ABSTRACT
OBJECTIVE: To analyze the serum metabolic targets of the "Zhibian (BL54) through Shuidao (ST28)" acupuncture technique in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI. METHODS: We used an intraperitoneal injection of CTX to establish the POI rat model (POI group) and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian (BL54) through Shuidao (ST28) technique (ZS + POI group) on ovarian function. Then, nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RESULTS: After acupuncture intervention, the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved. Moreover, UPLC-Q-TOF/MS results showed that the ZS + POI group showed a significant reversal of the levels of 6 differential metabolites. Among them, the levels of four serum metabolic markers, divanillyltetrahydrofuran ferulate, trans-ferulic acid, tryptamine, and neuraminic acid, increased significantly. Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects. CONCLUSIONS: The "Zhibian (BL54) through Shuidao (ST28)" acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects, which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.
Subject(s)
Acupuncture Therapy , Metabolomics , Primary Ovarian Insufficiency , Animals , Primary Ovarian Insufficiency/therapy , Primary Ovarian Insufficiency/blood , Primary Ovarian Insufficiency/metabolism , Female , Rats , Humans , Rats, Sprague-Dawley , Acupuncture Points , Ovary/metabolism , Disease Models, AnimalABSTRACT
ObjectiveRoot rot is one of the most serious diseases in the cultivation and production of Atractylodes lancea. Trichoderma spp. are effective in the biocontrol of root rot without causing environmental pollution. This study aims to isolate and study a Trichoderma strain capable preventing and controlling root rot from the rhizosphere of A. lancea and to solve the problem of disease prevention and control in the planting and production of A. lancea. MethodTrichoderma T2204 was isolated by the dilution-coating method and identified by ITS sequencing. The inhibitory activities of T2204 and its volatiles against two pathogenic fungal strains were examined by dual-culture and co-culture experiments. The biocontrol potential of T2204 on root rot of A. lancea and the effect of T2204 on the accumulation of medicinal compounds in the rhizosphere of A. lancea were investigated by pot experiments and GC-MS, respectively. In addition, the optimal medium, photoperiod, temperature, pH, and carbon and nitrogen sources for the culture of T2204 were explored. ResultThe Trichoderma isolate T2204 was identified as T. citrinoviride and had direct inhibitory effects on two highly pathogenic strains causing root rot. In the dual-culture experiments with the two pathogenic strains, T2204 showcased the inhibition rates of 77.90% and 76.80%, respectively. In the co-culture experiments with the two pathogenic strains, the volatile organic compounds produced by T2204 showed the inhibition rates of 57.11% and 81.11%, respectively. The pot experiments showed that the survival rate of A. lancea seedlings infected by root rot reached 100% after inoculation with T2204 and was only 50% in the case without inoculation of T2204. After 150 days of cultivation, the dry weight and atractylodin content of the rhizome of A. lancea plants treated with T2204 increased by 32% (P<0.05) and 11%, respectively, compared with the untreated group. The optimal conditions for the growth of T2204 were PDA or PSA medium, photoperiod of 12 h dark/12 h light, 25-30 °C, pH 5-6, carbon sources of glucose, D-fructose, soluble starch, and maltose, and the nitrogen sources of ammonium sulfate and ammonium dihydrogen phosphate. The optimal conditions for the sporulation of T2204 were PSA or CMA medium, photoperiod of 12 h dark/12 h light, 20-30 °C, pH 8, carbon source of sucrose, and nitrogen source of sodium nitrate. ConclusionT2204 could improve the growth and root rot resistance of A. lancea and promote the accumulation of medicinal compounds. The findings laid a foundation for the industrialized production and application of T2204 in the production of A. lancea in the future.
