Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

Control of the spider-like interference structure in photoelectron momentum distributions of a helium atom in a few-cycle nonlinear chirped laser pulse.

We investigate theoretically the photoelectron momentum distributions (PMDs) of the helium atom in the few-cycle nonlinear chirped laser pulse. The numerical results show that the direction of the spider-like interference structure in PMDs exhibits periodic variations with the increase of the chirp parameter. It is illustrated that the direction of the spider-like interference structure is related to the direction of the electron motion by tracking the trajectories of the electrons. We also demonstrate that the carrier-envelope phase can precisely control the opening of the ionization channel. In addition, we investigate the PMDs when a chirp-free second harmonic (SH) laser pulse is added to the chirped laser field, the numerical results show that the interference patterns can change from only spider-like interference structure to both spider-like and ring-like interference structures.

An adolescent with primary cutaneous follicle center lymphoma: a case report and literature review.

Primary cutaneous follicle center lymphoma (PCFCL) differs from follicular lymphoma in biological behavior and molecular profile and is treated as a distinct entity, according to the 5th edition of the World Health Organization classification of hematolymphoid tumors. It is an uncommon cutaneous B-cell lymphoma that is considerably rare in children and adolescents. To date, only 13 cases of individuals younger than 20 years of age have been reported in the literature. The lack of relevant clinical epidemiological data in this population has hampered the investigation of its clinical and diagnostic aspects. Here we report the case of a 17-year-old male with PCFCL, who may be the first PCFCL patient under 20 years of age reported in China. He was admitted to the hospital with a solitary nodule on his face. After complete surgical excision, the patient's facial mass was histologically identified as PCFCL. The patient's prognosis was favorable, with no recurrence at 17 months of follow-up after the surgical resection. We present a case of an adolescent PCFCL patient and systematically review the literature with a view to increase the awareness of the disease and inform the diagnosis and treatment of this age group.

Targeting ESM1/ VEGFα signaling axis: a promising therapeutic avenue for angiogenesis in cervical squamous cell carcinoma.

Background: Endothelial-specific molecule 1 (ESM1) dysregulation is widespread in various malignancies. However, the exact significance of ESM1 in cervical squamous cell carcinoma (CSCC) is not yet well understood. Methods: The expression of ESM1 in CSCC was probed by immunohistochemistry (IHC) assay using human specimens and validated and explored ESM1 in CSCC based on TNMplot and TCGA (The Cancer Genome Atlas Program) data repository. Further, the GSEA analysis and in vitro experiments of human CSCC cell lines, including SiHa and ME-180, were performed to investigate the masked molecular mechanisms of ESM1 in CSCC. Results: ESM1 was overexpressed in clinical CSCC tissues compared with paracancer controls, was an independent prognostic factor and was associated with poor prognosis in CSCC patients. These findings were further confirmed in the TNMplot and TCGA datasets. Furthermore, GSEA analysis revealed that the ESM1 high expression group was significantly enriched in carcinoma angiogenesis and the VEGFα signaling pathway. In addition, in vitro assays with human CSCC cell lines, including SiHa and ME-180, demonstrated that knockdown of ESM1 expression inhibited tumor cell proliferation, migration and invasion, resulting in attenuated VEGFα expression and blocked phosphorylation of VEGFR2 and ERK-1/2. Conclusion: In CSCC patients, ESM1 was considerably overexpressed. Upregulation of ESM1 is predictive of poor clinical outcomes in CSCC. Furthermore, ESM1 overexpression promoted carcinoma angiogenesis and CSCC progression through the VEGF/ERK signaling pathway. Hence, ESM1 and associated genes might be useful prognostic biomarkers or therapeutic targets for CSCC individuals.

Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report.

Waldenström macroglobulinemia (WM) rarely leads to pulmonary embolism. Due to its low incidence, the underlying pathophysiology, prognosis, and optimal treatment remain largely unexplored and uninvestigated. In this study, a patient with a double-clonal WM, a rare subtype, presented with pulmonary embolism. The patient had a small number of plasma cells without morphological abnormalities, and an effective therapeutic response was observed. Nonetheless, the clinical prognosis requires a long-term follow-up.

CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in uterine corpus endometrial carcinoma.

