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1.
Adv Healthc Mater ; : e2401105, 2024 Jun 18.
Article En | MEDLINE | ID: mdl-38889446

Chronic wound healing is a major challenge in clinical practice. Secondary dressing damage and antibiotic resistance are the main obstacles for traditional wound dressings. Resina Draconis (RD), a natural resin traditionally used in powder form for wound care, is now considered unsuitable due to the lack of gas permeability and moist environment required for wound healing. Here, we incorporated RD in situ by constructing a 3D coiled fibrous scaffold with polycaprolactone (PCL)/polyethylene oxide (PEO). Due to the high porosity of 3D scaffold, the RD-3D dressings have a favorable swelling capacity, providing permeability and moisture for wound repair. Meanwhile, the transformation of RD powder into 3D dressings fully demonstrated capabilities of RD in rapid hemostasis, bactericidal and inflammation-regulating activities. In vivo evaluations using pressure ulcer and infected wound models confirmed the high efficacy of RD-3D dressing in early wound healing, particularly beneficial in the infected wound model compared to bFGF. Further biological analysis showed that resveratrol, loureirin A and loureirin B, as potentially bioactive components of RD, individually contributed to different aspects of wound healing. Collectively, RD-3D integrated dressings represent a simple, cost-effective and safe approach to wound healing, providing an alternative therapy for translating medical dressings from bench to bedside. This article is protected by copyright. All rights reserved.

2.
ACS Nano ; 2024 Jun 14.
Article En | MEDLINE | ID: mdl-38874427

The formation of uniform, nondendritic seeds is essential to realizing dense lithium (Li) metal anodes and long-life batteries. Here, we discover that faceted Li seeds with a hexagonal shape can be uniformly grown on carbon-polymer composite films. Our investigation reveals the critical role of carbon defects in serving as the nucleation sites for their formation. Tuning the density and spatial distribution of defects enables the optimization of conditions for faceted seed growth. Raman spectral results confirm that lithium nucleation indeed starts at the defect sites. The uniformly distributed crystalline seeds facilitate low-porosity Li deposition, effectively reducing Li pulverization during cycling and unlocking the fast-charging ability of Li metal batteries. At a 1 C rate, full cells using LiNi0.8Mn0.1Co0.1O2 cathode (4.5 mA h cm-2) paired with a lithium anode grown on carbon composite films achieve a 313% improvement in cycle life compared to baseline cells. Polymer composites with carbonaceous materials rich in defects are scalable, low-cost substrates for high-rate, high-energy-density batteries.

3.
Sci Rep ; 14(1): 11682, 2024 05 22.
Article En | MEDLINE | ID: mdl-38778225

To explore altered patterns of static and dynamic functional brain network connectivity (sFNC and dFNC) in Primary angle-closure glaucoma (PACG) patients. Clinically confirmed 34 PACG patients and 33 age- and gender-matched healthy controls (HCs) underwent evaluation using T1 anatomical and functional MRI on a 3 T scanner. Independent component analysis, sliding window, and the K-means clustering method were employed to investigate the functional network connectivity (FNC) and temporal metrics based on eight resting-state networks. Differences in FNC and temporal metrics were identified and subsequently correlated with clinical variables. For sFNC, compared with HCs, PACG patients showed three decreased interactions, including SMN-AN, SMN-VN and VN-AN pairs. For dFNC, we derived four highly structured states of FC that occurred repeatedly between individual scans and subjects, and the results are highly congruent with sFNC. In addition, PACG patients had a decreased fraction of time in state 3 and negatively correlated with IOP (p < 0.05). PACG patients exhibit abnormalities in both sFNC and dFNC. The high degree of overlap between static and dynamic results suggests the stability of functional connectivity networks in PACG patients, which provide a new perspective to understand the neuropathological mechanisms of optic nerve damage in PACG patients.


