Plate subduction leads to complex exhumation processes on continents.The Huangling Massif lies at the northern margin of the South China Block.Whether the Huangling Massif was exhumed as a watershed of the middle reac...Plate subduction leads to complex exhumation processes on continents.The Huangling Massif lies at the northern margin of the South China Block.Whether the Huangling Massif was exhumed as a watershed of the middle reaches of the Paleo-Yangtze River during the Mesozoic remains under debate.We examined the exhumation history of the Huangling Massif based on six granite bedrock samples,using apatite fission track(AFT)and apatite and zircon(U-Th)/He(AHe and ZHe)thermochronology.These samples yielded ages of 157–132 Ma(ZHe),119–106 Ma(AFT),and 114–72 Ma(AHe),respectively.Thermal modeling revealed that three phases of rapid cooling occurred during the Late Jurassic–Early Cretaceous,late Early Cretaceous,and Late Cretaceous.These exhumation processes led to the high topographic relief responsible for the emergence of the Huangling Massif.The integrated of our new data with published sedimentological records suggests that the Huangling Massif might have been the watershed of the middle reaches of the Paleo-Yangtze River since the Cretaceous.At that time,the rivers flowed westward into the Sichuan Basin and eastward into the Jianghan Basin.The subduction of the Pacific Plate beneath the Asian continent in the Mesozoic deeply influenced the geomorphic evolution of the South China Block.展开更多
AIM: To compare apelin-13, a ligand of G-proteincoupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor(VEGF) serum levels in type 2 diabetes mellitus(T2DM)...AIM: To compare apelin-13, a ligand of G-proteincoupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor(VEGF) serum levels in type 2 diabetes mellitus(T2DM) with or without retinopathy, and to investigate the relationship between the serum concentration of apelin-13 and diabetes retinopathy.METHODS: Sixty-nine patients with T2 DM were enrolled.Of the 69 patients, 16 had proliferative diabetic retinopathy(PDR group), 23 had non-PDR(NPDR group)and 30 had no retinopathy(T2DM group). Subjects’ information, including demographics, medical history,and use of medications were recorded. Their serum samples were collected for measuring the levels of C-reactive protein(CRP), serum lipid and glycosylated hemoglobin. Apelin-13 and VEGF serum levels were measured by enzyme-linked immunosorbent assay.Kruskal-Wallis test and one-way ANOVA were used to compare the differences among these groups. Chi-square test was used to assess categorical variables.Correlations between variables were investigated by Spearman rho correlation test and stepwise regression analysis. All statistical analyses were performed through SPSS 17.0 software.RESULTS: Sex, age, body mass index(BMI), blood pressure, CRP, hemoglobin A1c(Hb A1c) have no significantly difference in the three groups. Serum level of apelin-13 was significantly elevated in PDR group as compared with T2 DM group(P =0.041). Differences of VEGF serum concentration in the three groups were statistically significant(P =0.007, P =0.007 and P 【0.001,respectively). Spearman rho correlation test showed that serum apelin-13 was positively correlated with BMI,serum triglycerides, VEGF, but not with age, duration of diabetes, blood pressure, CRP, Hb A1 c and total-cholesterol. Stepwise regression analysis showed that BMI also significantly associated with serum apelin-13(P =0.002), while VEGF and serum triglycerides were irrelevant. CONCLUSION: This study elucidated a positive association of apelin-13 serum level with PDR, but not with VEGF. Apelin-13 may influence the promotion of PDR but unrelated with VEGF.展开更多
Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patien...Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.展开更多
DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,th...DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,the neural mechanisms underlying cooperation among specific functional networks remain unclear from a global perspective.In this study,[^(18)F]-fluorodeoxyglucose positron emission tomography(FDG-PET)was performed on 19 male tree shrews after four different visual discrimination tasks,including baseline,learning expert(LE),reversal naive(RN),and reversal expert(RE).展开更多
Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8...Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.展开更多