Background: The C-X-C motif chemokine ligand-9 (CXCL9) is related to the progression of multiple neoplasms. Yet, its biological functions in uterine corpus endometrioid carcinoma (UCEC) remain shrouded in confusion. Here, we assessed the prognostic significance and potential mechanism of CXCL9 in UCEC. Methods: Firstly, bioinformatics analysis of the public cancer database, including the Cancer Genome Atlas / the Genotype-Tissue Expression project (TCGA+ GTEx, n=552) and Gene Expression Omnibus (GEO): GSE63678 (n=7), were utilized for the CXCL9 expression-related analysis in UCEC. Then, the survival analysis of TCGA-UCEC was performed. Futher, the gene set enrichment analysis (GSEA) was carried out to reveal the potential molecular signaling pathway in UCEC associated with CXCL9 expression. Moreover, the immunohistochemistry (IHC) assay of our validation cohort (n=124) from human specimens were used to demonstrate the latent significance of CXCL9 in UCEC. Results: The bioinformatics analysis suggested that CXCL9 expression was significantly upregulated in UCEC patients; and hyper-expression of CXCL9 was related to prolonged survival. the GSEA enrichment analysis showed various immune response-related pathways, including T/NK cell, lymphocyte activation, cytokine-cytokine receptor interaction network, and chemokine signaling pathway, mediated by CXCL9. In addition, the cytotoxic molecules (IFNG, SLAMF7, JCHAIN, NKG7, GBP5, LYZ, GZMA, GZMB, and TNF3F9) and the immunosuppressive genes (including PD-L1) were positively related to the expression of CXCL9. Further, the IHC assay indicated that the CXCL9 protein expression was mainly located in intertumoral and significantly upregulated in the UCEC patients; UCEC with high intertumoral CXCL9 cell abundance harbored an improved prognosis; a higher ratio of anti-tumor immune cells (CD4+, CD8+, and CD56+ cell) and PD-L1 was found in UCEC with CXCL9 high expression. Conclusion: Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC. It hinted that CXCL9 may serve as an independent prognostic biomarker or therapeutic target in UCEC patients, which augmented anti-tumor immune effects to furnish survival benefits.

Preliminary study of TRPV4 affects chondrocyte degeneration / 中国骨伤

OBJECTIVE@#To explore and verify that transient receptor potential vanilloid 4(TRPV4) affects chondrocyte degeneration.@*METHODS@#Neonatal SD rats were selected, primary chondrocytes were extracted, and identified by toluidine blue staining and alcian blue staining;an in vitro chondrocyte inflammation model was constructed by IL-1β, and TRPV4 inhibitor was used to treat chondrocytes under inflammatory conditions, and the chondrocytes were treated by RT-PCR method was used to detect matrix metallopeptidase 13(MMP-13), a disintegrin and metalloproteinase with thrombospondin 5, (ADAMTS-5)、nitric oxide synthase 2(NOS2)、Collagen, type II alpha 1(Col2α1)and aggrecan (Acan) mRNA in chondrocytes; primary chondrocytes were treated with different concentrations of TRPV4 overexpression plasmid, and the optimal overexpression dose was screened. The mRNA expressions of TRPV4, MMP-13, ADAMTS-5, NOS2, Col2α1 and Acan in chondrocytes under the optimal TRPV4 overexpression dose were detected.@*RESULTS@#Toluidine blue staining and Alcian blue staining identified the extracted cells as primary chondrocytes;RT-PCR showed that TRPV4, MMP-13, ADAMTS-5, NOS2 mRNA in chondrocytes treated with TRPV4 inhibitor under inflammatory conditions. The expression of Col2α1 mRNA was significantly decreased (P<0.05), and the expression of Col2α1 mRNA was increased (P<0.05). Although there was no significant difference in the expression of Acan mRNA, the overall trend was also increasing. The expression of Col2α1 and Acan mRNA in chondrocytes was significantly decreased (P<0.05), and the expression of NOS2 mRNA was increased(P<0.05), but there was no significant difference in MMP-13 and ADAMTS-5 (P>0.05).@*CONCLUSION@#Inhibiting the expression of TRPV4 can down-regulate the expression of genes related to chondrocyte degeneration.

Ascorbic acid 6-palmitate modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated BV-2 cells via PERK/elF2α mediated endoplasmic reticulum stress.

BACKGROUND: Neuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells. METHODS: Immortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK). RESULTS: L-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation. CONCLUSION: Together, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.

Synthesis of disordered mesoporous silica loaded with ultrasmall-sized CuO nanoparticles based on an alkali-free strategy and its excellent catalytic performance in the reduction of organic dye.