ABSTRACT
With the maturity and development of surgical techniques, as well as the improvement of perioperative management level, the success rate of kidney transplantation has been significantly improved. However, due to evident differences in heredity and antigenicity between donors and recipients, rejection will occur after kidney transplantation, which will affect the survival of renal grafts. Immunosuppression is an important treatment for rejection, which is of significance to reduce the risk of rejection and enhance graft survival rate. Nevertheless, immunosuppressants may cause multiple complications while lowering the incidence of rejection, such as infection, cardiovascular diseases and tumors, etc., which seriously affect the quality of life of patients and may even lead to their death. Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts. In this article, the development history of organ transplantation, immune induction therapy and immune maintenance therapy was reviewed, and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed, aiming to provide reference for improving clinical prognosis of kidney transplant recipients.
ABSTRACT
Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data(including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography), imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
Subject(s)
Humans , Connexins/genetics , Connexin 26/genetics , Hearing Loss, Central/genetics , Deafness/genetics , MutationABSTRACT
Objective:To dentify the genetic and audiological characteristics of families affected by late-onset hearing loss due to GSDMEgene mutations, aiming to explore clinical characteristics and pathogenic mechanisms for providing genetic counseling and intervention guidance. Methods:Six families with late-onset hearing loss from the Chinese Deafness Genome Project were included. Audiological tests, including pure-tone audiometry, acoustic immittance, speech recognition scores, auditory brainstem response, and distortion product otoacoustic emission, were applied to evaluate the hearing levels of patients. Combining with medical history and physical examination to analyze the phenotypic differences between the probands and their family members. Next-generation sequencing was used to identify pathogenic genes in probands, and validations were performed on their relatives by Sanger sequencing. Pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics Guidelines. Meanwhile, the pathogenic mechanisms of GSDME-related hearing loss were explored combining with domestic and international research progress. Results:Among the six families with late-onset hearing loss, a total of 30 individuals performed hearing loss. The onset of hearing loss in these families ranged from 10 to 50 years(mean age: 27.88±9.74 years). In the study, four splicing mutations of the GSDME were identified, including two novel variants: c. 991-7C>G and c. 1183+1G>T. Significantly, the c. 991-7C>G was a de novo variant. The others were previously reported variants: c. 991-1G>C and c. 991-15_991-13del, the latter was identified in three families. Genotype-phenotype correlation analysis revealed that probands with the c. 991-7C>G and c. 1183+1G>T performed a predominantly high-frequency hearing loss. The three families carrying the same mutation exhibited varying degrees of hearing loss, with an annual rate of hearing deterioration exceeding 0.94 dB HL/year. Furthermore, follow-up of interventions showed that four of six probands received intervention(66.67%), but the results of intervention varied. Conclusion:The study analyzed six families with late-onset non-syndromic hearing loss linked to GSDME mutations, identifying four splicing variants. Notably, c. 991-7C>G is the first reported de novo variant of GSDME globally. Audiological analysis revealed that the age of onset generally exceeded 10 years,with variable effectiveness of interventions.
Subject(s)
Humans , Adolescent , Young Adult , Adult , Child , Hearing Loss, Sensorineural/diagnosis , Deafness/genetics , Mutation , Hearing Loss/genetics , PedigreeABSTRACT
Nicotinamide adenine dinucleotide(NADH) in its reduced form of is a key coenzyme in redox reactions, essential for maintaining energy homeostasis.NADH and its oxidized counterpart, NAD+, form a redox couple that regulates various biological processes, including calcium homeostasis, synaptic plasticity, anti-apoptosis, and gene expression. The reduction of NAD+/NADH levels is closely linked to mitochondrial dysfunction, which plays a pivotal role in the cascade of various neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease.Auditory neuropathy(AN) is recognized as a clinical biomarker in neurodegenerative disorders. Furthermore, mitochondrial dysfunction has been identified in patients with mutations in genes like OPA1and AIFM1. However, effective treatments for these conditions are still lacking. Increasing evidence suggests that administratering NAD+ or its precursors endogenously may potentially prevent and slow disease progression by enhancing DNA repair and improving mitochondrial function. Therefore, this review concentrates on the metabolic pathways of NAD+/NADH production and their biological functions, and delves into the therapeutic potential and mechanisms of NADH in treating AN.
