Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.展开更多
OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxi...OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.展开更多
Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets...Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.展开更多
Prekallikrein deficiency is a disorder that often remains undiagnosed. Prekallikrein activates factor XII, which initiates the intrinsic coagulation pathway. Prekallikrein deficiency results in prolonged Partial Throm...Prekallikrein deficiency is a disorder that often remains undiagnosed. Prekallikrein activates factor XII, which initiates the intrinsic coagulation pathway. Prekallikrein deficiency results in prolonged Partial Thromboplastin Time and Activated Clotting Time in absence of anticoagulants or active bleeding. This case report describes the anesthesia management of a patient with Prekallikrein deficiency who underwent cardiac surgery with Cardiopulmonary Bypass for correction of a congenital cardiac malformation. We highlight the importance of understanding the different tests available for the diagnosis of coagulation factors deficiency during administration of heparin in the setting of cardiovascular procedures under general anesthesia.展开更多
Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BC...Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.展开更多
Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were admi...Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives.The clinical feature analysis included the evaluation of visual acuity,intraocular pressure,slit-lamp anterior segment examination,fundus photography,and spectral domain optical coherence tomography.To identify the mutation responsible for aniridia,targeted next-generation sequencing was used as a beneficial technique.Results A total of 4 mutations were identified,consisting of two novel frameshift mutations(c.314delA,p.K105Sfs*33 and c.838_845dup AACACACC,p.S283Tfs*85),along with two recurring nonsense mutations(c.307C>T,p.R103X and c.619A>T,p.K207*).Complete iris absence,macular foveal hypoplasia,and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families,while corneal lesions,cataracts,and glaucoma exhibited heterogeneity both among the families and within the same family.Conclusion In our study,two novel PAX6 mutations associated with aniridia were identified in Chinese families,which expanded the phenotypic and genotypic spectrum of PAX6 mutations.We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.展开更多
AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers ...AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.展开更多
Phosphorus(P) levels alter the allelopathic activity of rice seedlings against lettuce seeds. In this study, we investigated the effect of P deficiency on the allelopathic potential of non-pigmented and pigmented rice...Phosphorus(P) levels alter the allelopathic activity of rice seedlings against lettuce seeds. In this study, we investigated the effect of P deficiency on the allelopathic potential of non-pigmented and pigmented rice varieties. Rice seedlings of the white variety Khao Dawk Mali(KDML105, non-pigmented) and the black varieties Jao Hom Nin(JHN, pigmented) and Riceberry(RB, pigmented) were cultivated under high P(HP) and low P(LP) conditions. Morphological and metabolic responses to P deficiency were investigated. P deficiency inhibited shoot growth but promoted root growth of rice seedlings in all three varieties. Moreover, P deficiency led to decreased cytosolic phosphate(Pi) and total P concentrations in both shoot and root tissues. The subsequent reduction in internal P concentration enhanced the accumulation of phenolic compounds in both shoot and root tissues of the seedlings. Subsequently, allelopathy-based inter-and intra-specific interactions were assessed using water extracts from seedlings of the three varieties grown under HP and LP conditions. These extracts were tested on seeds of lettuce, the weed Dactyloctenium aegyptium, and the same rice variety. The shoot and root extracts from P-deficient seedlings reduced the germination of all recipient plants. Specifically, the shoot extract from P-deficient KDML105 seedlings reduced the germination index(GI) of lettuce seeds to 1%, while those from P-deficient RB and JHN seedlings produced GIs of 32% and 42%, respectively. However, when rice seeds were exposed to their own LP shoot and root extracts, their GIs increased up to 4-fold, compared with the HP extracts. Additionally, the shoot extracts from P-deficient plants also stimulated the germination of D. aegyptium by about 2–3-fold, whereas the root extracts did not have this effect. Therefore, P starvation led to the accumulation and exudation of phenolics in the shoots and roots of rice seedlings, altering their allelopathic activities. To adapt to P deficiency, rice seedlings potentially release signaling chemicals to suppress nearby competing species while simultaneously promoting their own germination and growth.展开更多
Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechani...Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechanisms on the crosstalk between ethylene-and N-regulated leaf senescence remain a mystery in maize.In this study,ethylene biosynthesis gene ZmACS7 overexpressing(OE-ZmACS7)plants were used to study the role of ethylene regulating leaf senescence in response to N deficiency,and they exhibited the premature leaf senescence accompanied by increased ethylene release,decreased chlorophyll content and F_v/F_m ratio,and accelerated chloroplast degradation.Then,we investigated the dynamics changes of transcriptome reprogramming underlying ethylene-accelerated leaf senescence in response to N deficiency.The differentially expressed genes(DEGs)involved in chlorophyll biosynthesis were significantly down-regulated,while DEGs involved in chlorophyll degradation and autophagy processes were significantly up-regulated,especially in OE-ZmACS7 plants in response to N deficiency.A gene regulatory network(GRN)was predicted during ethylene-accelerated leaf senescence in response to N deficiency.Three transcription factors(TFs)ZmHSF4,Zmb HLH106,and ZmEREB147 were identified as the key regulatory genes,which targeted chlorophyll biosynthesis gene ZmLES22,chlorophyll degradation gene ZmNYC1,and autophagy-related gene ZmATG5,respectively.Furthermore,ethylene signaling key genes might be located upstream of these TFs,generating the signaling cascade networks during ethylene-accelerated leaf senescence in response to N deficiency.Collectively,these findings improve our molecular knowledge of ethylene-accelerated maize leaf senescence in response to N deficiency,which is promising to improve NUE by manipulating the progress of leaf senescence in maize.展开更多
Needle chlorosis(NC)in Pinus taeda L.systems in Brazil becomes more frequent after second and third harvest rotation cycles.In a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grow...Needle chlorosis(NC)in Pinus taeda L.systems in Brazil becomes more frequent after second and third harvest rotation cycles.In a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grown in soils originating from contrasting parent materials,and soils and needles(whole,green and chlorotic portions)from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on P.taeda were analyzed for various elements and properties.All soils had very low base levels(Ca^(2+),Mg^(2+)and K^(+))and P,suggesting a possible lack of multiple elements.YNC symptoms started at needle tips,then extended toward the needle base with time.First flush needles had longer portions with YNC than second flush needles did.Needles from the lower crown also had more symptoms along their length than those higher in the canopy.Symptoms were similar to those reported for Mg.In chlorotic portions,Mg and Ca concentrations were well below critical values;in particular,Mg levels were only one third of the critical value of 0.3 g kg^(-1).Collectively,results suggest that Mg deficiency is the primary reason for NC of P.taeda in various parent soils in Brazil.展开更多
Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are susceptible to hemolytic anemia when exposed to pro-oxidant substances. This study investigates the hemolytic impact of Artemisia annua (A. annu...Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are susceptible to hemolytic anemia when exposed to pro-oxidant substances. This study investigates the hemolytic impact of Artemisia annua (A. annua) extracts in G6PD-deficient subjects through a mixed experimental approach. In the in vitro phase, red blood cells from G6PD-deficient individuals and rats induced with Dehydroepiandrosterone (DHEA) were exposed to various concentrations of A. annua infusion, with distilled water and physiological saline as positive and negative controls respectively. The in vivo study involved G6PD-deficient Wistar rats divided into three groups receiving A. annua infusion, quinine (positive control), and distilled water (negative control) via gavage. Blood samples were collected for biochemical and hematological analyses. Notably, at a 40% concentration of A. annua infusion, there was a significant increase in the hemolysis rate of G6PD-deficient red blood cells compared to controls (p A. annua exhibited elevated aspartate aminotransferase (129.25 ± 4.55 U/L vs. 80.09 ± 4.03 U/L;p A. annua infusion tested positive for saponins. These findings underscore the risk of hemolysis in G6PD-deficient individuals upon ingesting A. annua.展开更多
Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperative...Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperatively. However, although anemia and iron deficiency are significant global health problems, there are still disparities in the recognition and implementation of “Patient Blood Management” (PBM) as a comprehensive approach to mitigating the risks associated with these diseases. The purpose of the study is to review best practices for the treatment of anemia based on the Enhanced Recovery After Surgery (ERAS) protocol and PBM recommendations. Methods: This study reviewed the literature on preoperative iron deficiency anemia in patients undergoing gynecological surgery. We identified references through searches in PubMed using relevant search terms. Results: Among the various strategies used in PBM, perhaps the most important is the early detection and management of anemia. In gynecological surgery, there are several approaches to reducing perioperative blood loss, highlighting the use of gonadotropin-releasing hormone (GnRH) agonists (aGnRh) and antifibrinolytics. Oral and intravenous iron supplementation can be performed in addition to blood transfusion to treat anemia. Conclusion: Addressing preoperative and postoperative anemia through systematic correction, following the guidelines of the ERAS protocol and PBM guidelines, is essential to improving perioperative outcomes in women undergoing gynecological surgery.展开更多
Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in mo...Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.展开更多
Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive fa...Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.展开更多
Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD patt...Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.展开更多
Protein C(PC)is a key component of the vitamin K-dependent coagulation pathway.It exerts anticoagulant effects by inactivating factors V and VIII.Acquired or inherited PC deficiency results in a prothrombotic state,wi...Protein C(PC)is a key component of the vitamin K-dependent coagulation pathway.It exerts anticoagulant effects by inactivating factors V and VIII.Acquired or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous thromboembolism.However,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic stroke.This editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.展开更多
In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not ...Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.展开更多
Stomachache is one of the most common diseases of digestive system, among which stomach pain of deficiency cold of spleen and stomach is the most common. Acupuncture and moxibustion therapy as an external treatment of...Stomachache is one of the most common diseases of digestive system, among which stomach pain of deficiency cold of spleen and stomach is the most common. Acupuncture and moxibustion therapy as an external treatment of traditional Chinese medicine for relieving stomach pain due to deficiency of spleen and stomach, has the advantages of convenient operation, small adverse reactions and remarkable curative effect, which is easy for patients to accept. In this paper, acupuncture and moxibustion therapy such as moxibustion and warm acupuncture therapy for stomach pain of spleen and stomach deficiency cold type is summarized to provide evidence-based basis for clinical treatment of stomach pain of spleen and stomach deficiency cold type.展开更多
Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and mole...Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
基金Supported by the National Natural Science Foundation of China:Study on the Mechanism of Suspension Moxibustion with Moxa Stick in Treating Hydrocortisone Rats with Kidney-Yang Deficiency based on Hippocampus(amygdala)-HPA Axis(No.81660817)。
文摘OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.
文摘Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.
文摘Prekallikrein deficiency is a disorder that often remains undiagnosed. Prekallikrein activates factor XII, which initiates the intrinsic coagulation pathway. Prekallikrein deficiency results in prolonged Partial Thromboplastin Time and Activated Clotting Time in absence of anticoagulants or active bleeding. This case report describes the anesthesia management of a patient with Prekallikrein deficiency who underwent cardiac surgery with Cardiopulmonary Bypass for correction of a congenital cardiac malformation. We highlight the importance of understanding the different tests available for the diagnosis of coagulation factors deficiency during administration of heparin in the setting of cardiovascular procedures under general anesthesia.
文摘Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.
文摘Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives.The clinical feature analysis included the evaluation of visual acuity,intraocular pressure,slit-lamp anterior segment examination,fundus photography,and spectral domain optical coherence tomography.To identify the mutation responsible for aniridia,targeted next-generation sequencing was used as a beneficial technique.Results A total of 4 mutations were identified,consisting of two novel frameshift mutations(c.314delA,p.K105Sfs*33 and c.838_845dup AACACACC,p.S283Tfs*85),along with two recurring nonsense mutations(c.307C>T,p.R103X and c.619A>T,p.K207*).Complete iris absence,macular foveal hypoplasia,and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families,while corneal lesions,cataracts,and glaucoma exhibited heterogeneity both among the families and within the same family.Conclusion In our study,two novel PAX6 mutations associated with aniridia were identified in Chinese families,which expanded the phenotypic and genotypic spectrum of PAX6 mutations.We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.
文摘AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.
