1.Application of Functionalized Liposomes in The Delivery of Natural Products
Cheng-Yun WANG ; Xin-Yue LAN ; Jia-Xuan GU ; Xin-Ru GAO ; Long-Jiao ZHU ; Jun LI ; Bing FANG ; Wen-Tao XU ; Hong-Tao TIAN
Progress in Biochemistry and Biophysics 2024;51(11):2947-2959
Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.
2.Retrospective cohort study on the relationship between MTHFR and ABCB1 gene polymorphisms and high-dose methotrexate toxicity in children with acute lymphoblastic leukemia
Rui XU ; Jing LI ; Yu HU ; Li-fu Wu-jü-dan·A MAI ; Rui ZHANG ; Wen JIANG ; Xuan SUN ; Lin WANG ; Jun ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(13):1963-1967
Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95%confidence interval(CI)=1.038-5.320,P<0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P>0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95%CI 1.371-19.424,P<0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95%CI 1.165-15.362,P<0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P>0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P>0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.
3.Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cra-nial Sutures in Northern Chinese Han Adults
Xuan WEI ; Yu-Shan CHEN ; Jie DING ; Chang-Xing SONG ; Jun-Jing WANG ; Zhao PENG ; Zhen-Hua DENG ; Xu YI ; Fei FAN
Journal of Forensic Medicine 2024;40(2):128-134,142
Objective To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation(MPR),and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population.Methods The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected.Volume reconstruction(VR)and MPR were performed on the skull,and 160 cranial suture tomography images were generated for each sample.Then the MPR images of cranial sutures were scored according to the closure grading criteria,and the mean closure grades of sagittal suture,coronal sutures(both left and right)and lambdoid sutures(both left and right)were calculated respectively.Finally taking the above grades as independent variables,the linear regression model and four machine learning models for age estimation(gradient boosting regression,support vector regression,decision tree regression and Bayesian ridge regression)were established for northern Chinese Han adults age estimation.The accu-racy of each model was evaluated.Results Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest.All four machine learning models had higher age estimation accuracy than linear regression model.The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years.Conclusion The combination of skull CT-MPR and machine learning model can be used for age esti-mation in northern Chinese Han adults,but it is still necessary to combine with other adult age estima-tion indicators in forensic practice.
4.Instructional design and exploration on the experiment teaching of forensic science and biological evidence based on post competency cultivation
Xiaoni ZHAN ; Gehua WEN ; Jiaxin XING ; Jinfeng XUAN ; Jun YAO ; Jinghua MENG ; Jingchun BAO ; Xu WU
Chinese Journal of Medical Education Research 2024;23(6):782-786
The traditional experimental teaching mode of forensic science and biological evidence is mostly confined to experimental operation, which is not capable of cultivating students' comprehensive quality and post competency. Therefore, it is urgent to seek an innovative teaching and training mode. At present, the experimental teaching of forensic science and biological evidence is dominated by teachers. There are some problems, such as insufficient training of students' scientific thinking and innovation ability, single teaching and evaluation model, and disconnection from the practical application. This paper proposes an experimental teaching design scheme of forensic science and biological evidence based on post competency training. The course is implanted in the framework of simulated cases, and the virtual simulation experiment platform and group discussion learning method are used to achieve a training model oriented by social needs and centered on students. In the preliminary study on the students who were trained in this mode of selected sections, we found that, compared with traditional teaching, the time for students to complete the prescribed experimental operation in this teaching mode was shortened by 4 minutes on average, and the average score of theoretical course test case analysis questions was increased by 1.5 points. In conclusion, the instructional design of the experiment teaching forensic science and biological evidence can effectively improve students' post-competency, and it deserves further exploration and application.
5.A QCM Biosensor for Screening Arsenic(Ⅲ)Aptamers and Detecting Arsenic(Ⅲ)
Chu-Jun ZHENG ; Shi-Quan QIAN ; Xin-Pei LI ; Xu YAN ; Hai-Xuan HUANG ; Yu-Xuan WANG ; Yu-Wei YE ; Min YUAN
Chinese Journal of Biochemistry and Molecular Biology 2024;40(9):1282-1288
A quartz crystal microbalance(QCM)-systematic evolution of ligands by the exponential en-richment(SELEX)technique was developed to screen out aptamers with high affinity for arsenic(Ⅲ).A random single strand DNA library was designed and fixed on the mercaptoethylamine-modified crystal plate with arsenic(Ⅲ)as the target,and the free aptamer was captured in the solution,and the QCM-SELEX screening method was constructed.After 6 rounds of screening,the secondary library was se-quenced with high throughput method,and the 6S1 dissociation coefficient Kd value was 0.36 μmol/L based on QCM resonance frequency.Using 6S1 as a probe,the QCM biosensor was constructed for the detection of arsenic(Ⅲ).The sensor has a good linear relationship in the range of 0.01 μmol/L~0.2μmol/L,and the detection limit of arsenic(Ⅲ)is 5.2 nmol/L(3σ),indicatinggood selectivity.
