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This study employed a precipitation method to synthesize zinc oxide@quaternised chitosan nanoparticles (ZnO@QAC NPs) containing different concentrations of zinc oxide, namely ZnO@QAC-2, ZnO@QAC-4, and ZnO@QAC-6. Subsequently, these nanoparticles were incorporated into matrices consisting of gelatine (Gn) and polyvinyl alcohol (PVA) separately, which were prepared by casting to form a biodegradable film. We assessed the physicochemical properties of ZnO@QAC NPs and physicochemical characteristics, antioxidant properties, antimicrobial activity and grape preservation efficacy of the film. Compared to the control group, the films showed a reduction in water vapor permeability by >9.38 %, an increase in tensile strength by over 51.95 %, over 70 % scavenging of ABTS free radicals, and good biocompatibility. Additionally, the antimicrobial activity of the films containing ZnO@QAC-6 increased by 37.6 %. In the grape preservation experiment, the weight loss of grapes wrapped in ZnO@QAC-2 film was reduced by 40.13 % on day 15 compared to unwrapped grapes. These results demonstrate that ZnO@QAC/PVA/Gn films have considerable potential for food packaging applications.
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Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVß5, p-AMPK, and autophagy-related markers. Integrin αVß5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVß5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVß5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.
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Proteínas Quinasas Activadas por AMP , Autofagia , Fibronectinas , Glaucoma , Microglía , Enfermedades Neuroinflamatorias , Receptores de Vitronectina , Animales , Masculino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad , Fibronectinas/metabolismo , Glaucoma/tratamiento farmacológico , Glaucoma/inmunología , Glaucoma/metabolismo , Lipopolisacáridos , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/inmunología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/etiología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/metabolismo , Receptores de Vitronectina/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/metabolismoRESUMEN
Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency.
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Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable Haemophilus influenzae (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates in vitro, suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma.
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Antibacterianos , Asma , Quitosano , Escherichia coli , Ratones Endogámicos BALB C , Neutrófilos , Staphylococcus aureus , Animales , Staphylococcus aureus/efectos de los fármacos , Asma/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Neutrófilos/efectos de los fármacos , Quitosano/administración & dosificación , Quitosano/química , Escherichia coli/efectos de los fármacos , Femenino , Haemophilus influenzae/efectos de los fármacos , Nanogeles/química , Ovalbúmina/administración & dosificación , Mucinas , Polilisina/química , Polilisina/administración & dosificación , Infecciones por Haemophilus/tratamiento farmacológico , Ratones , Polietileneimina/química , Polietileneimina/administración & dosificación , GelesRESUMEN
The decrease in eggshell quality seriously affects production efficiency. Guinea fowl (GF) eggs possess strong eggshells because of their unique crystal structure, and few systematic studies have compared laying hen and GF eggs. Sixty eggs were collected from both 40-week-old Dwarf Layer-White (DWL-White) laying hens and GF, and the eggshell quality, ultrastructure, bubble pores, and composition were measured. The results showed that the DWL-White eggs had a higher egg weight and a lower eggshell strength, strength per unit weight, thickness, and ratio than the GF eggs (p < 0.01). There were differences in the mammillary layer thickness ratio, the effective layer thickness ratio, the quantity of bubble pores (QBPs), the ratio of the sum of the area of bubble pores to the area of the eggshell in each image (ARBE), and the average area of bubble pores (AABPs) between the DWL-White and GF eggs (p < 0.01). The composition analysis demonstrated that there were differences in the organic matter, inorganic matter, calcium, and phosphorus between the DWL-White and GF eggs (p < 0.01). There were positive associations between the mammillary knob number in the image and the QBPs and ARBE and a negative correlation with the AABPs in the DWL-White eggs (p < 0.01). This study observed distinctions that offer new insights into enhancing eggshell quality.