基金supported by the National Science Research and Innovation Fund and Prince of Songkla University, Thailand (Grant No. SCI6601035S)a Graduate Fellowship from the Faculty of Science, Prince of Songkla University, Thailand (Grant No. 1-2565-02-017)。
文摘Phosphorus(P) levels alter the allelopathic activity of rice seedlings against lettuce seeds. In this study, we investigated the effect of P deficiency on the allelopathic potential of non-pigmented and pigmented rice varieties. Rice seedlings of the white variety Khao Dawk Mali(KDML105, non-pigmented) and the black varieties Jao Hom Nin(JHN, pigmented) and Riceberry(RB, pigmented) were cultivated under high P(HP) and low P(LP) conditions. Morphological and metabolic responses to P deficiency were investigated. P deficiency inhibited shoot growth but promoted root growth of rice seedlings in all three varieties. Moreover, P deficiency led to decreased cytosolic phosphate(Pi) and total P concentrations in both shoot and root tissues. The subsequent reduction in internal P concentration enhanced the accumulation of phenolic compounds in both shoot and root tissues of the seedlings. Subsequently, allelopathy-based inter-and intra-specific interactions were assessed using water extracts from seedlings of the three varieties grown under HP and LP conditions. These extracts were tested on seeds of lettuce, the weed Dactyloctenium aegyptium, and the same rice variety. The shoot and root extracts from P-deficient seedlings reduced the germination of all recipient plants. Specifically, the shoot extract from P-deficient KDML105 seedlings reduced the germination index(GI) of lettuce seeds to 1%, while those from P-deficient RB and JHN seedlings produced GIs of 32% and 42%, respectively. However, when rice seeds were exposed to their own LP shoot and root extracts, their GIs increased up to 4-fold, compared with the HP extracts. Additionally, the shoot extracts from P-deficient plants also stimulated the germination of D. aegyptium by about 2–3-fold, whereas the root extracts did not have this effect. Therefore, P starvation led to the accumulation and exudation of phenolics in the shoots and roots of rice seedlings, altering their allelopathic activities. To adapt to P deficiency, rice seedlings potentially release signaling chemicals to suppress nearby competing species while simultaneously promoting their own germination and growth.
基金funded by the National Natural Science Foundation of China (31871546)China Postdoctoral Science Foundation (2022M720418)。
文摘Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechanisms on the crosstalk between ethylene-and N-regulated leaf senescence remain a mystery in maize.In this study,ethylene biosynthesis gene ZmACS7 overexpressing(OE-ZmACS7)plants were used to study the role of ethylene regulating leaf senescence in response to N deficiency,and they exhibited the premature leaf senescence accompanied by increased ethylene release,decreased chlorophyll content and F_v/F_m ratio,and accelerated chloroplast degradation.Then,we investigated the dynamics changes of transcriptome reprogramming underlying ethylene-accelerated leaf senescence in response to N deficiency.The differentially expressed genes(DEGs)involved in chlorophyll biosynthesis were significantly down-regulated,while DEGs involved in chlorophyll degradation and autophagy processes were significantly up-regulated,especially in OE-ZmACS7 plants in response to N deficiency.A gene regulatory network(GRN)was predicted during ethylene-accelerated leaf senescence in response to N deficiency.Three transcription factors(TFs)ZmHSF4,Zmb HLH106,and ZmEREB147 were identified as the key regulatory genes,which targeted chlorophyll biosynthesis gene ZmLES22,chlorophyll degradation gene ZmNYC1,and autophagy-related gene ZmATG5,respectively.Furthermore,ethylene signaling key genes might be located upstream of these TFs,generating the signaling cascade networks during ethylene-accelerated leaf senescence in response to N deficiency.Collectively,these findings improve our molecular knowledge of ethylene-accelerated maize leaf senescence in response to N deficiency,which is promising to improve NUE by manipulating the progress of leaf senescence in maize.
