1.Imaging of lung cancer with molecular beacons delivered by octreotide-modified chitosan nanoparticles
Xue MA ; Jing WU ; Hongli ZHANG ; Yong LI ; Juan SONG ; Yuanli LI ; Liang LU ; Haizhen ZHU
Tianjin Medical Journal 2024;52(1):61-67
Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P<0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P<0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P<0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.
2.Transcriptomic analysis of SR8278 improving lacrimal gland dysfunction in-duced by jet lag in mice
Shenzhen HUANG ; Di QI ; Xiaoting PEI ; Dingli LU ; Hongli SI ; Duliurui HUANG ; Wenxiao ZHANG ; Mengru BA ; Shuting XUAN ; Zhijie LI
Recent Advances in Ophthalmology 2024;44(4):264-269
Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P<0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P<0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P<0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P<0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P<0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.
3.Efficacy and safety of transepithelial photorefractive keratectomy combined with accelerated corneal cross-linking for refractive error in thin or irregular cornea
Linli ZHANG ; Yu DI ; Ying LI ; Hongli DENG ; Yan REN ; Lu WANG
Chinese Journal of Experimental Ophthalmology 2024;42(4):361-366
Objective:To evaluate the efficacy and safety of transepithelial photorefractive keratectomy (Trans-PRK) combined with accelerated corneal cross-linking (CXL) for refractive error in patients with thin or irregular corneas, excluding keratoconus.Methods:An observational case series study was performed.Fifty-five right eyes of 55 myopic patients diagnosed with thin or irregular corneas, who underwent Trans-PRK combined with prophylactic CXL surgery, were included at Baotou Chaoju Eye Ophthalmic Hospital from August 2017 to July 2018.Uncorrected distance visual acuity (UDVA) of the operated eye was measured using international standard visual acuity charts, and refractive diopters were measured by computer and comprehensive refraction before surgery and at 1 week, 1, 3, 6, and 12 months after surgery.Corneal morphology was assessed with the Pentacam anterior segment analyzer before surgery and at 3, 6, and 12 months after surgery.Intraocular pressure (IOP) was measured with a non-contact tonometer before surgery and at 1, 3, 6, and 12 months after surgery.The incidence of postoperative complications was recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Baotou Chaoju Ophthalmic Hospital (No.btcj-u-1). Written informed consent was obtained from each subject.Results:Preoperative, 1-week, 1-, 3-, 6-, and 12-month postoperative UDVA (LogMAR) were 0.52(0.55, 0.78), 0.22(0.12, 0.17), 0.10(0.04, 0.07), 0.00(-0.04, -0.16), -0.08(-0.05, -0.03) and -0.08(-0.06, -0.04), respectively, showing a statistically significant overall difference ( Z=249.44, P<0.001). UDVA at each postoperative time point was improved compared to preoperative, and UDVA at 3, 6, and 12 months postoperatively was significantly improved compared to 1 week and 1 month postoperatively (all at P<0.001). The spherical diopter at each postoperative time point decreased significantly compared to preoperative, with the spherical diopter at 1, 3, 6, and 12 months postoperatively being lower than that at 1 week postoperatively, and the 12-month postoperative spherical diopter being lower than that at 3 and 6 months postoperatively, showing statistically significant differences (all at P<0.001). The cylindrical degree at 1, 3, 6, and 12 months postoperatively was lower than that at preoperative and 1 week postoperatively, with statistically significant differences (all at P<0.05). After the operation, the spherical equivalent of the operated eye gradually decreased with time, tending toward emmetropia.The spherical equivalent at each postoperative time point decreased compared to preoperative, with the spherical equivalent at 1, 3, 6, and 12 months postoperatively being lower than that at 1 week postoperatively, and the spherical equivalent at 12 months postoperatively being lower than that at 3 and 6 months postoperatively, showing statistically significant differences (all at P<0.001). The corneal K1 and K2 values at 3, 6, and 12 months postoperatively were significantly lower than preoperatively (all at P<0.001), and the corneal K1 and K2 values at 3 months postoperatively tended to stabilize.The IOP of the operated eye at 3, 6, and 12 months postoperatively was significantly lower than preoperatively, and the IOP at 6 and 12 months postoperatively was lower than that at 1 and 3 months postoperatively, with statistically significant differences (all at P<0.001). One eye developed grade 0.5 corneal haze at 1 week postoperatively, which spontaneously resolved to transparency at 1 month postoperatively. Conclusions:Trans-PRK combined with accelerated CXL has good efficacy, stability and safety for refractive error patients with thin or irregular corneas, except for keratoconus.
