The repair of bone defects is heavily influenced by the dynamic osteogenic microenvironment. Static scaffolds constructed by traditional 3D printing technology cannot simulate the dynamic nature of the microenvironment during bone defect repair due to the fixed structure, uncontrollable release of active factors, and difficult regeneration of blood vessels, among other factors. Breaking through the limitations of these static scaffolds and realizing the intelligent and dynamic regulation of the osteogenic microenvironment is a key scientific issue in the field of bone tissue engineering. 4D printing technology combines the dynamic responsiveness of bone restoration materials with the concept of intelligent design to regulate the micro and macro structure of scaffolds. This technology provides a new method for bone tissue engineering by responding to endogenous and exogenous stimuli and creating a better osteogenic microenvironment through functionalized design, including drug delivery and antibacterial function. However, this technology currently suffers from challenges related to dynamic response material design, insufficient precision of printing technology, and mismatches between multi-stimulus response systems, metabolic rhythms of bone tissue, and functionalized composite scaffolds. Future research should focus on the development of smart response materials with excellent dynamic responses and bioactivity, the creation of new printing technologies, and the design of personalized and precise bone repair solutions. The aim of this paper is to review the current research status of 4D printing for bone tissue engineering in terms of material types, response mechanisms, and applications to provide a theoretical basis for the development and clinical application of functional bone repair materials in the future.

ObjectiveTo investigate the effect of Tangzhi pills on the improvement of insulin resistance （IR） in the liver with type 2 diabetes （T2DM） by regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway based on differential genes and its possible molecular mechanism. MethodT2DM rat models were prepared by high fat （HFD） diet combined with streptozotocin （STZ） intraperitoneal injection. The experiment was divided into blank group， model group， metformin hydrochloride group （0.18 g·kg^-1）， Tangzhi pills high （1.08 g·kg^-1）， medium （0.54 g·kg^-1） and low （0.27 g·kg^-1） dose groups. Rat serum， liver， and pancreatic tissue were collected， and the pathological tissue of the liver and pancreas was observed using hematoxylin-eosin （HE） staining. The fasting blood glucose level （FBG） was detected， and oral glucose tolerance （OGTT） tests were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS） and glycated hemoglobin （GHb） levels in rats. IR homeostasis model index （HOMA-IR）， β cellular homeostasis index （HOMA-β）， and insulin sensitivity index （ISI） were calculated. Biochemical methods were used to determine the levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL-C）， and high-density lipoprotein （HDL-C） in rat serum. Transcriptomics obtained differentially expressed mRNA from liver tissue and enriched differentially expressed pathways. Real-time reverse transcriptase polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of cyclic adenylate responsive element binding protein 3-like protein 2 antibody （CREB3l2）， B-lymphocyte tumor 2 （Bcl-2）， Toll-like receptor 2 （TLR2）， cyclin-dependent kinase inhibitor 1A （CDNK1A）， and DNA damage induced transcription factor 4-like protein （DDIT4） in liver tissue. Western blot was used to detect the protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， glucose transporter 4 （GLUT4）， insulin receptor （INSR）， and insulin receptor substrate 2 （IRS2）. ResultThe pharmacodynamic experiment results showed that compared with model group， Tangzhi pills groups repaired liver and pancreatic tissue to varying degrees， reduced blood sugar （P<0.01）， and promoted a decrease in serum FINS， GHb， and HOMA-IR （P<0.05， P<0.01）. In addition， HOMA-β and ISI increased （P<0.05， P<0.01）. The levels of TC， TG， and LDL-C decreased （P<0.05， P<0.01）， while the levels of HDL-C increased （P<0.05， P<0.01）. The transcriptomics experimental results confirmed that the PI3K/Akt signaling pathway was significantly expressed in both the blank group and model group， as well as in the high-dose Tangzhi pills group and model group. CDNK1A， DDIT4， CREB3l2， Bcl-2， and TLR2 were significantly differentially expressed mRNA during TG intervention in T2DM. Compared with the model group， the protein expression of p-PI3K， p-Akt， GLUT4， INSR， and IRS2 increased in all Tangzhi pills groups （P<0.01）. The mRNA expression of CREB3l2， Bcl-2， and TLR2 increased （P<0.01）， while that of CDNK1A and DDIT4 decreased （P<0.01）. ConclusionTangzhi pills may regulate the PI3K/Akt signaling pathway based on the differential mRNA expression of CREB3l2， Bcl-2， TLR2， CDNK1A， and DDIT4， thereby improving IR in the liver with T2DM.

