ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Long-term burden of illness and associated medication usage make osteoporosis(OP) a common complication of respiratory diseases. The pathogenic risk factors and treatment strategies for respiratory diseases related OP are similar to primary OP. However, due to differences in the pathogenesis of each disease, there are distinctions in the characteristics of bone loss and treatment approaches. Therefore, targeted diagnostic and therapeutic plans need to be formulated. This article provides a comprehensive review of secondary OP caused by common respiratory diseases in terms of epidemiological characteristics, related risk factors or possible mechanisms, changes in bone metabolic indexes or characteristics of bone damage, and progress in diagnosis and treatment. The aim of this review is to offer insights into the prevention and treatment of secondary OP related to respiratory diseases and promote the development of a multidisciplinary collaborative approach.

Objective To observe the value of intratumoral and peritumoral radiomics based on diffusion weighted imaging(DWI)for predicting histological grade of breast cancer.Methods Preoperative DWI data of 700 patients with single breast cancer diagnosed by pathology were retrospectively analyzed.The patients were divided into training set(n= 560,including 381 of grade Ⅰ+Ⅱ and 179 of grade Ⅲ)and test set(n=140,including 95 of grade Ⅰ+Ⅱ and 45 of grade Ⅲ)at the ratio of 8∶2.Intratumoral ROI(ROIintra)was manually delineated on DWI,which was automatically expanded by 3 mm and 5 mm to decline peritumoral ROI(ROIperi,including ROI3 mm and ROI5 mm),then intratumoral-peritumoral ROI(ROIintra+3 mm,ROIintra+5 mm)were obtained.The optimal radiomics features were extracted and screened,and the radiomics model(RM)for predicting the histological grade of breast cancer were constructed.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated to evaluate the predictive efficacy of each model.Calibration curve method was used to evaluate the calibration degree,while decision curve analysis(DCA)was performed to explore the clinical practicability of each model.Results AUC of RMintra,RM+3 mm,RM+5mm,RMintra+3 mm and RMintra+5 mm was 0.750,0.724,0.749,0.833 and 0.807 in training set,while was 0.723,0.718,0.736,0.759 and 0.782 in test set,respectively.In training set,significant differences of AUC was found(all P＜0.01),while in test set,no significant difference of AUC was found among models(all P＞0.05).The calibrations of models were all high.DCA showed that taken 0.02-0.88 as the threshold,the clinical net benefit of RMintra+per were greater in training set,while taken 0.40-0.72 as the threshold,the clinical net benefit of RMintra+per was greater in test set.Conclusion Both DWI intratumoral and peritumoral radiomics could effectively predict histological grade of breast cancer.Combination of intratumoral and peritumoral radiomics was more effective.

Objective To accurately depict the actual tongue position of vowels in pinyin based on ultrasound tongue image(UTI),and accordingly propose targeted pronunciation training strategies to improve speech rehabili-tation and teaching quality.Methods Forty-five pieces of pronunciation material containing the six vowels a,o,e,i,u,ü(covering all the rhymes in Mandarin)were selected,and 16 subjects aged 20～25 years old with a proficien-cy level of Mandarin 2A or above were recruited to collect speech and ultrasonic data simultaneously.When process-ing the data,segmental labelling was first performed with Praat,then AAA was used to extract the coordinates of the tongue shape and palatal line of the target segments.Finally,the actual tongue positions of the six pinyin letters were determined based on articulatory tongue position comparison.Results Vowel a has[A]and[ε]2 types of tongue positions;o has[o]1 type of tongue position;e has[?],[e]and[?]3 types of tongue positions;i has[i],[(ι)]and[(ι)]3 types of tongue positions;u has[u]1 type of tongue position;and ü has[y]1 type of tongue posi-tion.A retroflex vowel is a vowel target tongue position followed by a tongue curl stroke.Conclusion ① The rhymes are classified into 11 categories,which allowing for a more accurate and systematic teaching.② The six vowel ultrasonic data provides a visual means for learning vowels,which is more intuitive than the traditional pinyin teaching.