Multi-wall carbon nanotubes reinforced Mg-14Li-1Al composite(MWCNTs/Mg-14Li-1Al) was prepared by the processes of electrophoretic deposition, friction stir processing, and cold rolling. The microstructure and mechanic...Multi-wall carbon nanotubes reinforced Mg-14Li-1Al composite(MWCNTs/Mg-14Li-1Al) was prepared by the processes of electrophoretic deposition, friction stir processing, and cold rolling. The microstructure and mechanical properties of the composite were investigated. The results show that, the microhardness of the composite is up to HV 84.4, which is 91.38% higher than that of the as-cast matrix alloy(HV 44.1). The yield strength and ultimate tensile strength of the composite are 259 and 313 MPa, which are 135.45% and 115.86% higher than those of the as-cast matrix alloy, respectively, and a high specific strength of 221.98 k N·m/kg is obtained. In the composite, the MWCNTs serve as nucleation particles during the friction stir processing and cold rolling, causing dynamic recrystallization and grain refinement. Furthermore, MWCNTs hinder the movement of dislocations and transfer the load from the matrix alloy, thus improving the strength.展开更多
Self-renewal and differentiation of skeletal stem and progenitor cells(SSPCs)are tightly regulated processes,with SSPC dysregulation leading to progressive bone disease.While the application of single-cell RNA sequenc...Self-renewal and differentiation of skeletal stem and progenitor cells(SSPCs)are tightly regulated processes,with SSPC dysregulation leading to progressive bone disease.While the application of single-cell RNA sequencing(scRNAseq)to the bone field has led to major advancements in our understanding of SSPC heterogeneity,stem cells are tightly regulated by their neighboring cells which comprise the bone marrow niche.However,unbiased interrogation of these cells at the transcriptional level within their native niche environment has been challenging.Here,we combined spatial transcriptomics and scRNAseq using a predictive modeling pipeline derived from multiple deconvolution packages in adult mouse femurs to provide an endogenous,in vivo context of SSPCs within the niche.This combined approach localized SSPC subtypes to specific regions of the bone and identified cellular components and signaling networks utilized within the niche.Furthermore,the use of spatial transcriptomics allowed us to identify spatially restricted activation of metabolic and major morphogenetic signaling gradients derived from the vasculature and bone surfaces that establish microdomains within the marrow cavity.Overall,we demonstrate,for the first time,the feasibility of applying spatial transcriptomics to fully mineralized tissue and present a combined spatial and single-cell transcriptomic approach to define the cellular components of the stem cell niche,identify cell-cell communication,and ultimately gain a comprehensive understanding of local and global SSPC regulatory networks within calcified tissue.展开更多
Objective:To investigate the effect of liraglutide combined with basal insulin on blood glucose control, lipid metabolism and oxidative stress in patients with newly diagnosed type 2 diabetes mellitus complicated by o...Objective:To investigate the effect of liraglutide combined with basal insulin on blood glucose control, lipid metabolism and oxidative stress in patients with newly diagnosed type 2 diabetes mellitus complicated by obesity.Methods: A total of 58 patients with newly diagnosed type 2 diabetes mellitus complicated by obesity who were diagnosed and treated in Xi'an No. 4 Hospital between February 2017 and August 2017 were divided into the control group (n=29) who received basal insulin therapy and the liraglutide group (n=29) who received liraglutide combined with basal insulin therapy according to random number table. The differences in the levels of glycolipid metabolism indexes and the contents of oxidative stress indexes were compared between the two groups before and after treatment.Results: Before treatment, the differences in the levels of glycolipid metabolism indexes in peripheral blood and the contents of oxidative stress indexes in serum were not statistically significant between the two groups. After 1 month of treatment, glucose metabolism indexes FBG and HOMA-IR levels in peripheral blood of liraglutide group were lower than those of control group;lipid metabolism indexes TC, TG, ApoB levels in peripheral blood were lower than those of control group, ApoA1 level was higher than those of control group;serum oxidation indexes MDA and LHP contents were lower than those of control group whereas anti-oxidation indexes GSH-Px and T-AOC contents were higher than those of control group.Conclusion: Liraglutide combined with basal insulin therapy can further control the glucolipid metabolism levels and inhibit the systemic oxidative stress response in patients with newly diagnosed type 2 diabetes mellitus complicated by obesity.展开更多
Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy...Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.展开更多
Background:Glioblastoma multiforme(GBM)is a kind of extremely malignant brain tumor with a poor prognosis.The problem of high recurrence rates and drug resistance has been difficult to solve.Cuproptosis is a newly dis...Background:Glioblastoma multiforme(GBM)is a kind of extremely malignant brain tumor with a poor prognosis.The problem of high recurrence rates and drug resistance has been difficult to solve.Cuproptosis is a newly discovered mode of cell death,which is related to the occurrence and progression of GBM.Methods:We screened TCGA and GEO databases to comprehensively analyze the regulation patterns of cuproptosis in GBM based on cuproptosis-related genes(CRGs).The expression levels,copy number variants(CNV),and mutation of CRGs in GBM were probed.Different regulation patterns of cuproptosis were identified and performed GSVA analysis.Then we constructed a prognostic model based on genes that were differentially expressed in all regulation patterns.The immune cells and tumor microenvironment in different risk groups were compared.Finally,the potential therapeutic drugs were predicted.Results:We identified two key differentially expressed genes under different regulation patterns of cuproptosis and constructed a risk prognostic model.There were significant differences in immune infiltration and drug sensitivity between high and low risk groups.Conclusions:We established a risk prognostic model based on two genes and explored its relationship with immune characteristics,which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of GBM patients.展开更多
Staphylococcus epidermidis is one of the leading pathogens of nosocomial infections. Twenty- eight strains of biofilm-negative Staphylococcus epidermidis, of which thirteen strains considered as the clinical strains w...Staphylococcus epidermidis is one of the leading pathogens of nosocomial infections. Twenty- eight strains of biofilm-negative Staphylococcus epidermidis, of which thirteen strains considered as the clinical strains were isolated from catheters, blood and urine of patients in Huashan Hospital (Shanghai, China) and fifteen strains considered as commensal strains were isolated from the skin of healthy students who had no contact with hospitals in recent half year, were investigated for the adherence to human umbilical vein endothelial cell line ECV304 and human cervical adenocarcinoma cell line Hela, respectively. Our results showed that the clinical strains were much more adhesive to both cells than commensal ones. The endothelial adherence may be a virulence factor associated with this bacterial pathogenesis.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant Nos.41671011,41871019,41877292,41972212)Research Foundation of Chutian Scholars Program of Hubei Province(Grant No.8210403)Shanxi Key Research and Development program:Feng Cheng(Grant No.2021SF2-03).
文摘Plate subduction leads to complex exhumation processes on continents.The Huangling Massif lies at the northern margin of the South China Block.Whether the Huangling Massif was exhumed as a watershed of the middle reaches of the Paleo-Yangtze River during the Mesozoic remains under debate.We examined the exhumation history of the Huangling Massif based on six granite bedrock samples,using apatite fission track(AFT)and apatite and zircon(U-Th)/He(AHe and ZHe)thermochronology.These samples yielded ages of 157–132 Ma(ZHe),119–106 Ma(AFT),and 114–72 Ma(AHe),respectively.Thermal modeling revealed that three phases of rapid cooling occurred during the Late Jurassic–Early Cretaceous,late Early Cretaceous,and Late Cretaceous.These exhumation processes led to the high topographic relief responsible for the emergence of the Huangling Massif.The integrated of our new data with published sedimentological records suggests that the Huangling Massif might have been the watershed of the middle reaches of the Paleo-Yangtze River since the Cretaceous.At that time,the rivers flowed westward into the Sichuan Basin and eastward into the Jianghan Basin.The subduction of the Pacific Plate beneath the Asian continent in the Mesozoic deeply influenced the geomorphic evolution of the South China Block.
