1.New insights into translational research in Alzheimer's disease guided by artificial intelligence, computational and systems biology.
Shulan JIANG ; Zixi TIAN ; Yuchen YANG ; Xiang LI ; Feiyan ZHOU ; Jianhua CHENG ; Jihui LYU ; Tingting GAO ; Ping ZHANG ; Hongbin HAN ; Zhiqian TONG
Acta Pharmaceutica Sinica B 2025;15(10):5099-5126
Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.
2.Natural killer cell-derived granzyme B as a therapeutic target for alleviating graft injury during liver transplantation.
Kai WANG ; Zhoucheng WANG ; Xin SHAO ; Lijun MENG ; Chuanjun LIU ; Nasha QIU ; Wenwen GE ; Yutong CHEN ; Xiao TANG ; Xiaodong WANG ; Zhengxing LIAN ; Ruhong ZHOU ; Shusen ZHENG ; Xiaohui FAN ; Xiao XU
Acta Pharmaceutica Sinica B 2025;15(10):5277-5293
Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB+ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg -/- Rag2 -/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.
3.A meta-analysis of prevalent characteristics of injury-related behaviors among adolescents based on Chinese literature
Xiaodi BAI ; Yunlan JIANG ; Ting XU ; Siyu LIN ; Heyao XU ; Shulan LIU ; Xinyao ZHOU
Shanghai Journal of Preventive Medicine 2024;36(10):969-976
ObjectiveTo conduct a meta-analysis of the prevalent characteristics of the injury-related behaviors among adolescents in China based on Chinese literature, so as to inform the prevention and control of injury-related behaviors of this population. MethodsA cross-sectional study on the prevalent characteristics of adolescent injury-related behaviors was conducted with the data collected from CNKI, VIP, Wanfang Data, CBM, PubMed, and Web of Science. The review included publications from the inception of the databases to November 2023. Meta-analysis was performed with Stata 15.1 software. ResultsA total of 40 articles were included in this study, and the meta-analysis results showed that cycling violation rate was 38% (95%CI: 32%‒43%), walking violation rate was 29% (95%CI: 22%‒36%), rate of unsafe swimming was 13% (95%CI: 11%‒14%), suicidal ideation rate was 13% (95%CI: 12%‒15%) and the prevalence of fighting was 19% (95%CI: 17%‒22%). Subgroup analysis showed that the cycling violation rate was (44%) for boys and 34% (95%CI: 28%‒40%) for girls. Adolescents in Northeast, East, and Southwest of China had the highest rate of cycling violation (44%), of which junior high school students had the highest rate of violation [42% (95%CI: 36%‒49%)]. As for the walking violation rate, male students [29% (95%CI: 21%‒37%)] was higher than that of female students [22% (95%CI: 15%‒30%)]. Adolescents in North of China had the highest rate of walking violation [54% (95%CI: 30%‒76%)], of which vocational school students accounted for 38% (95%CI:21%‒56%) of the total violation. In terms of the detection rate of unsafe swimming, male students [18% (95%CI: 14%‒24%)] was higher than that of female students [8% (95%CI: 6%‒10%)]. Adolescents in Central South China had the highest rate of unsafe swimming [15% (95%CI: 12%‒18%)], of which, vocational school students accounted for the highest [15% (95%CI: 10%‒19%)]. When it comes to the prevalence of suicidal ideation, female students [16% (95%CI: 13%‒19%)] was higher than that of male students [13% (95%CI: 11%‒15%)]. Adolescents in Southwest of China had the highest rate of suicidal ideation [17% (95%CI: 10%‒25%)], of which high school students accounted for the highest [15% (95%CI: 12%‒18%)]. Finally, the detection rate of fights was 30% (95%CI: 26%‒34%) for boys and 11% (95%CI: 10%‒14%) for girls. Adolescents from Southwest of China had the highest rate [29% (95%CI: 24%‒34%)] for fights, and junior high school students accounted for the highest [26% (95%CI: 22%‒31%)]. ConclusionThe prevalence of harmful behaviors among adolescents in China is notably high, with statistical differences across gender, region, and school stages. These behaviors pose a risk to adolescent health, underscoring the need for targeted interventions by health and educational authorities.