In this paper, disordered mesoporous silica loaded with ultrasmall-sized and highly dispersed CuO nanoparticles was obtained by an alkali-free strategy. Pre-prepared copper bromoacetate (CuBA) and (3-aminopropyl)triethoxysilane (APTES) were selected as reactants, which can be covalently connected with each other for the formation of functional hybrid precursors. Simultaneously, the protonated amino group with the ability to promote the hydrolysis of silane was generated, avoiding any additional catalyst. The covalent introduction of copper salt by chemical bonding promised the molecular-level dispersion of copper ions, favouring the in situ generation of ultrasmall-sized and highly dispersed CuO nanoparticles in the silica matrix. The average diameter of this obtained composited silica material is around 700 nm, and CuO nanoparticles with an average diameter of ∼3 nm were uniformly dispersed in the silica matrix. Typically, disordered mesopores were obtained under the thermolysis of organic chains in the hybrid silica matrix; the BET surface area is 77 m2 g-1 and the pore diameter is about 2.5 nm. The catalytic property was investigated and the results show that this obtained CuO@mSiO2 material has good catalytic performance in the reduction of organic dye with NaBH4 as the reducing agent.

Aloe-Emodin Induces Mitochondrial Dysfunction and Pyroptosis by Activation of the Caspase-9/3/Gasdermin E Axis in HeLa Cells.

Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), derived from some Chinese edible medicinal herbs, exerts a potential anticancer activity on various cancer cells, making it a drug candidate for cancer therapy. Yet, the role of aloe-emodin in pyroptosis, a new type of cell death, is uncharacterized. In this study, we explored the molecular mechanisms of aloe-emodin-triggered pyroptosis. Aloe-emodin inhibited proliferation and migration and triggered caspase-dependent cell death of HeLa cells in a dose-dependent manner. Aloe-emodin caused mitochondrial dysfunction and induced pyroptosis by activating the caspase-9/3/GSDME axis. Transcriptional analysis showed extensive changes in gene expressions in cellular pathways, including MAPK, p53, and PI3K-Akt pathways when treated with aloe-emodin. This study not only identified a novel role of aloe-emodin in pyroptotic cell death, but also performed a systematical genome-wide analysis of cellular pathways responding to aloe-emodin, providing a theoretical basis for applying anthraquinone derivatives in the treatment of GSDME-expressing cancers.

Amentoflavone attenuates Listeria monocytogenes pathogenicity through an LLO-dependent mechanism.

BACKGROUND AND PURPOSE: L. monocytogenes remain a leading cause of foodborne infection. Listeriolysin O (LLO), an indispensable virulence determinant involved in diverse pathogenic mechanisms of L. monocytogenes infection, represents a promising therapeutic target. In this study, we sought to identify an effective inhibitor of LLO pore formation and its mechanism of action in the treatment of L. monocytogenes infection. EXPERIMENTAL APPROACH: Haemolysis assays were carried out to screen an effective LLO inhibitor. The interaction between candidate and LLO was investigated using surface plasmon resonance and molecular docking. The effect of candidate on LLO-mediated cytotoxicity, barrier disruption and immune response were investigated. Finally, the in vivo effect of candidate on mice challenged with L. monocytogenes was examined. KEY RESULTS: Amentoflavone, a natural flavone present in traditional Chinese herbs, effectively inhibited LLO pore formation by engaging the residues Lys93, Asp416, Tyr469 and Lys505 in LLO. Amentoflavone dose-dependently reduced L. monocytogenes-induced cell injury in an LLO-dependent manner. In the Caco-2 monolayer model, amentoflavone maintained the integrity of the epithelial barrier exposed to LLO. Amentoflavone inhibited the inflammatory response evoked by L. monocytogenes in an LLO-dependent manner, and inhibition was attributed to ability to block perforation-associated K+ efflux and Ca2+ influx. In the mouse infection model, amentoflavone treatment significantly reduced bacterial burden and pathological lesions in target organs, with a significant increase in survival rate. CONCLUSIONS AND IMPLICATIONS: Amentoflavone reduced the pathogenicity of L. monocytogenes by specifically inhibiting LLO pore formation, and this may represent a potential treatment for L. monocytogenes infection.

Photoelectron interference of He atoms in the attosecond ionization gating.

We theoretically investigate the photoelectron momentum distribution of He atoms by numerically solving the time-dependent Schro¨dinger equation (TDSE) in few-cycle ionization gating, which is synthesized by two linearly polarized laser pulses. When applying the TDSE, we can clearly see the spider-like structures in the photoelectron momentum spectra. We also find that the spider-like structures can be isolated by changing the relative phase. The directionality of the spider-like structure is changed from right-side to left-side and the ring-like interference structure gradually appears in the photoelectron momentum spectra when increasing the relative phase. The interference patterns observed in TDSE are recaptured well by the quantum-trajectory Monte Carlo (QTMC) model. We separate the ionization time window of the tunneling electron by analyzing the ionization rate. With the help of QTMC simulation, we illustrate the change of the interference structure and its directionality in the photoelectron momentum spectra. By changing the relative phase, the forward-backward asymmetry of the momentum distribution of the emitted electrons can also be controlled. Moreover, we find that the relative contribution of the nonrescattering and the rescattering trajectories can be controlled. These properties are beneficial for the application of photoelecron holography in probing atomic and molecular structures and dynamics.