基金Supported by National Natural Science Foundation of China (No.30971392 No.81170741)Science Foundation of Xi'an Bureau of Public Health (No.2013020)
文摘AIM: To compare apelin-13, a ligand of G-proteincoupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor(VEGF) serum levels in type 2 diabetes mellitus(T2DM) with or without retinopathy, and to investigate the relationship between the serum concentration of apelin-13 and diabetes retinopathy.METHODS: Sixty-nine patients with T2 DM were enrolled.Of the 69 patients, 16 had proliferative diabetic retinopathy(PDR group), 23 had non-PDR(NPDR group)and 30 had no retinopathy(T2DM group). Subjects’ information, including demographics, medical history,and use of medications were recorded. Their serum samples were collected for measuring the levels of C-reactive protein(CRP), serum lipid and glycosylated hemoglobin. Apelin-13 and VEGF serum levels were measured by enzyme-linked immunosorbent assay.Kruskal-Wallis test and one-way ANOVA were used to compare the differences among these groups. Chi-square test was used to assess categorical variables.Correlations between variables were investigated by Spearman rho correlation test and stepwise regression analysis. All statistical analyses were performed through SPSS 17.0 software.RESULTS: Sex, age, body mass index(BMI), blood pressure, CRP, hemoglobin A1c(Hb A1c) have no significantly difference in the three groups. Serum level of apelin-13 was significantly elevated in PDR group as compared with T2 DM group(P =0.041). Differences of VEGF serum concentration in the three groups were statistically significant(P =0.007, P =0.007 and P 【0.001,respectively). Spearman rho correlation test showed that serum apelin-13 was positively correlated with BMI,serum triglycerides, VEGF, but not with age, duration of diabetes, blood pressure, CRP, Hb A1 c and total-cholesterol. Stepwise regression analysis showed that BMI also significantly associated with serum apelin-13(P =0.002), while VEGF and serum triglycerides were irrelevant. CONCLUSION: This study elucidated a positive association of apelin-13 serum level with PDR, but not with VEGF. Apelin-13 may influence the promotion of PDR but unrelated with VEGF.
基金the Beijing Natural Science Foundation (No. 7174306)。
文摘Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.
基金supported by the National Natural Science Foundation of China(11975249,81771923,12175268,32071029,31861143037)China Postdoctoral Science Foundation(2021T140668)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32020000)。
文摘DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,the neural mechanisms underlying cooperation among specific functional networks remain unclear from a global perspective.In this study,[^(18)F]-fluorodeoxyglucose positron emission tomography(FDG-PET)was performed on 19 male tree shrews after four different visual discrimination tasks,including baseline,learning expert(LE),reversal naive(RN),and reversal expert(RE).
基金Scientific and Technical Development Project of Jiangsu Province (No. BS2006005)
文摘Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.
基金supported by the National Natural Science Foundation of China (Nos. 51871068, 51971071, 52011530025, and U21A2049)the National Key Research and Development Program of China (No. 2021YFE0103200)+1 种基金the Zhejiang Province Key Research and Development Program, China (No. 2021C01086)the Fundamental Research Funds for the Central Universities, China (No. 3072021CFT1010)。
文摘Multi-wall carbon nanotubes reinforced Mg-14Li-1Al composite(MWCNTs/Mg-14Li-1Al) was prepared by the processes of electrophoretic deposition, friction stir processing, and cold rolling. The microstructure and mechanical properties of the composite were investigated. The results show that, the microhardness of the composite is up to HV 84.4, which is 91.38% higher than that of the as-cast matrix alloy(HV 44.1). The yield strength and ultimate tensile strength of the composite are 259 and 313 MPa, which are 135.45% and 115.86% higher than those of the as-cast matrix alloy, respectively, and a high specific strength of 221.98 k N·m/kg is obtained. In the composite, the MWCNTs serve as nucleation particles during the friction stir processing and cold rolling, causing dynamic recrystallization and grain refinement. Furthermore, MWCNTs hinder the movement of dislocations and transfer the load from the matrix alloy, thus improving the strength.
基金funded by R01HD107034 and R21HD106162 by the NIH/NICHD(MCS)the Faculty of Surgery Pilot Research Award and grant HT94252310327 from the DoD(R.J.T.)。
文摘Self-renewal and differentiation of skeletal stem and progenitor cells(SSPCs)are tightly regulated processes,with SSPC dysregulation leading to progressive bone disease.While the application of single-cell RNA sequencing(scRNAseq)to the bone field has led to major advancements in our understanding of SSPC heterogeneity,stem cells are tightly regulated by their neighboring cells which comprise the bone marrow niche.However,unbiased interrogation of these cells at the transcriptional level within their native niche environment has been challenging.Here,we combined spatial transcriptomics and scRNAseq using a predictive modeling pipeline derived from multiple deconvolution packages in adult mouse femurs to provide an endogenous,in vivo context of SSPCs within the niche.This combined approach localized SSPC subtypes to specific regions of the bone and identified cellular components and signaling networks utilized within the niche.Furthermore,the use of spatial transcriptomics allowed us to identify spatially restricted activation of metabolic and major morphogenetic signaling gradients derived from the vasculature and bone surfaces that establish microdomains within the marrow cavity.Overall,we demonstrate,for the first time,the feasibility of applying spatial transcriptomics to fully mineralized tissue and present a combined spatial and single-cell transcriptomic approach to define the cellular components of the stem cell niche,identify cell-cell communication,and ultimately gain a comprehensive understanding of local and global SSPC regulatory networks within calcified tissue.
