ABSTRACT
OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.
Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.
Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Diabetic Nephropathies , Drug Therapy, Combination , Renin-Angiotensin System , Humans , Diabetic Nephropathies/drug therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Renin-Angiotensin System/drug effects , Angiotensin Receptor Antagonists/therapeutic use , Astragalus Plant , Randomized Controlled Trials as Topic , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Treatment Outcome , Creatinine/blood , Glycated Hemoglobin , Proteinuria/drug therapyABSTRACT
BACKGROUND: Breastfeeding is recognized internationally as the most scientific and effective way to feed infants and young children. According to the World Health Organization in 2022, the exclusive breastfeeding rate within 6 months is 34.1% in China, which is still far from the goal of "more than 60% exclusive breastfeeding rate of infants within 6 months" by 2030 required by China's State Council. It is necessary to promote breastfeeding and provide maternal breastfeeding guidance to increase exclusive breastfeeding. Factors influencing breastfeeding can be explained by the society ecosystems theory, distributed in macro, mezzo and micro systems. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of these facilities. But there is sparse research on integrating resources in the macro, mezzo and micro systems of maternal breastfeeding processes to promote breastfeeding behavior. A randomized controlled trial will test the effect of a breastfeeding promotion intervention model based on the society ecosystems theory versus usual prenatal and postnatal care on maternal and infant health and the exclusive breastfeeding rate at 6 months. METHODS/DESIGN: The study is a single-blind, parallel design, randomized controlled trial with an intervention group (n = 109) and a control group (n = 109) that compares the effect of a breastfeeding promotion intervention model based on the society ecosystems theory with usual prenatal and postnatal care. The intervention covers macro- (policy, culture), mezzo- (family-hospital-community) and micro- (biological, psychological and social) systems of the maternal breastfeeding process. Infant feeding patterns, neonatal morbidity and physical and mental health of antenatal and postpartum women will be collected at baseline (28 to 35 weeks of gestation), 1-, 4-, and 6-month postpartum. DISCUSSION: This is a multifaceted, multifactorial, and multi-environmental breastfeeding promotion strategy to help mothers and their families learn breastfeeding knowledge and skills. The study provides a new modality for adding breastfeeding interventions to prenatal and postnatal care for healthcare providers in the hospital and the community. TRIAL REGISTRATION: Chinese Clinical Trial Registry at www.chictr.org.cn , ChiCTR2300075795.
Maternal education and support during breastfeeding can increase maternal breastfeeding self-efficacy, promote breastfeeding behaviors, and improve maternal and infant health outcomes. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of any of these facilities. But there is sparse research on integrating in multifaceted, multifactorial, and multi-environmental resources of maternal breastfeeding processes to help pregnant women and their families learn breastfeeding knowledge and skills. The current study optimizes the existing breastfeeding promotion intervention program and construct a breastfeeding promotion intervention program to correct the public's perception of breastfeeding, increase breastfeeding self-efficacy and improve breastfeeding behavior, thus increasing the breastfeeding duration and improving maternal and infant outcomes. The program includes presenting breastfeeding-related policies and support facilities; prenatal educational sessions combined with theories and skills on breastfeeding, development of lactation, infants feeding and cares for maternal families; postnatal hands-on instruction and WeChat group peer support from hospital; home visits, group counseling and experience sharing from community and one-on-one personalized counseling throughout the intervention. The present study will be conducted to evaluate the effect of breastfeeding promotion intervention including prenatal and postnatal care on the breastfeeding duration, breastfeeding attitudes, knowledge, and self-efficacy, maternal and infant health.
