Objective:Multi-facial reflective type of nano-ultrasound contrast agents（UCAs）loaded with hollow self-decomposable silica nanoparticles（SiO 2 NP）of different particle sizes were prepared to investigate the effect of the particle size of SiO 2 NP on the structural and physicochemical characteristics of the nano-UCAs，as well as on the intensity of ultrasound contrast. Methods:Two types of SiO 2 NP with large and small particle sizes（SiO 2 NP L and SiO 2 NP S）were prepared by adjusting the material ratios，and nano-UCAs with different particle sizes of SiO 2 NP S loaded at a concentration of 2 mg/ml were prepared by the thin film hydration method（SiO 2 NP L@NBs and SiO 2 NP S@NBs），and compared with the commercial SonoVue and the prepared nano-bubbles（NBs）for comparing the particle size，zeta potential and stability，scanning electron microscopy to observe the structure，CCK8 method to assess cytotoxicity，and comparison of ultrasonography imaging intensity in in vivo and in vitro experiments. Results:The particle sizes of the two SiO 2 NP（SiO 2 NP L and SiO 2 NP S）were（213.270 ± 16.890）nm and（53.870 ± 8.246）nm，respectively，and the particle size of the synthesized nano-UCA was SiO 2 NP L@NBs（628.40 ± 89.97）nm and SiO 2 NP S@NBs（493.40 ± 36.35）nm respectively，there was no difference in particle size（ P>0.05）. The scanning electron microscope showed a "fig" structure. The stability of SiO 2 NP S@NBs was better than that of SiO 2 NP L@NBs and SonoVue. Safety tests showed that both SiO 2 NP L@NBs and SiO 2 NP S@NBs were safe and usable. Compared with NBs，the intensity of contrast-enhanced ultrasound contrast in SiO 2 NP@NBs with multiple reflection interfaces was significantly enhanced，and the enhanced intensity of contrast-enhanced ultrasound in vitro and in vivo in the SiO 2 NP L@NBs group was significantly higher than that of the NBs group，the SiO 2 NP S@NBs group，and the SonoVue group（all P<0.05）. There was no significant difference in the enhanced intensity of in vitro contrast-enhanced ultrasound between the SiO 2 NP S@NBs group and that of SonoVue（ P>0.05），and the enhanced intensity of contrast-enhanced ultrasound in vivo was significantly higher than that in the SonoVue group（ P<0.05）. Conclusions:The large and small SiO 2 NPs prepared by adjusting the material ratio do not affect the nanoparticle size of UCA.The ultrasonic enhancement ability of nano-UCA with large particle size SiO 2 NP is stronger，but the stability time at room temperature is shorter than that of nano-UCA with small particle size SiO 2 NP.

The dual induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has resulted in a cure rate exceeding 90% for patients with acute promyelocytic leukemia (APL). However, relapse due to ATO resistance remains a pressing clinical challenge. This article reviews recent research progress of PML mutations, metabolic adaptation, ATO metabolism, miRNA, snoRNA, the pathogenic mechanisms of the PML::RARA fusion protein and resistance mechanisms of autophagy. Additionally, the paper also discusses the clinical application of new treatment strategies such as venetoclax and gemtuzumab ozogamicin based on the drug-resistance mechanisms.

Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases， malignant tumors， central nervous system diseases， and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development， the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe， America， and China， the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects， including lack of relevant laws and regulations， a higher risk of radiopharmaceuticals， dilemmas in ethical review， and insufficient radiation protection. Response principles and measures were proposed from four aspects， including improving regulations and policies， enhancing radiological protection for all parties involved in the research， strengthening ethical review， and reinforcing the training of relevant personnel， to enhance the quality and level of clinical research on radiopharmaceuticals.

Objective To identify novel biomarkers for predicting the risk of latent tuberculosis infection(LTBI)activation using bio-informatics and machine-learning algorithms and to establish a risk model.Methods The GSE112104 and GSE193777 datasets were obtained from the Gene Expression Omnibus.Differential gene expression and weighted gene co-expression network analyses were per-formed to identify ferroptosis-related differentially expressed genes(FRG-DEGs)associated with LTBI activation.Three machine-learning algorithms,least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest,were used to identify ferroptosis-related hub genes(FRG-hubs).The reliability of these genes was validated using independent validation datasets and reverse transcription polymerase chain reaction(PCR).A risk model was established using R software.Results In the GSE 112104 dataset,296 genes were upregulated and 1 569 genes were downregulated in active tuberculosis compared to those in LTBI.Among the LTBI progressors,506 genes were upregulated and 1 132 genes were downregulated.Weighted correlation network analysis identified five gene modules,with the blue module showing the strongest correlation with LTBI activation(cor=0.62,P=0.000 04),con-taining 1 340 genes.Intersections with 728 ferroptosis-related genes resulted in eight FRG-DEGs.The machine-learning algorithms iden-tified four FRG-hubs:PLA2G6,GLS2,JUN,and AMN,whose expression decreased with LTBI activation.Reverse transcription PCR con-firmed this trend.A risk model based on these genes yielded an area under the curve of 0.98 to 1.00.Conclusion This study successfully identified novel biomarkers for predicting the risk of LTBI activation and developed an accurate predictive risk model.

