Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve ...Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.展开更多
In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use ...In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.展开更多
AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures,...AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category(lamotrigine or levetiracetam, n=16), an "intermediate risk" category(carbamazepine, oxcarbazepine, phenytoin, or valproate, n=34) and a "high risk" category(topiramate, n=5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant(P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category(P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient(ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient(linear regression analysis, P > 0.15) were observed. CONCLUSION Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.展开更多
Acupuncture at the Taichong (LR 3), Sanyinjiao (SP 6) and Ciliao (BL 32) points combined with TCM drugs for soothing the liver, replenishing the kidney, freeing the seminal passage, and eliminating the stasis showed e...Acupuncture at the Taichong (LR 3), Sanyinjiao (SP 6) and Ciliao (BL 32) points combined with TCM drugs for soothing the liver, replenishing the kidney, freeing the seminal passage, and eliminating the stasis showed effective for functional retrograde ejaculation in 25 cases. The total effective rate of 68.0% was significantly better than imipramine used in the control group (P<0.05).展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
The fundamental limitations of most vascular-based functional neuroimaging techniques are placed by the fact how fine the brain regulates the blood supply system.In vivo mapping of the cerebral microcirculation with h...The fundamental limitations of most vascular-based functional neuroimaging techniques are placed by the fact how fine the brain regulates the blood supply system.In vivo mapping of the cerebral microcirculation with high resolution and sensitivity hence becomes unprecedentedly compelling.This paper reviews the theoretical background of the laser speckle contrast imaging(LSCI)technique and attempts to present a complete framework stemming from a simple biophysical model.Through the sensitivity analysis,more insights into the tool optimization are attained for in vivo applications.Open questions of the technical aspects are discussed within this unified framework.Finally,it concludes with a brief perspective of future research in a way analogous to the magnetic resonance imaging(MRI)technique.Such exploration could catalyze their development and initiate a technological fusion for precise assessment of blood flow across various spatial scales.展开更多
Objective: To understand the effects of several commonly used antipsychotics on the renal function of patients with mental illness. Method: Collected patients with mental illness who were hospitalized in our hospital ...Objective: To understand the effects of several commonly used antipsychotics on the renal function of patients with mental illness. Method: Collected patients with mental illness who were hospitalized in our hospital from January 2020 to June 2021, and selected as the research subjects patients with psychiatric disorders who were treated with 2 kinds of commonly used antipsychotic drugs;and collected 3 ml of venous blood before treatment and one month after treatment for renal function tests;observed the changes of renal function indexes before and after treatment. Results: In the collected 694 patients with mental illness, before using antipsychotic drugs, the renal function indexes were BUN: 4.42 ± 1.92 mmol/l;Cr: 70.97 ± 16.92 μmol/l;CCr: 88.37 ± 21.07 ml/min;β2-MG: 1.67 ± 0.61 mg/L;UA: 359.90 ± 112.82 μmol/l;CYS-C: 0.92 ± 0.24 mg/L. One month after using antipsychotics, BUN: 3.77 ± 1.37 mmol/l;Cr: 70.46 ± 16.71 μmol/l;CCr: 87.78 ± 20.63 ml/min;β2-MG: 1.75 ± 0.64 mg/L;UA: 332.53 ± 91.48 umol/l;CYS-C: 0.92 ± 0.24 mg/L;the renal function indexes of urea nitrogen, β2 microglobulin, uric acid and other items all changed significantly. The differences before and after treatment were statistically significant, P < 0.01. Conclusion: Several commonly used antipsychotic drugs have a greater impact on the renal function of patients with mental illness. During the treatment, the changes in renal function should be monitored regularly, if severe renal damage is found, the treatment plan or dosage should be adjusted in time to avoid endangering life.展开更多
