OBJECTIVE To optimize the extraction process of organic acids from Angelica sinensis using deep eutectic solvents （DESs）， and conduct characterization， antioxidant activity evaluation， and extraction mechanism analysis. METHODS The conductor-like screening model for realistic solvation with segment activity coefficients （COSMO-SAC） was employed to screen the types of DESs. With total organic acid content as the response value， single-factor experiments and Box-Behnken response-surface methodology were used to optimize the extraction conditions. Using A. sinensis decoction pieces and/or A. sinensis methanol extract as references， scanning electron microscope and Fourier transform infrared spectrometer （FTIR） were applied to characterize the products. Additionally， the 1，1-diphenyl-2-picrylhydrazyl （DPPH） and 2，2′-azino-bis（3-ethylbenzothiazoline-6- sulfonic acid） （ABTS） free radical scavenging capacities were determined. Density functional theory （DFT） was used to analyze the extraction mechanism of ferulic acid and chlorogenic acid by the DESs. RESULTS & CONCLUSIONS The optimal DESs was choline chloride-propanediol. The optimal extraction conditions for organic acids from A. sinensis were as follows： choline chloride- propanediol molar ratio of 1∶1， DESs water content of 70%， solid-liquid ratio of 1∶10， heating temperature of 57 ℃， and heating and stirring time of 8 min. In three validation experiments， the total organic acid content was 2.92 mg/g， yielding a relative error of 0.34% compared to the predicted value （2.91 mg/g）. Compared with A. sinensis decoction pieces and methanol extracts， the agglomerated structure of the DESs extract powder almost disappeared， showing the presence of lamellar structures similar to those of the intestinal wall. Compared with the methanol extract， the DES extract exhibited higher FTIR characteristic peak intensity and peak area integration， as well as stronger scavenging capacities against DPPH and ABTS free radicals. The extraction of organic acids from A. sinensis by DESs is the result of the combined effects of polarity matching， hydrogen bonding， and structural adaptation.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective:To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs.Methods:An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-? t test was used for pairwise comparison. Results:ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2 +/+), heterozygous mutant (ALDH2 +/-), and homozygous mutant (ALDH2 -/-), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P ?

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

Objective:To analyze the development status,frontiers and hotspots of radiomics research in the past five years from 2019 to 2023,and to provide theoretical reference and guidance for radiomics research in China.Methods:The relevant literature in the field of radiomics published in the core database of Web of Science(WOS)from January 1,2003 to August 10,2023 were searched.According to the inclusion and exclusion criteria,6,777 eligible literatures were screened and obtained,including 6,254 articles in the past five years from January 1,2019 to August 10,2023.Bibliometric methods were used to analyze the clustering of countries and regions,institutions,journals,authors,keywords and draw visual maps.Results:The 6,777 radiomics-related articles published between 2003 and 2023 were first published in 2011,and the number of papers tended to stabilize in 2018,and then the number showed a significant trend of increasing year by year.Among the 6,254 articles published from 2019 to 2023,China(3,564 articles),United States(1,164 articles),and Italy(530 articles)ranked the top 3 in terms of publication volume,with close cooperation between countries.General Electric of the United States published the most papers(448 articles),and the journal Frontiers in Oncology(704 papers)ranked first in terms of paper publication volume.From 2019 to 2023,the diseases of concern in the field of radiomics are rectal cancer,hepatocellular carcinoma,breast cancer,and lung cancer(especially non-small cell lung cancer).Conclusion:Although China ranks first in the number of national publications,the quality of research still needs to be improved.In the future,the research trend in the field of radiomics may be the diagnosis and differential diagnosis of various diseases,the prediction and evaluation of curative effect,the evaluation of tumor disease metastasis and the identification of gene phenotype based on radiomics combined with multiple imaging techniques.

