1.Biosensor analysis technology and its research progress in drug development of Alzheimer's disease
Shu-qi SHEN ; Jia-hao FANG ; Hui WANG ; Liang CHAO ; Piao-xue YOU ; Zhan-ying HONG
Acta Pharmaceutica Sinica 2024;59(3):554-564
Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.
2.Allergy Associated With N-glycans on Glycoprotein Allergens
Yu-Xin ZHANG ; Rui-Jie LIU ; Shao-Xing ZHANG ; Shu-Ying YUAN ; Yan-Wen CHEN ; Yi-Lin YE ; Qian-Ge LIN ; Xin-Rong LU ; Yong-Liang TONG ; Li CHEN ; Gui-Qin SUN
Progress in Biochemistry and Biophysics 2024;51(5):1023-1033
Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.
3.Advances in the construction of models and applications of Alzheimer's disease based on microfluidic chips
Piao-xue YOU ; Lan CHEN ; Shu-qi SHEN ; Liang CHAO ; Hui WANG ; Zhan-ying HONG
Acta Pharmaceutica Sinica 2024;59(6):1569-1581
Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dysfunctions related to thinking, learning, and memory of the brain. AD has multiple pathological characteristics with complicated causes, constructing a suitable pathological model is crucial for the research of AD. Microfluidic chip technology integrates multiple functional units on a chip, which can realize microenvironmental control similar to the physiological environment. It is well applied in the construction of pathological model, early diagnosis as well as drug screening of AD. This paper focuses on the construction of AD microfluidic chips model from the perspective of cell type, culture formats and the chips structure as well as the research progress of microfluidic chips in AD application based on the pathological characteristics of AD, which will provide a reference for further elucidation of AD mechanism and drug development.
4.The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1
Wan LIU ; Fei LIANG ; Tie-quan CAI ; Ying LI ; Le LI ; Shu-cai YANG ; Ying LIU ; Yan ZHAO
Acta Pharmaceutica Sinica 2024;59(1):135-142
Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (
5.Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images.
Rong-Rui WANG ; Jia-Liang CHEN ; Shao-Jie DUAN ; Ying-Xi LU ; Ping CHEN ; Yuan-Chen ZHOU ; Shu-Kun YAO
Chinese journal of integrative medicine 2024;30(3):203-212
OBJECTIVE:
To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.
METHODS:
Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.
RESULTS:
A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.
CONCLUSIONS
The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.
Humans
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Non-alcoholic Fatty Liver Disease/diagnostic imaging*
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Ultrasonography
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Anthropometry
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Algorithms
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China
6.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
7.Hydroxylsafflor yellow A alleviating cerebral ischemia-reperfusion injury in rats by regulating cyclooxygenase-2/prostaglandin E2 signaling pathway
Ying-Chun YANG ; Ying YANG ; Xiao-Liang ZHANG ; Sai-Hong GAO ; Qing-Liang JIANG ; Yu-Feng LI ; Shu-Yu JIA
Acta Anatomica Sinica 2024;55(4):468-474
Objective To observe the effect of hyolroxylsafflor(HSYA)on cyclooxygenase-2(COX-2)/prostaglandin E2(PGE2)signaling pathway,and to investigate the protective effect and mechanism of HSYA on cerebral ischemia-reperfusion injury(CIRI).Methods Totally 90 SD male rats were randomly divided into sham-operated group(S group),operation group(CIRI group),HSYA group and celecoxib group(C group),HSYA group subdivided into HSYA low dose group(HSYA-L group),HSYA medium dose group(HSYA-M group)and HSYA high dose group(HSYA-H group),15 rats in each group.CIRI model was prepared by thread embolism method.The rats in each group were given intraperitoneal injection 30 minutes before operation.HSYA groups were given HSYA 10 mg/kg,15 mg/kg,25 mg/kg respectirely;C group was given celecoxib 40 mg/kg;S group and CIRI group were given the same amount of normal saline.Neurofunctional scores of each group of rats were performed immediately after recovery from modeling,cerebral infarction volume was measured 24 hours after reperfusion;At the same time,neuronal injury was observed by Nissl staining,the changes of COX-2 mRNA and protein were detected by Real-time PCR and Western blotting,and the changes of PGE2,tumor necrosis factor α(TNF-α)and interleukin(IL)-1β were detected by ELISA.Results Compared with the S group,in the CIRI group,neurofunctional scores increased dramatically(P<0.05),the volume of cerebral infarction increased dramatically(P<0.05),the damage of neurons increased and the number of neurons decreased dramatically(P<0.05),the expressions of COX-2 mRNA and protein increased dramatically(P<0.05),meanwhile the expressions of PGE2,TNF-α and IL-1β were also found dramatically increased(P<0.05);Compared with the CIRI group,in the HSYA group and C group,neurofunctional scores decreased dramatically(P<0.05),the volume of cerebral infarction was reduced dramatically(P<0.05),the damage of neurons decreased and the number of neurons increased dramatically(P<0.05),the expressions of COX-2 mRNA and protein,PGE2,TNF-α and IL-1β decreased dramatically(P<0.05).The differences between HSYA groups and both HSYA-L group and HSYA-M group compared with the C group were obvious(P<0.05),while no obvious differences were found in HSYA-H group compared with the C group(P>0.05).Conclusion HSYA alleviates reperfusion injury in ischemic stroke may be related to the inhibition of COX-2/PGE2 signaling pathway.