Subject(s)
Breast Feeding , Health Promotion , Infant , Infant, Newborn , Child , Female , Pregnancy , Humans , Child, Preschool , Breast Feeding/psychology , Health Promotion/methods , Ecosystem , Single-Blind Method , Mothers/psychology , Randomized Controlled Trials as TopicABSTRACT
AIMS: In this study, the effect of intracerebral ventricle injection with a miR-124-3p agomir or antagomir on prognosis and on subventricular zone (SVZ) neural stem cells (NSCs) in adult rats with moderate traumatic brain injury (TBI) was investigated. METHODS: Model rats with moderate controlled cortical impact (CCI) were established and verified as described previously. The dynamic changes in miR-124-3p and the status of NSCs in the SVZ were analyzed. To evaluate the effect of lateral ventricle injection with miR-124-3p analogs and inhibitors after TBI, modified neurological severity scores (mNSSs) and rotarod tests were used to assess motor function prognosis. The variation in SVZ NSC marker expression was also explored. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of predicted miR-124-3p targets was performed to infer miR-124-3p functions, and miR-124-3p effects on pivotal predicted targets were further explored. RESULTS: Administration of miR-124 inhibitors enhanced SVZ NSC proliferation and improved the motor function of TBI rats. Functional analysis of miR-124 targets revealed high correlations between miR-124 and neurotrophin signaling pathways, especially the TrkB downstream pathway. PI3K, Akt3, and Ras were found to be crucial miR-124 targets and to be involved in most predicted functional pathways. Interference with miR-124 expression in the lateral ventricle affected the PI3K/Akt3 and Ras pathways in the SVZ, and miR-124 inhibitors intensified the potency of brain-derived neurotrophic factor (BDNF) in SVZ NSC proliferation after TBI. CONCLUSION: Disrupting miR-124 expression through lateral ventricle injection has beneficial effects on neuroregeneration and TBI prognosis. Moreover, the combined use of BDNF and miR-124 inhibitors might lead to better outcomes in TBI than BDNF treatment alone.
Subject(s)
Brain Injuries, Traumatic , Brain-Derived Neurotrophic Factor , MicroRNAs , Neural Stem Cells , Animals , Brain Injuries, Traumatic/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Down-Regulation , Lateral Ventricles/metabolism , MicroRNAs/metabolism , Neural Stem Cells/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.
Subject(s)
Hepatitis B, Chronic , Alanine/therapeutic use , Alanine Transaminase , Drugs, Chinese Herbal , Hepatitis B, Chronic/drug therapy , Humans , Liver/pathology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathologyABSTRACT
With the expected rise in patients undergoing refractive lenticule extraction worldwide, the number of discarded corneal stromal lenticules will increase. Therefore, establishing a lenticule bank to collect, catalog, process, cryopreserve, and distribute the lenticules (for future therapeutic needs) could be advantageous. In this study, we validated the safety of lenticule banking that involved the collection of human lenticules from our eye clinic, transportation of the lenticules to a Singapore Ministry of Health-licensed lenticule bank, processing, and cryopreservation of the lenticules, which, after 3 months or, a longer term, 12 months, were retrieved and transported to our laboratory for implantation in rabbit corneas. The lenticule collection was approved by the SingHealth Centralised Institutional Review Board (CIRB). Both short-term and long-term cryopreserved lenticules, although not as transparent as fresh lenticules due to an altered collagen fibrillar packing, did not show any sign of rejection and cytotoxicity, and did not induce haze or neovascularization for 16 weeks even when antibiotic and steroidal administration were withdrawn after 8 weeks. The lenticular transparency progressively improved and was mostly clear after 4 weeks, the same period when we observed the stabilization of corneal hydration. We showed that the equalization of the collagen fibrillar packing of the lenticules with that of the host corneal stroma contributed to the lenticular haze clearance. Most importantly, no active wound healing and inflammatory reactions were seen after 16 weeks. Our study suggests that long-term lenticule banking is a feasible approach for the storage of stromal lenticules after refractive surgery. Impact statement Since 2011, close to 3 million refractive lenticule extraction procedures have been performed. The majority of the extracted lenticules are discarded. The lenticules could have been cryopreserved and retrieved at a later date for therapeutic or refractive applications. Therefore, establishing a lenticule bank to collect, catalog, process, cryopreserve, and distribute the lenticules could be advantageous. In this study, we simulated a lenticule banking service in a validated health authority-licensed facility and showed that long-term cryopreservation of the lenticules in the facility was safe and feasible in vivo.
Subject(s)
Corneal Surgery, Laser , Animals , Cornea/surgery , Corneal Stroma/surgery , Corneal Surgery, Laser/methods , Cryopreservation , Humans , Rabbits , Refraction, OcularABSTRACT
The assembly of gigantic heterometallic metal clusters remains a great challenge for synthetic chemistry. Herein, based on the slow release strategy of lanthanide ions and in situ formation of lacunary polyoxometalates, two giant 3d-4f polyoxometalate inorganic clusters [LaNi12 W35 Sb3 P3 O139 (OH)6 ]23- (LaNi12 ) and [La10 Ni48 W140 Sb16 P12 O568 (OH)24 (H2 O)20 ]86- (La10 Ni48 ) are obtained. The nanoscopic inorganic cluster La10 Ni48 possesses a super tetrahedron structure, which can be viewed as assembly from four LaNi12 molecules encapsulating a central [La6 (SbO3 )4 (H2 O)20 ]6+ octahedron core. This giant aesthetic La10 Ni48 tetrahedron containing 214 metal ions is the largest 3d-4f cluster reported thus far in polyoxometalate system. More interestingly, the LaNi12 and La10 Ni48 display high stability in solution and La10 Ni48 displays excellent proton conductivity.
