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Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.
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In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.
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@#Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.
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OBJECTIVE: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features. METHODS: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations. RESULTS: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis. CONCLUSIONS: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.
Subject(s)
Humans , Infant, Newborn , Infant , Enterocolitis, Necrotizing/diagnostic imaging , Infant, Newborn, Diseases , Prognosis , ROC Curve , UltrasonographyABSTRACT
The drug delivery system with "gatekeeper" is designed to achieve a stable entrapment state of the payload under normal physiological conditions through the gatekeepers. With tumor microenvironment or stimulation of exogenous factors, the gatekeeper is detached or altered to promote the responsive release of the drug. In this paper, we focus on applications of stimuli-responsive linkages and stimuli-responsive groups, and review research progresses of drug delivery system with "gatekeeper" developed over the past 10 years.
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Extracellular acidity has been associated with many pathological states, such as cancer, ischemic stroke, neurotrauma and infection, which makes it an effective target for therapy and diagnosis of such diseases. As a polypeptide vector, pH low insertion peptides (pHLIPs) are endowed with high sensitivity to extracellular acidic environment, which can insert the membrane and deliver payload to pathological cells in a pH dependent manner. Here, theranostic applications of pHLIP in disease, are reviewed in two aspects:pHLIP-mediated single-molecule transporter and nano-sized carrier.
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The key of gene therapy is to deliver the functional gene to the target tissue in the body. The safe and efficient gene carrier is particularly important in the targeted delivery. Multifunctional envelope-type nano device (MEND), based on concept "Programmed packaging", is a new type of gene carrier system, with high encapsulation efficiency, favourable stability, high transfection efficiency, easy preparation, etc. MEND is designed to control intracellular trafficking as well as the tissue distribution of encapsulated compounds such as nucleic acids/proteins/peptides, permitting them to function at the appropriate location. In this paper, research progresses in MEND are reviewed in accordance with three types of payloads:the small interfering RNA (siRNA), DNA and proteins/peptides in recent years.
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·AIM: To investigate the incidence of neonatal eye disease, early intervention and follow-up observation. ·METHODS: Totally 9 654 newborns born in our hospital from December 2015 to December 2017 were screened for ophthalmic diseases and symptomatic interventions, and the results were statistically analyzed. ·RESULTS: There were 8 467 newborn infants ( 8 532 eyes) who were screened, accounting for 87. 70% of the total; 7 047 of the normal group accounted for 89. 94% for this group, and 1 420 of the high risk group accounted for 78. 06% for this group. Screening found that some newborns had congenital and acquired ophthalmic diseases. ·CONCLUSION: The screening of newborns for eye diseases can detect the abnormalities of newborns' eyes as soon as possible and intervene to improve the efficacy and accuracy of the treatment. Especially for high-risk neonates, eye screening is even more necessary.
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Objective: To observe the effect of electroacupuncture (EA) at Huantiao (GB 30) and Weizhong (BL 40) on thigmesthesia, gait function, and expression levels of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) in rabbits with lumbar intervertebral disc herniation (LIDH). Methods: Forty healthy New Zealand rabbits were randomly divided into a blank control group, a model group, an EA at acupoint group and an EA at non-acupoint group, with 10 rabbits in each group. The LIDH pathological model of rabbit was established using the self-made LIDH model maker. The thigmesthesia and gait function of rabbits were recorded by Siegal method. The serum IgG and IgM expression levels were detected by enzyme-linked immunosorbent assay. Results: EA at Huantiao (GB 30) and Weizhong (BL 40) could improve the clinical symptoms of thigmesthesia and gait function, and inhibit the expressions of serum IgG and IgM in the LIDH rabbits, which were significantly different compared with those in the model group and EA at non-acupoint group. Conclusion: EA at Huantiao (GB 30) and Weizhong (BL 40) can improve the clinical symptoms of LIDH rabbits, which is associated with inhibition of the serum IgG and IgM expressions and reduction of the immunoinflammatory factor release. This may be one of the mechanisms of EA at Huantiao (GB 30) and Weizhong (BL 40) in the treatment of LIDH.
