Tetralogy of Fallot is the most common cause of cyanotic congenital heart disease,and it is related with the high incidence of pulmonary regurgitation in repaired tetralogy of Fallot that usually requires pulmonary valve replacement.Transcatheter pulmonary valve replacement can replace traditional surgery in treating pulmonary regurgitation,which can make up for the shortcoming of large injury.Echocardiography is important in assessing ventricular function,however,conventional echocardiographic parameters have several limitations.This study reviewed the application of two-dimensional speckle tracking imaging in evaluating the right and left ventricular function after transcatheter pulmonary valve replacement in pulmonary valve regurgitation after repaired tetralogy of Fallot.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

AIM: To observe changes in fundus microcirculation of myopic adolescents after wearing orthokeratology by applying optical coherence tomography angiography(OCTA).METHODS: Prospective study. A total of 40 cases(40 eyes)of adolescents with low to moderate myopia who chose orthokeratology to correct visual acuity at our hospital from April 2021 to June 2022 were collected. The uncorrected distant visual acuity and axial length were evaluated at 1, 3 and 6mo before and after wearing orthokeratology, respectively. Furthermore, the changes in superficial vessel density(SVD), deep vessel density(DVD), central retinal thickness(CRT), foveal avascular zone area(FAZ-A), foveal avascular zone perimeter(FAZ-P), retinal nerve fiber layer(RNFL)thickness and radial peripapillary capillaries density(RPCD)were observed by applying OCTA.RESULTS: The uncorrected distant visual acuity was significantly improved at 1, 3 and 6mo after wearing orthokeratology(P<0.001). There was no statistically significant difference in axial length before and after wearing orthokeratology(P>0.05). Moreover, there were significant differences in both SVD of fovea quadrant and DVD of fovea and lower quadrant(P<0.01), but there were no differences in CRT, FAZ-A and FAZ-P, RNFL thickness and RPCD(P>0.05).CONCLUSION: Wearing orthokeratology can significantly improve visual acuity and increase local retinal vessel density in the macula in adolescents with low to moderate myopia.

This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.
Dendrobium ; Minerals ; Discriminant Analysis ; Multivariate Analysis ; Nitrogen Isotopes

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.
Humans ; Blood-Brain Barrier ; Liposomes ; Micelles ; Drug Delivery Systems ; Biological Transport ; Brain ; Brain Diseases

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

Aneurysm, False ; Carotid Artery Diseases ; Carotid Artery, Internal ; Humans ; Paracentesis ; Peritonsillar Abscess

Vascular cognitive impairment (VCI) is a clinical syndrome with impairment of at least one cognitive domain caused by vascular risk factors or cerebrovascular diseases, and its pathogenesis is not completely clear so far. Microglia are innate immune cells in the brain. They participate in many processes such as neuroinflammation, synaptic pruning, myelin regeneration, neurogenesis and connection. They are associated with the occurrence and development of various neurological diseases such as cerebral infarction, Alzheimer's disease, Parkinson's disease, and autism. Recent studies have shown that microglia play an important role in the development of VCI. This article reviews the role of microglia in VCI.

Objective:To evaluate the efficacy of combination of intranasal dexmedetomidine and esketamine for preoperative sedation in pediatric patients with congenital heart disease.Methods:Fifty American Society of Anesthesiologists physical status Ⅱ or Ⅲ pediatric patients, aged 1-3 yr, undergoing elective cardiac surgery for left-to-right shunt type congenital heart diseases, were divided into dexmedetomidine group (group D, n=25) or dexmedetomidine combined with esketamine group (group DK, n=25) using a random number table method.Dexmedetomidine 3.9 μg/kg was intranasally delivered in group D. Dexmedetomidine 3.3 μg/kg combined with esketamine 2 mg/kg was intranasally administered in group DK.The Children′s Hospital of Wisconsin Sedation Scale score, SpO 2, HR, and pulmonary artery systolic pressure (PAP) were recorded before and at 30 min after administration, and the rate of decrease in SpO 2, HR and PAP after administration was calculated.The onset time of sedation and occurrence of adverse effects such as nausea and vomiting, bradycardia and respiratory depression during sedation were recorded. Results:Inadequate sedation and over-sedation were not observed in either group.Compared with group D, Children′s Hospital of Wisconsin Sedation Scale scores were significantly decreased at 30 min after administration, the onset time of sedation was shortened, and the decrease rate of HR was decreased in group DK ( P<0.05), and there were no significant changes in HR, SpO 2 and PAP before and after administration ( P>0.05). In group DK, nausea and vomiting occurred in 2 cases, but the symptoms were mild and no medication intervention was needed.No other adverse effects such as bradycardia and respiratory depression were found in either group. Conclusion:Combination of intranasal dexmedetomidine and esketamine can optimize the efficacy of preoperative sedation in pediatric patients with congenital heart disease, esketamine may induce nausea and vomiting, and the fasting time should be strictly controlled during sedation.