OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed， Embase， Web of Science， CNKI， Wanfang data， VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature， extracting data， and evaluating the quality of the literature， descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included， involving 12 models. Nine studies used Logistic regression algorithm for modeling， and the number of included predictive factors ranged from 3 to 11； the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias； 10 studies had high applicability risk. A total of 31 predictive factors were extracted， including 15 items of basic patient information， 3 test indicators， and 5 items of medication information， and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm， with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved， and the overall risk of bias is relatively high.

OBJECTIVE To investigate the potential mechanism of berberine improving diabetes mellitus type 2 （T2DM） combined with metabolic-associated fatty liver disease （MAFLD） by regulating ceramide. METHODS Thirty-two db/db mice with blood glucose levels＞11.1 mmol/L （T2DM model） were divided into four groups： model group， berberine low- and high-dose groups [100， 200 mg/（kg·d）] and metformin group [300 mg/（kg·d）]， with 8 mice in each group. Additionally， 8 wt/wt mice were selected as the normal control group. Mice in each group were administered the corresponding drug solution or water by gavage once daily for a continuous period of 6 weeks. During the experiment， the body weight of the mice was monitored， and the differences in final body weight were analyzed. After the last administration， the body shape of the mice in each group was observed， and their fasting blood glucose （FBG） and the lipid indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured. Fasting serum insulin （FINS） levels were also measured， and the insulin resistance index HOMA-IR） and insulin sensitivity index （ISI） were calculated. Liver weight， liver index and serum liver function indicators [alanine transaminase （ALT）， aspartate transaminase（AST）] were assessed， and hepatic histopathological changes were observed. Additionally， the expression of fatty acid synthesis-related proteins [sterol regulatory element-binding protein 1 （SREBP1）， fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）] in liver tissue was examined. Serum samples from the normal control group， model group， and berberine high-dose group were collected for non-targeted lipidomics analysis and validation. RESULTS Compared with the model group， the pathological changes， including disordered liver tissue cell arrangement and lipid vacuoles， were significantly improved in the berberine low- and high-dose groups. The significant decreases or down-regulations were observed in body weight in the last week， as well as FBG， TC， TG， and LDL-C levels， HOMA-IR （except for the berberine low-dose group）， liver weight， liver index， AST and ALT levels， and protein expressions of SREBP1， FASN and ACC1. Additionally， HDL-C levels， FINS （except for the berberine high-dose group）， and ISI （except for the berberine low-dose group） were significantly increased （P＜0.05）. A total of 21 potential differential metabolites， including multiple types of ceramides， were identified； these metabolites were primarily enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Verification experiments confirmed that high-dose berberine significantly reduced the serum content of ceramide in model mice （P＜0.05）. CONCLUSIONS Berberine reduces insulin resistance， improves liver damage and lipid accumulation in the T2DM combined with MAFLD mice， and these effects may be related to the reduction of ceramide content.

Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods*

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective To investigate the effects of transcranial direct current stimulation(tDCS)on the topologic attributes of brain functional network in the patients with mild cognitive impairment(MCI).Meth-ods Thirty-three included patients with MCI were randomly divided into the real stimulation group(18 ca-ses)and pseudo-stimulation group(15 cases).All patients received the tDCS treatment for consecutive 10 d.The left dorsolateral prefrontal cortex(DLPFC)was stimulated by the anode,while the right orbital socket DLPFC was stimulated by the cathode.The neuropsychological scale assessment and resting state functional magnetic resonance imaging(rs-fMRI)image collection were performed before and after treatment.The GRETNA software was used to preprocess the rs-fMRI images and analyze the graph theory.The Pearson correlation analysis was used to calculate the correlation between behavioral indicators and network attribute indicators of significant difference between the two groups.Results There were statistically significant differ-ences in the node attributes(intermediate number centrality,degree centrality and local efficiency of nodes)before and after treatment,and between the two groups after treatment(P＜0.05).Compared with before treatment,the scores of MMSE,MoCA,AVLT-N7 and BNT after treatment in the real stimulation group were significantly increased[(25.89±2.16)points,(21.16±2.77)points,(4.95±1.81)points,(19.47±3.13)points].Conclusion tDCS could effectively regulate the local topological attributes of nodes in the cognitive-related brain region of MCI and improve the cognitive function.

Methylation modification is one of the most common epigenetic modification regulation in eukaryotes, including histone methylation, DNA methylation, RNA methylation, etc., which plays an important regulatory role in physiological processes and pathologic occurrence and development. Tooth root development is carried out by both epithelial and mesenchymal cells and involves a variety of cell-molecular interactions. In recent years, a large number of studies have found that methylation plays a key role in the regulation of tooth root development and expands the mechanism network of tooth root development. In this paper, we review the role and mechanism of methylation modification during root development.

Objective To evaluate the correlation between alterations in DNase1 and DNase1L3 enzyme activities and impairment of NET degradation in patients with sporadic SLE, and to investigate the underlying mechanism. Methods 46 sporadic SLE patients and 30 age- and sex-matched healthy individuals were recruited. Serum levels of DNase1, DNase1L3 and corresponding autoantibodies were detected by ELISA. DNase1 and DNase1L3 were isolated by immunoprecipitation; NETs and enzyme degradation activities were detected using a modified immunofluorescence. DNase1L3 secretion by PBMCs was analyzed by ELISPOT, Western blotting and reverse transcription PCR. Results Levels of H3-dsDNA and Ela-dsDNA complexes were significantly elevated in SLE patients. LDGs in SLE population was significantly higher than in the control group, and LDGs was positively correlated with H3-dsDNA and Ela-dsDNA NETs complexes. The ability of SLE patients to degrade NET in vitro was significantly lower than that of the control group. Degradation experiments of DNase1 and DNase1L3 in different proportions showed that the decrease in DNase1L3 activity was the primary contributor to the elevated NET residue level. The concentration of DNase1L3 autoantibodies in SLE patients was significantly elevated compared to the control group. In addition, the capacity of PBMCs to secrete DNase1L3 was significantly lower in the SLE patients compared to the control group. Conclusion Decreased secretion of DNase1L3 and the presence of relevant autoantibodies notably impede NET degradation in patients with SLE, offering new directions for the monitoring and treatment of SLE patients.
Humans ; Autoantibodies ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Extracellular Traps ; Lupus Erythematosus, Systemic