Objective:To establish a hyperuricemia rat model through the high temperature-humidity treatment, and monitor its vital signs and biochemical indicator characteristics, as well as observe the changes of renal histomorphology and ultrastructure.Methods:Male SD rats were randomly divided into control(CON) group, potassium oxonate(PO) group and high temperature-humidity(HTH) group, 6 rats each. The experiment lasted for 6 consecutive weeks. Rats from PO group was given 250 mg/kg PO by gavage every day. The rats from HTH group were treated with a special thermostatic incubator for one hour each day after gavaging 250 mg/kg PO. Serum uric acid, creatinine and other indicators were detected every 2 weeks. After 6 weeks, the kidney tissues were collected. The morphological changes and urate crystal deposition of kidney tissues were observed by hematoxylin-eosin staining, Masson′s trichrome staining and gomori staining, while the ultramicrostructural changes of kidney were observed by transmission electron microscope.Results:Two weeks after the experiment, the average serum uric acid values of PO group and HTH group increased significantly, HTH group was higher than PO and CON groups[(133.9±17.8), (107.6±12.4), and (85.7±4.1) μmol/L, P=0.001]. And after 6 weeks, the HTH group was still higher than the other two groups[(115.1±27.8), (82.7±13.9), and (72.9±17.8) μmol/L, P=0.008). The average serum creatinine in HTH group was slightly higher than that in PO group and CON group at 6 weeks[(46.2±4.7), (38.1±6.0), and (28.3±6.3) μmol/L, P=0.001]. Light microscope showed partial renal tubular dilatation in PO group, but renal tubular epithelial cells swelling and inflammatory cells infiltration were more significant in HTH group. The ultrastructural changes such as glomerular podocyte swelling were found in HTH group by transmission electron microscope. Conclusion:In this study, we had successfully established a hyperuricemia rat model by simulating the high temperature-humidity environment combined with potassium oxyzinate after 2 weeks of experiment. After 6 weeks of modeling, it was found that the high temperature-humidity induced rat models possessed a relatively higher and stabler serum uric acid level than that of the traditional chemical medicine induced rats. The method can be applied to the research of pathogenesis and pharmacotherapy of hyperuricemia caused by high temperature-humidity environment.

Background: The terminology of nonalcoholic fatty liver disease (NAFLD) was changed to metabolic dysfunction ⁃ associated fatty liver disease (MAFLD) in 2020. NAFLD has been confirmed to be a risk factor for colorectal neoplasms, but the association between MAFLD and colorectal neoplasms is conflicting. Aims: To investigate the correlation of MAFLD with colorectal adenoma and early colorectal cancer. Methods: The clinical information of 701 patients who met the criteria and were admitted to Renmin Hospital of Wuhan University from January 2021 to August 2021 was collected retrospectively. Among them, 274 colorectal adenoma patients with low ⁃ grade intraepithelial neoplasia or without intraepithelial neoplasia were classified as adenoma group, 21 patients with high ⁃ grade intraepithelial neoplasia, intramucosal carcinoma, and submucosal carcinoma were classified as early cancer group, and 406 patients with normal colonoscopy or non⁃adenomatous polyps were served as control group. The general information and prevalence of MAFLD between these groups were compared. Furthermore, the correlation of MAFLD with colorectal adenoma and early colorectal cancer, and the gender difference of these correlations were analyzed by Logistic regression models. Subgroup analysis was performed based on the clinicopathological characteristics of colorectal adenoma. Results: When adjusting the confounding variables including gender, age, smoking, alcohol drinking, diabetes, hypertension, and serum creatinine, MAFLD was significantly associated with the prevalence of colorectal adenoma (OR=1.83, 95% CI: 1.04 ⁃ 3.22, P=0.037) and early colorectal cancer (OR=3.91, 95% CI: 1.14⁃13.42, P=0.031). When stratified as gender, the significant association remained in females (OR=4.04, 95% CI: 1.56 ⁃ 10.47, P=0.004), but not in males. In addition, no correlation was found between MAFLD and the location, size, number, and advanced histology of colorectal adenoma (all P>0.05). Conclusions: MAFLD is an independent risk factor for colorectal adenoma and early colorectal cancer. MAFLD is specifically associated with increased risk of colorectal adenoma in females but not in males.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

As one of the important factors to realize the rational allocation of resources and the establishment of interpersonal network, the concept and theory of social capital have been developing continuously in the global health service system, which has attracted the attention of nursing managers at home and abroad. This paper introduces the theory of social capital and its development in the field of nursing, summarizes the measurement tools of social capital of medical staff, analyzes and summarizes the application of social capital theory in nurse leadership, nursing risk management, nursing talent team construction, nurse job satisfaction, nurse retention intention and other aspects and points out the shortcomings and development trends of the current research in this field. It is suggested to construct and develop the theoretical framework and measurement tools of social capital suitable for China's nursing industry, increase the research on the application effect of social capital theory in human resource management, risk management and quality management in nursing management and provide effective management methods for nursing managers, so as to provide reference for improving the level of nurses' social capital and improving the quality of nursing service.