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To explore the genetic causal association between pulmonary artery hypertension (PAH) and iron status through Mendelian randomization (MR), we conducted MR analysis using publicly available genome-wide association study (GWAS) summary data. Five indicators related to iron status (serum iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and transferrin saturation) served as exposures, while PAH was the outcome. The genetic causal association between these iron status indicators and PAH was assessed using the inverse variance weighted (IVW) method. Cochran's Q statistic was employed to evaluate heterogeneity. We assessed pleiotropy using MR-Egger regression and MR-Presso test. Additionally, we validated our results using the Weighted median, Simple mode, and Weighted mode methods. Based on the IVW method, we found no causal association between iron status (serum iron, ferritin, TIBC, sTfR, and transferrin saturation) and PAH (p ß > 0.05). The Weighted median, Simple mode, and Weighted mode methods showed no potential genetic causal association (p ß > 0.05 in the three analyses). Additionally, no heterogeneity or horizontal pleiotropy was detected in any of the analyses. Our results show that there are no genetic causal association between iron status and PAH.
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Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.
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Diabetes Mellitus Tipo 1 , Duodeno , Mucosa Intestinal , Humanos , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Niño , Duodeno/metabolismo , Duodeno/patología , Femenino , Masculino , Proliferación Celular , Adolescente , Células Enteroendocrinas/metabolismo , Células Enteroendocrinas/patología , Intercambiador 3 de Sodio-Hidrógeno/metabolismo , Intercambiador 3 de Sodio-Hidrógeno/genética , Diferenciación Celular , Organoides/metabolismo , Organoides/patología , Antígeno Ki-67/metabolismoRESUMEN
In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogel demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogel effectively inhibited tumor growth, prolonged animal survival time and promoted anti-tumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogel exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective anti-tumor treatment and suppression of tumor recurrence.
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Doxorrubicina , Hidrogeles , Inmunoterapia , Péptidos , Especies Reactivas de Oxígeno , Animales , Hidrogeles/química , Hidrogeles/administración & dosificación , Doxorrubicina/química , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Péptidos/química , Péptidos/administración & dosificación , Péptidos/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Melanoma Experimental/terapia , Melanoma Experimental/inmunología , Ratones Endogámicos C57BL , Polietilenglicoles/química , Línea Celular Tumoral , Temperatura , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Portadores de Fármacos/químicaRESUMEN
The dilemma between the thickness and accessible active site triggers the design of porous crystalline materials with mono-layered structure for advanced photo-catalysis applications. Here, a kind of sub-nanometer mono-layered nanosheets (Co-MOF MNSs) through the exfoliation of specifically designed Co3 cluster-based metal-organic frameworks (MOFs) is reported. The sub-nanometer thickness and inherent light-sensitivity endow Co-MOF MNSs with fully exposed Janus Co3 sites that can selectively photo-reduce CO2 into formic acid under simulated flue gas. Notably, the production efficiency of formic acid by Co-MOF MNSs (0.85 mmol g-1 h-1) is ≈13 times higher than that of the bulk counterpart (0.065 mmol g-1 h-1) under a simulated flue gas atmosphere, which is the highest in reported works up to date. Theoretical calculations prove that the exposed Janus Co3 sites with simultaneously available sites possess higher activity when compared with single Co site, validating the importance of mono-layered nanosheet morphology. These results may facilitate the development of functional nanosheet materials for CO2 photo-reduction in potential flue gas treatment.
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The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.
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Proteína 2 de Unión a Metil-CpG , Ubiquitina-Proteína Ligasas , Femenino , Humanos , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , ADN/metabolismo , Metilación de ADN , Proteína 2 de Unión a Metil-CpG/genética , Proteína 2 de Unión a Metil-CpG/metabolismo , Oocitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.