Objective:To investigate the optimal reconstruction grade of IDream reconstruction technique in reducing image noise,optimizing image quality,and displaying liver cysts through the subjective assessment on the display of computed tomography (CT) image with differently reconstructive grades in IDream reconstruction technique of iterative reconstruction algorithm,and the objective evaluation of image quality of upper abdomen. Methods:The imaging data of CT plain scan of 53 patients with hepatic cysts who underwent plain scans on upper abdomen at Peking Union Medical College Hospital from August to September 2021 were retrospectively collected. All images were reconstructed to standard window images by using 6 kinds of methods that included filtered back projection (FBP) and IDream grades 1 to 5,which resulted in 6 groups of images that included FBP group and IDream grades 1-5. The CT values and standard deviation (SD) values of the liver,abdominal aorta,erector spine muscle,fat and spleen in images of each group were measured and recorded,respectively. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images were calculated. Two CT diagnostic physicians with more than 8 years of experience conducted subjective scoring for the display in the images of hepatic cysts of each group. The objective parameters and the subjective scores of hepatic cysts of reconstructive images with different grades were compared. A one-way analysis of variance was adopted to analyze the objective parameters,and Kruskal-Wallis H test was conducted on the subjective score of the display of hepatic cysts. Results:There were no statistically significant differences in the CT values among different reconstruction grades on the liver,abdominal aorta,fat,erector spine muscle and spleen (P>0.05). In the FBP group and IDream grades 1 to 5 groups,the SD values of images gradually decreased with the increasing of the reconstruction grades,which were respectively (18.11±5.03),(15.37±4.97),(13.26±4.83),(11.68±4.56),(10.99±4.36) and (10.60±4.21) Hu. The SNR and CNR of the liver gradually increased. The differences in SD values,SNR,and CNR among the six groups of images were all statistically significant (F=20.75,17.72,3.15,P<0.05),respectively. The subjective scores for the display of hepatic cysts from the FBP group to IDream grades 1 to 4 were respectively (3.12±0.35),(3.63±0.46),(4.02±0.42),(4.61±0.48) and (4.63±0.48),which were gradually increasing,while the score for the IDream grade 5 group slightly decreased to (4.53±0.47). The subjective scores for hepatic cysts in the images of IDream grades 3 and 4 groups were the highest. The comparison of the average subjective scores of the images of hepatic cysts among the six reconstruction grades showed statistically significant differences (H=192.17,P<0.05). Conclusion:In CT plain scan on the upper abdomen,with the increasing of IDream reconstruction grades,the image noises gradually decrease,and objective parameters of images gradually enhance,and the reconstructions of IDream grades 3 and 4 can obtain the optimal image quality of upper abdomen at the objective score of hepatic cysts.

Objective:To investigate the optimal reconstruction grade of IDream reconstruction technique in reducing image noise,optimizing image quality,and displaying liver cysts through the subjective assessment on the display of computed tomography (CT) image with differently reconstructive grades in IDream reconstruction technique of iterative reconstruction algorithm,and the objective evaluation of image quality of upper abdomen. Methods:The imaging data of CT plain scan of 53 patients with hepatic cysts who underwent plain scans on upper abdomen at Peking Union Medical College Hospital from August to September 2021 were retrospectively collected. All images were reconstructed to standard window images by using 6 kinds of methods that included filtered back projection (FBP) and IDream grades 1 to 5,which resulted in 6 groups of images that included FBP group and IDream grades 1-5. The CT values and standard deviation (SD) values of the liver,abdominal aorta,erector spine muscle,fat and spleen in images of each group were measured and recorded,respectively. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images were calculated. Two CT diagnostic physicians with more than 8 years of experience conducted subjective scoring for the display in the images of hepatic cysts of each group. The objective parameters and the subjective scores of hepatic cysts of reconstructive images with different grades were compared. A one-way analysis of variance was adopted to analyze the objective parameters,and Kruskal-Wallis H test was conducted on the subjective score of the display of hepatic cysts. Results:There were no statistically significant differences in the CT values among different reconstruction grades on the liver,abdominal aorta,fat,erector spine muscle and spleen (P>0.05). In the FBP group and IDream grades 1 to 5 groups,the SD values of images gradually decreased with the increasing of the reconstruction grades,which were respectively (18.11±5.03),(15.37±4.97),(13.26±4.83),(11.68±4.56),(10.99±4.36) and (10.60±4.21) Hu. The SNR and CNR of the liver gradually increased. The differences in SD values,SNR,and CNR among the six groups of images were all statistically significant (F=20.75,17.72,3.15,P<0.05),respectively. The subjective scores for the display of hepatic cysts from the FBP group to IDream grades 1 to 4 were respectively (3.12±0.35),(3.63±0.46),(4.02±0.42),(4.61±0.48) and (4.63±0.48),which were gradually increasing,while the score for the IDream grade 5 group slightly decreased to (4.53±0.47). The subjective scores for hepatic cysts in the images of IDream grades 3 and 4 groups were the highest. The comparison of the average subjective scores of the images of hepatic cysts among the six reconstruction grades showed statistically significant differences (H=192.17,P<0.05). Conclusion:In CT plain scan on the upper abdomen,with the increasing of IDream reconstruction grades,the image noises gradually decrease,and objective parameters of images gradually enhance,and the reconstructions of IDream grades 3 and 4 can obtain the optimal image quality of upper abdomen at the objective score of hepatic cysts.