4.Changes in Intestinal Toxicity and Component Analysis of Mongolian Medicine Euphorbiae Pekinensis Radix before and after Processing with Milk
Lu LIU ; Hongli YU ; Hao WU ; Xinzhi WANG ; Xiaobing CUI ; Yu CAO ; Weihao LIN ; Changli SHEN ; Jie CAO
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(3):278-288
OBJECTIVE To explore the correlation between changes in intestinal toxicity and changes in component composition of the Mongolian medicine Euphorbiae pekinensis Radix(EPR)before and after processing with milk.METHODS Mice were given 95%ethanol extract of raw EPR,milk-processed EPR and water-processed EPR by gavage.The purgative effect and intestinal inflam-matory toxicity changes of EPR before and after milk processing were investigated using the fecal water content and the levels of inflam-matory factors TNF-α and IL-1β in each intestinal segment of mice as indicators;LC-MS/MS was used to analyze the composition changes of the 95%alcohol extract of EPR before and after milk processing.RESULTS Compared with the blank group,the raw and water processed products of EPR could significantly increase the water content of mouse feces and the levels of TNF-α and IL-1β in each intestinal segment(P<0.05);compared with the raw product group,all indicators in the milk processing group were significantly reduced(P<0.05),while there was no significant difference in the water processing group,indicating that water processing cannot at-tenuate toxicity,and the auxiliary material milk is the key auxiliary material to reduce the toxicity of EPR.Mass spectrometry analysis results showed that a total of 50 components were identified in EPR,including 38 terpenoid components,6 phenolic acid components,and 6 other components.The content of each component decreased to varying degrees after milk processing.Principal component analy-sis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed on the mass spectrum data of raw ma-terials and products,and it was found that the components of raw materials and products can be obviously clustered into 2 categories.13 differential components of raw materials and products were screened through t test,and 11 of which were terpene compo-nents,indicating that the composition of terpene components changed significantly after milk processing.17 components derived from EPR were detected in the residual liquid of milk excipients after processing,of which 16 were terpenoids,indicating that the terpenoid components of EPR were transferred to the excipient milk during the soaking and processing processes.CONCLUSION The toxicity of EPR is reduced and the purgative effect is alleviated after milk processing.The attenuation mechanism may be that during the milk soaking and processing processes,terpenoid components are transferred to the milk,and the content of toxic components in the decoc-tion pieces is reduced,thereby reducing the toxicity.
5.Exploration of New Pathways for Intelligent Transformation and Upgrading of Chinese Medicine Processing under the Con-text of"New Quality Productive Forces"
Lin LI ; Weidong LI ; Lianlin SU ; De JI ; Hongli YU ; Yabo SHI ; Xi MEI ; Yu LI ; Mingxuan LI ; Jiuba ZHANG ; Tulin LU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(7):653-660
The current production of Chinese herbal decoction pieces faces several issues including strong subjectivity,unstable quality,low production efficiency,and a lack of intelligent systems.In order to expedite the intelligent transformation and upgrading of Chinese medicine processing,this paper delves deeply into the problems and challenges encountered in establishing a digital and intel-ligent production model for Chinese herbal pieces.Addressing the slow progress in fundamental research on traditional Chinese medi-cine processing mechanisms,the absence of online digital quality characterization techniques,the low level of production equipment in-telligence,and the lack of evaluation standards for high-quality decoction pieces,this paper proposes a"New Quality Productive Forces"formation approach driven by technological innovation.Through interdisciplinary integration methods,the paper explores the mechanisms of Chinese medicine processing in depth,clarifies the correlation between the processing procedures and the"medicinal properties-quality"relationship,and employs bionic sensing and artificial intelligence to achieve a holistic quality characterization of decoction pieces.Additionally,the use of cloud-edge collaborative big data systems is proposed to enhance intelligent upgrades of the production lines.The paper also aims to establish a high-quality decoction piece evaluation system integrating"physical-chemical-bio-logical"multimodal data fusion.This approach aims to steer the Chinese medicine processing towards becoming more efficient,precise,and sustainable,thereby promoting high-quality sustainable development of the Chinese herbal decoction industry and providing both theoretical and practical support for the modernization of traditional Chinese medicine.