Subject(s)
Humans , NAD/metabolism , Neurodegenerative Diseases/metabolism , Mitochondria , Oxidation-Reduction , Mitochondrial DiseasesABSTRACT
Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‒49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‒17.9%, which was significantly higher than that (6.9%‒7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Subject(s)
Humans , Apoptosis Inducing Factor/metabolism , NAD/metabolism , Dimerization , ApoptosisABSTRACT
Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
ABSTRACT
Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI
ABSTRACT
COVID-19, caused by SARS-CoV-2, has recently affected over 300,000 people and killed more than 10,000. The manner in which the key immune cell subsets change and their states during the course of COVID-19 remain unclear. Here, we applied single-cell technology to comprehensively characterize transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19. Compared with healthy controls, in patients in the early recovery stage (ERS) of COVID-19, T cells decreased remarkably, whereas monocytes increased. A detailed analysis of the monocytes revealed that there was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1B+ monocytes in the ERS. CD4+ and CD8+ T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naive B cells decreased. Our study identified several novel B cell-receptor (BCR) changes, such as IGHV3-23 and IGHV3-7, and confirmed isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicted that IL-1{beta} and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2 and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting that COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19. Highlights- The immune response was sustained for more than 7 days in the early recovery stage of COVID-19, suggesting that COVID-19 patients are still vulnerable after hospital discharge. - Single-cell analysis revealed a predominant subset of CD14++ IL1{beta}+ monocytes in patients in the ERS of COVID-19. - Newly identified virus-specific B cell-receptor changes, such as IGHV3-23, IGHV3-7, IGHV3-15, IGHV3-30, and IGKV3-11, could be helpful in the development of vaccines and antibodies against SARS-CoV-2. - IL-1{beta} and M-CSF were discovered as novel mediators of inflammatory cytokine storm, and TNFSF13, IL-2, IL-4, and IL-18 may be beneficial for recovery.
ABSTRACT
The aim of this study was to explore the clinical features, hearing prognosis and differential diagnosis of recurrent low frequency sensorineural hearing loss (RLFD) . The clinical characteristics, clinical manifestations, audiological examination and auxiliary examination of RLFD patients were retrospectively analyzed. We summarized clinical features, draw the pure tone audiometry curves, and analyze the diagnosis of RLFD. Forty-seven patients (53 ears) with RLFD had a hearing review time of 1-124 months. The course of disease ranged from 3 to 320 months with an average course of 29 months. ①The incidence of tinnitus in the accompanying symptoms was 93.6%(44 cases), and the ear suffocation was 83.0%(39 cases), 38.3% (18 cases) of the patients developed vestibular symptoms during the course of the disease. ②During the observation period, 27 cases(57.4%) were diagnosed with related diseases: 7 cases(14.9%) Meniere's disease, 6 cases(12.8%) vestibular migraine, 2 cases(4.3%) with Meniere's disease and migraine, and 1 case(2.1%) with idiopathic intracranial hypotension 11 cases(23.4%) were possible cochlear migraine; ③Migraine-related RLFD had a younger onset age, more common in women; ④83.0%(44 ears)of the affected ears had stable or improved low-frequency hearing during the observation period, 17.0%(9 ears)of the affected ears experienced low-frequency hearing; ⑤18.9%(10 ears)of the affected ears had high-frequency hearing loss; ⑥RLFD had 6 types of audiological outcomes: low-frequency improvement combined with high-frequency stability; low-frequency stability combined with high-frequency stability; low frequency progress combined with high frequency stability type; low frequency improvement combined with high frequency progress type; low frequency stability combined with high frequency progress type; low frequency progress combined with high frequency progress type; ⑦Rising type hearing curve low frequency hearing prognosis is good, mountain type and descending low frequency hearing prognosis is poor. Tinnitus and ear stuffiness are the early symptoms and the most disturbing symptoms in patients with RLFD. The mechanism of Migraine may play an important role in the pathogenesis of RLFD. The rare causes such as intracranial hypotension syndrome should not be ignored. Most of the patients with RLFD had stable or improved hearing after long-term fluctuation, but some patients with low or high frequency hearing might decline. The type of initial hearing curve was a prognostic factor. Long-term hearing follow-up is helpful for prognosis evaluation.
