OBJECTIVE: To review the current applications of machine learning in orthopaedic trauma and anticipate its future role in clinical practice. METHODS: A comprehensive literature review was conducted to assess the status of machine learning algorithms in orthopaedic trauma research, both nationally and internationally. RESULTS: The rapid advancement of computer data processing and the growing convergence of medicine and industry have led to the widespread utilization of artificial intelligence in healthcare. Currently, machine learning plays a significant role in orthopaedic trauma, demonstrating high performance and accuracy in various areas including fracture image recognition, diagnosis stratification, clinical decision-making, evaluation, perioperative considerations, and prognostic risk prediction. Nevertheless, challenges persist in the development and clinical implementation of machine learning. These include limited database samples, model interpretation difficulties, and universality and individualisation variations. CONCLUSION The expansion of clinical sample sizes and enhancements in algorithm performance hold significant promise for the extensive application of machine learning in supporting orthopaedic trauma diagnosis, guiding decision-making, devising individualized medical strategies, and optimizing the allocation of clinical resources.
Artificial Intelligence ; Orthopedics ; Machine Learning ; Algorithms

Genome-wide association studies (GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts (OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability, suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line (HIOEC) using RNA-seq, ATAC-seq, H3K27ac ChIP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only (NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification pipeline. In total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epithelium-expressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.
Chromatin ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Epithelium ; Genome-Wide Association Study ; Humans

Drug metabolism and pharmacokinetics (DMPK) are the science to study the process of drug absorption, distribution, metabolism and excretion. It is very important to evaluate the characteristics of DMPK for the early development of drugs and the later clinical precision medication. The innovative construction of DMPK models promotes the development and improvement of drug evaluation system. Based on our research results, this review summarized the latest progress and application of innovative DMPK models, focusing on the following two aspects: (1) CRISPR/Cas9 gene editing rat models, including Cyp2e1

Objective:To observe the changes of insulin secretion in the early stage of severe scald in rats, and to explore its signal transduction mechanism.Methods:Twenty-four male Wistar rats aged 7 weeks were divided into sham injury alone (SIA) group, sham injury+ BPV (HOpic) (SIB) group, scald alone (SA) group, and scald+ BPV (HOpic) (SB) group using the random number table, with 6 rats in each group. Full-thickness scald of 50% total body surface area was inflicted in rats of SA and SB groups by a 6-s immersion of the abdomen and a 12-s immersion of the back in 94 ℃ hot water. Rats in SIA and SIB groups received sham injuries through immersion of the back and abdomen in 37 ℃ warm water for 6 and 12 seconds respectively. From 0 (immediately) to 2 day (s) after injury, the rats in groups SB and SIB were intraperitoneally injected with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway enhancer BPV (HOpic) solution (0.5 mg/mL) at the dosage of 0.6 mg/kg once a day, and the rats in groups SA and SIA were intraperitoneally injected with the same volume of dimethyl sulfoxide once a day. At post injury hour (PIH) 72, the tail blood of rats was sampled for measuring fasting blood glucose (FBG) with a glucometer, and the pancreatic tissue samples of rats was harvested for observing the pathological manifestations of islets by hematoxylin-eosin staining, counting the docked granules per 10 μm membrane of islet beta cells and calculating the proportion of insulin vesicles through the observation of the ultrastructure of islet beta cells by transmission electron microscope, and detecting the phosphorylation level of Akt in the pancreatic PI3K/Akt signaling pathway by Western blotting. Data were statistically analyzed with one-way analysis of variance and least significant difference test.Results:(1) At PIH 72, the rat FBG levels in SIA and SIB groups were normal and similar ( P>0.05). Compared with the levels of those two groups, the rat FBG level in SA group was increased significantly ( P<0.01), while the level in SB group showed no obvious change ( P>0.05). Compared with that in SA group, the rat FBG level in SB group was decreased significantly ( P<0.01). (2) At PIH 72, the morphology of rat islets was complete and the islet cells distributed regularly in SIA and SIB groups. Compared with those in SIA and SIB groups, the morphology of rat islets was incomplete, the insulin vesicles in islets were common, the islet cells distributed irregularly, and the cytoplasm of some islet beta cells was lightly stained or translucent in SA group; the morphology of islets in SB group did not change obviously. Compared with those in SA group, the morphology of islets was comparatively complete, the insulin vesicles in islets were less common, the islet cells distributed comparatively regularly, and the lightly stained or translucent cytoplasm of islet beta cells was less in SB group. (3) At PIH 72, the number of docked granules per 10 μm membrane of rat islet beta cells and the proportion of insulin vesicles in SIA and SIB groups were similar ( P>0.05). Compared with those in SIA and SIB groups, the number of docked granules per 10 μm membrane of rat islet beta cells in SA group was decreased significantly ( P<0.01), while the proportion of insulin vesicles was increased significantly ( P<0.01); the number of docked granules per 10 μm membrane of rat islet beta cells in SB group was obviously decreased ( P<0.05), while the proportion of insulin vesicles did not change obviously ( P>0.05). Compared with those in SA group, the number of docked granules per 10 μm membrane of rat islet beta cells in SB group was significantly increased ( P<0.01), while the proportion of insulin vesicles was significantly decreased ( P<0.01). (4) At PIH 72, the phosphorylation levels of Akt in SIA, SIB, SA, and SB groups were 0.91±0.03, 0.98±0.03, 0.78±0.08, and 0.87±0.08, respectively. Compared with that in SIA group, the phosphorylation level of Akt was increased obviously in SIB group ( P<0.05) but was decreased significantly in SA group ( P<0.01), while the level in SB group did not change obviously ( P>0.05). Compared with the level in SIB group, the phosphorylation levels of Akt in SA and SB groups were decreased significantly ( P<0.01). Compared with that in SA group, the phosphorylation level of Akt in SB group was increased significantly ( P<0.05). Conclusions:At the early stage post severe scald in rats, the activity of the pancreatic PI3K/Akt signaling pathway and the function of insulin secretion are reduced. Improving the activity of the pancreatic PI3K/Akt signaling pathway in rats can ameliorate the function of insulin secretion and recover the physiological level of blood glucose.