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@#AIM: To explore the application value of scleral adjustable sutures in trabeculectomy and scleral biological amniotic membrane implantation for angle closure glaucoma. <p>METHODS: The clinical data of 94 patients(106 eyes)with angle closure glaucoma who underwent trabeculectomy and scleral biological amniotic membrane implantation were analyzed retrospectively. According to scleral adjustable suture used, the subjects were divided into the application group(study group, 54 patients 60 eyes)and the non-application group(control group, 40 patients 46 eyes). The occurrence of early shallow anterior chamber, continuous shallow anterior chamber and related complications in 2wk after surgery was observed and compared between the two groups. The formation of functional filtration bleb in 3mo after surgery was analyzed, and the improvement of intraocular pressure before surgery and 1mo after surgery was recorded.<p>RESULTS: In 2wk after surgery, the incidence rates of early shallow anterior chamber and continuous shallow anterior chamber in the study group were significantly lower than those in the control group(<i>P</i><0.05), while there were no significant differences in the incidence rates of complications between the two groups(<i>P</i>>0.05). One month after surgery, the intraocular pressure of the two groups were significantly lower than that before surgery(<i>P</i><0.05), and the difference of intraocular pressure before and after surgery in the study group was significantly higher than the control group. Three months after surgery, the formation rate of functional filtration bleb in the study group was significantly higher than that in the control group(<i>P</i><0.05). <p>CONCLUSION: The application of scleral adjustable sutures in trabeculectomy and scleral biological amniotic membrane implantation can effectively reduce the risk of shallow anterior chamber, which is of positive significance in improving intraocular pressure and formation of functional bleb in patients with angle closure glaucoma.
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Cell-penetrating peptides are composed of positively-charged amino acids that can mediate molecules or nano-carriers across cell membranes. However, most of the known cell-penetrating peptides have no cell-or tissue-specificity, with affinity to almost all types of cells in internalization. The non-specificity of cell-penetrating peptides is a significant obstacle in the application to targeted delivery of imaging probes and therapeutic agents. Accordingly, many studies focused on selective switching of systemically-delivered inert cell-penetrating peptides into active forms in diseased tissues. Tsien groups introduced the concept of activatable cell-penetrating peptides in 2004. Subsequently, a growing number of similar delivery systems (molecular or nano-sized) have been documented, and the sensitive factors have included enzyme, lower pH, light and exogenous component. In this paper, we make an overview of the development of activatable delivery system in recent years.
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Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
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Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Subject(s)
Humans , Cell-Penetrating Peptides , Chemistry , Drug Delivery Systems , Enzymes , Chemistry , Neoplasms , Drug TherapyABSTRACT
OBJECTIVE@#To investigate the precise species of tick vector and the Borrelia spirochete pathogen at the Heilongjiang Province international border with Russia.@*METHODS@#In this study, ticks were collected from 12 Heilongjiang border crossings (including grasslands, shrublands, forests, and plantantions) to determine the rate and species type of spirochete-infected ticks and the most prevalent spirochete genotypes.@*RESULTS@#The ticks represented three genera and four species of the Ixodidae family [Ixodes persulcatus, Dermacentor silvarum, Haemaphysalis concinna and Haemaphysalis japonica]. Ixodes persulcatus had the highest amount of Borrelia burgdorferi sensu lato infection of 25.6% and the most common species of Borrelia isolated from Ixodes persulcatus was Borrelia garinii, strain PD91.@*CONCLUSIONS@#Our results suggest that Borrelia garinii PD91-infected Ixodes persulcatus may be the principal cause of Lyme disease in the border crossing areas of Heilongjiang Province.
