BACKGROUND: Previous studies have demonstrated that berberine represses multiple tumors and tumor stem cells, but the effect of berberine on lung cancer stem cells (LCSCs) remains unclear. OBJECTIVE: To explore the effect of berberine on the proliferation and apoptosis of LCSCs and the possible mechanism. METHODS: CD133+ LCSCs were separated from A549 cells by immunomagnetic beads. The effects of different concentrations (0, 2.5, 5, 10, 20, 40 mg/L) of berberine on the proliferation and apoptosis of LCSCs were determined by MTT and flow cytometry analysis, respectively. In order to further affirm the effect of berberine on the proliferation and apoptosis of LCSCs, the expression levels of Ki67, Bax and Bcl-2 protein were detected by western blot. In addition, to investigate the potential mechanism by which berberine exerts regulatory effects on LCSCs, the expression levels of Hedgehog signaling pathway-associated proteins (PTCH1, SHH, Gli-1 and SMO) were determined. RESULTS AND CONCLUSION: After magnetic cell sorting, the content of the CD133+ fraction was enriched up to 84.13%. MTT and flow cytometry assays showed that berberine inhibited proliferation and promoted apoptosis of LCSCs in a concentration-dependent manner. Western blot analysis showed that the expression levels of Ki67, Bcl-2, PTCH1, SHH, Gli-1 and SMO proteins of LCSCs cultured in the medium with 20 mg/L berberine were dramatically decreased compared to the control, while the expression level of Bax protein was markedly increased compared to the control. These findings suggest that berberine may inhibit proliferation and promote apoptosis for LCSCs through the Hedgehog signaling pathway.BACKGROUND: Previous studies have demonstrated that berberine represses multiple tumors and tumor stem cells, but the effect of berberine on lung cancer stem cells (LCSCs) remains unclear. OBJECTIVE: To explore the effect of berberine on the proliferation and apoptosis of LCSCs and the possible mechanism. METHODS: CD133+ LCSCs were separated from A549 cells by immunomagnetic beads. The effects of different concentrations (0, 2.5, 5, 10, 20, 40 mg/L) of berberine on the proliferation and apoptosis of LCSCs were determined by MTT and flow cytometry analysis, respectively. In order to further affirm the effect of berberine on the proliferation and apoptosis of LCSCs, the expression levels of Ki67, Bax and Bcl-2 protein were detected by western blot. In addition, to investigate the potential mechanism by which berberine exerts regulatory effects on LCSCs, the expression levels of Hedgehog signaling pathway-associated proteins (PTCH1, SHH, Gli-1 and SMO) were determined. RESULTS AND CONCLUSION: After magnetic cell sorting, the content of the CD133+ fraction was enriched up to 84.13%. MTT and flow cytometry assays showed that berberine inhibited proliferation and promoted apoptosis of LCSCs in a concentration-dependent manner. Western blot analysis showed that the expression levels of Ki67, Bcl-2, PTCH1, SHH, Gli-1 and SMO proteins of LCSCs cultured in the medium with 20 mg/L berberine were dramatically decreased compared to the control, while the expression level of Bax protein was markedly increased compared to the control. These findings suggest that berberine may inhibit proliferation and promote apoptosis for LCSCs through the Hedgehog signaling pathway.

Objective To investigate Helicobacter pylori combined with N-methyl-N-nitrosourea (MNU) gavage for preparing balb/c mouse gastric cancer model.Methods Eighty balb/c mice were randomly divided into four groups after 1-week adaptive feed,normal group,model group Ⅰ,Ⅱ and Ⅲ,20 cases in each group.The model group Ⅰ,Ⅱ and Ⅲ were given Helicobacter pylori bacteria liquid (CFU=109/mL) gavage,once every other day for 5 times;then,the freshly configured MNU solution 0.15,0.3,0.6 mL gavages were in turn given,MNU and pure water allocation ratio was 5mg:3mL.Once gavage per week for continuous 10 weeks.Results The model group II had 66.67% adenocarcinoma,the model group I were gastritis with mild atypical hyperplasia,and all mice in the model group III died.Conclusion This method can prepare the gastric cancer model.