Objective: To investigate the effects of antiplatelet drug combined with magnesium sulfate on platelet function and trophoblast apoptosis in patients with preeclampsia. Methods: A total of 68 patients with preeclampsi...Objective: To investigate the effects of antiplatelet drug combined with magnesium sulfate on platelet function and trophoblast apoptosis in patients with preeclampsia. Methods: A total of 68 patients with preeclampsia who were treated in this hospital between September 2016 and September 2017 were chosen as the research subjects and divided into the control group (n=34) and the study group (n=34) by the random number table method. Control group received magnesium sulfate spasmolysis, and study group received low-dose aspirin combined with magnesium sulfate therapy. The differences in the levels of platelet function parameters as well as the expression levels of apoptosis-related genes and invasion-related genes in placental tissues were compared between the two groups of patients after treatment. Results:After treatment, the platelet function parameter PLT level in study group was higher than that in control group whereas MPV and PDW levels were lower than those in control group;pro-apoptosis genes Caspase-3, p53 and bax mRNA expression levels in placental tissues were lower than those of control group whereas anti-apoptosis gene bcl-2 mRNA expression level was higher than that of control group;pro-invasion genes MMP-2, MMP-9 and CXCL16 mRNA expression levels in placental tissues were higher than those of control group whereas anti-invasion genes RECK and DPPⅣ mRNA expression levels were lower than those of control group. Conclusion: Low-dose aspirin combined with magnesium sulfate treatment of patients with preeclampsia can effectively optimize the platelet function and inhibit the apoptosis of placental trophoblast cells and promote their invasion function.展开更多
Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV...Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.展开更多
Objective To explore the immune function injur y and its mechanism in drug abuser.Methods The immune function changes in50drug abusers were compared with normal healthy populations by detection of the indexes of subgr...Objective To explore the immune function injur y and its mechanism in drug abuser.Methods The immune function changes in50drug abusers were compared with normal healthy populations by detection of the indexes of subgroups of Th cells,transformation rate of lymphocytes,IgA,IgM,IgG,IgE,com pliment C 3 ,C 4 ,IL-1,IL-2,IL-6TNF and NO.Result In peripheral blood the percentage o f Th 1 cell,transformation rate of lymphocyte,IgA,IgM,IgG,IgE content,complime nt C4,C4,IL-1,IL-2,IL-6,and TNF le vels were significantly lower than normal (P <0.01).The value of Th 1 /Th 2 was lower than normal as well(P <0.05).NO content was significantly higher than normal (P <0.001).Conclusion The mechanism of immune function inj ury in drug abuser might be correlative to direct injury of drugs and their inhibition effect on the thymu s-hypothalamus-hypophysis-adren al axis.展开更多
Objective: to explore the methods of drug adjustment and pharmaceutical care for the anti-infection treatment plan of clinical pharmacists for methicillin-sensitive staphylococcus aureus bacteremia patients with renal...Objective: to explore the methods of drug adjustment and pharmaceutical care for the anti-infection treatment plan of clinical pharmacists for methicillin-sensitive staphylococcus aureus bacteremia patients with renal hyperfunction. Methods: clinical pharmacists analyzed the three aspects of knowledge-knowledge of bacteria, medicine and people. Identify bacteria, pathogen distribution, drug resistance mechanism. Identify drugs, pharmacokinetics and pharmacodynamics of drugs, etc. Identify person, pathophysiological changes in patients, severity. Through the comprehensive analysis of multiple factors, the individual drug administration plan was formulated. Results Although the initial treatment failed, clinical pharmacists focused on the analysis of factors such as insufficient blood concentration and rapid metabolism of β -lactam antibiotics in patients with renal hyperfunction from the perspective of renal hyperfunction. Through individual drug administration, patients received timely and effective anti-infection treatment and pharmaceutical care. Conclusion Clinical pharmacists should analyze the causes of anti-infection failure in various aspects when participating in the formulation and adjustment of clinical treatment plans, especially for patients with renal hyperfunction, the effectiveness of anti-infection can be guaranteed only when the characteristics of metabolic distribution are fully considered.展开更多
Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial ant...Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.展开更多
Amino acids are the building blocks of proteins and play vital roles in both biological systems and drug development.In recent years,increasing attention has been given to the functionalization of amino acid derivativ...Amino acids are the building blocks of proteins and play vital roles in both biological systems and drug development.In recent years,increasing attention has been given to the functionalization of amino acid derivatives.Since the introduction of therapeutic insulin in the early 20th century,the conjugation of drug molecules with amino acids and peptides has been pivotal in driving advancements in drug discovery and become an integral part of modern medical practice.Currently,over a hundred peptide-drug conjugates have received global approval and are widely used to treat diseases such as diabetes,cancer,chronic pain,and multiple sclerosis.Key technologies for conjugating peptides with bioactive molecules include antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),and proteolysis targeting chimeras(PROTACs).Significant efforts have been dedicated to developing strategies for the modification of amino acids and peptides,with particular focus on site-selective C-H alkylation/arylation reactions.These reactions are crucial for synthesizing bioactive molecules,as they enable the precise introduction of functional groups at specific positions,thereby improving the pharmacological properties of the resulting compounds.展开更多
