BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Background::Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods::Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. Results::The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.Conclusion::The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

Cervical lymph node metastasis in thyroid cancer is closely related to the disease recurrence and prognosis of patients. Accurate judgment of lymph node metastasis is vital for tumor stage and treatment in patients with thyroid cancer, which can effectively improve the prognosis of patients. However, preoperative detection of cervical lymph node metastasis is the key points and difficulties in individualized treatment of thyroid cancer. Currently, fine needle aspiration washout fluid thyroglobulin is often used to assess cervical lymph node metastasis of differentiated thyroid cancer preoperatively, and it has a higher diagnostic efficacy. The continuous exploration and application of tumor markers and emerging biomarkers have provided new perspectives for the preoperative diagnosis of lymph node metastasis in thyroid cancer. As a new non-invasive detection technique, liquid biopsy is convenient to obtain samples and has broad clinical application in early diagnosis of cervical lymph node metastasis of thyroid cancer. In addition, the analysis and application of liquid biopsy biomarkers will help the development of clinical diagnosis and treatment strategies, and provide the possibility of early precision therapy for thyroid cancer patients. This review summarizes current research surrounding the molecular markers related to cervical lymph node metastasis of thyroid cancer.

Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.

OBJECTIVE To test and compare the median effective dose(ED50) of ciprofol for gastroscope in patients of different genders and ages. METHODS Patients who planed to undergo gastroscope examination and treatment from March 2023 to April 2023 were selected, and divided into four groups according to stratified random method: N1 group(non-elderly male patients), N2 group(non-elderly female patients), N3 group(elderly male patients), and N4 group(elderly female patients). All patients received intravenous injection of 0.1 μg·kg−1 sufentanil followed by injection of the test dose of ciprofol according to Dixon’s modified sequential method. Gastroscope was performed after the disappearance of the eyelash reflex. The initial dose of ciprofol in all four groups was 0.4 mg·kg−1, and the ratio of adjacent doses was 1∶1.1. The next patient would receive a 10% increase in the dose of ciprofol if the patient experienced positive reactions such as coughing, frowning, and body movements during the endoscopy process. Otherwise, it would be judged as a negative reaction, and the next patient would receive a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points. The Probit regression analysis method was used to calculate the ED50 of ciprofol for four groups. RESULTS The ED50 of ciprofol combined with 0.1 μg·kg−1 sufentanil for gastroscope in the non-elderly men, non-elderly women, elderly men, and elderly women were 0.409, 0.373, 0.356, 0.327 mg·kg−1, respectively. The ED50 of ciprofol in the N1 group was significantly higher compared with the N2 group and N3 group(P<0.05). The ED50 of ciprofol in the N4 group was significantly lower compared with the N2 group and N3 group(P<0.05). CONCLUSION The ED50 of ciprofol is significantly different among gastroscope patients of different genders and ages, which is lower in female patients than in male patients, and is lower in older patients than in non-elderly patients.

Objective To investigate the differential diagnostic value of 18F-fluorodeoxyglucose(18F-FDG)/PET/CT combined with serum lactate dehydrogenase(LDH),β2-microglobulin(β2-MG),and C-reactive protein(CRP)in sarcoidosis and lymphoma.Methods The 18F-FDG PET/CT images of 19 patients with sarcoidosis and 33 patients with lymphoma were analyzed retrospectively.The lymph node maximum diameter,density,distribution morphology,maximum standardized uptake value(SUVmax),extra-nodal involvement,and serum LDH,β2-MG,and CRP results were analyzed and compared.Results There was no statistically significant difference between sarcoidosis and lymphoma in lymph node density,necrosis rate,and SUVmax(P＞0.05).There was statistically significant difference in the maximum diameter between lymph nodes in sarcoidosis(2.4±0.7)cm and lymphoma(3.3±1.3)cm(P＜0.05).The incidence of symmetric enlargement of mediastinal and hilar lymph nodes was 84.2％in sarcoidosis,the lymph node fusion rate was 21.1％,the lung involvement rate was 57.8％,the spleen involvement rate was 10.5％,and the rates of lymphoma were 15.2％,63.6％,0.0％,and 36.4％,with statistically significant differences(P＜0.05).There were statistically significant differences in LDH and β2-MG between the two groups(P＜0.05),but the differences in CRP were not statistically significant(P＞0.05).Conclusion PET/CT can show the anatomy of mediastinal and hilar lymph nodes and extra-nodal affected organs as well as glucose metabolism,showing a certain differential diagnostic value of sarcoidosis and lymphoma when combined with serum LDH and β2-MG levels.