ABSTRACT
Multifunctional lanthanide coordination polymers (CPs) have the advantages of acting in two or more fields simultaneously. Herein, two single lanthanide CPs, formulated as LnL(D/L-Hlac)(H2O)2·0.5H2O (Ln = Eu (1), Tb (2); H2L = 4,4'-(pyridine-3,5-diyl)dibenzoic acid) and their doped lanthanide analogue Tb0.9373Eu0.0627L(D/L-Hlac)(H2O)2·0.5H2O (3) were prepared through hydrothermal methods. Luminescence measurements reveal that 1 displays red photoluminescence and its Commission International ed'Eclairage (CIE) coordinates are almost invariant in the temperature range from 80 to 300 K, while the emission color of 2 changes from yellow to green and its CIE coordinates change from (0.36132, 0.56365) at 80 K to (0.30448, 0.45566) at 300 K. Significantly, 3 not only displays white-light emission with CIE coordinates of (0.32999, 0.33406) but also exhibits a thermal sensitivity of 2.27% K-1 at 230-300 K. The obviously larger thermal sensitivity in 3 in comparison to that of 1.07% K-1 for 2 demonstrates that lanthanide CPs with both a heat-sensitive fluorescent thermometer and high-efficiency white-light emission can be expected by doping Eu(III) ions into Tb(III)-based CPs.
ABSTRACT
Four pairs of chiral 3D coordination polymers (CPs), [Zn2(BDC)(lac)(DMF)]·guest (2) (H2BDC = benzene dicarboxylic acid; H2lac = lactic acid; guest = 1.5DMF + i-PrOH), [Co2(BDC)(lac)(DMF)]·guest (3) (guest = DMF + 2H2O), [Fe4(BDC)3(lac)2(DMF)2](CO3)·guest (4) (guest = DMF + 2H2O), and {Zn11(BPDC)6(lac)6[NH2(CH3)2]2}·guest (H2BPDC = 3,3'-biphenyldicarboxylic acid; guest = 6DMF + 18H2O) (5), are prepared through the reactions of racemic lactic acid (rac-H2lac) with different metal ions and auxiliary ligands. Structural analyses and DFT calculations reveal that forming more and stronger coordination bonds between the auxiliary ligand and metal ions is more conducive to the spontaneous resolution of enantiomers in 3D CPs than simply increasing the entropy of the auxiliary ligand itself.
ABSTRACT
OBJECTIVE: To investigate the expression of HSP90 in bone marrow samples of multiple myeloma (MM) patients and explore its clinical significance. METHODS: Maxvision immunohistochemistry technique was used to detect the protein expression level of HSP90 76 MM patients and 29 normal healthy donors. The clinical characteristics of the patients were collected, and the correlation between the HSP90 expression and the clinical characteristics was analyzed. RESULTS: The count of MM patients with positive HSP90 protein was significantly higher than that of normal healthy donor, and there were no significant correlation between HSP90 expression and age, sex, hemoglobin (Hb), creatinine (CREA), blood calcium, lactate dehydrogenase (LDH), bone marrow plasma cell proportion and MM subtypes (P>0.05), but HSP90 expression was correlated with ß2-microglobulin (ß2-MG) and ISS stage (P<0.05). The survival time was lower in MM patients with high expression HSP90 as compared with low expression HSP90 MM patients. CONCLUSION: HSP90 protein was over-expressed in MM patients, and was correlated with ß2-microglobulin, ISS stage and OS of MM patients.
