary interventions, encompassing their immunomodulatory effects, other biological impacts, and underlying molecular mechanisms. This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.


Assuntos
Dieta Cetogênica , Neoplasias , Humanos , Restrição Calórica , Dieta , Jejum , Neoplasias/terapia
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