Glaucoma, Angle-Closure , Magnetic Resonance Imaging , Humans , Glaucoma, Angle-Closure/physiopathology , Glaucoma, Angle-Closure/diagnostic imaging , Female , Male , Middle Aged , Aged , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Case-Control Studies , Brain/diagnostic imaging , Brain/physiopathology , Brain/pathology
4.
Heliyon ; 10(8): e29684, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38665549

Phthalates, widely utilized in industrial products, are classified as endocrine-disrupting chemicals (EDCs). Although certain phthalate and their metabolites have been implicated in cancer development, the reported findings have exhibited inconsistencies. Therefore, we conducted the comprehensive literature search to assess the association between phthalate and their metabolites and cancer risk by identifying original studies measuring phthalates or their metabolites and reporting their correlation with cancer until July 4, 2023. The Odds Ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted and analyzed to estimate the risk. Pooled data from eleven studies, including 3101 cancer patients and 6858 controls, were analyzed using a fixed- or random-effects model based on heterogeneity tests. When comparing extreme categories of different phthalates and their metabolites, we observed a significant association between urinary phthalates and phthalate metabolites (MEHHP, MECPP, DBP and MBzP) and cancer risk. The findings of our meta-analysis reinforce the existing evidence that urinary phthalates and phthalate metabolites is strongly associated with cancer development. Further investigations are warranted to elucidate the underlying mechanisms of this association. These results may offer novel insights into cancer development.

5.
Eur J Pharmacol ; 971: 176392, 2024 May 15.
Article En | MEDLINE | ID: mdl-38365107

The excessive elevation of angiotensin II (ANG II) is closely associated with the occurrence and development of aortic dissection (AD)-related acute lung injury (ALI), through its binding to angiotensin II receptor type I (AT1R). MiR-145-5p is a noncoding RNA that can be involved in a variety of cellular physiopathological processes. Transfection with miR-145-5p was found to downregulated the expression of A disintegrin and metalloprotease 17 (ADAM17) and reduced the levels of angiotensin-converting enzyme 2 (ACE2) in lung tissue, while concurrently increasing plasma ACE2 levels in the AD combined with ALI mice. ADAM17 was proved to be a target of miR-145-5p. Transfection with miR-145-5p decreased the shedding of ACE2 and alleviated the inflammatory response induced by ANG II through targeting ADAM17 and inhibiting the AT1R/ADAM17 pathway in A549 cells. In conclusion, our present study demonstrates the role and mechanism of miR-145-5p in alleviating ANG II-induced acute lung injury, providing a new insight into miRNA therapy for reducing lung injury in patients with aortic dissection.


Acute Lung Injury , Aortic Dissection , MicroRNAs , Humans , Animals , Mice , Angiotensin-Converting Enzyme 2/genetics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Alveolar Epithelial Cells/metabolism , ADAM17 Protein/genetics , Angiotensin II/pharmacology , Angiotensin II/metabolism , MicroRNAs/genetics , Acute Lung Injury/chemically induced , Acute Lung Injury/genetics , Acute Lung Injury/metabolism
6.
Acta Cardiol ; : 1-11, 2023 Dec 14.
Article En | MEDLINE | ID: mdl-38095548

BACKGROUND: Postoperative gastrointestinal complications (GICs) were potentially fatal to patients who underwent aortic arch surgery. The aim of this study was to construct a prediction model of GICs. METHODS: We retrospectively studied the medical records of 3063 patients who underwent aortic arch surgery. Patients were randomly divided into derivation and validation cohorts at a ratio of 4:1. A nomogram was constructed in the derivation cohort. RESULTS: A total of 157 patients with GICs were identified. In the derivation cohort, multivariate analysis identified six predictors of GICs including hypertension, ASA classification, preinduction MAP, aortic cross-clamp time, CPB time, and intraoperative transfusion of red blood cells. Compared with the patients without GICs, the patients with GICs had higher mortality, and longer ICU and hospital stays. We also divided the patients into four intervals according to the risk of GICs. CONCLUSIONS: This study developed a reliable prediction model of GICs after aortic arch surgery. This prediction model had been well verified in our research centre, and further external verification was required before it can be recommended for clinical application.