Study on the influence of sex on age-related changes in renal function / 中华老年医学杂志

Objective:To evaluate the influence of sex on age-related changes in the glomerular filtration rate(GFR)in healthy individuals.Methods:A retrospective survey was performed.A total of 36 911 healthy subjects, of whom 43.61%(16 096 cases)were men, were enrolled and divided into six age groups: 18-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old.The estimated glomerular filtration rate(eGFR)was evaluated by the full age spectrum(FAS)equation.General linear regression analysis was used to calculate the annual decline rate of eGFR, and differences between the sexes in the same age group were evaluated using analysis of covariance.The chi-square test was used to compare the proportions of subjects with different eGFR levels between the sexes.Results:Regardless of sex, body mass index(BMI), systolic blood pressure(SBP)and fasting blood glucose(FBG)all increased gradually with age, while diastolic blood pressure(DBP)increased initially and then turned downward.The means of above results in men were generally higher than those in women of the same age.Before the age of 40, the levels of eGFR in men and women were relatively stable, with the mean eGFR in women higher than that in men[(121.98±16.77)ml·min -1·1.73 m -2vs.(111.01±13.36)ml·min -1·1.73 m -2, t=-53.793, P=0.000]; After the age of 40, eGFR decreased with age in both sexes, and the decline rate of eGFR in women was faster than that in men before the age of 70.Men had generally higher mean serum creatinine(Scr), blood urea nitrogen(BUN)and serum uric acid(UA)than women.With the increase of age, BUN levels increased gradually in men and women, but Scr levels started to increase after the age of 40 only in women and did not show a clear increase in men. Conclusions:There are sex-related differences with aging, as measured with many parameters.Young and middle-aged women have significantly higher eGFR than men of the same age, but eGFR declines faster with aging in women.

Clinical analysis of 30 cases of basal ganglia germinoma in children / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis.@*METHODS@#The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma.@*RESULTS@#A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker β-human chorionic gonadotropin (β-HCG) were normal in 8 patients.The serum β-HCG was normal in 11 patients but the cerebrospinal fluid β-HCG was slightly elevated, and the serum and cerebrospinal fluid β-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement.@*CONCLUSION@#The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.

Effect of comorbidities on the risk of chronic kidney disease with aging / 中华老年医学杂志

Objective:To explore the effect of comorbidities on the risk of chronic kidney disease with aging.Methods:A total of 103 682 subjects were recruited at the health management center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020 for a retrospective cross-sectional study.Participants were divided into four groups according to age 18-44(55 055 case), 45-59(31 023 case), 60-74(12 793 case), ≥75(4 811 case)age group.We calculated and compared the prevalences of estimated glomerular filtration rate(eGFR)<60 ml/min/1.73m 2, which was used as a parameter for kidney dysfunction, indifferent age groups and participants with different comorbidities.The association between comorbidities and the prevalence of kidney dysfunction was analyzed by Logistic regression. Results:Levels of blood pressure, body mass index, serum creatinine, eGFR and blood lipids varied with aging, as did the prevalences of hypertension, diabetes, obesity and comorbidities.In all participants and groups based on the types of chronic diseases, the prevalence of kidney dysfunction increased with aging, substantially so in ≥75 age group.After adjustment for age and sex, there was a marked increase in the risk of kidney dysfunction in 45-59 age group adults with hypertension or diabetes( OR=9.163, 95% CI: 3.264-25.727; OR=4.640, 95% CI: 1.028-20.936), and the risk of renal dysfunction increased in people with hypertension+ diabetes or with the coexistence of three diseases, compared with people with a single disease( OR=16.441, 95% CI: 5.325-50.783; OR=15.985, 95% CI: 4.237-60.312); In the 60-74 age group, hypertension alone also significantly increased the risk of renal dysfunction( OR=3.950, 95% CI: 1.911-8.165). With comorbidities, the most significant influence was the coexistence of three diseases( OR=6.245, 95% CI: 2.521-15.468), followed by hypertension+ obesity( OR=5.640, 95% CI: 2.550-12.476)and hypertension+ diabetes( OR=4.330, 95% CI: 1.990-9.421); In ≥75 age group, chronic diseases and comorbidities were associated with a high risk of renal dysfunction, with obesity alone and hypertension obesity posing the highest risk( OR=6.746, 95% CI: 2.193-20.757; OR=6.570, 95% CI: 3.178-13.582), followed by the coexistence of three diseases( OR=4.749, 95% CI: 2.110-10.687). Conclusions:The prevalence of hypertension, diabetes, and obesity varies with aging.The effect of chronic diseases on the risk of chronic kidney disease with reduced renal function in the elderly population is different from that in the non-elderly population.