6.Exploration on thematic morning report based on post-competence in standardized residents training in hospital in intensive care unit
Hongye MA ; Lei ZHANG ; Peng LU ; Litao GUO ; Jingjing SUN ; Hongli JIANG ; Yu LIU
Chinese Medical Ethics 2024;37(1):113-119
Objective:To explore the role of conducting a"thematic morning report"based on post-competency in the standardized residents training in hospital in the Intensive Care Unit(ICU).Methods:A total of 60 resident training physicians who participated in the standardized residents training in hospital in the ICU of this hospital from January 2020 to December 2022 were included,and randomly divided into an observation group and a control group,with 30 in each group.The observation group adopted an interactive teaching method of themed morning report based on post-competency,while the control group adopted the traditional teaching method.The assessment results of clinical theoretical knowledge and operational skills of the two groups of resident training physicians under different teaching methods were compared.The 360°assessment method was used to record the multi-directional evaluation of patients or their families,nurses,colleagues,and teaching teachers on the post-competence of resident training physicians(self-learning ability,team collaboration ability,effective communication ability,and learning interest).Results:The assessment scores of clinical theoretical knowledge and practical skills in the observation group after teaching were higher than those in the control group,with statistically significant differences(theoretical assessment:t=2.101,P<0.05;practical assessment:t=9.647,P<0.05).The post-competence scores of nurses,colleagues,and teaching teachers on resident training physicians in the observation group were higher than those in the control group after one-month regular training,and the differences were statistically significant(nurses'evaluation of self-learning ability:t=3.182,P=0.002,team collaboration ability:t=3.978,P<0.05,effective communication ability:t=2.180,P=0.0335,learning interest:t=3.884,P<0.05;colleagues'evaluation of self-learning ability:t=2.888,P=0.005,team cooperation ability:t=6.816,P<0.05,effective communication ability:t=3.833,P<0.05,learning interest:t=4.086,P< 0.05;teaching teacher's evaluation of self-learning ability:t=3.429,P=0.001,team cooperation ability:t=3.086,P=0.003,effective communication ability:t=3.493,P=0.001,learning interest:t=3.126,P=0.003).There was a statistically significant difference in the satisfaction scores of patients or their familymembers towards the two groups of resident training physicians(t=3.126,P=0.003).Conclusion:The use of the interactive teaching method of thematic morning report based on post-competency in the standardized residents training in hospital in the ICU can not only improve the theoretical practice and case analysis test scores of resident training physicians,but also improve the post-competence and the satisfaction of patients and their families.
7.Preparation and identification of humanized monoclonal antibody against periostin
Xuejiao LI ; Hang ZHAO ; Shuo ZHANG ; Huiying KANG ; Yannan ZHOU ; Shuang JIA ; Xu LU ; Hongli ZHAO ; Yang HAI
Chinese Journal of Immunology 2024;40(12):2628-2633
Objective:To prepare a humanized monoclonal antibody against periostin and establish a stable cell line.Meth-ods:Based on anti-periostin mouse monoclonal antibody developed by our laboratory,total RNA was extracted,and variable region sequences were obtained by RT-PCR amplification of VH and VL genes.The mouse antibody CDR region was transplanted into the human antibody framework receptor region,and the gene was subcloned into the expression vector PATX-GS2,and stably transfected into CHO cells.Monoclonal cell lines were obtained by MSX pressure screening and limited dilution.Results:VH and VL genes were amplified by RT-PCR,and the sequence of the light and heavy chain variable region were determined.Antibody humanization were successfully stablished by CDR transplantation method a murine antibody to a human framework,and a eukaryotic expression plasmid was constructed,which was transfected into CHO cells for expression,and human anti-periostin antibody was successfully obtained.ELISA and Western blot results showed that the humanized antibody had good anti-periostin activities and binding affinity.Conclu-sion:In this study,anti-periostin humanized monoclonal antibody has been successfully prepared,which can specifically bind to peri-ostin proteins in vivo and have biological activity,providing scientific data for the precise treatment of retinal fibrosis,tissue and organ fibrosis,and malignant tumors.