Polyethylene glycol(PEG)is a polymer with different molecular weights formed by the polymerization of ethylene oxide monomers.Due to its ability to significantly reduce the immunogenicity of protein drugs and extend t...Polyethylene glycol(PEG)is a polymer with different molecular weights formed by the polymerization of ethylene oxide monomers.Due to its ability to significantly reduce the immunogenicity of protein drugs and extend their half-life,as well as its high safety profile,it has been approved by the U.S.Food and Drug Administration(FDA)as the gold standard for delivering protein drugs.Although numerous PEGylated protein drugs have been marketed,the focus of research on PEGylated protein drugs has primarily been on reducing immunogenicity and extending in vivo circulation half-life.However,the understanding of how PEG modification affects the structure and function of proteins is still limited,with“activity”often being the sole criterion for evaluating changes in protein structure and function.A deeper exploration of the existence and interaction between PEG chains and proteins is of great significance for understanding the properties exhibited by PEGylated proteins.This review summarizes strategies for PEG site-specific modification of proteins,the interaction states between PEG and proteins,and the effects of PEG chains on protein spatial structure,solubility,activity,and thermal stability.It also summarizes the characterization techniques for PEG-protein interactions,aiming to predict or explain the functions of PEGylated protein drugs through the analysis of PEG-protein interactions.展开更多
目的建立一个综合了生物信息学和化学信息学的网络信息平台M&Function,致力于新药筛选和研究。方法通过数据挖掘,整合小分子药物的名称、结构、功能、分类等信息,建立一个小分子药物信息资源库。在此基础上,借助基于最大公共子结构(...目的建立一个综合了生物信息学和化学信息学的网络信息平台M&Function,致力于新药筛选和研究。方法通过数据挖掘,整合小分子药物的名称、结构、功能、分类等信息,建立一个小分子药物信息资源库。在此基础上,借助基于最大公共子结构(maximum common substructure,MCS)和Fingerprint的结构比对软件,通过统计分析,建立了功能预测系统,对活性小分子进行生物学功能预测。结果 M&Function平台拥有丰富的数据信息、内嵌的图形显示和数据统计插件人性化的网站设计,具有直观、高效、简便易用、测试数据结果可靠等优点。结论 M&Function平台不仅是一个小分子药物信息资源库,也是一个小分子功能预测平台,可以为高通量先导化合物的筛选提供信息准备和数据支持。网站可以通过http://lifecenter.sgst.cn/mcs/home.do进行访问。展开更多
BACKGROUND Long-term antipsychotic therapy in psychiatric patients carries significant cardiovascular risks,including QT interval prolongation,myocardial injury,and functional impairment.Guanxinning,a traditional Chin...BACKGROUND Long-term antipsychotic therapy in psychiatric patients carries significant cardiovascular risks,including QT interval prolongation,myocardial injury,and functional impairment.Guanxinning,a traditional Chinese medicine formulation,has demonstrated cardioprotective potential in preclinical studies,but clinical evidence in this population remains limited.AIM To evaluate the cardioprotective effects of Guanxinning against antipsychotic-induced cardiac injury in long-term hospitalized psychiatric patients.METHODS A randomized,double-blind,placebo-controlled trial was conducted with 120 psychiatric inpatients receiving chronic antipsychotic therapy.Participants were allocated to:Intervention group:Conventional antipsychotics+Guanxinning tablets(0.38 g×4 tablets,ter in die);Control group:Conventional antipsychotics+identical placebo;Cardiac assessments at baseline and 12 months included:Electrocardiography(corrected QT interval),echocardiography(left ventricular ejection fraction,left ventricular end-diastolic diameter),serum biomarkers(cardiac troponin I,B-type natriuretic peptide,superoxide dismutase,malondialdehyde,high-sensitivity C-reactive protein).RESULTS Compared to controls,the Guanxinning group showed:Electrophysiological improvement:Corrected QT shortening(438±25 milliseconds vs 465±30 milliseconds,P<0.01).Functional enhancement:Left ventricular ejection fraction increase(58.5%±5.2%vs 53.8%±4.8%,P<0.05),left ventricular end-diastolic diameter reduction(49.8±3.5 mm vs 52.6±3.8 mm,P<0.05),Biochemical modulation:Reduced myocardial injury markers(cardiac troponin I:0.009 ng/mL vs 0.014 ng/mL;B-type natriuretic peptide:52 pg/mL vs 78 pg/mL,P<0.001),improved oxidative stress(superoxide dismutase:↑13.3 U/mL;malondialdehyde:↓0.9 nmol/mL,P<0.001),attenuated inflammation(high-sensitivity C-reactive protein:2.0 mg/L vs 3.2 mg/L,P<0.001).CONCLUSION Guanxinning significantly mitigates antipsychotic-induced cardiac injury in psychiatric patients,demonstrating:Normalization of electrophysiological parameters,Preservation of systolic/diastolic function,suppression of oxidative stress and inflammation.These findings support its clinical application as an adjunctive cardioprotective therapy,potentially through inhibition of myocardial apoptosis and antioxidant upregulation.展开更多
基金supported by Key Project of China Rehabilitation Research Center,Nos.2022ZX-05,2018ZX-08(both to JB)。
文摘Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.