7.
J Orthop Surg Res ; 18(1): 792, 2023 Oct 24.
Article En | MEDLINE | ID: mdl-37875947

OBJECTIVE: Secoisolariciresinol diglucoside (SDG) is a phytoestrogen that has been reported to improve postmenopausal osteoporosis (PMOP) caused by estrogen deficiency. In our work, we aimed to investigate the mechanism of SDG in regulating the expressions of ERs on PMOP model rats. METHODS: Ovariectomization (OVX) was used to establish PMOP model in rats. The experiment was allocated to Sham, OVX, SDG and raloxifene (RLX) groups. After 12-week treatment, micro-CT was used to detect the transverse section of bone. Hematoxylin and Eosin staining and Safranine O-Fast Green staining were supplied to detect the femur pathological morphology of rats. Estradiol (E2), interleukin-6 (IL-6), bone formation and bone catabolism indexes in serum were detected using ELISA. Alkaline phosphatase (ALP) staining was used to detect the osteogenic ability of chondrocytes. Immunohistochemistry and Western blot were applied to detect the protein expressions of estrogen receptors (ERs) in the femur of rats. RESULTS: Compared with the OVX group, micro-CT results showed SDG could lessen the injury of bone and improve femoral parameters, including bone mineral content (BMC) and bone mineral density (BMD). Pathological results showed SDG could reduce pathological injury of femur in OVX rats. Meanwhile, SDG decreased the level of IL-6 and regulated bone formation and bone catabolism indexes. Besides, SDG increased the level of E2 and conversed OVX-induced decreased the expression of ERα and ERß. CONCLUSION: The treatment elicited by SDG in OVX rats was due to the reduction of injury and inflammation and improvement of bone formation index, via regulating the expression of E2 and ERs.


Osteoporosis, Postmenopausal , Osteoporosis , Female , Humans , Rats , Animals , Receptors, Estrogen , Interleukin-6 , Osteoporosis/drug therapy , Osteoporosis/etiology , Osteoporosis/metabolism , Estrogens , Bone Density , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/etiology , Ovariectomy/adverse effects
8.
Psychiatry Res ; 328: 115450, 2023 10.
Article En | MEDLINE | ID: mdl-37683318

Positive allosteric modulators of γ-aminobutyric acid-A (GABAA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and other disorders. Recently, some new GABAkines (zuranolone and brexanolone) have been administrated to patients with major depressive disorder (MDD) or postpartum depression (PPD) in randomized controlled trials (RCTs). This study aims to systematically review and examine the efficacy and safety of zuranolone or brexanolone for treatment of depression. A systematic literature retrieval was conducted through August 20, 2023. RCTs evaluating the efficacy and safety of zuranolone or brexanolone for treatment of depression were included. Eight studies (nine reports) were identified in the study. The percentages of patients with PPD achieving Hamilton Depression Rating Scale (HAM-D) response and remission were significantly higher after brexanolone or zuranolone administration compared with placebo at different points. The percentages of patients with MDD achieving HAM-D response and remission were significantly increased during the zuranolone treatment period compared with placebo. In addition, zuranolone caused more adverse events in patients with MDD compared with placebo. Our findings support the effects of brexanolone on improving the core symptoms of depression in patients with PPD, and the potential of zuranolone in treating patients with MDD or PPD.