OBJECTIVETo investigate the effect of advanced oxidation protein products (AOPP) on proliferation, differentiation, and oxidative stress in rat osteoblasts.

METHODSThe cell proliferation and differentiation of osteoblasts isolated from neonatal SD rat skull were evaluated following treatment with different concentrations (50, 100, 200, and 400 µg/ml) of AOPP using CCK-8 kit and ALP assay kit, respectively. The levels of reactive oxygen species (ROS) in the treated cells were analyzed using 2', 7'-dichlorofluorescin diacetate, and the transcription levels of ALP, collagen I and RAGE were assessed using real-time PCR.

RESULTSCompared with the control group, AOPP-treated osteoblasts showed obviously inhibited proliferation and differentiation with down-regulated expressions of ALP and collagen I and increased ROS production and RAGE expression.

CONCLUSIONAOPP can inhibit the proliferation and differentiation of rat osteoblasts partially by up-regulating RAGE and inducing ROS production.

Advanced Oxidation Protein Products ; pharmacology ; Alkaline Phosphatase ; metabolism ; Animals ; Cell Differentiation ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Osteoblasts ; cytology ; drug effects ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism

Objective:To establish a mouse model of gastric cancer by inoculating MKN45 cells into mice with normal immune function utilizing microcarrier technology. Methods:A total of 60 male C57BL/6 mice were randomly divided into three groups, namely, 2D, con-trol, and 3D groups, according to the coculture system of MKN45 and microcarrier. The mouse models of gastric carcinoma were estab-lished by hypodermic injection. The time of tumorigenesis, rate of tumor formation, and pathological features were observed in each group. Results:In the 3D group, the time of tumor formation was short, whereas the rate of tumor formation was high (80%). No de-tectable tumor formations were observed in the 2D and control groups. HE and immunohistochemical staining of the transplantation tumor model showed evident characteristics of human gastric cancer. Conclusion:A human gastric cancer model in normal immune mice was successfully established. The onset and development mechanism of gastric cancer could be more effectively investigated in mice with normal immune function through this model. Moreover, a more valuable and new animal model for the research and devel-opment of anticancer drug was established.

Objective To explore the causal relationship between family resilience and mental health in military personnel population.Methods A total of 204 military personnel were recruited from an army unit stationed in Western China with cluster convenience sampling.Family Resilience Scale(FRS)and Symptom Checklist 90(SCL-90)were used to survey them twice,in an interval of 4 months.Amos 26.0 was applied to construct a cross-lag model and analyze the data.Results After controlling mental symptoms from the first survey,family resilience in the first measure significantly predicted mental symptoms in the second measure(β=-0.14,P＜0.05).After controlling for family resilience from the first survey,mental symptoms in the first measure significantly predicted family resilience in the second measure(β=-0.13,P＜0.05).Conclusion The relationship between family resilience and mental health is mutually causal in military personnel,and one predicts the other one.Our findings highlight the key dimensions of the relationship between the two.

Objective:To determine the characteristics of cervical neuroblastoma and the effect of resection extent on survival and outcomes.Methods:We performed a retrospective review of 32 children with cervical neuroblastoma treated at Beijing Children′s Hospital between April 2013 and August 2020. Data were collected from the medical record. The individualized therapy was designed based on staging and risk group. Based on the extent of resection, patients were divided into incomplete and complete resection groups. Event free and overall survival rates were compared between two groups using the Kaplan-Meier method.Results:The ages of patients ranged from 1 month to 81 months, with a median age of 11 months, including 7 males and 15 females. Twenty-nine patients (90.6%) presented with cervical painless mass. The average diameter of the primary tumors was (5.12±1.43) cm. Tumors were located in the parapharyngeal space in 25 cases (78.1%) and in the root of the neck in 7 cases (21.9%). None had MYCN amplification. According to International Neuroblastoma Staging System (INSS), 15 patients (46.9%) were identified as stage 1, 11 patients (34.3%) as stage 2B, 3 patients (9.4%) as stage 3 and 3 patients (9.4%) as stage 4. There were 12 patients (37.5%) at low risk, 17 patients (53.1%) at intermediate risk and 3 patients at high risk according to Children′s Oncology Group (COG) risk classification system. All patients underwent tumor resection. Postoperatively Horner′s syndrome occurred in 13 patients (40.6%), pneumonia in 9 patients (28.1%), pharyngeal dysfunction in 8 patients (25.0%) and transient hoarseness in 4 patients (12.5%). At a median follow-up of 36.5 months, the overall survival rate was 96.4%, with no significant difference between incomplete and complete resection groups (100.0% vs. 96.3%, χ 2=0.19, P=0.667); the event free survival rate was 78.1%, with a significant difference between the two groups (40.0% vs. 85.2%, χ2=6.71, P=0.010). Conclusions:Primary cervical neuroblastoma has a young onset age, mostly in low and medium risk groups, and represents favorable lesions with good outcomes after multidisciplinary therapy. Less aggressive surgery with preservation of important structures is recommended. Complete resection should not be attempted if it would compromise vital structures.