6.Nomogram Based on Ultrasonographic Features in Differentiating Benign from Malignant Bladder Neoplasms
Jing ZHANG ; Yu LIANG ; Erxi FAN ; Tong XU ; Xuan LI ; Fuhong HUANG ; Jun SONG ; Juan LIU
Chinese Journal of Medical Imaging 2024;32(8):841-844
Purpose To construct a nomogram model based on ultrasonographic features and to evaluate its value in differentiating benign from malignant bladder neoplasms.Materials and Methods A total of 538 consecutive bladder neoplasm patients(including 84 benign cases and 454 malignant cases)confirmed by surgery or biopsy pathology from January 2016 to January 2022 were retrospectively enrolled,the ultrasonographic features(including lesion number,location,maximum diameter,echogenicity,morphology,basement,calcification,color Doppler flow imaging signal)and brief clinical data(gender,age,urinary tract malignant tumors history and gross haematuria)were all collected for univariate and multivariate Logistic regression analysis.Independent predictors for malignant bladder neoplasm were screened and nomogram model based on univariate Logistic regression analysis was constructed.Internal validation was performed by Bootstrap resampling.Meanwhile,the receiver operating characteristic curve,calibration curve and decision curve were drawn.Results Univariate and multivariate Logistic regression analysis showed patient gender(OR=1.822,P=0.038),age(OR=1.044,P=0.000),lesion location(OR=0.359,P=0.000)and color Doppler flow imaging signal(OR=2.052,P=0.007)were independent factors in predicting the malignancy of bladder lesions.Area under the curve of the nomogram prediction model based on univariate Logistic regression analysis were 0.780,the sensitivity,specificity and accuracy of the prediction model were 72.91%,71.43%and 72.68%,respectively.The calibration curve and decision curve showed good consistency and clinical practicability of the model.Conclusion The nomogram model based on ultrasonographic features and simple clinical characteristics shows good predictive accuracy in differentiating bladder neoplasms and has potential clinical application value.
7.Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria.
Li-Long PAN ; Zheng-Nan REN ; Jun YANG ; Bin-Bin LI ; Yi-Wen HUANG ; Dong-Xiao SONG ; Xuan LI ; Jia-Jia XU ; Madhav BHATIA ; Duo-Wu ZOU ; Chun-Hua ZHOU ; Jia SUN
Acta Pharmaceutica Sinica B 2023;13(10):4202-4216
Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.
8.Efficacy and safety of transumbilical single-incision laparoscopic appendectomy for acute complicated appendicitis:a single center,retrospective study
Fuzhou HAN ; Huanwei QU ; Wenqiang LI ; Guoshuai XU ; Nan YAO ; Xinlong HU ; Jiaying WANG ; Xuan HAN ; Jun QU
Journal of Clinical Surgery 2023;31(12):1172-1175
Objective To investigate the efficacy and safety of transumbilical single-port laparoscopic appendicectomy in acute complicated appendicitis.Methods Retrospective analysis was conducted for the data of 1104 patients with complicated appendicitis who underwent emergency laparoscopic appendectomy at the Department of General Surgery of Aerospace Center Hospital from April 2014 to August 2022;among them,788 patients underwent transumbilical single-port laparoscopic appendectomy(SILA)and 316 cases underwent traditional three-port laparoscopic appendectomy(LA);the operation time,intraoperative blood loss,leukocyte value on the first day after surgery,postoperative exhaust time,hospital stay,postoperative pathology and postoperative complications were statistically analyzed.Results The surgical duration of the single hole laparoscopic appendectomy(SILA)group was(68.26±22.29)minutes,intraoperative blood loss was(15.93±13.10)ml,postoperative exhaust time was(2.29±0.52)days,and white blood cells were(11.12±1.67)× 109/L on the first day after surgery,and the surgical duration of the hree hole laparoscopic appendectomy(LA)groupwas(66.47± 20.40)minutes,intraoperative blood loss was(16.65±12.98)ml,postoperative exhaust time was(2.23±0.58)days,and white blood cells were(11.35±1.54)× 109/L on the first day after surgery,there was no statistically significant difference in the data between each group(P>0.05).After 1 month of follow-up,no incisional hernia and other complications occurred in the two groups,the cosmetic effect of abdominal incision in SILA group was satisfactory,the hospitalization time of SILA group was(4.60± 1.18)days,which was shorter than that in the traditional LA group(4.93±1.71)days,and the difference was statistically significant(P<0.05).Conclusion Based on proficiency in traditional LA operations,SILA is safe and viable;in addition to the hidden aesthetic function of scars,it does not prolong the operation time and increase the risk of postoperative complications.