Depression, Postpartum , Depressive Disorder, Major , Female , Humans , Antidepressive Agents/therapeutic use , Depression, Postpartum/drug therapy , Depression , Randomized Controlled Trials as Topic , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/chemically induced
9.
Heliyon ; 9(8): e19263, 2023 Aug.
Article En | MEDLINE | ID: mdl-37664759

Massive Open Online Courses (MOOCs) are a new phenomenon in education worldwide. In China, MOOCs have been widely used in medical courses. However, the effects of MOOCs on improving clinical skills are controversial. Therefore, we conducted the study to verify whether the application of MOOCs in medical courses can improve participants' clinical skills in China. A systematic literature search was carried out using the PubMed, Embase, Web of Science, CNKI and Wanfang databases according to the predetermined criteria. The Hedges' g and its corresponding 95% confidence interval were selected to assess the effects of MOOCs on participants' clinical skills. Subgroup analyses, sensitivity analysis and publication bias test were performed in the study. A total of thirty-two records (thirty-two studies) with 3422 participants were identified in our study. There was a significant improvement in clinical skill scores of participants in the MOOC group compared with the control group. Subgroup analyses showed similar results in different student groups. Our study supported the notion that the MOOC-based teaching method appeared to be a more effective method than the conventional teaching technique for the improvement of participants' clinical skills in China.

10.
Mater Today Bio ; 22: 100756, 2023 Oct.
Article En | MEDLINE | ID: mdl-37593218

Indigo naturalis (IN) has been extensively used as a topical treatment for psoriasis. However, clinical applications of IN in ointment were hampered by its limited transdermal efficiency and dark stains. To address the aforementioned issues, nanopatches carrying IN were fabricated using poly(ε-caprolactone, PCL)/poly(ethylene oxide, PEO) and topically applied to psoriasiform skin. The ideal ratio of 5% PCL/PEO was established to be 80:20 (w/w), and 15% IN as payload was confirmed. Investigations on the three principal active components of IN release indicated that indirubin and tryptanthrin were released in bursts, while indigo was released in a limited and controlled manner. Further biological analyses confirmed a favorable biocompatibility of amphiphilic IN-PCL/PEO, which coincided with the intended therapeutic outcomes as measured by severity index scoring and pathological evaluations in vivo. The advantages of IN as nanopatches over ointment could be due to improved transdermal distribution of indirubin and tryptanthrin, resulting in effective management of epidermal hyperplasia and blood vessel remodeling. Meanwhile, due to the lower preservation of epidermal indigo, IN-PCL/PEO nanopatches caused no skin coloration. Similarly, during a 4-week topical treatment of IN-PCL/PEO nanopatches, the safety and anti-psoriatic benefits were obtained in an initial human test. The conversion of IN from topical cream to electrospun nanofibers opens up new avenues for bench-to-bedside translation of this herbal therapy and provides mechanistic insight into IN's roles in the management of psoriasis.

11.
Medicine (Baltimore) ; 102(33): e34704, 2023 Aug 18.
Article En | MEDLINE | ID: mdl-37603505

Hypoxemia is one of the most common complications in patients after Stanford type A acute aortic dissection surgery. The aim of this study was to investigate the association of circulating ANG II level with postoperative hypoxemia and to identify the risk factors for postoperative hypoxemia in Stanford type A acute aortic dissection patients. In this study, 88 patients who underwent Stanford type A acute aortic dissection surgery were enrolled. Postoperative hypoxemia is defined by the oxygenation index (OI). Perioperative clinical data were collected and the serum ANG II and sACE2 levels were measured. The differences in the basic characteristics, intraoperative details, biochemical parameters, laboratory test data and clinical outcomes were compared between the hypoxemia group and the non-hypoxemia group by univariate analysis. Multivariate logistic regression analysis was performed on the variables with P < .1 in univariate analysis or that were considered clinically important to identify risk factors for postoperative hypoxemia. Twenty-five patients (28.4%) were considered to have postoperative hypoxemia (OI ≤ 200 mm Hg). The ANG II concentration remained a risk factor associated with postoperative hypoxemia [OR = 1.018, 95% CI (1.003-1.034), P = .022]. The other risk factors remaining in the logistic regression model were BMI [OR = 1.417, 95% CI (1.159-1.733), P = .001] and cTnI [OR = 1.003, 95% CI (1.000-1.005), P = .032]. Elevated levels of ANG II, BMI and cTnI are risk factors for postoperative hypoxemia in patients with Stanford type A acute aortic dissection.