ABSTRACT
Objective:To investigate the effect of Suhuang Zhike Capsule on airway inflammation in patients with acute episode of allergic rhinitis and asthma syndrome.Methods:Eighty patients with allergic rhinitis and asthma syndrome were admitted to North China University of Science and Technology Affiliated Hospital from June 2016 to September 2017.A prospective cohort study was carried out and randomly divided into treatment group and control group with 40 patients in each group.The control group was treated with conventional anti-inflammatory, expectorant and antiasthmatic therapy, while the treatment group was treated with Suhuang Zhike Capsule.The changes of nasal symptoms and asthma clinical symptoms in the two groups were compared before and after treatment, and the changes of nitric oxide in exhaled air, eosinophils in blood and induced sputum were measured.Results:Compared with the control group, there was no significant difference in the number of eosinophils in the exhaled nitric oxide, eosinophil count in blood and induced sputum before treatment in the treatment group ((161.45±4.67)×10 -9 vs.(163.12±4.56)×10 -9, (1.59±0.53)×10 9/L vs.(1.60±0.51)×10 9/L, (1.11±0.06)×10 9/L vs.(1.18±0.09)×10 9/L; t values were 0.10, 0.44, 1.75, respectively, all P>0.05). After treatment, the exhaled nitric oxide, eosinophil count in blood and induced sputum in the treatment group were significantly lower than those before treatment((30.86±5.54)×10 -9 vs. (161.45±4.67)×10 -9; (0.32±0.05)×10 9/L vs. (1.59±0.53)×10 9/L; (0.06±0.02)×10 9/L vs. (1.11±0.06)×10 9/L, t values were 91.32, 41.63, 51.77, respectively, all P<0.01). In the treatment group, the effective rate of nasal symptom control was 85.0% (34/40) significantly higher than 62.5% (25/40) in the control group (χ 2=5.23, P<0.05), and the effective rate of asthma clinical symptom control was significantly higher than that in the control group(90.0%(36/40), 72.5%(29/40), χ 2=4.02, P<0.05). Conclusion:Suhuang Zhike capsule can obviously improve the airway inflammatory response of patients with allergic rhinitis asthma syndrome in the acute attack stage, and the combination of conventional treatment plan is helpful to improve the curative effect.
ABSTRACT
Objective@#The aim of this study was to explore the clinical features, hearing prognosis and differential diagnosis of recurrent low frequency sensorineural hearing loss (RLFD) . @*Method@#The clinical characteristics, clinical manifestations, audiological examination and auxiliary examination of RLFD patients were retrospectively analyzed. We summarized clinical features, draw the pure tone audiometry curves, and analyze the diagnosis of RLFD. @*Result@#Forty-seven patients (53 ears) with RLFD had a hearing review time of 1-124 months. The course of disease ranged from 3 to 320 months with an average course of 29 months. ①The incidence of tinnitus in the accompanying symptoms was 93.6%(44 cases), and the ear suffocation was 83.0%(39 cases), 38.3% (18 cases) of the patients developed vestibular symptoms during the course of the disease. ②During the observation period, 27 cases(57.4%) were diagnosed with related diseases: 7 cases(14.9%) Meniere's disease, 6 cases(12.8%) vestibular migraine, 2 cases(4.3%) with Meniere's disease and migraine, and 1 case(2.1%) with idiopathic intracranial hypotension 11 cases(23.4%) were possible cochlear migraine; ③Migraine-related RLFD had a younger onset age, more common in women; ④83.0%(44 ears)of the affected ears had stable or improved low-frequency hearing during the observation period, 17.0%(9 ears)of the affected ears experienced low-frequency hearing; ⑤18.9%(10 ears)of the affected ears had high-frequency hearing loss; ⑥RLFD had 6 types of audiological outcomes: low-frequency improvement combined with high-frequency stability; low-frequency stability combined with high-frequency stability; low frequency progress combined with high frequency stability type; low frequency improvement combined with high frequency progress type; low frequency stability combined with high frequency progress type; low frequency progress combined with high frequency progress type; ⑦Rising type hearing curve low frequency hearing prognosis is good, mountain type and descending low frequency hearing prognosis is poor. @*Conclusion@#Tinnitus and ear stuffiness are the early symptoms and the most disturbing symptoms in patients with RLFD. The mechanism of Migraine may play an important role in the pathogenesis of RLFD. The rare causes such as intracranial hypotension syndrome should not be ignored. Most of the patients with RLFD had stable or improved hearing after long-term fluctuation, but some patients with low or high frequency hearing might decline. The type of initial hearing curve was a prognostic factor. Long-term hearing follow-up is helpful for prognosis evaluation.