Objective To investigate the effect of miR-495-3p targeting budding uninhibited by benzimidazoles(BUB1)on signal transducer and activator of transcription 3(STAT3)signaling pathway on biological behavior of esophageal cancer(EC)cells.Methods The differentially expressed genes in EC tissues and normal tissues were screened by the cDNA microarray technique.The differentially expressed genes were analyzed by bioinformatics methods.The target genes of miRNAs were predicted by the TargetScan database and verified by a dual luciferase gene reporter assay.KYSE150 cells were divided into blank control group,NC mimics group and miR-495-3p mim-ics group.The activity of KYSE150 cells were detected by the CCK-8 method.Cell cycle and apoptosis were meas-ured by flow cytometry.The expression of BUB1 mRNA was measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR).The levels of BUB1,STAT3,phosphor(p)-STAT3,cyclin dependent kinase 1(CCNB1),cyclin dependent kinase 1(CDK1),B-cell lymphoma-2(Bcl-2),cysteinyl aspar-tate-specific proteinase-3(Caspase-3)and cysteinyl aspartate-specific proteinase-3(Caspase-9)were measured by Western blot.The migration and invasion abilities of the cells were measured by wound-healing and Transwell inva-sion assays.Results Differentially expressed genes were involved in biological processes,signaling pathways and network construction,which were mainly related to cell cycle.BUB1 is the key(Hub)gene,and BUB1 is the tar-get gene of miR-495-3p.In vitro experiments showed that overexpression of miR-495-3p could significantly inhibit the migration and invasion of EC cells and induce apoptosis and G2/M phase arrest.After treatment with overex-pression of miR-495-3p,the expression of Caspase-3 and Caspase-9 in EC cells increased significantly(P＜0.01),while the expression of Bcl-2,BUB 1,CCNB1,CDK1 and p-STAT3 decreased significantly(P＜0.01).Moreover,the STAT3 signaling pathway might play an important role in this process.Conclusion miR-495-3p may influence the biological behavior of esophageal cancer cells by down-regulating BUB 1-mediated STAT3 signaling pathway.

Objective:To study the position of computed tomography(CT)slice of marker points of radiotherapy,which was determined by control scan(CS)method,on the application effect of patients with head and neck tumors who received radiotherapy.Methods:Based on Control Scan(CS)method,a calculator program of mark-point slice position was made,which was an enterprise WeChat program that could be used in calculating position and CT position scan of patients with head and neck tumor(slice thickness was 3mm).A total of 60 patients with head and neck tumor were selected,and the patients who underwent CT positioning scan by using CS method were divided into observation group,and patients who underwent CT position scan by using conventional method were divided into control group,with 30 cases in each group.The number of cases with three metal marker points displayed at the same slice,and the number of slices containing the CT images of marker point between the located CT scan were compared.Results:The number of patients in the observation group and the control group who showed three markers at the same level at the same time were respectively 26 cases and 13 cases,and observation group increased by 13 cases(43.4%)than control group,and the difference was significant(x2=12.382,P<0.05).The number of CT images with only 1 slice of observation group and control group were respectively 4 cases and 0 cases,which increased by 4 cases(13.3%)than the control group,and the difference was significant(x2=2.411,P<0.05).Conclusions:The CT localization scan of radiotherapy,which uses CS to assist patients with head and neck tumor,can precisely calculate and obtain the primary position of target of CT localization scan.It can take the images of 3 mental marker points of patient who receives radiotherapy to occur at the same CT slice as soon as possible,which has better application effect.It can effectively improve the convenience and work effectiveness of radiotherapy.

Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

Objective To observe the effectiveness of ultrasound wide beam(WB)-based harmonic motion imaging(HMI)(WB-HMI)for locating irradiation focus of high intensity focused ultrasound(HIFU)for in vitro tissue.Methods WB-HMI technology was developed with acoustic radiation force and ultrasound imaging as the key technology.For in vitro porcine tenderloin and bovine liver tissue,different amplitude modulation(AM)frequencies(25-100 Hz)and excitation acoustic power(0.7-28 W)were used to achieve WB-HMI localization of HIFU irradiation focus,and the differences of WB-HMI localization of HIFU irradiation focus under different parameter combinations were observed.Taken the actual focus position on ultrasonic image after HIFU as the standard and the focus positioning error＜1 mm as the effective standard of WB-HMI locating irradiation focus,the locating success rate was calculated.Results The larger the acoustic power,the larger the displacement amplitude of irradiation focus by WB-HMI at the same AM frequency,while the smaller the AM frequency,the larger the displacement amplitude of irradiation focus located by WB-HMI under the same acoustic power.Under different AM frequencies,for in vitro porcine tenderloin,the success rate of WB-HMI for locating HIFU radiation focus was higher than 90.00％when acoustic power was 15 W or 22 W,whereas the success rate showed a decreasing trend when the acoustic power was 28 W.For in vitro bovine liver tissue,the success rate of WB-HMI localization was 100％when acoustic power was ≥7.0 W.Conclusion WB-HMI could be used to effectively locate HIFU irradiation focus for isolated tissue.

Diabetic nephropathy(DN)is one of the most serious microangiopathies in diabetes mellitus and the leading cause of death in patients with end-stage renal disease.Ferroptosis,as a mode of programmed cell death,is mainly manifested by excessive accumulation of intracellular lipid peroxides and iron.Ferroptosis is involved in a series of pathological processes such as damage to DN renal podocytes,mesangial cells,and renal tubular epithelial cells.Chinese materia medica has the characteristics of significant therapeutic effects and minimal adverse reactions in the treatment of diseases,and has been widely used in the prevention and treatment of DN.This article summarized the key factors regulating ferroptosis in DN,as well as the active components and TCM formulas targeting the inhibition of ferroptosis in the prevention and treatment of DN,providing reference for the development of DN targeted drugs.

Diabetic kidney disease(DKD)is the leading cause of end-stage renal disease.Chinese materia medica shows unique advantages in intervening DKD.Silent information regulator 1(SIRT1)protein plays a vital role in the occurrence and development of DKD.This article was about the SIRT1 signaling pathway and the main molecular regulatory mechanisms to sort out the role of Chinese materia medica in regulating SIRT1 in podocytes,oxidative stress and inflammatory response.It was found that Chinese materia medica monomers and compounds were capable of regulating the PGC-1 α signaling pathway,Nrf2/ARE signaling pathway,AMPK signaling pathway,NF-κB p65 signaling pathway,and PI3K/AKT/FoxO1 signaling pathway by targeting SIRT1,exerting pharmacological effects such as inhibiting cell apoptosis,improving mitophagy,inhibiting inflammatory response,etc.,thus intervening in DKD,which can provide reference for relevant research.