基金supported by Postdoctoral Science Foundation of China 2017M611268
文摘In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.
文摘AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category(lamotrigine or levetiracetam, n=16), an "intermediate risk" category(carbamazepine, oxcarbazepine, phenytoin, or valproate, n=34) and a "high risk" category(topiramate, n=5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant(P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category(P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient(ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient(linear regression analysis, P > 0.15) were observed. CONCLUSION Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.
文摘Acupuncture at the Taichong (LR 3), Sanyinjiao (SP 6) and Ciliao (BL 32) points combined with TCM drugs for soothing the liver, replenishing the kidney, freeing the seminal passage, and eliminating the stasis showed effective for functional retrograde ejaculation in 25 cases. The total effective rate of 68.0% was significantly better than imipramine used in the control group (P<0.05).
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金supported by grant 358/04-3 of“The Israeli Science Foundation”.
文摘The fundamental limitations of most vascular-based functional neuroimaging techniques are placed by the fact how fine the brain regulates the blood supply system.In vivo mapping of the cerebral microcirculation with high resolution and sensitivity hence becomes unprecedentedly compelling.This paper reviews the theoretical background of the laser speckle contrast imaging(LSCI)technique and attempts to present a complete framework stemming from a simple biophysical model.Through the sensitivity analysis,more insights into the tool optimization are attained for in vivo applications.Open questions of the technical aspects are discussed within this unified framework.Finally,it concludes with a brief perspective of future research in a way analogous to the magnetic resonance imaging(MRI)technique.Such exploration could catalyze their development and initiate a technological fusion for precise assessment of blood flow across various spatial scales.
文摘Objective: To understand the effects of several commonly used antipsychotics on the renal function of patients with mental illness. Method: Collected patients with mental illness who were hospitalized in our hospital from January 2020 to June 2021, and selected as the research subjects patients with psychiatric disorders who were treated with 2 kinds of commonly used antipsychotic drugs;and collected 3 ml of venous blood before treatment and one month after treatment for renal function tests;observed the changes of renal function indexes before and after treatment. Results: In the collected 694 patients with mental illness, before using antipsychotic drugs, the renal function indexes were BUN: 4.42 ± 1.92 mmol/l;Cr: 70.97 ± 16.92 μmol/l;CCr: 88.37 ± 21.07 ml/min;β2-MG: 1.67 ± 0.61 mg/L;UA: 359.90 ± 112.82 μmol/l;CYS-C: 0.92 ± 0.24 mg/L. One month after using antipsychotics, BUN: 3.77 ± 1.37 mmol/l;Cr: 70.46 ± 16.71 μmol/l;CCr: 87.78 ± 20.63 ml/min;β2-MG: 1.75 ± 0.64 mg/L;UA: 332.53 ± 91.48 umol/l;CYS-C: 0.92 ± 0.24 mg/L;the renal function indexes of urea nitrogen, β2 microglobulin, uric acid and other items all changed significantly. The differences before and after treatment were statistically significant, P < 0.01. Conclusion: Several commonly used antipsychotic drugs have a greater impact on the renal function of patients with mental illness. During the treatment, the changes in renal function should be monitored regularly, if severe renal damage is found, the treatment plan or dosage should be adjusted in time to avoid endangering life.