4.Accuracy of digital guided implant surgery:expert consensus on nonsurgical factors and their treatments
Shulan XU ; Ping LI ; Shuo YANG ; Shaobing LI ; Haibin LU ; Andi ZHU ; Lishu HUANG ; Jinming WANG ; Shitong XU ; Liping WANG ; Chunbo TANG ; Yanmin ZHOU ; Lei ZHOU
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(5):321-329
The standardized workflow of computer-aided static guided implant surgery includes preoperative exami-nation,data acquisition,guide design,guide fabrication and surgery.Errors may occur at each step,leading to irrevers-ible cumulative effects and thus impacting the accuracy of implant placement.However,clinicians tend to focus on fac-tors causing errors in surgical operations,ignoring the possibility of irreversible errors in nonstandard guided surgery.Based on the clinical practice of domestic experts and research progress at home and abroad,this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection,data collection,guide de-signing and manufacturing and describes strategies to resolve errors so as to gain expert consensus.Consensus recom-mendation:1.Preoperative considerations:the appropriate implant guide type should be selected according to the pa-tient's oral condition before surgery,and a retaining screw-assisted support guide should be selected if necessary.2.Da-ta acquisition should be standardized as much as possible,including beam CT and extraoral scanning.CBCT performed with the patient's head fixed and with a small field of view is recommended.For patients with metal prostheses inside the mouth,a registration marker guide should be used,and the ambient temperature and light of the external oral scan-ner should be reasonably controlled.3.Optimization of computer-aided design:it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers.Properly designing the retaining screws,extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors.4.Improving computer-aided production:it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postpro-cessing procedures.
5.Baseline NIHSS score and D-dimer in early prediction of large vessel occlusion in patients with acute ischemic stroke
Gang ZHANG ; Deliang HU ; Shulan ZHOU ; Lina MAO ; Lili JIANG ; Jinsong ZHANG ; Xufeng CHEN ; Gannan WANG ; Lei JIANG
Chinese Journal of Emergency Medicine 2023;32(2):236-240
Objective:Early identification of ischemic stroke patients with large vessel occlusion can improve referral efficiency and shorten reperfusion time. The purpose of this study was to analyze the characteristics of patients with large vessel occlusion and identify factors that could predict large vessel occlusion.Methods:The clinical data of 432 patients with ischemic stroke treated through emergency green channel were retrospectively analyzed, and the differences between the large vessel occlusion group (LVO group) and the non-large vessel occlusion group (non-LVO group) were compared, and two independent risk factors of the LVO group were screened out by logistics regression analysis: baseline NIHSS score and D-dimer value. The predicted cutoff values of NIHSS score and D-dimer were further determined by the receiver operating characteristic (ROC) curve.Results:A total of 432 patients with ischemic stroke had complete imaging data, with a mean age of 68.5±12.4 years, including 275 (63.7%) males, and 245 (56.7%) in the LVO group and 187 (43.3%) in the non-LVO group. Age, hemorrhagic transformation, thrombolytic therapy, endovascular treatment, atrial fibrillation, baseline NIHSS score [14.0 (6.0-20.0) vs. 3.0 (1.0-6.0), P<0.05], and D-dimer value at admission [0.9(0.4-2.3) mg/L vs. 0.3 (0.2-0.5)mg/L, P<0.05] were statistically significant different between the two groups. Multivariate Logistic regression analysis showed that higher baseline NIHSS score( OR=1.22,95% CI: 1.17-1.27)and higher D-dimer value( OR=3.10,95% CI: 2.14-4.47)were independent risk factors for large vessel occlusion. Baseline NIHSS score combined with D-dimer value was a good predictor of large vessel occlusion(AUC 0.85 [0.81-0.89]). ROC curve suggested that NIHSS score >6.5 and D-dimer >0.57 mg/L were the cutoff values for predicting large vessel occlusion. Conclusions:Higher baseline NIHSS score and D-dimer value are valuable for early prediction of large vessel occlusion, patients with NIHSS score >6.5 points and D-dimer >0.57 mg/L should be promptly transported to an advanced stroke center for treatment.