Aortic Dissection , Humans , Risk Factors , Aortic Dissection/surgery , Blood Gas Analysis , Logistic Models , Postoperative Period , Troponin I
12.
Carbohydr Polym ; 319: 121181, 2023 Nov 01.
Article En | MEDLINE | ID: mdl-37567717

The current serious environmental problems have greatly encouraged the design and development of food packaging materials with environmental protection, green, and safety. This study aims to explore the synergistic effect and corresponding mechanism of cellulose nanocrystals (CNC) and CaCl2 to enhance the film-forming properties of pea protein isolate (PPI). The combination of 0.5 % CNC and 4.5 mM CaCl2 resulted in a 76.6 % increase in tensile strength when compared with pure PPI-based film. Meanwhile, this combination effectively improved the barrier performance, surface hydrophobicity, water resistance, and biodegradability of PPI-based film. The greater crystallinity, viscoelasticity, lower water mobility, and improved protein spatial conformation were also observed in CNC/CaCl2 composite film. Compared with the control, the main degradation temperature of composite film was increased from 326.23 °C to 335.43 °C. The CNC chains bonded with amino acid residue of pea protein at specific sites via non-covalent forces (e.g., hydrogen bonds, Van der Waals forces). Meanwhile, Ca2+ promoted the ordered protein aggregation at suitable rate and degree, accompanied by the formation of more disulfide bonds. Furthermore, proper Ca2+ could strengthen the cross-linking and interaction between CNC and protein, thereby establishing a stable network structure. The prepared composite films are expected to be used for strawberry preservation.


Nanoparticles , Pea Proteins , Cellulose/chemistry , Calcium , Calcium Chloride , Water/chemistry , Nanoparticles/chemistry
13.
Phytomedicine ; 118: 154942, 2023 Sep.
Article En | MEDLINE | ID: mdl-37421767

BACKGROUND: The continuous evolution of SARS-CoV-2 has underscored the development of broad-spectrum prophylaxis. Antivirals targeting the membrane fusion process represent promising paradigms. Kaempferol (Kae), an ubiquitous plant flavonol, has been shown efficacy against various enveloped viruses. However, its potential in anti-SARS-CoV-2 invasion remains obscure. PURPOSE: To evaluate capabilities and mechanisms of Kae in preventing SARS-CoV-2 invasion. METHODS: To avoid interference of viral replication, virus-like particles (VLPs) constructed with luciferase reporter were applied. To investigate the antiviral potency of Kae, human induced pluripotent stem cells (hiPSC)-derived alveolar epithelial cells type II (AECII) and human ACE2 (hACE2) transgenic mice were utilized as in vitro and in vivo models, respectively. Using dual split protein (DSP) assays, inhibitory activities of Kae in viral fusion were determined in Alpha, Delta and Omicron variants of SARS-CoV-2, as well as in SARS-CoV and MERS-CoV. To further reveal molecular determinants of Kae in restricting viral fusion, synthetic peptides corresponding to the conserved heptad repeat (HR) 1 and 2, involved in viral fusion, and the mutant form of HR2 were explored by circular dichroism and native polyacrylamide gel electrophoresis. RESULTS: Kae inhibited SARS-CoV-2 invasion both in vitro and in vivo, which was mainly attributed to its suppressive effects on viral fusion, but not endocytosis, two pathways that mediate viral invasion. In accordance with the proposed model of anti-fusion prophylaxis, Kae functioned as a pan-inhibitor of viral fusion, including three emerged highly pathogenic coronaviruses, and the currently circulating Omicron BQ.1.1 and XBB.1 variants of SARS-CoV-2. Consistent with the typical target of viral fusion inhibitors, Kae interacted with HR regions of SARS-CoV-2 S2 subunits. Distinct from previous inhibitory fusion peptides which prevent the formation of six-helix bundle (6-HB) by competitively interacting with HRs, Kae deformed HR1 and directly reacted with lysine residues within HR2 region, the latter of which was considered critical for the preservation of stabilized S2 during SARS-CoV-2 invasion. CONCLUSIONS: Kae prevents SARS-CoV-2 infection by blocking membrane fusion and possesses a broad-spectrum anti-fusion ability. These findings provide valuable insights into potential benefits of Kae-containing botanical products as a complementary prophylaxis, especially during the waves of breakthrough infections and re-infections.