Objective Few studies are reported on the construction of a finite element model of human complex knee joint using multimodality CT and MRI images.In this study, we developed a finite element model of the knee joint for total knee arthroplasty (TKA) using matched and fused CT and MRI data, hoping to provide a useful tool for the simulation study of knee joint biomechanics of TKA.Methods The CT and MRI image data about an intact knee of a 26-year-old male volunteer were imported into the Mimics software for the establishment of 3D models of bony and soft-tissue structures.A complete knee model was developed following the registration and fusion of the constructed 3D models based on the external landmarks.After the simulated implantation of TKA components, a finite element model of the TKA knee was constructed with the Hypermesh software.Then the finite element model was analyzed following the definition of its material behavior, boundary conditions and loading.Results The finite element model of the TKA knee, which was composed of bones, ligaments, components, polyethylene insert and bone cement, was developed from CT-MRI image registration and fusion and maintained its important spatial relationship among different structures in the TKA knee.The results obtained from the finite element analysis showed the characteristics of stress distribution in the TKA knee.Conclusion The finite element model of the knee joint for TKA can be established by matching and fusing CT and MRI image data, which can be employed as a useful tool for the study of knee joint biomechanics of TKA.

Objective To investigate the prevalence and prognostic value of anemia in male and female patients with chronic systolic heart failure (CSHF).Methods Data of in-hospital patients with CSHF were investigated between 2000 and 2010 from 12 hospitals in Hubei Province.Patients were divided into normal hemoglobin (Hb) group,mild anemia group,moderate anemia group,severe and extreme anemia group.According to age,body mass index (BMI) and correction of glomerular filtration rate (GFRc),patients were divided into several subgroups,respectively.Multivariate logistic regression was performed to determinate the associated factors with anemia.Kaplan-Meier curve was performed to evaluate the difference in all-cause mortality in male and female patients with anemia.Univariate and multivariate Cox proportion hazard analysis was performed to determinate the risk of all-cause mortality among different anemia group in male and female patients.Results A total of 16681 patients were enrolled.Anemia accounted for 23.79％ and 27.29％,separately,in male and female patients with CSHF.BMI and GFRc were related to anemia in both male and female patients with CSHF,while only age was related to anemia for female patients with CSHF.The hazard ratio of all-cause mortality was 1.08 (P ＜ 0.01),1.13 (P ＜ 0.O1) and 1.02 (P =0.74),respectively,for all,male and female anemia patients with CSHF,compared to normal Hb group.Compared to normal Hb group,the hazard ratio of mild anemia group,moderate anemia group,severe and extreme anemia group was 1.05 (P =0.14),1.20 (P ＜0.01) and 1.36 (P ＜0.01),respectively,for all CSHF patients;1.11 (P ＜ 0.01),1.35 (P ＜ 0.01) and 1.37 (P ＜ 0.01),respectively,for male;0.96 (P=0.48),1.08 (P=0.40) and3.47 (P＜0.01),respectively,for female.Conclusions Compared to male,female patients suffer higher prevalence of anemia in patients with CSHF.There is a significant difference in risk factors and prognosis of anemia between male and female patients with CSHF.

