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 observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

"Global cancer statistics 2022" based on the latest GLOBCAN data from the International Agency for Research on Cancer (IARC) was recently released, providing a systematic analysis of the incidence and mortality of 36 types of cancer across 185 countries worldwide. The international burden of cancer is expected to continue to increase over the next 30 years, posing a severe public health and social challenge for many countries, including China. This article offers a key point interpretation of the "Global cancer statistics 2022", focusing on the evolution of cancer epidemiology and future development trends. The aim is to broaden the international perspective on cancer prevention and treatment, with the hope of providing reference and guidance for cancer prevention and treatment efforts in our country.

Objective To investigate clinical characteristics and risk factors of different stages of urinary tract infection after kidney transplantation.Methods Clinical data of 209 kidney transplant recipients were retrospectively analyzed.According to time points of postoperative follow-up,all recipients were divided into 3 stages:within 1 month post-kidney transplantation,1-6 months post-kidney transplantation,and 7-12 months post-kidney transplantation.The incidence of urinary tract infection,urine culture results of recipients with urinary tract infection and drug resistance characteristics of common pathogens during different stages after kidney transplantation were analyzed.The strains of patients with recurrent urinary tract infection were identified.The risk factors of urinary tract infection and the effect of urinary tract infection on renal allograft function were analyzed.Results The urinary tract infection rate was 90.0％in the first stage,49.3％in the second stage and 22.5％in the third stage.The urinary tract infection rates of male recipients undergoing living-related organ donation in the second and third stages were lower than those of female recipients(both P＜0.05).Urine culture test yielded positive results in 60 cases,and 84 strains of pathogenic bacteria were detected,mainly Gram-negative bacteria,among which Klebsiella pneumoniae accounted for the highest proportion.Sixty-six recipients had recurrent urinary tract infection,and the detected pathogens included Klebsiella pneumoniae,Escherichia coli and Candida glabrata,etc.Univariate analysis showed that postoperative use of antithymocyte globulin was the risk factor for urinary tract infection in the first stage.Preoperative urinary tract infection and donor type were the risk factors for urinary tract infection in the second stage.Gender and age of the recipients were the risk factors for urinary tract infection in the third stage.Multivariate analysis revealed that postoperative use of antithymocyte globulin was the risk factor for urinary tract infection in the first stage.Gender and age of the recipients were the risk factors for urinary tract infection in the third stage(all P＜0.05).In the third stage,65 cases were cured and 38 cases were not cured.In the treated recipients,the serum creatinine level and white blood cell count were decreased after corresponding treatment than those before treatment(both P＜0.05).Conclusions Gram-negative bacteria are the main pathogens of urinary tract infection in kidney transplant recipients,and drug resistance is relatively high.Postoperative use of antithymocyte globulin,female and old age are the risk factors for urinary tract infection in kidney transplant recipients.

AIM:To investigate the effects of overexpressing α-Klotho(KL)in RAW264.7 cells stimulated by oxidative stress on the proliferation, migration, tube-formation and tight junction of human umbilical vein endothelial cells(HUVECs).METHODS:RAW264.7 cells were categorized into control, 4-hydroxynonenal(4HNE), and 4HNE+KL groups, with F4/80 expression assessed via immunofluorescence staining. Three groups of conditional media were prepared for HUVECs and culture divided into Mø-NC, Mø-4HNE, and Mø-4HNE+KL groups. Cell proliferation was evaluated using CCK8 assay, while scratch test and Transwell assays were employed to measure cell migration. Additionally, tube-formation assay was conducted to assess cell tubule formation, and Western blot assay was utilized to detect the protein expression levels of Claudin 5, Occludin and ZO 1.RESULTS:The results of immunofluorescence staining showed that the fluorescence intensity of F4/80 of RAW264.7 cells in the 4HNE group was significantly enhanced compared with the control group, while that of F4/80 in the 4HNE+KL group was significantly decreased compared with the 4HNE group(all P<0.05). The CCK8 assay results revealed a significant increase in the proliferation of HUVECs in the Mø-4HNE group compared with the Mø-NC group. Conversely, the proliferation of the Mø-4HNE+KL group exhibited a significant decrease compared with that in the Mø-4HNE group(all P<0.01). The results of scratch test and Transwell assays demonstrated a significant increase in the migration of HUVECs in the Mø-4HNE group compared with the Mø-NC group, while the migration of the Mø-4HNE+KL group exhibited a significant decrease compared with the Mø-4HNE group(all P<0.01). In the tube-formation assay, it was observed that the number of tubes formed by HUVECs in the Mø-4HNE group was significantly increased compared with the Mø-NC group, while that of tubes formed in the Mø-4HNE+KL group was significantly decreased compared with the Mø-4HNE group(all P<0.01). Additionally, the Western blot results revealed a significant decrease in the relative expression levels of Claudin 5, Occludin, and ZO 1 in the Mø-4HNE group compared with the Mø-NC group. Conversely, in the Mø-4HNE+KL group, there was a significant increase in the relative expression levels of Claudin 5, Occludin, and ZO 1 compared to the Mø-4HNE group(all P<0.01).CONCLUSIONS: KL inhibits the proliferation, migration, and tube-formation of HUVECs while enhancing the tight junction by changing the activation state of macrophages in the diabetic oxidative stress environment.