Subject(s)
Multiple Myeloma , Bone Marrow , HSP90 Heat-Shock Proteins , Humans , Prognosis , beta 2-MicroglobulinABSTRACT
Three series of copper hydride clusters [Cu8H6L6]2+ (1), [Cu4HX2L4]+ where X- = Cl- (2a), Br- (2b), I- (2c), N3- (2d) and SCN- (2e), and [Cu4HX3L3] where X- = Br- (3b) and I- (3c) (L = 2-(diphenylphosphino)pyridine, dppy) were synthesized and characterized by single-crystal X-Ray crystallography and standard spectroscopic techniques. The metal core of 1, Cu8, can be described as a bicapped octahedron, while those of 2 and 3 series adopt tetrahedral structures. The hydride positions were deduced from difference electron density maps and corroborated by NMR and DFT calculations. For 1, there are two µ4-H-, one each in the two tetrahedral cavities of the two capping atoms and four µ3-H- on the six triangular faces around the waist of the octahedron. For [Cu4HX2L4]+ and [Cu4HX3L3] series, the single µ4-H- resides in the center of the Cu4 tetrahedron. It was found that these three series of copper clusters are intimately connected and can convert from one to another under specific reaction conditions. Their transformation pathways were investigated in detail. Spontaneous resolution to form optically pure enantiomeric single crystals was observed for [Cu4H(SCN)2L4]+ (2e) and [Cu4HBr3L3] (3b). Photoluminescence was observed for [Cu4HX2L4]+, as well as [Cu4HX3L3] with strong emissions from green to yellow regions.
ABSTRACT
RATIONALE: The incidence of nonsmall cell lung cancer (NSCLC) is high. Most nonsmall cell lung cancers have undergone multiple metastases at the time of initial diagnosis, and the 5âyear survival rate is low. At present, comprehensive treatments, including systemic chemotherapy, targeted therapy, antiangiogenic therapy, and immunotherapy, prolong the survival of patients with advanced NSCLC. Herein, we report a case of NSCLC with long-term survival. PATIENT CONCERNS: A 61-year-old woman complained of dry cough and shortness of breath and visited our hospital in July 2011. Imaging examination revealed a left upper lung mass with multiple metastases to the liver, adrenal gland, and bone. DIAGNOSES: Stage IVB (cT2aN3M1c) lung adenocarcinoma was diagnosed, with multiple metastases of the lymph nodes, liver, adrenal gland, and bone. INTERVENTIONS AND OUTCOMES: The patient received systemic chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor-targeted therapy, and has survived for more than 9âyears. LESSONS: The patient benefited from maintenance chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor treatment and achieved long-term survival.
Subject(s)
Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/secondary , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/pathology , Maintenance Chemotherapy/methods , Adenocarcinoma of Lung/diagnostic imaging , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/epidemiology , Female , Humans , Incidence , Middle Aged , Molecular Targeted Therapy/methods , Neoplasm Staging/methods , Protein Kinase Inhibitors/therapeutic use , Survivors , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.
Subject(s)
Cerebral Hemorrhage/blood , Cerebral Hemorrhage/etiology , Hemostasis/physiology , Ischemic Stroke/blood , Ischemic Stroke/complications , Aged , Atrial Fibrillation , Case-Control Studies , Female , Fibrinogen , Humans , Magnetic Resonance Imaging , Male , Mean Platelet Volume , Middle Aged , Platelet Count , Retrospective Studies , Risk FactorsABSTRACT
Tyrosine kinase inhibitor (TKI) has significantly improved the treatment of chronic myeloid leukemia (CML), however the resistance often resulted in treatment failure. Currently, it is known that the survival of CML cells can be affected by regulating autophagy, oxidative stress and mitochondrial metabolism, among which autophagy is an evolution-conserved catabolism process, and closely related to the pathogenesis of CML, thus playing a dual role in regulating the biological characteristics of cells. On the one hand, autophagy can promote the apoptosis of CML cells, and also can induce the drug resistance of CML cells on the other hand. In this review, the effect of autophagy on CML cells was summarzed briefly, so as to provide a useful idea to explore the combination of TKI with the autophagy inhibitor or inducer to overcome the resistance of CML to TKI.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Apoptosis , Autophagy , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl , Humans , Protein Kinase Inhibitors/pharmacology , ResearchABSTRACT
Acute myeloid leukemia (AML) is a kind of malignant hematological disease with high mortality. Patients 5-year survival rate is less than 25% and that of elderly patients is lower than 10%. Although the standardized chemotherapy or hematopoetic stem cell transplantation can significantly improve the therapeutic efficacy for AML, but disease recurrence is still a difficult problem in most patients. Chemotherapy combined with immunotherapy has been regarded as the most promising treatment for AML in recent years, but immunotherapy is prone to immune escape, which has become an important factor affecting the therapeutic efficacy. Therefore, understanding the mechanism of immune escape of AML and taking corresponding measures in time to improve the therapeutic effect and reduce the recurrence of AML are of great significance. In this review, the important cells that cause immune escape, such as myeloid-derived suppressor cells (MDSC), natural killer cells (NK), and cell surface inhibitory receptor PD-1 (programmed death 1), which mediate immune escape of AML cells are summarized, so as to provide valuable reference for research to improve the effect of AML immunotherapy.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Aged , Humans , Immunotherapy , Killer Cells, Natural , Stem Cell TransplantationABSTRACT
A range of allylic alcohols are shown to readily react with ethereal H2O2 in the presence of catalytic amounts of Na2MoO4-gly or MoO2(acac)2, affording the CâC trans hydroxylation-hydroperoxylation products in good yields with high regio- and stereoselectivity. Use of enantiomers of cyclic substrates resulted in corresponding enantiopure diol-tert-hydroperoxides. The possibility of further conversion of the diol-tert-hydroperoxides into triols or linear building blocks with an isolated tert-peroxy group containing a quaternary center is also exemplified.