COVID-19 , Induced Pluripotent Stem Cells , Mice , Animals , Humans , SARS-CoV-2 , Amino Acid Sequence , Kaempferols/pharmacology , Spike Glycoprotein, Coronavirus , Induced Pluripotent Stem Cells/metabolism , Peptides/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
14.
Biochim Biophys Acta Gen Subj ; 1867(9): 130411, 2023 09.
Article En | MEDLINE | ID: mdl-37343605

The products synthesized by RNA polymerase I (Pol I) play fundamental roles in several cellular processes, including ribosomal biogenesis, protein synthesis, cell metabolism, and growth. Deregulation of Pol I products can cause various diseases such as ribosomopathies, leukaemia, and solid tumours. However, the detailed mechanism of Pol I-directed transcription remains elusive, and the roles of Pol I subunits in rRNA synthesis and cellular activities still need clarification. In this study, we found that RPA43 expression levels positively correlate with Pol I product accumulation and cell proliferation, indicating that RPA43 activates these processes. Unexpectedly, RPA43 depletion promoted HeLa cell migration, suggesting that RPA43 functions as a negative regulator in cell migration. Mechanistically, RPA43 positively modulates the recruitment of Pol I transcription machinery factors to the rDNA promoter by activating the transcription of the genes encoding Pol I transcription machinery factors. RPA43 inhibits cell migration by dampening the expression of c-JUN and Integrin. Collectively, we found that RPA43 plays opposite roles in cell proliferation and migration except for driving Pol I-dependent transcription. These findings provide novel insights into the regulatory mechanism of Pol I-mediated transcription and cell proliferation and a potential pathway to developing anti-cancer drugs using RPA43 as a target.


RNA Polymerase I , Transcription, Genetic , Humans , RNA Polymerase I/genetics , HeLa Cells , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism , Transcription Factors/metabolism , Cell Proliferation , Cell Movement
15.
Int Immunopharmacol ; 120: 110372, 2023 Jul.
Article En | MEDLINE | ID: mdl-37279642

INTRODUCTION: Melatonin is a hormone synthesized by the pineal gland, and has antioxidative effects in reducing acute kidney injury (AKI). In the past three years, an increasing number of studies have evaluated whether melatonin has a protective effect on AKI. The study systematically reviewed and assessed the efficacy and safety of melatonin in preventing AKI. MATERIAL AND METHODS: A systematic literature search was conducted in the PubMed, Embase, and Web of Science databases on February 15, 2023. Eligible records were screened according to the inclusion and exclusion criteria. The odds ratio and Hedges' gwith the corresponding 95% confidence intervals were selected to evaluate the effects of melatonin on AKI. We pooled extracted data using a fixed- or random-effects model based on a heterogeneity test. RESULTS: There were five studies (one cohort study and four randomized controlled trials) included in the meta-analysis. Although the glomerular filtration rate (GFR) may be significantly improved by melatonin, the incidence of AKI was not significantly decreased in the melatonin group compared with the control group in randomized controlled trials (RCTs). CONCLUSIONS: In our study, the present results do not support a direct effect of melatonin use on the reduction of AKI. More well-designed clinical studies with larger sample size are required in the future.