ABSTRACT
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
Objective To investigate the synergistic effects of tannic acid(TA) and cis-dichlorodiamine platinum(CDDP) on hepatocellular carcinoma HepG2 cells and its activation situation of endoplasmic reticulum stress(ERS) pathway.Methods Human hepatocellular carcinoma HepG2 cells were divided into the control group,TA group,CDDP group and TA+CDDP group,and were cultured in vitro for 24 h.The growth inhibitory effect of medication on HepG2 cells was detected by MTT assay.The pharmacodynamics synergistic effect between the two drugs was analyzed by the drug interaction index,drug dose reduction index and equivalent graphical method.The nucleus changes were observed by DAPI staining.Real time fluorescent quantitative PCR(q-RT-PCR) and Western blot were used to detect the levels of ERS markers glucose regulated protein (GRP)78 and GRP94.Results TA and CDDP had dose-dependent growth inhibition effect on HepG2 cells,their median effective concentrations(IC50) were 360.00 μmol/L and 1.80 μg/mL respectively.The combination treatment of 180.00 μmol/L TA and 0.90 μg/mL CDDP on HepG2 cells could enhance the inhibitory effect on cell growth.Ta and CDDP had synergistic effect for inhibiting hepatocellular carcinoma cells growth.Compared with the TA group and CDDP group,cell shrinkage and rounding were accelerated in the combined group,apoptotic cells were increased,nuclear had pyknosis,irregular edge and dense staining,nuclear fragmentations were increased and the expressions of GRP78 and GRP94 were up-regulated.Conclusion TA can enhance the effect of CDDP on anti-hepatic carcinoma HepG2 cells,and the synergy mechanism may be related to the activation of ERS pathway.
ABSTRACT
Objective To explore the choice of handling methods for bilateral internal ring during the transumbilical single-site laparoscopic orchiopexy for cryptorchidism with bilateral processus vaginalis unclosed in children,and evaluate the clinical effect.Methods Retrospective analysis was conducted for the clinical data of 102 children with cryptorchidism and bilateral processus vaginalis unclosed who were hospitalized at Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2011 to January 2016.They were divided into the observation group (55 cases) and the control group(47 cases).In the observation group,the internal rings of the affected side were destroyed and stitched with a needle between the edge of arcuate of musculus trasversus abdominis and fascia trans versalis of posterior peritoneum.If the diameter of opposite internal ring was less than 0.5 cm,only a circle was destroyed.Otherwise,a circle was destroyed and sutured with a needle.In the control group,the processing methods for orchiopexy and affected side internal ring were same as the observation group.Purse string suture was done for opposite internal rings of all cases in the control group.The parameters of operative duration,intraoperative blood loss,postoperative hospital stay,postoperative complications were compared between 2 groups.Results All operations were successful in both groups,spermatic cords were reserved and testicles were in scrotum of all cases.Operative duration was significantly shorter in the observation group than that in the control group [(42.02 ± 3.21) min vs.(48.43 ± 4.18) min,t =-8.739,P < 0.01].The differences in intraoperative blood loss,postoperative hospital stay and postoperative complications between 2 groups were not statistically significant[(4.38 ± 1.42) mL vs.(4.80 ± 1.37) mL,t =-1.533,P >0.05;(2.87 ±0.64) dvs.(2.98 ±0.61) d,t =-0.853,P >0.05;1.8% (1/55 cases) vs.2.1%(1/47 cases),x2 =0.013,P > 0.05].During a mean follow-up of 30(12-72) months,there was no case of testicular ascent or atrophy,or hernia,or hydrocele.Conclusions The transumbilical single-site 3-port laparoscopic orchiopexy for cryptorchidism has stable efficacy.The improved method for bilateral internal ring is simple and has satisfactory effect,which is worthy of clinical promotion.
