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.

Objective:To explore the incidence and risk factors of parastomal hernia after colostomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 145 patients undergoing colostomy in Xinxiang Central Hospital from January 2015 to January 2019 were collected. There were 86 males and 59 females, aged(59±11) years. Patients received pelvic and abdominal computed tomography once every 6 months after colostomy to detect the occurrence of parastomal hernia. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers, and chi-square test or Fisher exact probability was used for comparison between groups. Kaplan-Meier method was used to analyze the cumulative annual incidence of parastomal hernia. Logarithmic rank test was used to analyze the cumulative incidence based on clinical variables. COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Incidence of parastomal hernia after colostomy. All the 145 patients were followed up for 86(range, 60?108)months after colostomy, of which 46 cases had parastomal hernia and 99 cases had no parastomal hernia. There were significant differences in gender, age, body mass index (BMI) and chronic liver disease between patients with and without parastomal hernia after colostomy ( χ2=23.28, t=13.27, χ2=6.17, 5.82, P<0.05). (2) Annual cumulative incidence of parastomal hernia after colostomy. The 1-, 3-, and 5-year cumulative incidence of parastromal hernia after colostomy was 8.5%, 26.4% and 42.7%, respectively. When the follow-up time is more than 5 years, the incidence of parastromal hernia tended to be stable. The 5-year incidence of parastomal hernia after colostomy in female patients was higher than that in male patients (70.7% vs 20.3%, χ2=12.37, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients≥60 years old was higher than that in patients under 60 years old (49.8% vs 20.0%, χ2=10.52, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with BMI >28 kg/m 2 was higher than that in patients with BMI ≤28 kg/m 2 (55.3% vs 33.2%, χ2=11.76, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with chronic liver disease was higher than that in patients with non-chronic liver disease (45.2% vs 32.4%, χ2=15.32, P<0.05). (3) Analysis of risk factors for parastomal hernia after colostomy. Results of multivariate analysis showed that female, age >60 years old, BMI ≥28 kg/m 2 and chronic liver disease were independent risk factors for parastomal hernia after colostomy ( hazard ratio=2.70, 2.51, 1.85, 5.88, 95% confidence intervals as 1.39?6.74, 1.01?4.59, 1.02?4.87, 1.05?8.24, P<0.05). Conclusions:The incidence of parastomal hernia after colostomy is increasing year by year, and tends to be stable after 5 years. Female, age >60 years old, BMI≥28 kg/m 2, and chronic liver disease are independent risk factors for parastomal hernia after colostomy.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Objective To investigate the current status of taste disorders in type 2 diabetes mellitus(T2DM)and to explore whether the taste disorders persists after 3 months of novel corona virus(COVID-19)infection.Methods 95 T2DM out patients(23 without COVID-19 infection history,72 infected with COVID-19 3～4 months ago)visiting the Endocrine Department of the Strategic Support Force Medical Center from February 20 to March 10,2023 were collected.Taste test box was used to test the taste function.General information,biochemical indicators,taste disorders,etc.were compared between the two groups.Results The average age of T2DM patients in this group was(58.3±9.6)years old,61 patients were male(64.2%),the median duration of DM was 11 years,and the median HbA1c was 7.3%.In taste testing,the proportion of sour,sweet,bitter,salty taste perception disorders was 60.0%,45.3%,57.9%,41.1%,84.2%.The average number of days from infection to enrollment into COVID-19 group was 102.4 days.The proportion of acid,sweet,bitter and salty sensory disorders was 61.1%,44.4%,55.6%and 41.7%in COVID-19 group and 56.5%,47.8%,65.2%and 39.1%in non-COVID-19 group.The prevalence of taste disorders in COVID-19 group was higher than that in non-COVID-19 group(86.1%vs 78.3%).Conclusions Taste disorders are common in T2DM patients.Compared with uninfected T2DM patients,there is no significant difference in the prevalence of taste disorders 3 months after COVID-19 infection.

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.

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.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

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.