Objective:To explore the potential role of amyloid precursor protein (APP) in the sodium-channel-voltage-beta 2B (SCN2B)-mediated improvement of memory and cognitive function in Alzheimer's Disease (AD).Methods:The SCN2B gene knockout mice (SCN2B -/-) were hybridized with APP gene knockout mice (APP -/-), APP gene heterozygous mice (APP +/-) and APP gene transgenic mice (APP +/+), and the tail tissue of the same mouse was genotyped by PCR gene detection.The mice were divided into SCN2B -/-APP -/- group, SCN2B -/-APP +/- group and SCN2B -/-APP +/+ group.The C57BL/6 wild-type mice were Wild type (WT) group, with 9 mice in each group.SCN2B -/-APP -/-, SCN2B -/-APP +/-, SCN2B -/-APP +/+ transgenic mice and the wild-type mice at the age of 6 months, 12 months, and 18 months were tested by Morris water Maze and Y maze test to detect the cognitive function between each group.Meanwhile, SCN2B -/-APP -/-, SCN2B -/-APP +/-, SCN2B -/-APP +/+ transgenic mice aged 6, 12, 18 months and age-match wild-type were selected to detect neuronal processes in hippocampal CA1 region, and the number of neuronal processes in basal and distal regions of hippocampal CA1 region was quantitatively analyzed.SPSS 21.0 statistical software was used for data statistics and analysis.The differences between the two groups were compared and analyzed by independent-sample t test, the comparison between multiple groups was analyzed by one way analysis of variance (ANOVA), and repeated measurement ANOVA was used to analyze behavioral deta. Results:Repeated measurement ANOVA was used to analyze the data of water maze test. The data showed that the interaction effect of escape latency group and time was significant in 18 month old mice ( Ftime×group=3.63, P<0.01). Simple effect analysis showed that compared with SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the escape latency of mice in SCN2B -/-APP +/+ group was significantly prolonged from day 4 to 6 (4th day: (47.00±2.00)s, (43.11±1.96) s, (41.89±3.06)s, t=-4.16, 1.00, both P<0.05; 5th day: (45.22±2.54) s, (36.33±2.78) s, (37.00±2.45)s, t=-7.08, -0.54, both P<0.05; 6th day: (38.11±2.03)s, (34.11±2.32)s, (33.00±2.91)s, t=-3.90, 0.90, both P<0.05). The residence time in the target quadrant was shortened((18.00±1.73)s, (25.56±1.33)s, (24.33 ±1.94)s; t=10.37, 1.56, both P<0.05). (2) Y-maze results showed that compared with SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the number of novel arm entry in 18 month old mice in SCN2B -/-APP +/+ group was decreased((50.22±3.68), (57.22±3.74), (58. 44±5.14) ; t=3.40, -0.48, both P<0.05), and the residence time of stay in the new arm was reduced((10.89±0.62)min, (14.33±0.59)min, (13.89±0.74)min; t= 8.16, 0.44, both P<0.05), and the distance of movement in the new arm was significantly reduced ((37.26±2.01)m , (45.67±2.45)m , (46.11±3.27)m ; t=7.81, 0.91, both P<0.05). (3) Golgi staining showed that SCN2B -/-APP +/- group and SCN2B -/-APP -/-group, the number of apical dendrites in hippocampal neurons of 18 month old mice in SCN2b -/-App +/+ group(number of apical dendrites: (1.78±0.37), (3.67±0.81), (3.00±1.21); t=3.36, 1.41, both P<0.05) and the number of basal dendrites (the number of basal dendrites: (1.11±0.50), (3.11±0.50), (2.56±0.69); t=4.06, 1.21, both P<0.05). Conclusion:SCN2B knockdown can improve the ability of spatial learning and memory in aged mice.Overexpression of APP can partially offset the improvement of cognitive function caused by SCN2B knockdown, and may be affected by the number of basal and distal processes of neurons in the hippocampal CA1 region of the mice.

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (−μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.
Apoptosis* ; Blotting, Western ; Cardiotoxicity ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP1A2 ; Cytochromes c ; Doxorubicin ; Myocytes, Cardiac ; Real-Time Polymerase Chain Reaction ; Receptors, Aryl Hydrocarbon* ; RNA, Messenger ; RNA, Small Interfering ; Transfection