8.Localization and anatomical measurement of lateral compression Ⅱscrew guide needle insertion point for pelvic fracture
Yong-Zheng CHEN ; Zhen-Hua HU ; Shao-Juan LI ; Xia-Cun LIANG ; Li-Kang HOU ; Shu-Liang ZHU ; Xin-Ying BAI ; Jin-Jian HE ; De-Meng YANG ; Zhi-Guo CHEN
Acta Anatomica Sinica 2024;55(6):728-733
Objective To measure the distance between the lateral compression Ⅱ(LC-Ⅱ)screw guide needle and the surrounding important structures around the anterior inferior iliac spine in pelvic fractures and to locate the needle point,so as to provide anatomical reference for clinical nail placement.Methods Totally 40 adult gross specimens of embalming were implanted with LC-Ⅱ screw guide needle under the surveillance of C-arm machine,and the specimens were dissected.The shortest distance between the insertion point and the lateral femoral cutaneous nerve,femoral nerve,femoral artery,femoral vein,anterior superior iliac spine and inguinal ligament was measured.The triangle was constructed between the insertion point,anterior superior iliac spine and inguinal ligament,and the exact location of the entry point was calculated.Results The average distance between the insertion point of the male needle and the femoral vein was(50.67±7.29)mm>the anterior superior iliac spine(43.83±7.58)mm>the femoral artery(38.35±6.63)mm>the femoral nerve(31.17±1.67)mm=the inguinal ligament(28.69±6.59)mm>the lateral femoral cutaneous nerve(7.98±3.81)mm.The mean distance between the insertion point of the female needle and the anterior superior iliac spine was(45.28±7.07)mm=femoral vein(43.72±6.89)mm>femoral artery(33.76±6.33)mm>femoral nerve(25.66±6.46)mm=inguinal ligament(23.22±5.00)mm>lateral femoral cutaneous nerve(8.97±4.76)mm.The projection distance of the entry point was 31.77 mm for men and 38.41 mm for women.The Angle b was 42.81°for men and 31.71° for women.Conclusion The lateral femoral cutaneous nerve is most vulnerable to injury when LC-Ⅱ screw is inserted,and the risk of injury has nothing to do with sex.The insertion point positioning method a and b made LC-Ⅱ screw placement quickly,safely and accurately,and reduced fluoroscopy time and frequency.
9.Post-operative healthcare-associated infection influencing factors and me-diating effect of diagnosis-intervention packet payment differentials in colorectal cancer patients
Yu RONG ; Qian-Qian HUANG ; Jia-Yi OU ; Shu-Liang YU ; Ye-Ying SONG ; Wei-Qun LU ; Li-Ming REN ; Yao FU ; Jian-Hui LU
Chinese Journal of Infection Control 2024;23(11):1421-1429
Objective To explore the potential influencing factors of post-operative healthcare-associated infection(HAI)in colorectal cancer patients,as well as the mediating effect relationship between the influencing factors and the diagnosis-intervention packet(DIP)payment differentials.Methods Medical data of patients who underwent colorectal cancer surgery in a tertiary first-class cancer hospital in Guangzhou were retrospectively analyzed.According to HAI status,patients were divided into infection group and non-infection group.Baseline demographic information and differences in DIP payment differentials between two groups of patients were compared by rank sum test or chi-square test.The influence of each potential factor on the occurrence of HAI was analyzed by logistic re-gression.Mediating analysis was preformed by bootstrap method,and mediating effect of HAI and total hospitaliza-tion days on DIP payment differentials was evaluated.Results A total of 350 patients were included in analysis,50 were in the infection group and 300 in the non-infection group.The incidence of HAI was 14.29%.Logistic regres-sion analysis result showed that risk of HAI in patients with central venous catheterization ≥10.00 days was 13.558 times higher than that<10.00 days(P<0.001);risk of HAI in patients with urinary catheterization ≥3.00 days was 2.388 times higher than that<3.00 days(P=0.022).There were all statistically significant differences in DIP payment differentials among patients with different ages,prognostic nutritional index(PNI),HAI status,total length of hospitalization stay,duration of surgery,central venous catheterization days,and catheterization days(all P<0.05).The mediating analysis results showed that the occurrence of HAI resulted a change in DIP payment di-fferentials by affecting the total number of hospitalization days.The mediating effect value of total hospitalization days was 0.038,accounting for 35.68%of the total effect.Conclusion Medical institutions should pay attention to HAI resulting from prolonged central venous and urinary catheterization in patients underwent surgery for colorectal cancer,reducing the total length of hospital stay,thus reducing the overruns associated with the increased DIP pay-ment differentials.
10.The Role of Matrix Metalloproteinase-13 in Multiple Myeloma
Hai-Ying JIA ; Shu-Li GUO ; Liang YU ; Guo-Hong HUANG ; Chang-Min WANG
Journal of Experimental Hematology 2024;32(6):1776-1780
Objective:To investigate the role of matrix metalloproteinase-13 (MMP-13) in the development,diagnosis and prognosis of multiple myeloma (MM). Methods:Blood samples of 57 MM patients and 45 normal controls were collected,and real-time PCR was performed to detect the MMP-13 mRNA expression level in the study subjects,and the difference of MMP-13 mRNA level between MM patients and normal controls was compared. The correlations of MMP-13 with MM bone disease and its severity,ISS stage,DS stage,and treatment efficacy were analyzed. Results:The MMP-13 mRNA in patients with MM was significantly higher than that in normal controls (P<0.05). The MMP-13 mRNA in MM patients with bone disease was significantly higher than that in patients without bone disease,and the more severe the bone disease,the more obvious the increase in MMP-13 mRNA (P<0.05). The MMP-13 gene expression level was also significantly different between ISS and DS stage Ⅰ and stage Ⅲ patients (P<0.05),and the MMP-13 mRNA level was significantly decreased after treatment (P<0.05). Conclusion:The MMP-13 mRNA expression level is related to the occurrence and development of MM,and it has certain guiding significance in disease diagnosis and prognosis evaluation.

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