The cDNA fragment of JEV prME gene was cloned into the baculovirus shuttle vector (bacmid) to construct a recombinant baculovirus vector, defined as AcBac-prME. Then the recombinant baculovirus Ac-prME was obtained by transfecting Sf9 cells with AcBac-prME. Western blot analysis and immunofluorescence results indicated that both prM and E proteins were efficiently expressed in Sf9 cells. Electron microscopy suggested that prME was assembled into JEV-VLPs. To further evaluate the potential of JEV-VLPs as vaccine, the mice were immunized with JEV-VLPs and then challenged with lethal JEV. The results of mice survival and pathological changes demonstrated that the JEV-VLPs performed complete protection against JEV-P3 strain and relieved pathological changes in the mice brain significant. This study suggest that JEV-VLPs would be a potential vaccine for Japanese encephalitis virus.
Animals ; Antibodies, Viral ; immunology ; Encephalitis Virus, Japanese ; genetics ; immunology ; Encephalitis, Japanese ; immunology ; prevention & control ; virology ; Humans ; Japanese Encephalitis Vaccines ; administration & dosage ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Sf9 Cells ; Vaccination ; Vaccines, Virus-Like Particle ; administration & dosage ; genetics ; immunology ; Viral Envelope Proteins ; administration & dosage ; genetics ; immunology

Objective To study the effects and molecular mechanism of MAWBP in the proliferation, invasion and migration of human colorectal cancer cell lines. Methods Colorectal cancer cell lines, caco-2 and HT-29, were divided into MAWBP over-expressed group and control group. MAWBP was stablely over-expressed in both cell lines by lentivirus, and the positive clones were screened by puromycin. The expression of MAWBP gene at mRNA and protein levels was evaluated by RT-PCR and western blot. Cell proliferation was detected by MTT. Cell migration and invasion were detected by transwell experiment. The EMT related protein levels of Snail, E-cadherin, and MAPK pathway protein of ERK, p38, p-ERK, p-p38 were determined by western blot analysis. Results Compared with the control group, the expression of MAWBP was significantly higher in HT-29-MAWBP and caco2-MAWBP group . The cell proliferation , invasion and migration ability significantly reduced in the HT-29-MAWBP group. The expression of Snail, p-ERK and p-p38 significantly decreased, while the E-cadherin increased in HT-29-MAWBP and caco2-MAWBP group. Conclusions Over- expression of MAWBP exerts an inhibitory effect on the proliferation, invasion and migration of colorectal caner cells via inhibit the MAPK pathway and regulate the EMT process.

Cardiac arrhythmia is one of the most common cardiovascular diseases,with high morbidity and mortality,which threatens human health and lives. With the development of medicine, natural products are revealing ever-greater anti-arrhythmic benefits and potential. However,their targets have not been fully clarified. In the recent ten years ,scientists have been studying the molecular mechanisms of natural products that have been found to inhibit INa,ICa-L,Ito,IK1,IKr,IKM3,HERG channel current and steady state K+ current,promote IKs and IKATP,inhibit microRNA-1 expression and change cardiac microRNA expression profile,affect Na+-K+-ATPase and superoxide dismutase activity,inhibitβ receptor and angiotensinⅡ receptor,and regulate lipid metabolism,thus affecting cardiac rhythm and exerting anti-arrhythmic effect. This paper revies the research advances in the antiarrhythmic tar?gets of natural products.

Objective To observe the influence of XueShuanXinMaiNing(XSXMN)in the behavior and structures of cerebral cortex and hippocampus of the rats withβamyloid protein(Aβ)-induced Alzheimer’s disease(AD),and to explore its therapeutic effects on the rat AD.Methods 100 male Wistar rats were selected.According to weight, the rats were randomly divided into sham operation group, model group, positive drug group (donepezil hydrochloride,1.75 mg· kg-1 ),XSXMN 1.1 g· kg-1 group and XSXMN 2.2 g· kg-1 group. The rat AD models were made by injecting Aβinto hippocampus.After oral administration for 15 d,Morris water maze test, dark avoidance task and pathology test were performed.Results In Morris water maze test,compared with model group,the latency and swimming distance to platform of the rats in XSXMN 1.1 g·kg-1 group were decreased on the 2nd,4th and 5th day(P<0.05 or P<0.01);in XSXMN 2.2 g·kg-1 group,the latency to platform of the rats were decreased from the 3nd to 6th day(P<0.05 or P<0.01),the swimming distances to platform of the rats were decreased from the 3rd to 5th day(P<0.05 or P<0.01).On the 7th day,in XSXMN groups,the times of passing platform,time of staying on platform,distance of staying on platform,time of staying in effective area, distance of staying in effective area, time of staying on platform/total time, distance of staying on platform/total distance,time of staying on platform/total time were all increased significantly(P<0.05 or P<0.01)within 90 s. In dark avoidance task,compared with model group,the error latency and the error times of the rats in XSXMN groups had no obvious change on the 2nd day.The pathological results showed that there were degeneration nerve cells and necrosis nerve cells in the rat cerebral cortex in XSXMN groups,while in the rat hippocampus there were less number of nerve cells with obscure cell layer and many degeneration and necrosis cells were found;compared with model group,there was no obvious improvement.Conclusion XSXMN can improve the learning and memory function of the AD rats.