Objective:To develop and validate a risk model of postoperative 3-year all-cause mortality for the elderly patients with hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 325 elderly patients with hip fracture who had been treated at The Fourth Medical Center, The General Hospital of PLA from January 2020 to December 2021. There were 90 men and 235 women with an age of (80.9±8.9) years, and 191 intertrochanteric fractures and 134 femoral neck fractures. The patients with hip fractures admitted from January 2020 to June 2021 were assigned to a modeling group (244 cases), and those admitted from July to December 2021 to a validation group (81 cases). Recorded were age, gender, fracture type, pre-injury disease, hematological indicators, time from injury to surgery, previous use of anticoagulant drugs, bone density, American Society of Anesthesiologists (ASA) grading, body mass index, and blood transfusion volume in the 2 groups of patients. The data in the modeling group were used to screen the independent risk factors for the postoperative 3-year all-cause mortality in the elderly patients with hip fracture through logistic regression analysis and receiver operating characteristic (ROC) curve analysis and consequently to construct a prediction model. The data in the validation group were used to analyze the predictive performance of the model through the ROC curve, and the fitting degree of the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test.Results:Respectively, 75 cases in the modeling group and 29 cases in the validation group died 3 years after surgery. There was no statistically significant difference in the baseline data between the 2 groups, indicating comparability ( P>0.05). Logistic univariate analysis showed that gender, age, coronary atherosclerotic heart disease before injury, stroke before injury, pulmonary infection before injury, hemoglobin, albumin, high-density lipoprotein, body mass index, time from injury to surgery and ASA grade were related to the mortality of patients 3 years after surgery ( P<0.05). The ROC curve analysis showed that the variables with predictive ability included age, hemoglobin, albumin, body mass index, and time from injury to surgery. Logistic multivariate analysis showed male, age ≥ 83 years, pre-injury stroke, time from injury to surgery ≥ 4.5 days, ASA grade Ⅲ, and ASA grade Ⅳ were significantly related to the postoperative 3-year all-cause mortality in the elderly patients with hip fracture ( P<0.05). In the prediction model based on the above indicators, the area under the ROC curve was 0.792 (95% CI: 0.730 to 0.855, P<0.001), the cutoff value 0.459, sensitivity 56%, and specificity 90.5%, showing a good fit of the model ( χ2=5.818, P=0.668). Conclusions:Male, age ≥ 83 years, pre-injury stroke, time from injury to surgery ≥ 4.5 days, and ASA grades Ⅲ and Ⅳ are risk factors for postoperative 3-year all-cause mortality in the elderly patients with hip fracture. The risk prediction model based on these indicators demonstrates good predictive efficacy.

Objective:To evaluate the long-term constancy of image uniformity and noise of cone-beam computed tomography (CBCT) for the on-board imager (OBI) system of a Varian linac.Methods:Monthly quality assurance (QA) tests were carried out for the OBI system of a Clinac iX linac, and CBCT images of Catphan 504 phantom were obtained with six scanning protocols. The 6 protocols were high-quality head (HQH), low-dose head (LDH), pelvis spot light (PSL), standard-dose head (SDH), low-dose thorax (LDT) and pelvis, respectively. The 144 series of CBCT images acquired from Nanjing First Hospital, Nanjing Medical University between January 2020 and December 2021 were analyzed, and the data of image uniformity and noise were obtained by delineating regions of interest (ROI) in the images of CTP486 module. Image uniformity was expressed by the absolute value of the maximum difference between the average CT value of the ROI in the 3, 6, 9 and 12 o'clock directions and the central ROI. Image noise was expressed by the standard deviation of CT value of large circular ROI. The smaller the values of image uniformity and noise, the better the image quality. Statistical description was applied to obtain data of the maximum, minimum, mean and standard deviation for the above mentioned two parameters. Y was defined as the difference between the average CT value of ROI in each direction and the average CT value of central ROI, which was used to represent the monthly changes of image quality.Results:The image uniformity and noise of CBCT images of the OBI system were generally stable during 2 years. For the 6 protocols of HQH, LDH, PSL, SDH, LDT and pevlis, the image uniformity was (21.5±1.0), (21.4±2.2), (21.3±0.9), (18.3±1.3), (3.4±1.9) and (7.2±1.9) HU, respectively. The image noise was (19.2±0.2), (41.0±0.3), (14.2±0.3), (38.2±0.2), (16.0±0.9) and (13.5±0.9) HU, respectively. The average image uniformity of LDT was the smallest, and the average image noise of pelvis was the smallest. Under the 6 scanning protocols, the average CT values of central ROI involved in image uniformity were (32.3±2.7), (24.0±3.3), (19.3±2.4), (11.1±2.5), (67.2±2.1), (-24.6±1.7) HU, respectively. The average CT values were stable. The standard deviation of Y was < 3 HU, suggesting that the stability of image quality was favorable every month.Conclusions:The image uniformity and noise of CBCT images for the OBI system are generally stable in 2 years. Among the 6 scanning protocols, LDT yields the best image uniformity, and pelvis has the lowest image noise.