ABSTRACT
BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD) patients and effectively reduces poor mobility and dyskinesia. METHODS: Electronic databases were searched up to January 1, 2018. The inclusion criteria for this review were as follows: LCIG vs oral medication in advanced PD patients. RESULTS: Five trials, with a total of 198 patients, met all the inclusion criteria. The quality score of these studies ranged from 3 to 5. Two clinical trials showed that compared with oral medication, LCIG had a better treatment effect on on-time with troublesome dyskinesia (TSD) (p = 0.02) and on-time without TSD (p < 0.00001) in advanced PD patients. In addition, four of the 5 studies showed that the LCIG may have better efficacy than oral medication for improving the scores of the UPDRS, and two studies found that LCIG demonstrated better efficacy for improving the PDQ-39 scores. The video recording results indicated a potential decline in both dyskinesia and the "off" state in LCIG-treated patients. The incidence of adverse events was not significantly different between the LCIG and oral medication groups. CONCLUSION: Compared with oral treatment, LCIG exerts its effectiveness, mostly by reducing the time of on-time with TSD, increasing the time of on-time without TSD and scores of UPDRS and PDQ-39. It is suggesting that LCIG was likely to be a new type of administration used in clinical applications. However, due to methodological flaws, these findings should be viewed with caution, and more RCTs are needed in the field to complement our findings.
Subject(s)
Antiparkinson Agents/therapeutic use , Carbidopa/therapeutic use , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Administration, Oral , Antiparkinson Agents/administration & dosage , Carbidopa/administration & dosage , Drug Combinations , Gels/administration & dosage , Gels/therapeutic use , Humans , Levodopa/administration & dosageABSTRACT
AbstractããThe minimal residual disease (MRD) is the origin element that caused the relapse and drug resistance of hematological malignancies, the immune cells play a great role to clear MRD. A variety of immune cells have anti-tumor effects. However, tumor cells antagonize anti-tumor effects by reprogramming of constituents associated with tumor environment. Many different cell types, including immune cells, mesenchymal cells and tumor cells in tumor microenvironment release exosomes. The latest researches indicate that "cargo" and surface ligands carried by exosomes secreted by hematological malignant cells not only can affect the function of natural killer cell (migration, activation, proliferation, secretion and NKG2D expression), macrophage (migration and secretion) and dendritic cell (maturation and presentation), but also regulate the expression of PD-L1 and CCR2, CCL2 secretion and transformation of monocytes. The altered function of immune cells will eventually have effect on the progression of hematological malignancies.
Subject(s)
Exosomes , Hematologic Neoplasms , Humans , Killer Cells, Natural , Neoplasm Recurrence, Local , Tumor MicroenvironmentABSTRACT
Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. We explored the association between low triiodothyronine (T3) syndrome and HT in AIS patients. A total of 208 consecutive participants with HT and 208 age- and sex-matched stroke patients without HT were enrolled in this study. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction (HI) type 1 or 2 or parenchymal hematoma (PH) type 1 or 2. HT was also classified into asymptomatic or symptomatic. The incidence of low T3 syndrome was significantly higher among patients who developed HT than among those without HT. Moreover, the more severe the HT, the lower the detected T3 levels. Multivariate-adjusted binary logistic regression showed that low T3 syndrome was an independent risk factor for HT and symptomatic HT in AIS patients. Low T3 syndrome was also significantly associated with a higher risk of PH, but not with the risk of HI. Thus, low T3 syndrome was independently associated with the risk of HT, symptomatic HT, and severe HT (PH) in AIS patients, which suggests monitoring T3 could be a useful means of preventing HT in patients with ischemic stroke.
