Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM ...Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.展开更多
Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This stud...Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.展开更多
Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes ...Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.展开更多
受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、...受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。展开更多
目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于...目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。展开更多
Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal co rd injury,several reports have described impairments in cognitive abilities.Our group also has contr...Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal co rd injury,several reports have described impairments in cognitive abilities.Our group also has contributed significantly to the study of cognitive impairments in a rat model of spinal co rd injury.These findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes,drugs of abuse,and combined medication.They are related to changes in brain structures involved in cognition and emotion,such as the hippocampus.Chronic spinal cord injury decreases neurogenesis,enhances glial reactivity leading to hippocampal neuroinflammation,and trigge rs cognitive deficits.These brain distal abnormalities are recently called te rtiary damage.Given that there is no treatment for Tertiary Damage,insulin growth factor 1 gene therapy emerges as a good candidate.Insulin growth factor 1 gene thera py recove rs neurogenesis and induces the polarization from pro-inflammato ry towards anti-inflammatory microglial phenotypes,which represents a potential strategy to treat the neuroinflammation that supports te rtiary damage.Insulin growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is crucial.Insulin growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.展开更多
Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an u...Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97110 amino acids of apoptin(AP)(AA@G))was constructed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced combination therapy.展开更多
目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总...目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总并分析该类制剂的研发现状。结果与结论有成药潜力的PD-1/PD-L1小分子抑制剂共20种,包括CA-170(口服小分子抑制剂)、INCB086550(特异性PD-L1抑制剂)、DPPA-1(特异性抑制PD-1/PD-L1相互作用的多肽类拮抗剂)等,其中前两者已进入临床试验阶段。PD-1/PD-L1小分子抑制剂具有特异性抑制免疫检查点的药效作用特点,以及可口服、稳定性较好、膜通透性较高等优点,但其治疗效果仍需临床试验验证。展开更多
目的探讨程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)单抗联合化学药物治疗(以下简称化疗)在局部晚期非小细胞肺癌新辅助治疗中的疗效和安全性。方法回顾性分析2021年6月至2023年6月于首都医科大学附属北京友谊医院胸外...目的探讨程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)单抗联合化学药物治疗(以下简称化疗)在局部晚期非小细胞肺癌新辅助治疗中的疗效和安全性。方法回顾性分析2021年6月至2023年6月于首都医科大学附属北京友谊医院胸外科43例接受新辅助免疫治疗联合化疗的局部晚期(ⅡB~ⅢB)非小细胞肺癌患者的临床资料,评估其影像学及病理学疗效,并观察免疫相关不良反应。结果影像学疗效评价显示客观缓解率为76.7%,疾病控制率为93.0%。34例(79.1%)接受手术的患者中,R0切除率97.1%、完全病理缓解率为29.4%、主要病理缓解率为55.9%。1~2级免疫相关不良反应发生率为67.4%,3级及以上不良反应发生率为7.0%。结论新辅助PD-1单抗联合化疗治疗非小细胞肺癌疗效显著,病理缓解率及R0切除率高,免疫相关不良反应及手术并发症在可接受范围内,安全性较高。展开更多
A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banti...A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.展开更多
基金from CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-002)National Key Clinical Specialty Construction Project(ZK108000)+1 种基金National High-Level Hospital Clinical Research Funding(2022-PUMCH-B-024)National Natural Science Foundation of China,Joint Fund Project(U20A600).
文摘Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.
基金supported by the National Key Research and Development Program of China[2018YFB0407200]National Natural Science Foundation of China[61975239]Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences[2019-I2M-5061].
文摘Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.
基金Corresponding author.Address:Department of Gastroenterology,Shangrao People’s Hospital,Shangrao 334000,Jiangxi Province,China.E-mail address:zylinzy@qq.com(Z.-Y Lin)Department of Gastroenterology,Shangrao People’s Hospital,Shangrao 334000,Jiangxi Province,China.E-mail address:28535324@qq.com(H.-J.Lian).
文摘Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.
文摘受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。
文摘目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。
基金funded by grants PICT 2017 N°0509 from Argentine Ministry of Science and Technology and PIP 2017-2019 N°00301 from The National Research Council of Argentina granted to FLthe grant from The National Research Council of Argentina PIP 2014-2017(extended to 2020)0618 awarded to MJB。
文摘Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal co rd injury,several reports have described impairments in cognitive abilities.Our group also has contributed significantly to the study of cognitive impairments in a rat model of spinal co rd injury.These findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes,drugs of abuse,and combined medication.They are related to changes in brain structures involved in cognition and emotion,such as the hippocampus.Chronic spinal cord injury decreases neurogenesis,enhances glial reactivity leading to hippocampal neuroinflammation,and trigge rs cognitive deficits.These brain distal abnormalities are recently called te rtiary damage.Given that there is no treatment for Tertiary Damage,insulin growth factor 1 gene therapy emerges as a good candidate.Insulin growth factor 1 gene thera py recove rs neurogenesis and induces the polarization from pro-inflammato ry towards anti-inflammatory microglial phenotypes,which represents a potential strategy to treat the neuroinflammation that supports te rtiary damage.Insulin growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is crucial.Insulin growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81272488 and 81602802)the Shaanxi Province Innovation Capacity Support Program(Grant No.:2018TD-002).
文摘Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97110 amino acids of apoptin(AP)(AA@G))was constructed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced combination therapy.
文摘目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总并分析该类制剂的研发现状。结果与结论有成药潜力的PD-1/PD-L1小分子抑制剂共20种,包括CA-170(口服小分子抑制剂)、INCB086550(特异性PD-L1抑制剂)、DPPA-1(特异性抑制PD-1/PD-L1相互作用的多肽类拮抗剂)等,其中前两者已进入临床试验阶段。PD-1/PD-L1小分子抑制剂具有特异性抑制免疫检查点的药效作用特点,以及可口服、稳定性较好、膜通透性较高等优点,但其治疗效果仍需临床试验验证。
文摘目的探讨程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)单抗联合化学药物治疗(以下简称化疗)在局部晚期非小细胞肺癌新辅助治疗中的疗效和安全性。方法回顾性分析2021年6月至2023年6月于首都医科大学附属北京友谊医院胸外科43例接受新辅助免疫治疗联合化疗的局部晚期(ⅡB~ⅢB)非小细胞肺癌患者的临床资料,评估其影像学及病理学疗效,并观察免疫相关不良反应。结果影像学疗效评价显示客观缓解率为76.7%,疾病控制率为93.0%。34例(79.1%)接受手术的患者中,R0切除率97.1%、完全病理缓解率为29.4%、主要病理缓解率为55.9%。1~2级免疫相关不良反应发生率为67.4%,3级及以上不良反应发生率为7.0%。结论新辅助PD-1单抗联合化疗治疗非小细胞肺癌疗效显著,病理缓解率及R0切除率高,免疫相关不良反应及手术并发症在可接受范围内,安全性较高。
基金Supported by the Juvenile Diabetes Research Foundation,No.4-2006-1025Diabetes Australia Research TrustTelethon Perth Children’s Hospital Research Fund(TPCHRF)grant to Jiang FX.
文摘A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.