MANF: A Novel Endoplasmic Reticulum Stress Response Protein-The Role in Neurological and Metabolic Disorders.

The mesencephalic astrocyte-derived neurotrophic factor (MANF), also named as arginine-rich protein (ARP) or arginine-rich mutated in early-stage tumors (ARMET), is a novel evolutionary conserved protein related to unfolded protein response. Growing evidence suggests that MANF critically involves in many ER stress-related diseases with a protective effect. Here, we review the function of MANF based on its structure in neurological and metabolic disorders and summarize its potential applications in disease diagnosis and therapies.

Study on changes in the glomerular filtration rate with aging and their influencing factors / 中华老年医学杂志

Objective:To evaluate changes in the estimate glomerular filtration rate(eGFR)with aging and the risk factors.Methods:A retrospective cross-sectional study was performed based on people receiving physical examinations at the First Affiliated Hospital of Nanjing Medical University from January 2017 to January 2018.Subjects were divided into seven subgroups according to age: 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥80 years old.eGFR was estimated by the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPIScr)equation.Multivariate linear regression was used to analyze the correlation between eGFR and the influencing variables.The chi-square test was used to compare the incidences of eGFR<60 ml·min -1·1.73m -2in different age groups. Results:A total of 33 824 participants were included in this study.There was a negative linear eGFR-age correlation in the subjects.The mean annual rate of decline in eGFR was 0.83 ml·min -1·1.73m -2.Furthermore, the decline was steady and accelerated from the third and seventh decade onward( F=9.51, 5.37, both P=0.000). Multiple linear regression analysis showed that aging was the most prominent factor( β=-0.604, -0.534, both P=0.000), followed by serum uric acid(BUA)( β=-0.270, -0.280, both P=0.000), fasting blood-glucose(FBG)( β=-0.064, -0.046, both P=0.000), systolic blood pressure(SBP)( β=-0.015, -0.028, both P<0.05), and diastolic blood pressure(DBP)( β=-0.010, -0.026, both P<0.05). In non-elderly subjects, eGFR was found to have negative associations with body mass index(BMI)and albumin(ALB)( β=-0.028, -0.047, all P=0.000). However, in the elderly, eGFR was positively associated with ALB( β=0.022, P=0.031). eGFR showed no statistically significant correlation with BMI, TC and LDL-C.The prevalence of eGFR<60 ml·min -1·1.73m -2increased with age, at 1.55%(523/33 824)for all subjects, of whom 73.80%(386/523)were aged over 60.The incidence obviously increased from 0.22%(14/6 453)for aged 18-29 to 22.57%(214/948)for aged 80 and above( χ2=2433.71, P=0.000). Conclusions:eGFR decreases significantly with age.The incidence of eGFR<60 ml·min -1·1.73m -2in the elderly is high; eGFR is significantly correlated with BUA, FBG, SBP, DBP, and ALB in the elderly.

Skin diseases in the Da Qing Diabetes Study: a cross-sectional study / 中华医学杂志(英文版)

BACKGROUND@#The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM.@*METHODS@#We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated.@*RESULTS@#In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01).@*CONCLUSIONS@#There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

Investigation of electron vortices in time-delayed circularly polarized laser pulses with a semiclassical perspective.

We theoretically investigate strong-filed electron vortices in time-delayed circularly polarized laser pulses by a generalized quantum-trajectory Monte Carlo (GQTMC) model. Vortex interference patterns in photoelectron momentum distributions (PMDs) with various laser parameters can be well reproduced by the semiclassical simulation. The phase difference responsible for the interference structures is analytically identified through trajectory-based analysis and simple-man theory, which reveal the underlying mechanism of electron vortex phenomena for both co-rotating and counter-rotating component. This semiclassical analysis can also demonstrate the influences of laser intensity and wavelength on the number of arms of vortices. Furthermore, we show the influence of the Coulomb effect on the PMDs. Finally, the controlling of the ionization time intervals in the tens to hundreds of attosecond magnitude is qualitatively discussed.