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.Data-independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sj?gren's Syndrome
Tian YI-CHAO ; Guo CHUN-LAN ; Li ZHEN ; You XIN ; Liu XIAO-YAN ; Su JIN-MEI ; Zhao SI-JIA ; Mu YUE ; Sun WEI ; Li QIAN
Chinese Medical Sciences Journal 2024;39(1):19-28,中插3
Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.
3.Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review
Lin-Fei CHENG ; Chao-Qun YOU ; Cheng PENG ; Jia-Ji REN ; Kai GUO ; Tie-Long LIU
Chinese Journal of Traumatology 2024;27(3):134-146
Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.
4.Identification of senescence-related molecular subtypes and key genes for prostate cancer.
De-Chao FENG ; Wei-Zhen ZHU ; Xu SHI ; Qiao XIONG ; Jia YOU ; Qiang WEI ; Lu YANG
Asian Journal of Andrology 2023;25(2):223-229
We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.
Male
;
Humans
;
Endothelial Cells
;
Ligands
;
Prostatic Neoplasms/pathology*
;
Prostate/pathology*
;
Prostatectomy
;
Aldehyde Dehydrogenase, Mitochondrial
;
DNA-Binding Proteins
;
Transcription Factors
5. Correlation between sarcopenia,sarcopenic obesity and osteoporosis in adults of Han nationality in Liaoning province
Jia-Yi LI ; Huan-Jiu XI ; You-Feng WEN ; Chao GUI ; Xiao-Ming ZHANG ; Hai-Long ZHANG
Acta Anatomica Sinica 2023;54(2):238-243
Objective To understand the prevalence of sarcopenia,sarcopenic obesity and osteoporosis, and to analyze the influence of sarcopenia and sarcopenic obesity on osteoporosis. Methods After all the people signed the informed research agreement, the experimental subjects were selected from Han people over 20 years old in Liaoning region, and a total of 1266 cases were included. The distribution of muscle mass, fat mass and bone mineral density in different parts of adults were measured by bioelectrical impedance analyzer (BIA) and bone densitometer, and the correlation between sarcopenia and sarcopenic obesity and osteoporosis in adults was studied. Results With the increase of age, the muscle mass of limbs, trunk, total muscle mass and body weight of the Han adults in Liaoning showed a trend of increasing at first and then decreasing. There was no significant difference in the prevalence of sarcopenia and sarcopenic obesity between men and women, but there was a significant difference in the prevalence of osteoporosis between men and women. The prevalence of all three groups reached the peak in the age group above 60, and the difference was statistically significant.The risk factor for osteoporosis was sarcopenia and sarcopenic obesity. Conclusion Among adults of Han nationality in Liaoning, the prevalence of sarcopenic obesity,sarcopenia and osteoporosis is significantly different in age. Bone condition is affected by fat mass and muscle mass.
6.Research progress of virtual reality and augmented reality technology in colorectal surgery
Shuang LI ; Meng-Ying JIA ; Chao-Xiang YOU
China Medical Equipment 2023;20(12):201-206
With the rapid development of artificial intelligence and deep learning,virtual reality(VR)and augmented reality(AR)technologies have been widely used in the medical field with their unique advantages.Despite the rapid advances of techniques in colorectal surgery,the risk of colorectal surgery remained high due to the complexity of colorectal anatomy,and the burden of postoperative symptoms remained high.VR and AR technologies can help overcome some of these challenges.The application of VR and AR in colorectal surgery was reviewed,including education and training,surgical assistance,patient education,symptom management,etc.,in order to provide references for clinical application of VR and AR in colorectal surgery.
7.Biological characteristics of sheep peripheral blood mesenchymal stem cell.
Chao HAN ; Zhu Xing ZHOU ; You Rong CHEN ; Zi Hui DONG ; Jia Kuo YU
Journal of Peking University(Health Sciences) 2022;54(6):1151-1157
OBJECTIVE:
To obtain eripheral blood mesenchymal stem cells (PBMSCs) from sheep and rabbits by continuous mobilization of granulocyte colony-stimulating factor (G-CSF), and by comparing the success rates, cell yields and biological characteristics of the two sources of PBMSCs, and to provide the experimental basis for the preclinical study of PBMSCs transplantation to repair articular cartilage injury and cartilage tissue engineering.
METHODS:
Through morphological characteristics, flow cytometry analysis of its surface markers, and induction of trilineage differentiation of the two cells in vitro (ie: adipogenic differentiation, osteogenic differentiation, chondrogenic differentiation), the obtained cells were finally confirmed to be PBMSCs. The colony-forming units (CFUs) and the acquisition success rates of the two PBMSCs were counted and compared, and the production of the second generation of the two PBMSCs was counted and compared by hemocytometer, and the cell counting kit-8 was used to detect the doubling time of the two PBMSCs, and the results of trilineage differentiation were quantitatively analyzed by image processing.