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Inhibidor de la Unión a Diazepam , Ácido gamma-Aminobutírico , Animales , Ratones , Inhibidor de la Unión a Diazepam/farmacologíaRESUMEN
Daurisoline (DS) is an isoquinoline alkaloid that exerts anticancer activities in various cancer cells. However, the underlying mechanisms through which DS affects the survival of breast cancer cells remain poorly understood. Therefore, the present study was undertaken to investigate the potential anticancer effect of DS on breast cancer cells and reveal the mechanism underlying the enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by DS. Cell counting kit-8 (CCK-8) and 5-ethynyl-2-deoxyuridine (EdU) assay were used to evaluate the ability of cell proliferation. Flow cytometry was selected to examine the cell cycle distribution. TUNEL assay was used to detect the cell apoptosis. The protein expression was measured by Western blot analysis. DS was found to reduce the cell viability and suppress the proliferation of MCF-7 and MDA-MB-231 cells by causing G1 phase cell cycle arrest. DS could trigger apoptosis by promoting the cleavage of caspase-8 and PARP. The phosphorylation of ERK, JNK, and p38MAPK was upregulated clearly following DS treatment. Notably, SP600125 (JNK inhibitor) pretreatment significantly abrogated DS-induced PARP cleavage. DS inactivated Akt/mTOR and Wnt/ß-catenin signaling pathway and upregulated the expression of ER stress-related proteins. Additionally, DS amplified TRAIL-caused viability reduction and apoptosis in breast cancer cells. Mechanismly, DS upregulated the protein level of DR4 and DR5, and knockdown of DR5 attenuated the cotreatment-induced cleavage of PARP. Inhibition of JNK could block DS-induced upregulation of DR5. This study provides valuable insights into the mechanisms of DS inhibiting cell proliferation, triggering apoptosis, and enhancing TRAIL sensitivity of breast cancer cells.
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Background: Research on the risk factors for cervical cancer in Yunnan Province's four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking. Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention. Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis. Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P<0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P<0.01) was a causative factor of cervical cancer. Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.
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Injectable hydrogels are receiving increasing attention as local depots for sustained anticancer drug delivery. However, most current hydrogel-based carriers lack tissue-adhesive ability, a property that is important for the immobilization of drug-loaded systems at tumor sites to increase local drug concentration. In this study, we developed a paclitaxel (PTX)-loaded injectable hydrogel with firm tissue adhesion for localized tumor therapy. PTX-loaded bovine serum albumin (BSA) nanoparticles (PTX@BN) were prepared, and the drug-loaded hydrogel was then fabricated by cross-linking PTX@BN with o-phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) via a condensation reaction between OPA and the amines in BSA. The hydrogel showed firm adhesion to various organs and tumor tissues ex vivo due to the condensation reaction of unreacted OPA groups and amines in the tissues. The PTX-loaded nanocomposite hydrogels sustained PTX release over 30 days following the Korsmeyer-Peppas model and exhibited notable inhibition activities against mouse C26 colon and 4T1 breast cancer cells in vitro. Following peritumoral injection into mice with C26 or 4T1 tumors, the PTX@BN-loaded hydrogel significantly enhanced the antitumor efficacy and prolonged animal survival time compared to free PTX solutions with low systemic toxicity. Therefore, the adhesive, PTX-loaded nanocomposite hydrogels have the potential for efficient localized tumor therapy.
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Hidrogeles , Nanopartículas , Animales , Ratones , Adhesivos , Nanogeles , Línea Celular Tumoral , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Sistemas de Liberación de Medicamentos , Albúminas , Aminas , Portadores de Fármacos , Liberación de FármacosRESUMEN
BACKGROUND: As the second most prevalent hematologic malignancy, multiple myeloma (MM) affects plasma cells and is characterized by chromosomal abnormalities, particularly involving the immunoglobulin heavy chain switch region. MM represents a biologically and clinically heterogeneous hematological malignancy that serves as a clonal evolution model, exhibiting clonal heterogeneity throughout all stages from monoclonal gammopathy undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM. Although significant progress has been made in the treatment of MM, leading to improved patient outcomes, concerns are arising regarding disease relapse due to the presence and selection of pre-existing resistant clones or selective pressure during therapy. CASE PRESENTATION: We present a case of multiple myeloma (MM) in a female patient, who underwent an 8-year course of treatment, including chemotherapy, immunomodulators, hematopoietic stem cell transplantation, CD38 monoclonal antibody, and chimeric antigen receptor T-cell (CAR-T), and was recently diagnosed with concurrent progressive MM and acute myeloid leukemia (AML). This patient has witnessed the evolution of MM treatment paradigms. CONCLUSION: In this course, disease relapses occurred twice, one of which was manifested by a light chain escape (LCE). Moreover, through the course of the disease in this patient, we review the process of clonal evolution that may be relevant.