Objective To identify novel biomarkers for predicting the risk of latent tuberculosis infection(LTBI)activation using bio-informatics and machine-learning algorithms and to establish a risk model.Methods The GSE112104 and GSE193777 datasets were obtained from the Gene Expression Omnibus.Differential gene expression and weighted gene co-expression network analyses were per-formed to identify ferroptosis-related differentially expressed genes(FRG-DEGs)associated with LTBI activation.Three machine-learning algorithms,least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest,were used to identify ferroptosis-related hub genes(FRG-hubs).The reliability of these genes was validated using independent validation datasets and reverse transcription polymerase chain reaction(PCR).A risk model was established using R software.Results In the GSE 112104 dataset,296 genes were upregulated and 1 569 genes were downregulated in active tuberculosis compared to those in LTBI.Among the LTBI progressors,506 genes were upregulated and 1 132 genes were downregulated.Weighted correlation network analysis identified five gene modules,with the blue module showing the strongest correlation with LTBI activation(cor=0.62,P=0.000 04),con-taining 1 340 genes.Intersections with 728 ferroptosis-related genes resulted in eight FRG-DEGs.The machine-learning algorithms iden-tified four FRG-hubs:PLA2G6,GLS2,JUN,and AMN,whose expression decreased with LTBI activation.Reverse transcription PCR con-firmed this trend.A risk model based on these genes yielded an area under the curve of 0.98 to 1.00.Conclusion This study successfully identified novel biomarkers for predicting the risk of LTBI activation and developed an accurate predictive risk model.

Objective:Multi-facial reflective type of nano-ultrasound contrast agents（UCAs）loaded with hollow self-decomposable silica nanoparticles（SiO 2 NP）of different particle sizes were prepared to investigate the effect of the particle size of SiO 2 NP on the structural and physicochemical characteristics of the nano-UCAs，as well as on the intensity of ultrasound contrast. Methods:Two types of SiO 2 NP with large and small particle sizes（SiO 2 NP L and SiO 2 NP S）were prepared by adjusting the material ratios，and nano-UCAs with different particle sizes of SiO 2 NP S loaded at a concentration of 2 mg/ml were prepared by the thin film hydration method（SiO 2 NP L@NBs and SiO 2 NP S@NBs），and compared with the commercial SonoVue and the prepared nano-bubbles（NBs）for comparing the particle size，zeta potential and stability，scanning electron microscopy to observe the structure，CCK8 method to assess cytotoxicity，and comparison of ultrasonography imaging intensity in in vivo and in vitro experiments. Results:The particle sizes of the two SiO 2 NP（SiO 2 NP L and SiO 2 NP S）were（213.270 ± 16.890）nm and（53.870 ± 8.246）nm，respectively，and the particle size of the synthesized nano-UCA was SiO 2 NP L@NBs（628.40 ± 89.97）nm and SiO 2 NP S@NBs（493.40 ± 36.35）nm respectively，there was no difference in particle size（ P>0.05）. The scanning electron microscope showed a "fig" structure. The stability of SiO 2 NP S@NBs was better than that of SiO 2 NP L@NBs and SonoVue. Safety tests showed that both SiO 2 NP L@NBs and SiO 2 NP S@NBs were safe and usable. Compared with NBs，the intensity of contrast-enhanced ultrasound contrast in SiO 2 NP@NBs with multiple reflection interfaces was significantly enhanced，and the enhanced intensity of contrast-enhanced ultrasound in vitro and in vivo in the SiO 2 NP L@NBs group was significantly higher than that of the NBs group，the SiO 2 NP S@NBs group，and the SonoVue group（all P<0.05）. There was no significant difference in the enhanced intensity of in vitro contrast-enhanced ultrasound between the SiO 2 NP S@NBs group and that of SonoVue（ P>0.05），and the enhanced intensity of contrast-enhanced ultrasound in vivo was significantly higher than that in the SonoVue group（ P<0.05）. Conclusions:The large and small SiO 2 NPs prepared by adjusting the material ratio do not affect the nanoparticle size of UCA.The ultrasonic enhancement ability of nano-UCA with large particle size SiO 2 NP is stronger，but the stability time at room temperature is shorter than that of nano-UCA with small particle size SiO 2 NP.

The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.
Organoids ; Humans ; Tissue Engineering/methods* ; Coculture Techniques ; Regenerative Medicine ; Mouth