RESULTS:
Microscopically, the PBMSCs of fusiform sheep and rabbits were arranged in fish group, and the second generation of sheep and rabbit PBMSCs expressed CD44 and CD90, but not CD34 and CD45. The induction of trilineage differentiation of the two cells in vitro were successful. The CFUs of primary sheep and rabbits PBMSCs were: 7.27±1.56, 5.73±1.62, and the success rate of acquisition of sheep and rabbits PBMSCs were 78.57% and 36.67%. The number of the second-generation sheep and rabbits PBMSCs that obtained per milliliter of peripheral blood were: 29 582±2 138, 26 732±2 286, and the cell doubling times (h) of the third-generation sheep and rabbits PBMSCs were: 22.32±0.28, 33.21±0.64, the cell doubling time (h) of the fourth generation sheep and rabbits PBMSCs were: 23.62±0.56, 35.30±0.38, and the quantitative lipid ratio of sheep and rabbit PBMSCs were: 7.77%±3.81%, 17.05%±1.52%, sheep and rabbit PBMSCs chondroglobus acid mucopolysaccharide positive ratios were: 11.67%±0.53%, 8.14%±0.57%. There were statistical differences among the above groups (P < 0.05).
CONCLUSION
The continuous mobilization of G-CSF to obtain sheep PBMSCs is more efficient. Sheep PBMSCs have more abundant yield and stronger proliferation ability.Sheep PBMSCs can produce more acidic mucopolysaccharides and have lower adipogenic abi-lity under appropriate conditions. Sheep PBMSCs have good research prospects in repair of articular cartilage injury with autologous stem cell transplantation and preclinical animal in vivo experiment of cartilage tissue engineering.This experiment provides further experimental basis for this kind of research.
Sheep
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Rabbits
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Animals
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Osteogenesis
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Hematopoietic Stem Cell Transplantation
;
Cells, Cultured
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Transplantation, Autologous
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Mesenchymal Stem Cells
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Cell Differentiation
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Cartilage, Articular/injuries*
;
Granulocyte Colony-Stimulating Factor
8.Chest or Abdominal Compression for Prevention of Respiratory Depression in Patients under Propofol Sedation during Gastroscopy
Xiamait AERDAKE ; Jing-ru WEI ; Tian-you LU ; Kang-feng MAI ; Jia-ai LI ; Chao-jin CHEN ; Zi-qing HEI ; Xiao-yun LI
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(4):631-638
ObjectiveTo explore the preventive effects of chest compression, abdominal compression and combined thoracoabdominal compression on propofol-induced respiratory depression during gastroscopy. MethodsA total of 544 patients underwent propofol sedation during gastroscopy in our hospital were randomly divided into 4 groups (n=136 each): Group C (control group), Group T (chest compression group), Group A (abdominal compression group) and T&A (combined thoracoabdominal compression group). Altogether 20 chest, abdominal and combined thoracoabdominal compressions were started respectively on patients in Group T, A and T&A before performing gastroscopy and after unconsciousness at a rate of 30 compressions per minute with a compression depth of 2~3 cm. The incidence of oxygen desaturation (SpO2
9.Efficacy of laparoscopic proximal gastrectomy with double-tract reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for early upper gastric cancer.
Guang Lin QIU ; Chao WEI ; Meng Ke ZHU ; Shao Ning HAN ; Xiao Wen LI ; Hai Jiang WANG ; Pan Xing WANG ; Jia Huang LIU ; Hua You ZHOU ; Xin Hua LIAO ; Xiang Ming CHE ; Lin FAN
Chinese Journal of Gastrointestinal Surgery 2022;25(5):412-420
Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.
Albumins
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Anastomosis, Roux-en-Y/adverse effects*
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Cholesterol
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Gastrectomy/methods*
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Hemoglobins
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Humans
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Laparoscopy/methods*
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Postoperative Complications/etiology*
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Retrospective Studies
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Stomach Neoplasms/pathology*
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Treatment Outcome
;
Vitamin B 12
10.Icariin Inhibits Proliferation of CLC5 Hepatoma Cells via Akt/GSK3β/CDK Pathway
Yu-ting BI ; Dong-ming HUA ; Jia-cheng LIN ; Li-ping YOU ; Chao ZHENG ; Hai-long WU ; Xue-hua SUN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(12):96-102
ObjectiveTo study the effect of icariin on the proliferative capacity of hepatocellular carcinoma cell line CLC5 and the underlying mechanism. MethodThe targets of icariin were screened out by network pharmacology, and the target network and protein-protein interaction (PPI) network were constructed to predict the possible targets and pathways of icariin. CCK-8 assay was employed to explore the effects of different concentrations (0, 6.25, 12.5, 25, 50 μmol·L-1) of icariin on the viability of CLC5 cells. Further, CLC5 cells were treated with 0, 25, 50 μmol·L-1 icariin, and the effect of icariin on CLC5 cell proliferation was examined by Edu-488 assay and clone formation assay (CFA). Western blot was employed to measure the expression levels of proteins in the protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β)/cell cycle-dependent kinase (CDK) pathway in the CLC5 cells exposed to different concentrations of icariin. ResultNetwork pharmacological analysis revealed that icariin may inhibit the hepatocellular carcinoma via cell cycle arrest and inhibition of tumor cell proliferation. Compared with the blank group, icariin decreased the viability of CLC5 cells in a time- and concentration-dependent manner (P<0.01) and reduced the positive rate of Edu-488 and the colonies in CFA (P<0.05, P<0.01). Moreover, icariin down-regulated the protein levels of p-Akt, p-GSK3β, CDK4, and CyclinD1 (P<0.05, P<0.01). ConclusionIcariin may block cell cycle to suppress the proliferation of CLC5 cells via inhibiting the Akt/GSK3β/CDK pathway.

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