Acute Kidney Injury , Melatonin , Humans , Melatonin/therapeutic use , Acute Kidney Injury/drug therapy , Acute Kidney Injury/prevention & control
16.
Fa Yi Xue Za Zhi ; 39(2): 186-192, 2023 Apr 25.
Article En, Zh | MEDLINE | ID: mdl-37277382

OBJECTIVES: To survey the development status and actual needs of virtual autopsy technology in China and to clarify the applicability of forensic virtual autopsy laboratory accreditation. METHODS: The questionnaire was set up included three aspects:(1) the current status of virtual autopsy technology development; (2) the accreditation elements such as personnel, equipment, entrustment and acceptance, methods, environmental facilities; (3) the needs and suggestions of practicing institutions. A total of 130 forensic pathology institutions were surveyed by online participation through the Questionnaire Star platform. RESULTS: Among the 130 institutions, 43.08% were familiar with the characteristics of virtual autopsy technology, 35.38% conducted or received training in virtual autopsy, and 70.77% have establishment needs (including maintenance). Relevant elements were suitable for laboratory accreditation. CONCLUSIONS: Virtual autopsy identification has gained social recognition. There is a demand for accreditation of forensic virtual autopsy laboratory. After the preliminary assessment, considering the characteristics and current situation of this technology, China National Accreditation Service for Conformity Assessment (CNAS) can first carry out the accreditation pilot of virtual autopsy project at large comprehensive forensic institutions with higher identification capability, and then CNAS can popularize the accreditation in a wide range when the conditions are suitable.


Autopsy , Forensic Pathology , Laboratories , Forensic Medicine , Accreditation , Laboratories/standards , China
17.
Anticancer Drugs ; 34(7): 896-900, 2023 08 01.
Article En | MEDLINE | ID: mdl-37139936

Gilteritinib is currently approved in China for relapsed/refractory FLT3-mutated acute myeloid leukemia, and it is very important to monitor and report its adverse drug reaction (ADR) after post-marketing. This case report describes a patient who was diagnosed with acute myeloid leukemia harboring FLT3 mutations and developed a severe suspected immune-related enteritis during treatment with gilteritinib for maintenance therapy following allo-hematopoietic stem cell transplantation. According to the Naranjo probability scale, gilteritinib was defined as a 'possible' cause of ADR. Another suspicious inducement, graft-versus-host disease, can not be eluted and might represent a limitation in this case. To the best of our knowledge, this is the first report on gilteritinib-induced severe enteritis and will help physicians to keep vigilant, and detect and deal with time for possible ADR.


Aniline Compounds , Leukemia, Myeloid, Acute , Humans , Mutation , Aniline Compounds/therapeutic use , Pyrazines/adverse effects , Leukemia, Myeloid, Acute/genetics
18.
J Hazard Mater ; 453: 131379, 2023 07 05.
Article En | MEDLINE | ID: mdl-37054645

(R,S)-ketamine (ketamine) has been increasingly used recreationally and medicinally worldwide; however, it cannot be removed by conventional wastewater treatment plants. Both ketamine and its metabolite norketamine have been frequently detected to a significant degree in effluents, aquatic, and even atmospheric environments, which may pose risks to organisms and humans via drinking water and aerosols. Ketamine has been shown to affect the brain development of unborn babies, while it is still elusive whether (2 R,6 R)-hydroxynorketamine (HNK) induces similar neurotoxicity. Here, we investigated the neurotoxic effect of (2 R,6 R)-HNK exposure at the early stages of gestation by applying human cerebral organoids derived from human embryonic stem cells (hESCs). Short-term (2 R,6 R)-HNK exposure did not significantly affect the development of cerebral organoids, but chronic high-concentration (2 R,6 R)-HNK exposure at day 16 inhibited the expansion of organoids by suppressing the proliferation and augmentation of neural precursor cells (NPCs). Notably, the division mode of apical radial glia was unexpectedly switched from vertical to horizontal division planes following chronic (2 R,6 R)-HNK exposure in cerebral organoids. Chronic (2 R,6 R)-HNK exposure at day 44 mainly inhibited the differentiation but not the proliferation of NPCs. Overall, our findings indicate that (2 R,6 R)-HNK administration leads to the abnormal development of cortical organoids, which may be mediated by inhibiting HDAC2. Future clinical studies are needed to explore the neurotoxic effects of (2 R,6 R)-HNK on the early development of the human brain.