Subject(s)
Brain Ischemia/complications , Euthyroid Sick Syndromes/complications , Intracranial Hemorrhages/complications , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Stroke/complicationsABSTRACT
Two lanthanide-titanium oxo clusters (LTOCs), formulated as [Eu3Ti3(µ3-O)2(µ3-OH)(CH3O)2(Ac)2(CH3OH)(tbba)12]·CH3OH (1) and [Eu6Ti8(µ3-O)13(µ2-OH)(µ3-OCH3)2(µ2-OCH3)2(H2O)(CH3OH)2(tbba)19]·Htbba·10H2O (2), were synthesized through the solvothermal reaction of 4-tert-butylbenzoate ligand, Eu(Ac)3·3H2O, and Ti(OiPr)4 in methanol. Single-crystal structural analysis reveals that 1 crystallized in the orthorhombic space group Pnn2, and 2 crystallized in the triclinic space group P1. Structurally, the core of 1 can be viewed as a coplanar unit of [Eu3Ti3(µ3-O)2(µ3-OH)]16+ formed through each µ3-O2- and µ3-OH- bridging one Ti4+ and two Eu3+ ions, while that of 2 can be viewed as two units of [Eu3Ti3(µ3-O)3(µ2-O)4(µ2-OCH3)2(CH3OH)]5+ and [Eu3Ti5(µ3-O)6(µ2-OH)(µ3-OCH3)2(H2O)(CH3OH)]14+ connected through four µ2-O units from the [Eu3Ti3(µ3-O)3(µ2-O)4(µ2-OCH3)2(CH3OH)]5+ unit to respectively coordinate two Eu3+ and two Ti4+ ions from the [Eu3Ti5(µ3-O)6(µ2-OH)(µ3-OCH3)2(H2O)(CH3OH)]14+ unit. Measurement of their luminescence properties shows that the luminescence lifetime and quantum yield are 1212 µs and 69.6% for 1 and 857 µs and 56.2% for 2. When F- was introduced into 1 in a molar ratio of F- to 1 of 1:3, its quantum yield was increased 1.3 times, and the lifetime increased from 1.2 to 1.4 ms. However, no obvious enhancement in the emission intensity was observed in 2; even the molar ratio of F- to 2 is in the range from 2 to 1/4. Investigation on the structures of 1 and 2 reveals that the luminescence lifetime and quantum yield in 1 is significantly larger than that in 2 are attributed to the vibration of the nonradiative O-H vibration groups in 1 being significantly smaller than that in 2.
ABSTRACT
BACKGROUND: To investigate the association between exposure to environmental tobacco smoke (EVT) and the incidence of lung cancer (LC) in nonsmoking adults. METHOD: PubMed, Cochrane, Embase, Wanfang, CNKI, and VIP database were searched by the index words to identify the qualified case-control studies, and relevant literature sources were also searched. The latest research was done in June 2017. Odds radio (OR) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULT: Twenty RCTs were involved in the meta-analysis with 13,004 adults in the case group and 11,199 adults in the control group. The results indicated that compared with the nonexposure population, the risk of LC incidence was significantly higher in EVT exposure (OR: 1.64, 95% CI: 1.34-2.01), EVT male exposure (OR: 1.62, 95% CI: 1.16-2.28), EVT female exposure (OR: 1.57, 95% CI: 1.43-1.72), EVT exposure at workplace (OR: 1.78, 95% CI: 1.29-2.44), EVT exposure at home (OR: 1.53, 95% CI: 1.01-2.33), and EVT female exposure at home (OR: 1.55, 95% CI: 1.34-1.79). However, there is still no significant difference among the risk of LC incidence in EVT male exposure at workplace (OR: 1.51, 95% CI: 0.74-3.06), EVT female exposure at workplace (OR: 1.23, 95% CI: 0.99-1.53), and EVT male exposure at home (OR: 1.24, 95% CI: 0.68-2.26). CONCLUSION: EVT exposure is prospectively associated with a significantly increased risk of LC incidence. More high quality studies are required to address the association between EVT exposure and LC incidence.