Objective:To explore diagnostic value of artificial intelligence(AI)technique on intracranial aneurysm(IA)in multi-slices computed tomography angiography(CTA)for head and neck.Methods:A retrospective analysis was performed on the cases data of 137 patients with suspected IA who were firstly diagnosed in Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine from January 2022 to December 2023,all of them underwent CTA and digital subtraction angiography(DSA)examinations.The results of DSA examination were taken as the"gold standard".The work efficiency and detection effectiveness of two groups for IA were analyzed through manual post-processing and diagnosis(manual group)and CTA with intelligent assistant diagnostic system on head and neck(AI group).Results:In 137 patients with suspected IA,the DSA examination showed that there were 139 aneurysms in 112 patients.The post-processing time was(190.25±30.71)s in AI group,which was significantly shorter than that[(954.37±95.68)s]in manual group,and the difference was statistically significant(t=92.020,P＜0.001),and the image quality of AI group was higher.In the manual group,102 cases with aneurysms were found,which showed good consistency with the"gold standard"(Kappa=0.713),while the AI group found 93 cases with aneurysms,which showed moderate consistency with the"gold standard"(Kappa=0.518).Both groups had higher diagnostic accuracy for the presence or absence of subarachnoid hemorrhage of intracranial aneurysm,but the difference of that between them was not statistically significant difference(P＞0.05).The detection rates of anterior cerebral artery,middle cerebral artery,posterior cerebral artery,anterior communicating artery,posterior communicating artery,vertebral-basilar artery,and artery aneurysms of internal carotid in manual group and AI group were respectively 80.00％vs.80.00％,92.59％vs.81.48％,100.00％vs.100.00％,84.00％vs.52.00％,83.33％vs.0％,80.00％vs.60.00％,69.23％vs.57.69％,and both of them did not found lesions of posterior inferior cerebellar artery.The overall detection rates of two groups were respectively 78.42％and 57.55％,and the overall detection rate of lesion locations of manual group was higher than that of AI group,and the difference in overall coincidence rate between two groups was statistically significant(x2=13.899,P＜0.05).DSA confirmed 7 lesions which aneurysm's diameter was＜3 mm,and the manual group and the AI group identified respectively 3 cases and 1 case for the 7 lesions.A total of 60 lesions with 3～5 mm diameter were found by DSA,and the manual group and the AI group identified respectively 50 cases and 43 cases for the 60 lesions.A total of 72 lesions with＞5 mm diameter were found by DSA,and the manual group and the AI group identified respectively 63 cases and 63 cases,without statistically significant difference between them(P＞0.05).Conclusion:AI technique can significantly improve work efficiency of diagnosis for intracranial aneurysm,and obtain better processing effects of image.Although AI technique has shown a certain value of reference and auxiliary in diagnosing intracranial aneurysms,its diagnostic accuracy and precise in identifying lesion location are still lower than those of manual diagnosis,and it need further deep learning to improve its diagnostic ability.

OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa （HDP） on isoniazid （INH）-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+50 mg/mL HDP） and HDP high- concentration group （4 mmol/L INH+100 mg/mL HDP）. After grouping treating， the liver fluorescence area， fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+2 mg/mL HDP）， and HDP high-concentration group （4 mmol/L INH + 4 mg/mL HDP）. After grouping treating， the cell viability was detected， and the levels of alanine transaminase （ALT）， aspartate transaminase （AST）， and the content of glutathione （GSH） as well as the expression levels of silent information regulator 1 （Sirt1）， nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1） and quinone oxidoreductase 1 （NQO1） proteins were detected. RESULTS Compared with the model group， the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity （except for HDP low-concentration group） of zebrafish liver （P＜0.05 or P＜0.01）， and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group， the survival rate of L02 cells， the content of GSH （except for HDP low-concentration group）， the protein expression levels of Sirt1 （except for HDP low-concentration group）， Nrf2， NQO1， HO-1 （except for HDP low-concentration group） were significantly increased in HDP low- and high-concentration groups （P＜0.05 or P＜0.01）， and the levels of ALT and AST （except for HDP low-concentration group） were significantly decreased （P＜0.05）； the number of survival cells significantly increased， while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury， the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway， improving mitochondrial function and enhancing antioxidant capacity.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Objective:To analyze and compare the pathological data characteristics of patients with simple papillary thyroid carcinoma (PTC) and PTC combined with Hashimoto’s thyroiditis (HT), so as to provide clinical treatment ideas.Methods:A retrospective analysis was performed on the medical records of 326 PTC patients who met the requirements and underwent surgical treatment in the Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine from Jan. 2020 to May. 2022. There were 81 males and 245 females. They were divided into PTC group and HT-PTC group, according to whether they were combined with HT. Clinical data were collected and organized. The collection indicators included patient gender, age, body mass index (BMI), five preoperative thyroid function items including free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), BRAF gene mutation, single or bilateral lesions, single or multiple lesions, largest postoperative pathological tumor lesions diameter, cervical lymph node metastasis (LNM) status, etc. At the same time, all patients were divided into CLNM group and no CLNM group according to CLNM status. The two groups were compared in terms of gender, age ≥55 years old, whether combined with HT, number of lesions, unilateral and bilateral, extraglandular invasion, microcarcinoma, and BRAF gene. Statistical software was used to analyze the results. t test, χ2 test, and logistic regression analysis were adopted. P<0.05 indicates that the difference is statistically significant. Results:The proportion of female patients in both groups was higher, and the proportion of female patients in the HT-PTC group (90/100, 90%) was higher than that in the PTC group (155/226, 69.59%). HT-PTC patients were younger than patients in the PTC group (43.03±12.72 vs. 43.70±12.63) years old, and their TSH (2.71±1.69 vs. 2.02±1.46) uIU/mL was higher. The differences were statistically significant (all P<0.05). There were no statistically significant differences in BMI, FT3, FT4, T3, or T4 (all P>0.05). The HT-PTC group had a lower proportion of BRAF gene mutations [87/100 (87%) vs. 212/226 (93.8%) ], a smaller maximum tumor diameter (1.06±0.73 vs. 1.32±0.97 cm), and a lower proportion of CLNM [37 /100 (37%) vs. 118/226 (52.2%) ]. The number of LNMs with metastasis is less (3.33±2.21 vs. 4.76±4.00), and it was more likely to be multifocal [44/100 (44%) vs. 73/226 (32.74%) ]. All differences were statistically significant (all P<0.05), and the differences in bilateral gland lobes involvement and extra-glandular invasion were not statistically significant. When accompanied by CLNM, gender (male vs. female) [55/100 (35.45%/64.52%) vs. 26/145 (15.2%/84.85%) ], age ≥ 55 years (yes vs. no) [21/134 (13.55) %/86.45%) vs. 50/121 (29.24%/70.76%) ], HT (yes vs. no) [37/118 (23.87%/76.13%) vs. 63/108 (36.84%/63.16%), number of lesions (single focus vs. multiple focus) [90/65 (41.94%/50.06%) vs. 119/52 (69.59%/30.41%) ], microcarcinoma (yes vs. no) [83/72 (53.55%/45.45%) vs. 139/32 (81.29%/18.71%) ] and extraglandular invasion (with vs. without) [38/117 (24.52%/75.48%) vs. 27/144 (17.42%/84.21%) ] had statistics significance (both P<0.05). There was no statistical significance in bilateral lesion involvement or BRAF gene mutation (all P>0.05). Multivariate logistic regression analysis showed that age, microcarcinoma, HT, gender, and number of lesions were independent risk factors for CLNM, and male gender and multifocal cancer were risk factors for CLNM. Age ≥55 years, microcarcinoma, and combined HT were negatively associated with CLNM. Conclusions:HT may promote the occurrence of PTC, but can inhibit its development. In the short term, patients with HT can have a better prognosis than those with simple PTC.