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Gut flora is considered to modulate lipid transport from the intestine into the bloodstream, and thus may potentially participate in the development of GDM. Although previous studies have shown that the intestinal microbiota influences lipid transport and metabolism in GDM, the precise mechanisms remain elusive. To address this, we used a high-fat diet (HFD)-induced GDM mouse model and conducted 16s rRNA sequencing and fecal metabolomics to assess gut microbial community shifts and associated metabolite changes. Western blot, ELISA, and chromatin immunoprecipitation (ChIP) were utilized to elucidate how gut microbiota affect intestinal lipid transport and the insulin sensitivity of hepatic, adipose, and skeletal muscle tissues. We found that HFD impaired the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in pregnant mice. 16s rRNA sequencing demonstrated profound compositional changes, especially in the relative abundances of Firmicutes and Bacteroidetes. Metabolomics analysis presented a decline in the concentration of short-chain fatty acids (SCFAs) in the GDM group. Western blot analyses showed an upregulation of HDAC3 and a concurrent reduction in H3K27 acetylation in the intestine. ChIP-qPCR showed that PPAR-γ was inhibited, which in turn activated lipid-transporter CD36. ELISA and insulin signaling pathway detection in insulin-target organs showed high concentrations of circulating fatty acids and triglycerides and insulin resistance in insulin-target organs. Our results suggest that gut microbiota is closely associated with the development of GDM, partly because decreased gut flora-associated SCFAs activate CD36 by suppressing the HDAC3-H3K27ac-PPAR-γ axis to transport excessive fatty acids and triglycerides into blood circulation, thereby dysregulating the insulin sensitivity of insulin target organs.
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This article is committed to studying projective synchronization and complete synchronization (CS) issues for one kind of discrete-time variable-order fractional neural networks (DVFNNs) with time-varying delays. First, two new variable-order fractional (VF) inequalities are built by relying on nabla Laplace transform and some properties of Mittag-Leffler function, which are extensions of constant-order fractional (CF) inequalities. Moreover, the VF Halanay inequality in discrete-time sense is strictly proved. Subsequently, some sufficient projective synchronization and CS criteria are derived by virtue of VF inequalities and hybrid controllers. Finally, we exploit numerical simulation examples to verify the validity of the derived results, and a practical application of the obtained results in image encryption is also discussed.
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Itch is one of the most common clinical symptoms in patients with diseases of the skin, liver, or kidney, and it strongly triggers aversive emotion and scratching behavior. Previous studies have confirmed the role of the prelimbic cortex (Prl) and the nucleus accumbens core (NAcC), which are reward and motivation regulatory centers, in the regulation of itch. However, it is currently unclear whether the Prl-NAcC projection, an important pathway connecting these two brain regions, is involved in the regulation of itch and its associated negative emotions. In this study, rat models of acute neck and cheek itch were established by subcutaneous injection of 5-HT, compound 48/80, or chloroquine. Immunofluorescence experiments determined that the number of c-Fos-immunopositive neurons in the Prl increased during acute itch. Chemogenetic inhibition of Prl glutamatergic neurons or Prl-NAcC glutamatergic projections can inhibit both histaminergic and nonhistaminergic itch-scratching behaviors and rectify the itch-related conditioned place aversion (CPA) behavior associated with nonhistaminergic itch. The Prl-NAcC projection may play an important role in the positive regulation of itch-scratching behavior by mediating the negative emotions related to itch.
Subject(s)
Neural Pathways , Nucleus Accumbens , Pruritus , Rats, Sprague-Dawley , Animals , Pruritus/physiopathology , Nucleus Accumbens/physiology , Nucleus Accumbens/drug effects , Male , Rats , Neural Pathways/physiology , Neural Pathways/physiopathology , Disease Models, Animal , Neurons/physiology , Avoidance Learning/physiology , Behavior, Animal/physiology , Prefrontal Cortex/physiology , Prefrontal Cortex/metabolism , Proto-Oncogene Proteins c-fos/metabolismABSTRACT
Background: Litchi (Litchi chinensis) is an important sub-tropical fruit in the horticulture market in China. Breeding for improved fruit characteristics is needed for satisfying consumer demands. Budding is a sustainable method for its propagation. During our ongoing breeding program, we observed a litchi mutant with flat leaves and sharp fruit peel cracking in comparison to the curled leaves and blunt fruit peel cracking fruits of the mother plant. Methods: To understand the possible molecular pathways involved, we performed a combined metabolome and transcriptome analysis. Results: We identified 1,060 metabolites in litchi leaves and fruits, of which 106 and 101 were differentially accumulated between the leaves and fruits, respectively. The mutant leaves were richer in carbohydrates, nucleotides, and phenolic acids, while the mother plant was rich in most of the amino acids and derivatives, flavonoids, lipids and organic acids and derivatives, and vitamins. Contrastingly, mutant fruits had higher levels of amino acids and derivatives, carbohydrates and derivatives, and organic acids and derivatives. However, the mother plant's fruits contained higher levels of flavonoids, scopoletin, amines, some amino acids and derivatives, benzamidine, carbohydrates and derivatives, and some organic acids and derivatives. The number of differentially expressed genes was consistent with the metabolome profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enriched gene expressions showed consistent profiles as of metabolome analysis. Conclusion: These results provide the groundwork for breeding litchi for fruit and leaf traits that are useful for its taste and yield.