6. Bioinformatics analysis of differentially expressed circRNAs and microRNA-1 in HepG2 cells
Ye-ping DONG ; Xin-yi ZHOU ; Si-li FEI ; Chun LOU ; Tian TONG ; Meng-ting PANG ; Ying WANG
Journal of Medical Postgraduates 2020;33(3):246-250
ObjectivecircRNAs play an important role in tumor development, but the relationship between circRNAs and hepatocellular carcinoma remains to be further explored. The present study aimed to bioinformatically analyze the target gene of microRNA-1. Another aim was to screen circRNAs that are associated with target genes and differentially expressed in hepatocellular carcinoma cells, as well as provide theoretical basis for clinical screening of molecular markers and targeted therapies related to hepatocellular carcinoma.MethodsThe miRNA related database used for the prediction of microRNA-1 target genes, and the bioinformatic analysis of the target genes of microRNA-1 involved functional enrichment analysis and signal transduction pathway enrichment. Then, the circRNAs, which are related to the downstream target genes of microRNA-1, are screened through the circRNA database.ResultsThe number of microRNA-1 target genes was 230 in miRNA related database. Through GO analysis, it was found that the target genes of microRNA-1 had a strong tendency in regulation, and were mainly enriched in three aspects: biological function, biological process and cell localization.The target genes of microRNA-1 are involved in the function of proteins, regulation of biosynthesis, cofactor binding, enzyme regulation and other biological processes. Predicted target genes of miRNA-1 were significantly enriched in cancer signaling pathways, hepatitis B occurrence, endocytosis and splicing pathways. Further, 21 circRNAs related to the target gene of microRNA-1 were found in three circRNA databases, wherein hsa_circ_0004651 was highly expressed in hepatocellular carcinoma cell line HepG2 and its pavent gene was hnRNPD.ConclusionMicroRNA-1 influence the occurrence of hepatocellular carcinoma development through the regulation of protein and enzyme. Hsa_circ_0004651 may affect the development of hepatocellular carcinoma with microRNA-1 and its parental gene hnRNPD.
7.Application of two-stage crestal approach sinus elevation in severe atrophic posterior maxilla
Xi LIN ; Zhen ZHOU ; Shaobing LI ; Yan GAO ; Shiyi LI ; Peijun ZHU ; Shulan XU
Chinese Journal of Stomatology 2020;55(11):871-877
Objective:To investigate the feasibility of two-stage crestal approach sinus elevation in severe atrophic maxilla.Methods:A total of 25 patients (male: 13 cases,female: 12 cases) who attended Department of Implant Center, Stomatological Hospital, Southern Medical University from May 2016 to May 2018 were included in this study. The age of the patients was 32-49 years old. The inclusion criteria were: single or multiple tooth loss in posterior maxilla with residual bone height ranged from 1.5 to 3.0 mm and vertical bone width≥6 mm, no pathological changes or septum were detected in the sinus. The elevated sides were divided into three groups according to different buccal-palatal sinus width (SW): wide (16 case, SW>15 mm), normal (12 case, 12 mm≤SW≤15 mm), narrow (5 case, SW<12 mm). Finally, 23 patients with 33 implants were placed by the two-stage crestal approach for sinus elevation. Six months after implant placement, final restorations were delivered. Implant survival rate, implant stability quotient (ISQ), immediate vertical bone height (VBH) after surgeries, changes of sinus elevation height (cSEH), marginal bone loss (MBL) at 1 year follow-up were examined.Results:Twenty-three patients were finally included in the study, including 12 males and 11 females, aged (41.2±7.6) years old. All implants healed uneventfully. ISQ (wide: 50.81±2.69; normal: 60.58±2.54; narrow: 63.12±3.58), immediate VBH after 1st surgery [wide: (7.99±1.13) mm; normal: (8.95±0.81) mm; narrow: (9.18±0.90) mm] and 2nd surgery [wide: (11.46±0.88) mm; normal: (12.77±0.49) mm; narrow: (12.57±0.55) mm], cSEH six months after 1st [wide: (3.87±0.43) mm; normal: (2.01±0.65) mm; narrow: (1.49±0.33) mm] and 2nd [wide: (1.16±0.29) mm; normal: (1.04±0.33) mm ; narrow: (0.97±0.41) mm] surgery, MBL [wide: (0.91±0.05) mm; normal: (0.79±0.10) mm; narrow: (0.74±0.07) mm] were significantly different among three groups ( P<0.05). In all the three groups, cSEH was barely detected at 1-year follow-up ( P>0.05). Conclusions:Two-stage crestal approach for sinus elevation might be an alternative protocol in severe atrophic posterior maxilla, especially in cases with narrow and normal buccal-palatal width. There is an urgent need for long time follow-up and more clinical cases.