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Neoplasias Hematológicas , Leucemia Mieloide Aguda , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Humanos , Femenino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Paraproteinemias/patología , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Leucemia Mieloide Aguda/tratamiento farmacológico , InmunoterapiaRESUMEN
BACKGROUND: Day surgery is a new surgical model in which patients complete the admission, surgery, and discharge on the same day. OBJECTIVE: The present study aimed to explore the effect of pre-admission "quasi-collective" health education for patients with ophthalmic day surgery. METHODS: For this study, a total of 200 patients undergoing ophthalmic day surgery from February 2019 to December 2019 were enrolled as the research subjects. The patients were divided randomly into the observation group and the control group, with 100 cases in each group. For the control group, conventional health education was conducted after admission. On the day of admission, the admission education and peri-operative health education were performed. For the observation group, pre-admission health education was provided to the patients, and detailed education on the admission instructions, pre-operative precautions, and simulation of the intra-operative process were given by the medical staff. On the day of admission, the understanding of the education was evaluated, and any weaknesses in the health education were addressed. The anxiety status, method of handwashing, method of administering the drug to the eye, preoperative preparations, intra-operative training, preoperative medication, diet guidance, and postoperative care were compared between the two groups of patients. RESULTS: Before discharge, there were significant differences in the anxiety scores, impact, and satisfaction of health education between the two groups of patients, all of which were statistically significant (P< 0.05). CONCLUSION: The pre-admission "quasi-collective" health education for patients undergoing day surgery in ophthalmology was better than conventional health education.
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Oftalmología , Humanos , Procedimientos Quirúrgicos Ambulatorios , Cuidados Posoperatorios , Educación en Salud , EscolaridadRESUMEN
INTRODUCTION: Splenic marginal zone Lymphoma (SMZL) is a rare, chronic B lymphocyte proliferative disease. Generally, SMZL is accompanied by circulating atypical villous lymphocytes, known as SMZL with villous lymphocytes. Rituximab is a chimeric monoclonal antibody to CD20; recent but limited studies have confirmed its effectiveness in treating SMZL. Given the low incidence and selection of treatment, statistical comparisons of rituximab monotherapy with other available treatment options with the full range of data from previous clinical studies remain sparse. Here, we report a case of SMZL with villous lymphocytes treated by rituximab monotherapy, which is especially infrequently reported. CASE REPORT: A 63-year-old Chinese female was presented to the hospital with complaints of splenomegaly and pain in the spleen area. Immunohistochemistry analysis was positive for IGH, IGK, and IGL clonal rearrangement. Villous lymphocytes were found in peripheral blood and bone marrow, along with further immunotyping results. The case was considered as SMZL with villous lymphocytes. Based on the SMZLSG prognosis assessment, we applied rituximab monotherapy. After eight cycles of rituximab treatment, the patient's condition improved markedly, with blood constituent and size of the spleen returning to normal levels, achieving complete response, with no significant side effect observed. DISCUSSION: The patient provides a typical SMZL with villous lymphocytes case treated with rituximab monotherapy. Currently, the main treatment options include splenectomy and rituximab. After synthesizing a series of current views, we put forward our opinion about the selection of therapy for SMZL patients in order to gain maximum benefits for patients in need of treatment. CONCLUSION: Our analysis found no statistically significant difference between rituximab monotherapy and rituximab combined with chemotherapy, while rituximab treatments resulted in better therapeutic effects than chemotherapy. Rituximab monotherapy has favorable therapeutic effects and minor adverse effects (AEs) in treating SMZL.