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BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.
Subject(s)
Femoral Neck Fractures , Osteoporotic Fractures , Spinal Fractures , Humans , Female , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/complications , Body Mass Index , Retrospective Studies , Thinness/complications , Thinness/epidemiology , Bone Density , Absorptiometry, Photon , Spinal Fractures/diagnostic imaging , Spinal Fractures/epidemiology , Spinal Fractures/complications , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/epidemiology , Femoral Neck Fractures/complications , Obesity/complications , Obesity/epidemiology , Case-Control Studies , Lumbar Vertebrae/diagnostic imaging , China/epidemiologyABSTRACT
The plant cuticle is an important protective barrier on the plant surface, constructed mainly by polymerized cutin matrix and a complex wax mixture. Although the pathway of plant cuticle biosynthesis has been clarified, knowledge of the transcriptional regulation network underlying fruit cuticle formation remains limited. In the present work, we discovered that tomato fruits of the NAC transcription factor SlNOR-like1 knockout mutants (nor-like1) produced by CRISPR/Cas9 [clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9] displayed reduced cutin deposition and cuticle thickness, with a microcracking phenotype, while wax accumulation was promoted. Further research revealed that SlNOR-like1 promotes cutin deposition by binding to the promoters of glycerol-3-phosphate acyltransferase6 (SlGPAT6; a key gene for cutin monomer formation) and CUTIN DEFICIENT2 (SlCD2; a positive regulator of cutin production) to activate their expression. Meanwhile, SlNOR-like1 inhibits wax accumulation, acting as a transcriptional repressor by targeting wax biosynthesis, and transport-related genes 3-ketoacyl-CoA synthase1 (SlKCS1), ECERIFERUM 1-2 (SlCER1-2), SlWAX2, and glycosylphosphatidylinositol-anchored lipid transfer protein 1-like (SlLTPG1-like). In conclusion, SlNOR-like1 executes a dual regulatory effect on tomato fruit cuticle development. Our results provide a new model for the transcriptional regulation of fruit cuticle formation.
Subject(s)
Solanum lycopersicum , Transcription Factors , Transcription Factors/metabolism , Fruit/metabolism , Gene Expression Regulation, Plant , Phenotype , Waxes/metabolismABSTRACT
Traditional fermented milk from the western Sichuan plateau of China has a unique flavor and rich microbial diversity. This study explored the quality formation mechanism in fermented milk inoculated with Lactobacillus brevis NZ4 and Kluyveromyces marxianus SY11 (MFM), the dominant microorganisms isolated from traditional dairy products in western nan. The results indicated that MFM displayed better overall quality than the milk fermented with L. brevis NZ4 (LFM) and K. marxianus SY11 (KFM), respectively. MFM exhibited good sensory quality, more organic acid types, more free amino acids and esters, and moderate acidity and ethanol concentrations. Non-targeted metabolomics showed a total of 885 metabolites annotated in the samples, representing 204 differential metabolites between MFM and LFM and 163 between MFM and KFM. MFM displayed higher levels of N-acetyl-L-glutamic acid, cysteinyl serine, glaucarubin, and other substances. The differential metabolites were mainly enriched in pathways such as glycerophospholipid metabolism, arginine biosynthesis, and beta-alanine metabolism. This study speculated that L. brevis affected K. marxianus growth via its metabolites, while the mixed fermentation of these strains significantly changed the metabolism pathway of flavor-related substances, especially glycerophospholipid metabolism. Furthermore, mixed fermentation modified the flavor and quality of fermented milk by affecting cell growth and metabolic pathways.
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This paper is concerned with complete synchronization for discrete-time fractional-order fuzzy neural networks (DFFNNs) with time-varying delays. First, three original equalities and two Caputo σ-difference inequalities are established based on theory of discrete-time fractional Calculus. Next, a novel discrete-time adaptive controller with time-varying delay is designed, by virtue of 1-norm Lyapunov function and newly established lemmas herein as well as inequality techniques and contradiction method, some judgement conditions are derived to guarantee complete synchronization for the explored DFFNNs. Benefitting from discrete-time adaptive control strategy and our analysis method, the conservatism of the derived synchronization criteria is reduced. Ultimately, the effectiveness of our theoretical results and secure communication scheme are demonstrated through two numerical examples.