Objective:To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS).Methods:Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children′s Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis.Results:Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype ( HR=6.26, 95% CI: 1.52-25.87, P=0.011) and failure to reach R0 resection ( HR=9.37, 95% CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion:Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

Objective:To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS).Methods:A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children′s Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test.Results:A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis ( χ2=5.022, P=0.025), distant metastasis ( χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group ( χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion:Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Objective:To develop the children′s postoperative health-related quality of life scale for thyroid cancer and to test its reliability and validity.Methods:The first draft of the scale was developed through literature search, focus group meetings, and a pre-survey, and 116 children (76 for testing and 40 for external validation) with thyroid cancer attending Beijing Children′s Hospital of Capital Medical University were selected to answer the scale, to screen and categorize the questions and to form the final scale with multiple dimensions.Results:The children′s postoperative health-related quality of life scale for thyroid cancer contained 5 dimensions and 29 questions. Exploratory factor analysis showed that the cumulative variance explained by the 5 factors was 64.343%. Confirmatory factor analysis showed correlations between the questions and dimensions of this scale, fair convergent validity for the scale, and good discriminant validity. The validity of the validity scale showed that there was a existing correlation between the questions and the validity scale of this scale. The item-dimension correlation coefficients showed that the questions in each dimension were well differentiated. The total Cronbach′s α coefficient of the scale was 0.930, the folded half reliability was 0.843, and retest reliabilities at 2 weeks, 1 month, and 3 months after the initial test were respectively 0.936, 0.922, and 0.910.Conclusion:The developed children′s postoperative health-related quality of life scale for thyroid cancer has good reliability and validity and can be used to assess the health-related quality of life of children after thyroid cancer surgery.

Non-coding RNAs(ncRNAs) are special RNAs that they don't have protein coding function, but they can affect chromosome structure, gene transcription and participate in the processes of epigenetic modifications. ncRNAs include long non-coding RNAs, microRNA, etc. In recent years, it has been found that these ncRNAs can maintain bone remodeling by adjusting bone resorption and formation in osteoporosis(OP). In the future, it may be a key target of the drug action screening which is clarifying the regulatory mechanism of ncRNAs in the occurrence and development of OP. OP belongs to bone rheumatism category in traditional Chinese medicine, according to the theory of “the kidney generating marrow and dominating bone” in traditional Chinese medicine, kidney tonifying and bone strengthening formulas are used to treat the OP in clinic, and the curative effect is remarkable. It has been found that kidney tonifying and bone strengthening prescriptions can enhance the proliferation of osteoblasts or inhibit the differentiation of osteoclasts by up-regulating or down-regulating the expression of ncRNA, and finally maintain OP bone homeostasis, thus exerting therapeutic effect. However, the specific molecular mechanism is still in its exploratory stage. Therefore, this paper summarized the molecular mechanism of kidney tonifying and bone strengthening prescriptions regulating ncRNAs in the treatment of OP in recent years, in order to provide the new ideas for the screening of the key therapeutic targets of OP drugs and the prevention and treatment of OP with traditional Chinese medicine.