基金the National council for scientific and technological development(CNPq)and Higher Education Personnel Improvement Coordination(CAPES)。
文摘Needle chlorosis(NC)in Pinus taeda L.systems in Brazil becomes more frequent after second and third harvest rotation cycles.In a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grown in soils originating from contrasting parent materials,and soils and needles(whole,green and chlorotic portions)from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on P.taeda were analyzed for various elements and properties.All soils had very low base levels(Ca^(2+),Mg^(2+)and K^(+))and P,suggesting a possible lack of multiple elements.YNC symptoms started at needle tips,then extended toward the needle base with time.First flush needles had longer portions with YNC than second flush needles did.Needles from the lower crown also had more symptoms along their length than those higher in the canopy.Symptoms were similar to those reported for Mg.In chlorotic portions,Mg and Ca concentrations were well below critical values;in particular,Mg levels were only one third of the critical value of 0.3 g kg^(-1).Collectively,results suggest that Mg deficiency is the primary reason for NC of P.taeda in various parent soils in Brazil.
文摘Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are susceptible to hemolytic anemia when exposed to pro-oxidant substances. This study investigates the hemolytic impact of Artemisia annua (A. annua) extracts in G6PD-deficient subjects through a mixed experimental approach. In the in vitro phase, red blood cells from G6PD-deficient individuals and rats induced with Dehydroepiandrosterone (DHEA) were exposed to various concentrations of A. annua infusion, with distilled water and physiological saline as positive and negative controls respectively. The in vivo study involved G6PD-deficient Wistar rats divided into three groups receiving A. annua infusion, quinine (positive control), and distilled water (negative control) via gavage. Blood samples were collected for biochemical and hematological analyses. Notably, at a 40% concentration of A. annua infusion, there was a significant increase in the hemolysis rate of G6PD-deficient red blood cells compared to controls (p A. annua exhibited elevated aspartate aminotransferase (129.25 ± 4.55 U/L vs. 80.09 ± 4.03 U/L;p A. annua infusion tested positive for saponins. These findings underscore the risk of hemolysis in G6PD-deficient individuals upon ingesting A. annua.
文摘Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperatively. However, although anemia and iron deficiency are significant global health problems, there are still disparities in the recognition and implementation of “Patient Blood Management” (PBM) as a comprehensive approach to mitigating the risks associated with these diseases. The purpose of the study is to review best practices for the treatment of anemia based on the Enhanced Recovery After Surgery (ERAS) protocol and PBM recommendations. Methods: This study reviewed the literature on preoperative iron deficiency anemia in patients undergoing gynecological surgery. We identified references through searches in PubMed using relevant search terms. Results: Among the various strategies used in PBM, perhaps the most important is the early detection and management of anemia. In gynecological surgery, there are several approaches to reducing perioperative blood loss, highlighting the use of gonadotropin-releasing hormone (GnRH) agonists (aGnRh) and antifibrinolytics. Oral and intravenous iron supplementation can be performed in addition to blood transfusion to treat anemia. Conclusion: Addressing preoperative and postoperative anemia through systematic correction, following the guidelines of the ERAS protocol and PBM guidelines, is essential to improving perioperative outcomes in women undergoing gynecological surgery.
基金Open Project of Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake,Grant Number HZHLAB2201.
文摘Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.
文摘Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.
基金supported by the National Natural Science Foundation of China(32088101)National key Research and Development Program of China(2017YFC1700105,2021YFA1301603).
文摘Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.
文摘Protein C(PC)is a key component of the vitamin K-dependent coagulation pathway.It exerts anticoagulant effects by inactivating factors V and VIII.Acquired or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous thromboembolism.However,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic stroke.This editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2219-195 and No.BJ-2023-090).
文摘Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.
文摘Stomachache is one of the most common diseases of digestive system, among which stomach pain of deficiency cold of spleen and stomach is the most common. Acupuncture and moxibustion therapy as an external treatment of traditional Chinese medicine for relieving stomach pain due to deficiency of spleen and stomach, has the advantages of convenient operation, small adverse reactions and remarkable curative effect, which is easy for patients to accept. In this paper, acupuncture and moxibustion therapy such as moxibustion and warm acupuncture therapy for stomach pain of spleen and stomach deficiency cold type is summarized to provide evidence-based basis for clinical treatment of stomach pain of spleen and stomach deficiency cold type.
文摘Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.