文摘Objective:To investigate the effect of liraglutide combined with basal insulin on blood glucose control, lipid metabolism and oxidative stress in patients with newly diagnosed type 2 diabetes mellitus complicated by obesity.Methods: A total of 58 patients with newly diagnosed type 2 diabetes mellitus complicated by obesity who were diagnosed and treated in Xi'an No. 4 Hospital between February 2017 and August 2017 were divided into the control group (n=29) who received basal insulin therapy and the liraglutide group (n=29) who received liraglutide combined with basal insulin therapy according to random number table. The differences in the levels of glycolipid metabolism indexes and the contents of oxidative stress indexes were compared between the two groups before and after treatment.Results: Before treatment, the differences in the levels of glycolipid metabolism indexes in peripheral blood and the contents of oxidative stress indexes in serum were not statistically significant between the two groups. After 1 month of treatment, glucose metabolism indexes FBG and HOMA-IR levels in peripheral blood of liraglutide group were lower than those of control group;lipid metabolism indexes TC, TG, ApoB levels in peripheral blood were lower than those of control group, ApoA1 level was higher than those of control group;serum oxidation indexes MDA and LHP contents were lower than those of control group whereas anti-oxidation indexes GSH-Px and T-AOC contents were higher than those of control group.Conclusion: Liraglutide combined with basal insulin therapy can further control the glucolipid metabolism levels and inhibit the systemic oxidative stress response in patients with newly diagnosed type 2 diabetes mellitus complicated by obesity.
文摘Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.
文摘Background:Glioblastoma multiforme(GBM)is a kind of extremely malignant brain tumor with a poor prognosis.The problem of high recurrence rates and drug resistance has been difficult to solve.Cuproptosis is a newly discovered mode of cell death,which is related to the occurrence and progression of GBM.Methods:We screened TCGA and GEO databases to comprehensively analyze the regulation patterns of cuproptosis in GBM based on cuproptosis-related genes(CRGs).The expression levels,copy number variants(CNV),and mutation of CRGs in GBM were probed.Different regulation patterns of cuproptosis were identified and performed GSVA analysis.Then we constructed a prognostic model based on genes that were differentially expressed in all regulation patterns.The immune cells and tumor microenvironment in different risk groups were compared.Finally,the potential therapeutic drugs were predicted.Results:We identified two key differentially expressed genes under different regulation patterns of cuproptosis and constructed a risk prognostic model.There were significant differences in immune infiltration and drug sensitivity between high and low risk groups.Conclusions:We established a risk prognostic model based on two genes and explored its relationship with immune characteristics,which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of GBM patients.
基金This work was supported by the Chinese National Natural Science Foundation(30670108)Shanghai Municipal Science and Technology Commission(05PJ14025).
文摘Staphylococcus epidermidis is one of the leading pathogens of nosocomial infections. Twenty- eight strains of biofilm-negative Staphylococcus epidermidis, of which thirteen strains considered as the clinical strains were isolated from catheters, blood and urine of patients in Huashan Hospital (Shanghai, China) and fifteen strains considered as commensal strains were isolated from the skin of healthy students who had no contact with hospitals in recent half year, were investigated for the adherence to human umbilical vein endothelial cell line ECV304 and human cervical adenocarcinoma cell line Hela, respectively. Our results showed that the clinical strains were much more adhesive to both cells than commensal ones. The endothelial adherence may be a virulence factor associated with this bacterial pathogenesis.