文摘Objective: To investigate the effects of antiplatelet drug combined with magnesium sulfate on platelet function and trophoblast apoptosis in patients with preeclampsia. Methods: A total of 68 patients with preeclampsia who were treated in this hospital between September 2016 and September 2017 were chosen as the research subjects and divided into the control group (n=34) and the study group (n=34) by the random number table method. Control group received magnesium sulfate spasmolysis, and study group received low-dose aspirin combined with magnesium sulfate therapy. The differences in the levels of platelet function parameters as well as the expression levels of apoptosis-related genes and invasion-related genes in placental tissues were compared between the two groups of patients after treatment. Results:After treatment, the platelet function parameter PLT level in study group was higher than that in control group whereas MPV and PDW levels were lower than those in control group;pro-apoptosis genes Caspase-3, p53 and bax mRNA expression levels in placental tissues were lower than those of control group whereas anti-apoptosis gene bcl-2 mRNA expression level was higher than that of control group;pro-invasion genes MMP-2, MMP-9 and CXCL16 mRNA expression levels in placental tissues were higher than those of control group whereas anti-invasion genes RECK and DPPⅣ mRNA expression levels were lower than those of control group. Conclusion: Low-dose aspirin combined with magnesium sulfate treatment of patients with preeclampsia can effectively optimize the platelet function and inhibit the apoptosis of placental trophoblast cells and promote their invasion function.
文摘Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.
文摘Objective To explore the immune function injur y and its mechanism in drug abuser.Methods The immune function changes in50drug abusers were compared with normal healthy populations by detection of the indexes of subgroups of Th cells,transformation rate of lymphocytes,IgA,IgM,IgG,IgE,com pliment C 3 ,C 4 ,IL-1,IL-2,IL-6TNF and NO.Result In peripheral blood the percentage o f Th 1 cell,transformation rate of lymphocyte,IgA,IgM,IgG,IgE content,complime nt C4,C4,IL-1,IL-2,IL-6,and TNF le vels were significantly lower than normal (P <0.01).The value of Th 1 /Th 2 was lower than normal as well(P <0.05).NO content was significantly higher than normal (P <0.001).Conclusion The mechanism of immune function inj ury in drug abuser might be correlative to direct injury of drugs and their inhibition effect on the thymu s-hypothalamus-hypophysis-adren al axis.
文摘Objective: to explore the methods of drug adjustment and pharmaceutical care for the anti-infection treatment plan of clinical pharmacists for methicillin-sensitive staphylococcus aureus bacteremia patients with renal hyperfunction. Methods: clinical pharmacists analyzed the three aspects of knowledge-knowledge of bacteria, medicine and people. Identify bacteria, pathogen distribution, drug resistance mechanism. Identify drugs, pharmacokinetics and pharmacodynamics of drugs, etc. Identify person, pathophysiological changes in patients, severity. Through the comprehensive analysis of multiple factors, the individual drug administration plan was formulated. Results Although the initial treatment failed, clinical pharmacists focused on the analysis of factors such as insufficient blood concentration and rapid metabolism of β -lactam antibiotics in patients with renal hyperfunction from the perspective of renal hyperfunction. Through individual drug administration, patients received timely and effective anti-infection treatment and pharmaceutical care. Conclusion Clinical pharmacists should analyze the causes of anti-infection failure in various aspects when participating in the formulation and adjustment of clinical treatment plans, especially for patients with renal hyperfunction, the effectiveness of anti-infection can be guaranteed only when the characteristics of metabolic distribution are fully considered.
文摘Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.
文摘Amino acids are the building blocks of proteins and play vital roles in both biological systems and drug development.In recent years,increasing attention has been given to the functionalization of amino acid derivatives.Since the introduction of therapeutic insulin in the early 20th century,the conjugation of drug molecules with amino acids and peptides has been pivotal in driving advancements in drug discovery and become an integral part of modern medical practice.Currently,over a hundred peptide-drug conjugates have received global approval and are widely used to treat diseases such as diabetes,cancer,chronic pain,and multiple sclerosis.Key technologies for conjugating peptides with bioactive molecules include antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),and proteolysis targeting chimeras(PROTACs).Significant efforts have been dedicated to developing strategies for the modification of amino acids and peptides,with particular focus on site-selective C-H alkylation/arylation reactions.These reactions are crucial for synthesizing bioactive molecules,as they enable the precise introduction of functional groups at specific positions,thereby improving the pharmacological properties of the resulting compounds.
基金supported by National Natural Science Foundation of China(No.82173788).