A large number of people would be exposed to irradiation in large-scale nuclear and radiation accidents or nuclear terrorist attacks. Therefore, it is urgent to establish rapid and high-throughput biodosimetry for in triage, providing a basis for emergency management. Imaging flow cytometry (IFC) possesses the high through put advantages of traditional flow cytometry and the sensitivity and specificity of microscope, and has a good application prospect in the research and development of rapid, automated, and high-throughput biological dose estimation technology. This article reviews the application progress of IFC in biodosimetry, and provides a reference for the development of biological dose estimation and detection equipment for large-scale nuclear and radiation accidents.

Objective:To study the application of scenario simulation teaching combined with modular training in nursing education of medical rescue in manned space flight.Methods:Twenty nurses from the medical rescue team of Strategic Support Force Characteristic Medical Center were selected as the research objects. The research objects were randomly divided into the scenario simulation combined with practical training group (practical training group, n=10) and traditional teaching group (control group, n=10). Scenario simulation teaching combined with modular training and traditional teaching were used to carry out nursing training. After the training, theoretical assessment, operation assessment and satisfaction survey were organized. Results:The scenario simulation teaching combined with modular training group was significantly better than the traditional training group in theory assessment, operation assessment and satisfaction survey of nursing staff (all P<0.05). Conclusions:Scenario simulation teaching combined with modular training has obvious teaching effect, which can improve the ability and quality of nursing staff, and help to complete the manned space medical rescue mission efficiently.

Objective:To investigate the impact of switching to low iodine drinking water in areas with high water iodine levels on the iodine nutritional status and thyroid function of pregnant women.Methods:A cross-sectional survey was conducted in Gaoqing County, Zibo City, Shandong Province. Pregnant women who underwent prenatal examinations at the Obstetrics Clinic of Gaoqing County People's Hospital from 2019 to 2021 were selected as the survey subjects. With reference to the Criteria for the Classification of Water Source High Iodine Areas and High Iodine Disease Areas (GB/T 19380-2016), pregnant women with drinking water iodine > 100 μg/L were considered as the high water iodine group and ≤100 μg/L was the non-high water iodine group. Basic information, one random urine sample, fasting blood sample, 24-hour urine sample and drinking water sample of pregnant women were collected, and thyroid ultrasound examination was performed on pregnant women. Urinary iodine (UI) concentration (UIC) and drinking water iodine concentration (WIC) were measured by inductively coupled plasma mass spectrometry, and 24-hour urinary iodine excretion (UIE) and daily iodine intake (TII) of pregnant women were calculated. Serum thyroid hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and anti-thyroid autoantibodies (TgAb) were determined by automatic chemiluminescence immunoassay. Creatinine (CR) was determined using deproteinized endpoint microplate method and UI/CR was calculate. Results:A total of 797 pregnant women were included, and the UIC was 150.2 (88.1, 281.3) μg/L, the iodine nutrition was generally at an appropriate level. Among them, 584 pregnant women in the non-high water iodine group had a UIC of 120.9 (74.9, 191.5) μg/L, which was at the iodine deficiency level; 213 pregnant women in the high water iodine group had a UIC of 321.1 (201.9, 569.1) μg/L, which was at the iodine super-appropriate level; the differences in WIC, UIC, UIE, TII, and UI/CR between the two groups were statistically significant ( Z = 21.63, 13.34, 15.14, 15.14, 11.81, P < 0.001). After stratification by different gestational periods, the differences were statistically significant when comparing WIC and TSH in pregnant women in the non-high water iodine group and UI/CR in pregnant women in the high water iodine group by gestational period ( H = 59.13, 7.30, 13.60, P < 0.05). A total of 744 pregnant women were tested for thyroid function, and 128 cases of TSH > 2.5 mU/L, 15 cases of hypothyroxemia, and 19 cases of subclinical hypothyroidism were detected, with detection rates of 17.2%, 2.0%, and 2.6%, respectively. The differences were statistically significant when comparing TSH and TPOAb levels and the proportion of pregnant women with TSH > 2.5 mU/L in the high water iodine and non-high water iodine groups ( Z = 3.04, - 2.17, χ 2 = 6.94, P = 0.002, 0.030, 0.008). The thyroid glands of pregnant women were examined in 720 cases, and 30 cases of goiter and 150 cases of thyroid nodules were detected, with detection rates of 4.2% and 20.8%, respectively. The median thyroid volume was 8.92 ml in the high water iodine group and 8.60 ml in the non-high water iodine group, which were both within the normal range, with no statistically significant difference between the groups ( Z = - 0.75, P = 0.455). Conclusions:After changing to low iodine water, the overall iodine nutrition of pregnant women in Gaoqing County is now at an appropriate level, and the reduction of water iodine effectively reduces the risk of TSH abnormalities in local pregnant women. However, pregnant women in the non-high water iodine group are iodine deficiency, and pregnant women in the high water iodine group are at iodine super-appropriate, and the iodine nutrition level of pregnant women in this area is highly variable, which causes the "illusion" that the overall iodine level of local pregnant women is suitable.