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BACKGROUND AND OBJECTIVE: Although chronic obstructive pulmonary disease (COPD) is a common disease leading to further morbidity and significant mortality, there is still limited data on screening for COPD. The purpose of this study was to establish an early chronic obstructive pulmonary disease (COPD) screening system for the community and hospitals in Nanshan District in Shenzhen City, to improve the rate of early diagnosis and treatment of patients with COPD. METHODS: We identified individuals at high risk of COPD using a questionnaire survey and analyzed the relevant influencing factors in the early stages of COPD in high-risk groups. RESULTS: We collected a total of 5,000 COPD screening questionnaires, and a total of 449 patients were diagnosed with COPD by pulmonary function examination. The prevalence of COPD in people aged 20 and above in Nanshan District of Shenzhen City was estimated to be 8.98%, with a base of 5000. The severity classification as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was as follows: GOLD I accounted for 34.74%; GOLD II accounted for 37.64%; GOLD III accounted for 16.04%; and GOLD IV accounted for 11.58%. Common features of early COPD that we identified were: (1) patients were mainly males, accounting for 68.0%; (2) COPD was common among people aged 50-59 years, comprising 31%; (3) 96.0% of patients often had severe respiratory symptoms and had frequent coughs when they did not have a cold; (4) 57.2% of patients experienced shortness of breath when walking quickly on level ground or climbing gentle slopes; (5) 72.6% of patients had a family history of bronchial asthma and COPD. Multivariate ordinal multi-classification logistic regression showed that gender, age, shortness of breath, and the use of firewood, grass, and coal stoves were all influencing factors in pulmonary function grading. CONCLUSION: A screening questionnaire combined with a pulmonary function test should be adopted as a COPD screening strategy to be implemented at the primary level as a public health priority in China to reduce the incidence, disability, and mortality from COPD.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Masculino , Humanos , Femenino , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Pulmón , Disnea/epidemiología , Disnea/etiología , Diagnóstico PrecozRESUMEN
Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer; however, the underlying mechanisms are still not fully understood. Our study has revealed a close association between epigenetic regulation and cyclophosphamide (CTX)-induced ovarian damage. Specifically, CTX and its active metabolite 4-hydroperoxy cyclophosphamide (4-HC) were found to increase the apoptosis of granulosa cells (GCs) by reducing EZH2 and H3K27me3 levels, both in vivo and in vitro. Furthermore, RNA-seq and CUT&Tag analyses revealed that the loss of H3K27me3 peaks on promoters led to the overactivation of genes associated with transcriptional regulation and apoptosis, indicating that stable H3K27me3 status could help to provide a safeguard against CTX-induced ovarian damage. Administration of the H3K27me3-demethylase inhibitor, GSK-J4, prior to CTX treatment could partially mitigate GC apoptosis by reversing the reduction of H3K27me3 and the aberrant upregulation of specific genes involved in transcriptional regulation and apoptosis. GSK-J4 could thus potentially be a protective agent for female fertility when undergoing chemotherapy. The results provide new insights into the mechanisms for chemotherapy injury and future clinical interventions for fertility preservation.
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NASH is a highly prevalent metabolic syndrome that has no specific approved agents up to now. BBBP, which mainly contains bile acids, possess various pharmacological properties and some bile acids are available for NASH treatment. Herein, the therapeutic effects and underlying mechanisms of BBBP against NASH were systemically evaluated. In this study, mice received an HFHS diet over a 20-week period to induce NASH with or without BBBP intervention were used to evaluate the effect and underlying mechanisms of BBBP against NASH. Our results demonstrated that BBBP attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, and improved sensitivity to insulin and tolerance to glucose in mice fed an HFHS diet. Metabolomics and transcriptomic analysis revealed that BBBP suppressed the arginine biosynthesis by up-regulating NOS3 expression and the PI3K-Akt signaling pathway was also regulated by BBBP, as indicated by 55 DEGs. Bioinformatic analysis predicted the regulatory effect of the FXR/PXR-PI3K-AKT-NOS3 axis on arginine biosynthesis-related metabolites. These results were further confirmed by the significantly increased mRNA and protein levels of NOS3, PI3K (Pik3r2), and AKT1. And the increased levels of arginine biosynthesis related-metabolites, such as urea, aspartic acid, glutamic acid, citrulline, arginine, and ornithine, were confirmed accurately based on targeted metabolomics analysis. Together, our study uncoded the complicated mechanisms of anti-NASH activities of BBBP, and provided critical evidence inspiring the discovery of innovative therapies based on BBBP in the treatment of NASH.