Diabetic retinopathy(DR)is one of the most common microvascular complications of diabetes and has become one of the leading causes of blindness and visual impairment in diabetes patients.The pathogenesis of DR is multifaceted,involving inflammation,oxidative stress,neurovascular abnormalities,and other factors that present potential targets for disease management interventions.Currently,anti-vascular endothelial growth factor(VEGF)drugs serve as the primary treatment for advanced stages of DR when irreversible neurovascular damage and visual impairment have occurred.Additionally,some patients show poor or no response to anti-VEGF treatment.There is a lack of early intervention options for the initial phases of the disease.Therefore,there is an urgent need to develop novel local or systemic therapies based on the underlying mechanisms of DR to enable early prevention and treatment with the aim of preserving patients' vision.Medications targeting various pathways including anti-inflammatory agents(corticosteroids and nonsteroidal anti-inflammatory drugs),neurotrophic and neuroprotective drugs,drugs modulating biochemical pathways,antioxidant phytochemicals,and gene therapy can complement each other in terms of therapeutic effects to benefit a larger number of individuals affected by DR.This article reviews previous research reports on the pathogenesis,drug treatment methods,and potential therapeutic targets associated with DR in order to provide guidance for clinical practice.

Objective:To explore the current situation, hot spots and trends of research on the prevention and treatment of diabetes peripheral neuropathy with TCM; To provide reference for scientific research and clinical practice.Methods:Literature related to the prevention and treatment of diabetic peripheral neuropathy with TCM was retrieved from CNKI and Web of Science from the establishment of the databases to December 31, 2021. CiteSpace 6.1.3 software was used to visualize the knowledge map of the number of articles, journals, authors, institutions, keyword clustering, and keyword emergence.Results:A total of 793 core articles were included, including 692 in CNKI and 101 in Web of Science. The research on the TCM prevention and treatment of diabetes peripheral neuropathy was on the rise. Liu Tonghua (Beijing University of Chinese Medicine) wrote most Chinese articles, while Liang Xiaochun (Peking Union Medical College Hospital) wrote more English articles. The research institutions were mainly medical colleges and universities and their affiliated hospitals. Current research hotspots and future development trends mainly included the following aspects: TCM compounds, acupuncture therapy, oxidative stress, nerve conduction velocity, expression of related pathogenic genes, randomized controlled experiments, data mining, systematic evaluation, etc.Conclusion:At present, the research on the TCM prevention and treatment of diabetic peripheral neuropathy at home and abroad has gradually entered a stable development stage and has a certain research scale. However, it is necessary to strengthen the cooperation and communication between research teams and institutions and promote sustainable clinical efficacy evaluation and basic research development.

Objective To analyze three-dimensional(3D)radiographic characterizations of bone island(BI)in jaw using cone-beam computed tomography(CBCT).Methods CBCT data from four thousand patients were selected,reconstructed and analyzed using NNT 10.0 software.The sagittal,coronal and axial planes were used to analyze the 3D radiographic characteristics of BIs,including the localization,shape,density,boundary,the relationship between BIs and tooth and bone cortex,diameter and anatomical structures and complications involved.Their relationship with gender were analyzed.Results A total of 803 people had BIs,with the prevalence rate of 20.08%,including 338 males with 389 BIs and 465 females with 526 BIs.Both males and females had a dominant BI,and the ratio between male and female was 1∶1.38,but the difference was not statistically significant(P＞0.05).The BIs of both male and female mostly occurred in the mandibular premolars and molars area,and appeared irregular in shape,dense and contact with lingual bone cortex.Mostly BIs were apical type and with unclear boundary.The mean maximum diameter of mesial/distal direction was greater than buccal/lingual direction(P＜0.05).The most commonly involved anatomy structure was the inferior alveolar neural canal,cortical infil-tration and mental foramen.Conclusion There are no significant differences between males and females in the three-dimensional image characteristics of BIs in Chinese populations.CBCT can accurately and comprehensively analyze the 3D radiographic characteris-tics of BI and its relationship with the surrounding teeth and bone.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Rosacea is a chronic inflammatory disease. In addition to subjective evaluation, some objective quantifiable indices are needed for the diagnosis and treatment of rosacea. Some skin imaging and noninvasive measurement tools have been applied to clinical practice, and can provide quantitative or semi-quantitative indices to assist the diagnosis and treatment of rosacea. This review summarizes relevant research progress to provide evidence for clinical standardized application.