ABSTRACT
Objective To evaluate the clinical effect of treatment for high intra-abdominal cryptorchidism of children with transumbilical single-site and multichannel laparoscopic single stage Fowler-Stephens (F-S) orchiopexy.Methods The case records of the intra-abdominal cryptorchidism of children who had undergone transumbilical single-site laparoscopic single stage F-S orchiopexy were reviewed retrospectively in Children's Hospital Affiliated to Capital Institute of Pediatrics between January 2011 and January 2017,were assigned as the observation group,whose age ranged from 1 to 8 years and average age was 18 months,with 22 unilateral and 8 bilateral,38 testis in total.A total of 31 children with intra-abdominal cryptorchidism who had undergone laparoscopic two stage F-S orchiopexy were assigned as the control group,whose age was from 11 months to 9 years and average age was 20 months,with 23 unilateral and 8 bilateral,39 testis in total.Postoperative follow-ups were conducted with the evaluation index included the testical position,with or without atrophy.The procedure effect and postoperative complications were observed,and the difference between two operation methods was evaluated.Results Operations in all cases were successful in both groups without intraoperative complication.A total of 38 testis were operated with single stage F-S orchiopexy in the observation group,and 39 testis were operated with two stage F-S orchiopexy in the control group.Postoperative complications included scrotum wound infection one case and scrotum hematoma in one case in the observation group,and abdominal wall emphysema in one case,intestinal obstruction in one case as well as umbilicus infection 1 case in control group.Follow-ups ranged from 6 months to 6 years,median 24 months.All testicals were within the scrotum,and each group had 1 case of testical atrophy.The difference of postoperative complication and effect between two groups had no statistical significance(x2 =0.184,0.107,all P > 0.05).Conclusions Outcomes between single stage and two stage F-S orchiopexy are similar.The transumbilical single-site laparoscopic F-S orchiopexy not only has the satisfactory effect,but also saves some patients from reoperation and secondary anaesthesia,but doctors must be aware of the indications and contraindications of this procedure should be brought to attention.
ABSTRACT
Objective To detect the activation levels of endoplasmic reticulum stress ATF6-CHOP pathway,and to investigate the molecular mechanism of tannic acid (TA) combined with cisplatin (CDDP) against hepatocellular carcinoma.Methods HepG2 cells were cultured with 180 μM TA or/and 0.9 μg/ml CDDP for 24 h or 48 h.The levels of ATF6 (ATF6α),ATF6B (ATF6β) and CHOP were analyzed by real-time fluorescence quantitative PCR (q-RT-PCR) and western blot.Results We found that after 24 h or 48 h,compared with the control group,ATF6 mRNA and protein levels,ATF6B protein level,CHOP mRNA and protein levels were significantly increased in the TA group,CDDP group or combination group (P < 0.01 or P < 0.05).Conclusion TA can combine with CDDP to increase the levels of endoplasmic reticulum stress ATF6-CHOP pathway,and the ATF6-CHOP pathway may be one of the molecular mechanisms synergistic anti-hepatocellular carcinoma effect of TA and CDDP on HepG2 cells.