8.11β-Hydroxylase deficiency combined with subacute thyroiditis resulting in severe hypokalemia: A case report and literature review
Lihong FU ; Lihua LI ; Lu LIU ; Xiaohua LI ; Hongli ZHANG
Chinese Journal of Endocrinology and Metabolism 2024;40(5):436-439
11β-Hydroxylase deficiency(11β-OHD) is a relatively rare type of autosomal recessive hereditary disease congenital adrenal cortical hyperplasia. This article reports the diagnosis and treatment of a case of 11β-OHD combined with subacute thyroiditis leading to severe hypokalemia treated in our hospital, along with a review of relevant literature.
9.A case of Acromicric dysplasia with FBN1 mutation
Xiaowen XU ; Ping LU ; Jing DUAN ; Hongli DUAN ; Zhenbo DING ; Yance HE ; Shuhan PENG
Chinese Journal of Endocrinology and Metabolism 2023;39(3):265-268
Acromicric dysplasia(AD) is a rare skeletal dysplasia characterized by severe short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and radiological characteristics. The clinical data and genetic test results of one patient with AD in our hospital were analyzed, and the clinical characteristics of this case were summarized. The main manifestations of the child were short stature, short hands and feet, mild facial dysmorphism, short and stubby metacarpals and phalanges on hand X-ray. One mutation, FBN1: c.5141T>G(p.Met1714Arg), was identified in this child, the mutation is inherited from her short mother and grandfather. AD is a rare congenital skeletal dysplasia disorder associated with mutations in the FBN1 gene. It conforms to the pathogenesis of autosomal dominant genetic disease.
10.Value of a risk assessment model in predicting venous thromboembolism in patients with liver failure after artificial liver support therapy
Sufang LU ; Rui HUANG ; Hongli ZHAO ; Dandan WANG ; Yuzhen DING ; Hong ZHOU
Journal of Clinical Hepatology 2023;39(3):613-619
Objective To investigate the value of a risk assessment model in predicting venous thromboembolism (VTE) in patients with liver failure after artificial liver support therapy. Methods A retrospective analysis was performed for the clinical data of 124 patients with liver failure who received artificial liver support therapy in Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2019 to December 2021, among whom there were 41 patients with VTE (observation group) and 143 patients without VTE (control group). Related clinical data were compared between the two groups, and the Caprini risk assessment model was used for scoring and risk classification of the patients in both groups. The t -test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; the Mann-Whitney U rank sum test was used for comparison of ranked data between two groups. The logistic regression analysis was used to investigate the independent risk factors for VTE in patients with liver failure after artificial liver support therapy. The receiver operating characteristic (ROC) curve was used to investigate the value of Caprini score and the multivariate predictive model used alone or in combination in predicting VTE. Results The observation group had a significantly higher Caprini score than the control group (4.39±1.10 vs 3.12±1.04, t =6.805, P < 0.001). There was a significant difference between the two groups in risk classification based on Caprini scale ( P < 0.05), and the patients with high risk or extremely high risk accounted for a higher proportion among the patients with VTE. The univariate analysis showed that there were significant differences between the two groups in age ( t =6.400, P < 0.001), catheterization method ( χ 2 =14.413, P < 0.001), number of times of artificial liver support therapy ( Z =-4.720, P < 0.001), activity ( Z =-6.282, P < 0.001), infection ( χ 2 =33.071, P < 0.001), D-dimer ( t =8.746, P < 0.001), 28-day mortality rate ( χ 2 =5.524, P =0.022). The multivariate analysis showed that number of times of artificial liver support therapy (X 1 ) (odds ratio [ OR ]=0.251, 95% confidence interval [ CI ]: 0.111-0.566, P =0.001), activity (X 2 ) ( OR =0.122, 95% CI : 0.056-0.264, P < 0.001), D-dimer (X 3 ) ( OR =2.921, 95% CI : 1.114-7.662, P =0.029) were independent risk factors for VTE in patients with liver failure after artificial liver support therapy. The equation for individual predicted probability was P =1/[1+e -(7.425-1.384X 1 -2.103X 2 +1.072X 3 ) ]. The ROC curve analysis showed that Caprini score had an area under the ROC curve of 0.802 (95% CI : 0.721-0.882, P < 0.001), and the multivariate model had an area under the ROC curve of 0.768 (95% CI : 0.685-0.851, P < 0.001), while the combination of Caprini score and the multivariate model had an area under the ROC curve of 0.957 (95% CI : 0.930-0.984, P < 0.001). Conclusion The Caprini risk assessment model has a high predictive efficiency for the risk of VTE in patients with liver failure after artificial liver support therapy, and its combination with the multivariate predictive model can significantly improve the prediction of VTE.

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