Subject(s)
Algorithms , Neural Networks, Computer , Time , CommunicationABSTRACT
In this paper, synchronization issue of discrete-time fractional fuzzy neural networks (DFFNNs) with delays is solved via quantized control, and is applied in image encryption. Firstly, a novel fractional-order h-difference inequality which makes Lyapunov method more flexible and practical is strictly proved based on the properties of convex functions and theory of discrete fractional calculus. Secondly, by using compression mapping theorem and mathematical induction, we obtain two sufficient conditions to ensure the existence and uniqueness of solutions for DFFNNs. Whereafter, we design a suitable quantized controller, which not only saves channel resources but also reduces control costs. By utilizing our inequality and some analytical techniques, several conservative synchronization criteria for DFFNNs are acquired. Finally, two examples are arranged to illustrate the validity and practicability of our results.
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This paper presents new theoretical results on quasi-projective synchronization (Q-PS) and complete synchronization (CS) of one kind of discrete-time fractional-order delayed neural networks (DFDNNs). At first, three new fractional difference inequalities for exploring the upper bound of quasi-synchronization error and adaptive synchronization are established by dint of Laplace transform and properties of discrete Mittag-Leffler function, which vastly expand a number of available results. Furthermore, two controllers are designed including nonlinear controller and adaptive controller. And on the basis of Lyapunov method, the aforementioned inequalities and properties of fractional-order difference operators, some sufficient synchronization criteria of DFDNNs are derived. Because of the above controllers, synchronization criteria in this paper are less conservative. At last, numerical examples are carried out to illustrate the usefulness of theoretical upshots.
Subject(s)
Algorithms , Neural Networks, ComputerABSTRACT
Background and Aims: The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study. Methods: We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia. Results: After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1. Conclusion: Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.
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This article studies synchronization issues for a class of discrete-time fractional-order quaternion-valued uncertain neural networks (DFQUNNs) using nonseparation method. First, based on the theory of discrete-time fractional calculus and quaternion properties, two equalities on the nabla Laplace transform and nabla sum are strictly proved, whereafter three Caputo difference inequalities are rigorously demonstrated. Next, based on our established inequalities and equalities, some simple and verifiable quasi-synchronization criteria are derived under the quaternion-valued nonlinear controller, and complete synchronization is achieved using quaternion-valued adaptive controller. Finally, numerical simulations are presented to substantiate the validity of derived results.
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BACKGROUND: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. METHODS: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. RESULTS: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p < 0.001). Additionally, the incidence rates of hypoglycemia in the three groups above were 3.66%, 4.13%, and 7.78%, respectively (p = 0.042). The blood glucose values of neonates with hypoglycemia in the asphyxia group were lower than in the control group (p = 0.003). Furthermore, the blood glucose values of neonates with hyperglycemia were highest in the severe asphyxia group (p < 0.001). There were 778 and 117 cases with blood glucose records at four predefined time points in the mild and severe asphyxia group, respectively. The incidence of blood glucose disorders in the mild asphyxia group significantly decreased from postnatal 6 h (pï¼0.05). However, we found no obvious changes of the incidence of glucose disorders within postnatal 12 h in the severe asphyxia group (p = 0.589). CONCLUSION: Birth asphyxia is likely to cause neonatal blood glucose disorders, both hypoglycemia and hyperglycemia, during the early postnatal life. The neonates with severe asphyxia have higher incidence, worse severity and longer duration of blood glucose disorders than neonates with mild asphyxia.