9.Research on the construction and application value of artificial intelligent recognition model of nasal fracture
Haibiao ZHU ; Kunshu ZHU ; Mengzhou ZHANG ; Xuan WEI ; Chang LI ; Jun MA ; Yucong WANG ; Yue ZHONG ; Xu WANG ; Tiantong YANG
Chinese Journal of Forensic Medicine 2023;38(6):609-613
Objective The diagnosis of nasal fractures poses challenges in forensic clinical evaluation.This study aims to develop and enhance an artificial intelligence-based model for nasal fracture recognition,evaluate its performance,and provide assistance and support for forensic clinical identification.Methods Multi-center nasal CT images were selected and screened according to the consensus standards set by Chinese experts in nasal CT examination and diagnosis.A recognition model was constructed,followed by external verification and evaluation.Additionally,the diagnostic capabilities of qualified appraisers/doctors with different professional titles(primary,intermediate,and senior)were compared with the performance of the intelligent recognition model.The accuracy,sensitivity,specificity),and negative predictive value(NP)of the intelligent recognition model were comprehensively evaluated.Results The intelligent recognition model exhibited high diagnostic efficiency and stability.It improved the diagnostic accuracy of radiologists and appraisers in detecting nasal fractures while effectively bridging the gap between inexperienced doctors/appraisers and experienced ones.Conclusion The intelligent recognition model for nasal fractures can assist appraisers in enhancing their ability to locate such fractures on CT images and improve work efficiency while enhancing appraisal opinions'accuracy and scientificity.
10.Effect of salidroside on choroidal thickness and expression of hypoxia-inducible factor-1α, dopamine and its receptor in guinea pigs with myopia
Shuang ZHAO ; Xiang-Jie FANG ; Juan-Mei ZHANG ; Jun ZHAO ; Wan-Jing XU ; Ling-Fang ZHENG ; Yi-Xuan FU
International Eye Science 2023;23(8):1264-1268
AIM: To examine the effects of salidroside on choroidal thickness, hypoxia-inducible factor-1α(HIF-1α), dopamine(DA)and its D1 receptor expression in guinea pigs with lens-induced myopia(LIM).METHODS: A total of 18 two-week-old guinea pigs were randomly divided into the normal control(NC)group, the LIM group, and the LIM + salidroside(LIM+SA)group, with 6 guinea pigs in each group. The guinea pigs in the NC group were fed normally and intragastrically administered with 2 mL/d saline; those in the LIM group wore a -5D lens in front of their right eyes to establish a myopia model, then they were intragastrically administered with 2 mL/d saline. Finally, those in the LIM+SA group wore glasses along with intragastric administration of 2 mL/d salidroside at a dose of 100 mg/kg. The refraction, axial length, and choroidal thickness of guinea pigs in each group were measured 4wk following the establishment of the model. In addition, the relative mRNA expression and protein content of HIF-1α in the choroid and retina of guinea pigs in each group were detected by real-time quantitative PCR(qPCR)and immunohistochemistry(IHC). Finally, the DA concentration and its D1 receptor expression were detected by enzyme-linked immunosorbent assay(ELISA)and Western blot.RESULTS: At 4wk after model establishment, guinea pigs of LIM group and LIM+SA group exhibited increased negative refraction of the right eye, prolonged axial length, and decreased choroidal thickness compared to the NC group. The relative mRNA expression and protein content of HIF-1α in the choroid and retina of the guinea pigs increased. The concentration of DA and the expression of its D1 receptor both decreased. Moreover, compared to the LIM group, the diopter of the right eye of guinea pigs in LIM+SA group significantly reduced, the axial length was shorter, the thickness of choroid increased, the relative mRNA expression and protein content of HIF-1α in the choroid and retina decreased and the concentration of DA and the expression of its D1 receptor both increased.CONCLUSION: Salidroside can delay myopia progression in myopic guinea pigs by affecting choroidal thickness and the expression of HIF-1α, DA and its D1 receptor.

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