Subject(s)
Animals , Arachnid Vectors , Microbiology , Borrelia burgdorferi Group , Genetics , China , Emigration and Immigration , Ixodes , Microbiology , Lyme Disease , Microbiology , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , RNA , Genetics , RussiaABSTRACT
The objective of this study was to evaluate the role of reticulated platelets (RF) and platelet-associated antibody (PAIg) in differential diagnosis of idiopathic thrombocytopenic purpura (ITP). The immature platelet fraction (IPF) of 34 ITP patients, 36 non-ITP patients and 411 normal people were detected by Sysmex XE-5000 automated blood cell analyser and PAIgG content was detected by enzyme-linked immunosorbent assay. All results were analysed statistically. The results showed that IPF of ITP patients was significantly higher than that of non-ITP patients and normal people respectively (p < 0.05). For diagnosis of ITP, IPF positive rate of ITP patients was significantly higher than that of non-ITP patients (p < 0.05). There was no significant difference between the positive rate of PAIgG in ITP and non-ITP patients (p > 0.05). The sensibility, specificity and negative predictive value of IPF were higher than those of PAIgG, while the positive predictive value of IPF was a little lower than that of PAIgG. The area under receiver operating characteristic curve of IPF was larger than that of PAIgG. It is concluded that both IPF and PAIgG detection are valuable in differential diagnosis of ITP. The diagnostic value of IPF is better than that of PAIgG.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Blood Platelets , Allergy and Immunology , Case-Control Studies , Diagnosis, Differential , Immunoglobulin G , Blood , Platelet Count , Purpura, Thrombocytopenic, Idiopathic , Blood , DiagnosisABSTRACT
<p><b>OBJECTIVE</b>To assess HCH and DDT exposure levels and associated risk factors among 262 children aged 6-10 years in a northeastern rural area of China between April and May of 2008.</p><p><b>METHODS</b>Eight HCH and DDT metabolites in serum samples were monitored by gas chromatography. A questionnaire was administered to identify the sources of pesticides in children' serum samples.</p><p><b>RESULTS</b>At least one pesticide metabolite was detected in 81.7% of the tested children. Higher amounts of pp'DDD were detected in 50% of them. Children's age and their father's occupation as farmers, together with not changing work clothes after work, were the main risk factors for HCH and DDT exposure among them.</p><p><b>CONCLUSION</b>Children living in rural areas are experiencing multiple sources of organochlorine pesticide exposure. These pesticides may have been retained in the environment for a long period of time.</p>
Subject(s)
Child , Humans , China , Environmental Exposure , Hexachlorocyclohexane , Toxicity , Rural PopulationABSTRACT
Objective To dynamically investigate the effects of aluminum on the concentration of free intracellular Ca2+([Ca2+]i) and the expression of calcium channels in the hippocampus of rats. Methods Healthy 64 Wistar rats were taken as the experimental objects. And these rats were randomly divided into 16 groups according to their weights, and were instilled with AlCl3 at 0(control),37.3,74.7 and 248.7 mg/kg respectively. The experimental time exposed to AlCl3 was 45,75,120 d, among which the rats were given AlCl3 for 120 d fed normally for 30 d. The hippoeampus were segregated on day 45,75,120 and 150 d and the[Ca2+]i of hippocampus of rats were detected by fluorospectrophotometer. The expression of Ryanodine receptor 2 (RyR2) mRNA and α1C ubunit of L-type calcium ehannels(L-Ca2+α1C) mRNA were detected by RT-PCR analysis. Results [Ca2+]i was increased by AlCl3 in a dose-and time-dependant manner(F=23.136 and 19.089, P<0.01). There was a synergistic effect between the dose and time in [Ca2+]i (F=2.270, P<0.05). In time of 120,150 days, the [Ca2+]i of rats hippocampus in 37.3[(299.3±48.7), (342.7±35.3)nmol/L], 74.7[(391.2±47.9), (408.1±42.8)nmol/L] and 248.7 mg/kg group[(397.9±55.8), (405.2±22.7)nmol/L] significantly increased compared with control group [(195.1±29.9), (209.1±30.6)nmol/L; P<0.01]. The expression of RyR2 mRNA and L-Ca2+α1C mRNA were increased by AlCl3(F=23.301 and 60.812, P<0.01). The experimental time could lower the expression of L-Ca2+ α1C mRNA (F=6.088, P<0.01), but had no influences on the expression of RyR2 mR NA (F=1.361, P>0.05). There was interaction between the dose of AlCl3 and the time in the expression of L-Ca2+α1C mRNA (F=5.876,P< 0.01). On day 75,120 and 150 of the experiment, the expression of L-Ca2+α1C mRNA in rat hippocampus of 74.7 (1.03±0.16,1.18±0.18,0.92±0.11) and 248.7 mg/kg group(1.89±0.26, 1.25±0.10, 1.07±0.14) also increased compared with control group(0.63±0.09,0.78±0.16,0.69±0.11; P<0.05 or <0.01). On day 45,75, 120 and 150 of the experiment, the expression of RyR2 mRNA in 74.7(0.49±0.06,0.51±0.07,0.57±0.11, 0.47±0.11), 248.7(0.47±0.03,0.52±0.09, 0.70±0.10, 0.78±0.09)mg/kg AlCl3 groups was highly increased compared with control group (0.24±0.07, 0.32±0.04, 0.30±0.06, 0.27±0.06; P<0.05 or<0.01). Conclusion Al increases [Ca2+]i by increasing the expression of the RyR2 mRNA and L-Ca2+α1C mRNA, thus exerts an irreversible neuronal toxicity.
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OBJECTIVE: To prepare gliquidone solid dispersion and to investigate its dissolution rate. METHODS: The gliquidone solid dispersion was prepared by dissolvent- fusion method and dissolvent method with PEG- 6000( PEG) and PVP K30( PVP) as carriers. RESULTS: The results of in vitro dissolubility test showed that the higher the carrier ratio, the faster the drug dissolution. The in vitro dissolubility of solid dispersions was faster with PVP than with PEG as carrier. The dissolution rate of the gliquidone- PVP ( 1∶ 7) solid dispersion reached as high as above 70% in 10 minutes, which was superior to that of its bulk drug. CONCLUSION: The gliquidone solid dispersion has been prepared successfully.
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<p><b>OBJECTIVE</b>To investigate the high risk factors related to acute respiratory distress syndrome(ARDS) following serious thoracoabdominal injuries.</p><p><b>METHODS</b>The clinical data of 282 patients with serious thoracoabdominal injuries were retrospectively studied. Univariate and Cox multivariate regression analysis were used to determine the risk factors related to ARDS following serious thoracoabdominal injuries.</p><p><b>RESULTS</b>The incidence of ARDS was 31.9% (90/282) in patients with serious thoracoabdominal injuries. The mortality caused by ARDS was 37.8% (34/90). The univariate analysis and multivariate analysis demonstrated that the clinical conditions such as elder age, shock, dyspnea, abnormal arterial blood gas, hemopneumothorax, pulmonary contusion, flail chest, coexisting pulmonary diseases, multiple abdominal injury and high ISS score were the independent high risk factors related to ARDS.</p><p><b>CONCLUSION</b>There are many high risk factors related to ARDS following severe thoracoabdominal injuries, which should be detected early and treated timely to decrease the incidence and mortality of A RDS.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Abdominal Injuries , Age Factors , Blood Pressure , Contusions , Respiration , Respiratory Distress Syndrome , Risk Factors , Thoracic InjuriesABSTRACT
AIM: To study prescription and process of matrine controlled porosity osmotic pump tablet (matrine CPOPT) and to inspect release property in vitro. METHODS: The orthogonal experiment was designed to screen prescription and process which were definited with the evaluation of release of tablet. RESULTS: The optimization of prescription was definited: osmotic agent consisted of mannitol and lactose with a ratio of 1 ∶ 1(g/g); weight of osmotic agent was 2 fold increase of matrine; the cellulose acetate in coating liquid accounted for 15% (g/g) of PEG 400; The release behavior of matrine CPOPT was coincident with zero-order rate equation well and characteristic of controlled-release. CONCLUSION: Matrine CPOPT has good controlled-release in vitro effect and experiments for further in vivo test are available.