Subject(s)
Asphyxia Neonatorum , Hyperglycemia , Hypoglycemia , Infant, Newborn, Diseases , Humans , Infant, Newborn , Blood Glucose , Asphyxia , Retrospective Studies , Asphyxia Neonatorum/epidemiology , Infant, Newborn, Diseases/epidemiology , Hypoglycemia/epidemiology , Hypoglycemia/etiology , Hyperglycemia/epidemiology , China/epidemiologyABSTRACT
Interactions between alien plants and local enemies in introduced ranges may determine plant invasion success. However, little is known about whether herbivory-induced responses are transmitted across vegetative generations of plants and whether epigenetic changes are involved during this process. In a greenhouse experiment, we examined the effects of herbivory by the generalist herbivore Spodoptera litura on the growth, physiology, biomass allocation and DNA methylation level of the invasive plant Alternanthera philoxeroides in the first- (G1), second- (G2) and third-generation (G3). We also tested the effects of root fragments with different branching orders (i.e., the primary- or secondary-root fragments of taproots) of G1 on offspring performance. Our results showed that G1 herbivory promoted the growth of the plants in G2 that sprouted from the secondary-root fragments of G1 but had a neutral or negative effect on the growth of the plants in G2 from the primary-root fragments. The growth of plants in G3 was significantly reduced by G3 herbivory but not affected by G1 herbivory. Plants in G1 exhibited a higher level of DNA methylation when they were damaged by herbivores than when they were not, while neither plants in G2 nor G3 showed herbivory-induced changes in DNA methylation. Overall, the herbivory-induced growth response within one vegetative generation may represent the rapid acclimatization of A. philoxeroides to the unpredictable generalist herbivores in the introduced ranges. Herbivory-induced trans-generational effects may be transient for clonal offspring of A. philoxeroides, which can be influenced by the branching order of taproots, but be less characterized by DNA methylation.
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OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.
Subject(s)
Heart Failure , Hypotension , Neprilysin , Humans , Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Biphenyl Compounds/therapeutic use , Drug Combinations , East Asian People , Heart Failure/drug therapy , Heart Failure/genetics , Hypotension/chemically induced , Hypotension/genetics , Neprilysin/genetics , Polymorphism, Genetic , Stroke Volume , Tetrazoles/therapeutic use , Treatment Outcome , Valsartan/therapeutic useABSTRACT
Neuroblastoma has obvious heterogeneity. It is one of the few undifferentiated malignant tumors that can spontaneously degenerate into completely benign tumors. However, for its high-risk type, even with various intensive treatment options, the prognosis is still unsatisfactory. At the same time, a large number of research data show that the abnormal amplification and high-level expression of the MYCN gene are positively correlated with the malignant progression, poor prognosis, and mortality of neuroblastoma. In this context, this article explores the role of the N-Myc, MYCN gene expression product on its target genes related to the cell cycle and reveals its regulatory network in promoting tumor proliferation and malignant progression. We hope it can provide ideas and direction for the research and development of drugs targeting N-Myc and its downstream target genes.
Subject(s)
Neuroblastoma , Nuclear Proteins , Humans , Nuclear Proteins/metabolism , N-Myc Proto-Oncogene Protein/genetics , N-Myc Proto-Oncogene Protein/metabolism , Genes, myc , Cell Cycle/genetics , Neuroblastoma/pathology , Gene Expression Regulation, Neoplastic , Cell Line, TumorABSTRACT
The cuticle of plants, a hydrophobic membrane that covers their aerial organs, is crucial to their ability to withstand biotic and abiotic stressors. Fruit is the reproductive organ of plants, and an important dietary source that can offer a variety of nutrients for the human body, and fruit cuticle performs a crucial protective role in fruit development and postharvest quality. This review discusses the universality and diversity of the fruit cuticle composition, and systematically summarizes the metabolic process of fruit cuticle, including the biosynthesis, transport and regulatory factors (including transcription factors, phytohormones and environmental elements) of fruit cuticle. Additionally, we emphasize the postharvest functions and postharvest regulatory technologies of fruit cuticle, and propose future research directions for fruit cuticle.
Subject(s)
Membrane Lipids , Waxes , Humans , Membrane Lipids/metabolism , Waxes/chemistry , Fruit/chemistryABSTRACT
Itch is a complex and unpleasant sensory experience. Recent studies have begun to investigate the neural mechanisms underlying the modulation of sensory and emotional components of itch in the brain. However, the key brain regions and neural mechanism involved in modulating the attentional processing of itch remain elusive. Here, we showed that the prelimbic cortex (PrL) is associated with itch processing and that the manipulation of itch-responsive neurons in the PrL significantly disrupted itch-induced scratching. Interestingly, we found that increasing attentional bias toward a distracting stimulus could disturb itch processing. We also demonstrated the existence of a population of attention-related neurons in the PrL that drive attentional bias to regulate itch processing. Importantly, itch-responsive neurons and attention-related neurons significantly overlapped in the PrL and were mutually interchangeable in the regulation of itch processing at the cellular activity level. Our results revealed that the PrL regulates itch processing by controlling attentional bias.
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Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.
Subject(s)
Male , Adult , Humans , Aged , Lymphoma, Mantle-Cell/drug therapy , Prognosis , Retrospective Studies , Bone Marrow/pathology , Risk FactorsABSTRACT
OBJECTIVE@#To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding.@*METHODS@#One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells.@*RESULTS@#There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05).@*CONCLUSION@#Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.