文摘Polyethylene glycol(PEG)is a polymer with different molecular weights formed by the polymerization of ethylene oxide monomers.Due to its ability to significantly reduce the immunogenicity of protein drugs and extend their half-life,as well as its high safety profile,it has been approved by the U.S.Food and Drug Administration(FDA)as the gold standard for delivering protein drugs.Although numerous PEGylated protein drugs have been marketed,the focus of research on PEGylated protein drugs has primarily been on reducing immunogenicity and extending in vivo circulation half-life.However,the understanding of how PEG modification affects the structure and function of proteins is still limited,with“activity”often being the sole criterion for evaluating changes in protein structure and function.A deeper exploration of the existence and interaction between PEG chains and proteins is of great significance for understanding the properties exhibited by PEGylated proteins.This review summarizes strategies for PEG site-specific modification of proteins,the interaction states between PEG and proteins,and the effects of PEG chains on protein spatial structure,solubility,activity,and thermal stability.It also summarizes the characterization techniques for PEG-protein interactions,aiming to predict or explain the functions of PEGylated protein drugs through the analysis of PEG-protein interactions.
文摘目的建立一个综合了生物信息学和化学信息学的网络信息平台M&Function,致力于新药筛选和研究。方法通过数据挖掘,整合小分子药物的名称、结构、功能、分类等信息,建立一个小分子药物信息资源库。在此基础上,借助基于最大公共子结构(maximum common substructure,MCS)和Fingerprint的结构比对软件,通过统计分析,建立了功能预测系统,对活性小分子进行生物学功能预测。结果 M&Function平台拥有丰富的数据信息、内嵌的图形显示和数据统计插件人性化的网站设计,具有直观、高效、简便易用、测试数据结果可靠等优点。结论 M&Function平台不仅是一个小分子药物信息资源库,也是一个小分子功能预测平台,可以为高通量先导化合物的筛选提供信息准备和数据支持。网站可以通过http://lifecenter.sgst.cn/mcs/home.do进行访问。
基金Supported by the Special Project for Supporting the Development of Biomedicine and Health Industry in Hangzhou City,No.2022WJC123Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project,No.2022ZA143.
文摘BACKGROUND Long-term antipsychotic therapy in psychiatric patients carries significant cardiovascular risks,including QT interval prolongation,myocardial injury,and functional impairment.Guanxinning,a traditional Chinese medicine formulation,has demonstrated cardioprotective potential in preclinical studies,but clinical evidence in this population remains limited.AIM To evaluate the cardioprotective effects of Guanxinning against antipsychotic-induced cardiac injury in long-term hospitalized psychiatric patients.METHODS A randomized,double-blind,placebo-controlled trial was conducted with 120 psychiatric inpatients receiving chronic antipsychotic therapy.Participants were allocated to:Intervention group:Conventional antipsychotics+Guanxinning tablets(0.38 g×4 tablets,ter in die);Control group:Conventional antipsychotics+identical placebo;Cardiac assessments at baseline and 12 months included:Electrocardiography(corrected QT interval),echocardiography(left ventricular ejection fraction,left ventricular end-diastolic diameter),serum biomarkers(cardiac troponin I,B-type natriuretic peptide,superoxide dismutase,malondialdehyde,high-sensitivity C-reactive protein).RESULTS Compared to controls,the Guanxinning group showed:Electrophysiological improvement:Corrected QT shortening(438±25 milliseconds vs 465±30 milliseconds,P<0.01).Functional enhancement:Left ventricular ejection fraction increase(58.5%±5.2%vs 53.8%±4.8%,P<0.05),left ventricular end-diastolic diameter reduction(49.8±3.5 mm vs 52.6±3.8 mm,P<0.05),Biochemical modulation:Reduced myocardial injury markers(cardiac troponin I:0.009 ng/mL vs 0.014 ng/mL;B-type natriuretic peptide:52 pg/mL vs 78 pg/mL,P<0.001),improved oxidative stress(superoxide dismutase:↑13.3 U/mL;malondialdehyde:↓0.9 nmol/mL,P<0.001),attenuated inflammation(high-sensitivity C-reactive protein:2.0 mg/L vs 3.2 mg/L,P<0.001).CONCLUSION Guanxinning significantly mitigates antipsychotic-induced cardiac injury in psychiatric patients,demonstrating:Normalization of electrophysiological parameters,Preservation of systolic/diastolic function,suppression of oxidative stress and inflammation.These findings support its clinical application as an adjunctive cardioprotective therapy,potentially through inhibition of myocardial apoptosis and antioxidant upregulation.