Human Embryonic Stem Cells , Ketamine , Neural Stem Cells , Humans , Ketamine/metabolism , Antidepressive Agents/metabolism , Human Embryonic Stem Cells/metabolism , Neural Stem Cells/metabolism , Brain/metabolism
19.
Front Neurosci ; 17: 1053114, 2023.
Article En | MEDLINE | ID: mdl-36845423

Background: Previous studies on primary angle-closure glaucoma (PACG) primarily focused on local brain regions or global abnormal brain activity; however, the alteration of interhemispheric functional homotopy and its possible cause of brain-wide functional connectivity abnormalities have not been well-studied. Little is known about whether brain functional alteration could be used to differentiate from healthy controls (HCs) and its correlation with neurocognitive impairment. Methods: Forty patients with PACG and 40 age- and sex-matched healthy controls were recruited for this study; resting-state functional magnetic resonance imaging (rs-fMRI), and clinical data were collected. We used the voxel-mirrored homotopic connectivity (VMHC) method to explore between-group differences and selected brain regions with statistically significant differences as regions of interest for whole-brain functional connectivity analysis. Partial correlation was used to evaluate the association between abnormal VMHC values in significantly different regions and clinical parameters, with with age and sex as covariates. Finally, the support vector machine (SVM) model was performed in classification prediction of PACG. Results: Compared with healthy controls, patients with PACG exhibited significantly decreased VMHC values in the lingual gyrus, insula, cuneus, and pre- and post-central gyri; no regions exhibited increased VMHC values. Subsequent functional connectivity analysis revealed extensive functional changes in functional networks, particularly the default mode, salience, visual, and sensorimotor networks. The SVM model showed good performance in classification prediction of PACG, with an area under curve (AUC) of 0.85. Conclusion: Altered functional homotopy of the visual cortex, sensorimotor network, and insula may lead to impairment of visual function in PACG, suggesting that patients with PACG may have visual information interaction and integration dysfunction.

20.
Am Surg ; 89(12): 5450-5458, 2023 Dec.
Article En | MEDLINE | ID: mdl-36788032

BACKGROUND: Gastrointestinal complications need to be paid more attention, especially in critically ill patients. The purpose of this study was to identify the risk factors and short-term outcomes of gastrointestinal complications after open surgery for type A aortic dissection. METHODS: A retrospective single-institutional study including patients who underwent open surgery for type A aortic dissection during 2012-2020 was conducted. Univariate analysis and logistic regression analysis were used to identify risk factors associated with gastrointestinal complications. The related clinical outcomes were compared between the patients with and without gastrointestinal complications. RESULTS: Among the 2746 patients, 150 developed gastrointestinal complications. The development of gastrointestinal complications contributed to the higher rate of mortality (P = .008), longer stay in the intensive care unit (P < .001), and longer hospital stay (P < .001). Logistic regression analysis showed that age (odds ratio [OR] 1.020; 95% confidence interval [CI] 1.005-1.057; P = .011), American Society of Anesthesiologists classification greater than grade III (OR 1.724; 95%CI 1.179-2.521, P = .005), pre-induction mean arterial pressure (OR 0.978; 95%CI 0.965-0.990, P = .001), aortic cross-clamp time (OR 1.012; 95%CI 1.005-1.019, P = .001), cardiopulmonary bypass time (OR 1.007; 95%CI 1.002-1.011, P = .002), and intraoperative transfusion of red blood cells (OR 1.214; 95%CI 1.122-1.314, P = .001) were independent risk factors for gastrointestinal complications. CONCLUSIONS: The incidence of gastrointestinal complications after open surgery for type A aortic dissection was 5.5%, resulting in increased mortality and prolonged hospital stay. It is necessary to take suitable strategies to reduce the incidence of gastrointestinal complications.


Aortic Dissection , Humans , Retrospective Studies , Treatment Outcome , Aortic Dissection/surgery , Risk Factors , Aorta/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology
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