8.The diagnosis value of TNF-α ,IL-6 and NSE in cerebrospinal fluid of children with central nervous system infection
Shulan SHI ; Yanfei YANG ; Rongjie LI ; Junyi YANG ; Xingxing FENG ; Xiaojuan LI ; Bailing ZHOU ; Liyue KUI ; Tingyi DU
International Journal of Laboratory Medicine 2018;39(12):1470-1472
Objective To explore the diagnostic value of tumor necrosis factor-alpha (TNF-α) , interleukin-6 (IL-6) and neuron enolase (NSE) in the cerebrospinal fluid of children with central nervous sys-tem infection (CNSI).Methods 54 cases of CNSI hospitalized children ,admitted in the hospital from October 2015 to January 2017 ,were enrolled in the study and divided into viral meningitis group (30 cases) and suppu-rative meningitis group (24 cases).Another 20 cases who underwent cerebrospinal fluid examination and other related examinations were enrolled in the study as the control group.The levels of three biomarkers TNF-α , IL-6 and NSE in cerebrospinal fluid of three groups were detected by enzyme linked immunosorbent assay (ELISA).Results The levels of TNF-α ,IL-6 and NSE in purulent meningitis group were the hightest ,and the levels of these three factors in viral meningitis group were highter than the control group ,and the differ-ence was statistically significant in three groups (P<0.05).But there were a lot of data overlaps.There was no significant difference in the levels of TNF-α ,IL-6 and NSE between the brain group and the control group (P>0.05).Conclusion The detection of TNF-α ,IL-6 and NSE in cerebrospinal fluid has a certain clinical val-ue for the diagnosis of CNSI ,but it needs to be further verified by a large sample clinical trial.
9.An in vitro activity study of titanium surface modified by cluster-like anatase/rutile nanowires
Yan GAO ; Ying LIU ; Shulan XU ; Lei ZHOU
The Journal of Practical Medicine 2018;34(8):1248-1252
Objective Exploration of the titanium surface nano structure on the cellular bioactivity is of great significance to modifying the pure titanium surface. The unique cluster-like anatase/rutile nanowires (AR@NWs)was prepared and we further examined whether this surface was beneficial for early biological reaction in osteoblast.Methods Unique cluster-like anatase/rutile NWs(AR@NWs)was generated by using a simple hy-drothermal reaction via a three-step synthesis process.The crystal structure of nanowires on titanium surface was de-tected by X-ray diffractometer. The biological activity of nanowires was studied using in vitro cellular experiments. Results The AR@NWs was with a diameter of 200 nm. Three different types of NWs were generated during the production process,displaying different crystal structure and biological characteristics but similar surface topogra-phy and wettability.Compared with sodium titanate NWs(STi@NWs)and H2Ti2O5nanowires(HTi@NWs),AR@NWs surface was conductive to cell attachment. The data indicated that the surface titanium chemical composi-tion and crystal structure played an important role in the cell early response.To some extent,the generation of ana-tase and rutile compensated the cell-repelling properties of NWs. Conclusion Not only the surface physical prop-erties such as surface topography but also the surface chemistry plays an important role in promoting the cell early bioactivity.
10.Impacts of LASP-1 on osteogenic moving behavior and distribution of cell cycle of osteoblasts derived from different soue
Fang JIA ; Chunhua LAI ; Zhen ZHOU ; Yan GAO ; Zehong GUO ; Shulan XU
The Journal of Practical Medicine 2018;34(9):1428-1434
Objective To investigate the impacts of LASP-1 on the behavior and cell proliferation ability of tumor derived osteoblast-like cells and non tumor derived osteoblasts. Methods QRT-PCR and Western blot were performed to detect LASP-1 expressions in mouse bone marrow mesenchymal stem cells(BMMSC),human osteoblasts (hOB) and human osteosarcoma cell (MG-63). With the construction of recombinant vector and the transfection of shLASP-1,the expression changes in both LASP-1 and osteocalcin(OCN),and the cell number of cell-cycle phase distribution were analyzed. Results With up-or down-regulation of LASP-1,osteocalcin(OCN) expression,cell proliferation ability and the cell number of G2/M phase in non tumor cells(BMMSC,hOB)had no obvious changes. However,as for the tumor cells(MG-63),with an increased expression of LASP-1,the expression of OCN,cell proliferation number and the cell number at G2/M phase changed. There was no significant effect on the moving ability of each cell. Conclusions LASP-1 has no significant effect on the osteogenic proper-ties,cell proliferation ability and cell cycle distribution of non tumor derived cells,but has a regulatory effect on tumor derived cells(MG-63).


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