Objective:To investigate the mechanism of ursolic acid (UA) in inhibiting the growth and metastasis of breast cancer MDA-MB-231 (“231”) cells by downregulating ANXA6.Methods:This study conducted relevant in vitro cytology and molecular biology experiments in the Department of Clinical Laboratory and Central Laboratory of Putuo Hospital, Shanghai University of Traditional Chinese Medicine from February 2023 to August 2024. Human breast cancer 231 cells were cultured in vitro, and the effects of different concentrations of UA on the proliferation and invasion and metastasis of 231 cells were detected by CCK-8 and Transwell assays. Western Blot was used to detect the effect of UA on the expression of ANXA6 and invasion and metastasis-related proteins MMP9, β-catenin and N-cadherin in 231 cells. The 231 cells that interfered with and overexpressed ANXA6 were constructed by lentivirus transfection to generate stable ANXA6 interfering and overexpressing 231 cells, which were divided into 231/KD-ANXA6 group, 231/KD-NC group, 231/OE-ANXA6 group, and 231/OE-NC group. CCK-8 assay and Transwell assay were used to detect the proliferation activity, invasion and metastasis ability of 231 cells after interference and overexpression of ANXA6 and the effect of UA on the proliferation ability of 231 cells after interference and overexpression of ANXA6. Western Blot and RT-PCR assays were used to detect the expression of invasion and migration biomarkers such as MMP9, β-catenin, and N-cadherin in 231 cells after interference and overexpression of ANXA6. Immunohistochemistry was used to detect the expression level of ANXA6 in breast cancer tissues, and the relationship between ANXA6 expression and clinicopathological features and prognosis of breast cancer was analyzed.Results:The CCK-8 assay results showed that compared with the control group (0 μmol/L UA, 100.00%±7.37%), the proliferative activity of 231 cells at UA concentrations of 2.5, 5, 10, 20 and 40 μmol/L (90.23%±1.76%, t=2.24, P<0.05; 85.19%±4.23%, t=3.02, P<0.05; 65.45%±0.35%, t=8.11, P<0.01; 37.79%±0.98%, t=14.50, P<0.001; 18.18%±0.15%, t=19.23, P<0.001) were significantly decreased. Furthermore, UA (10, 15, 20 μmol/L) inhibited the invasion and metastasis ability of 231 cells; Western Blot assay showed that compared with the control group (0 μmol/L UA), the protein expressions of MMP9 (1.07±0.03 vs 0.99±0.11, t=1.27, P>0.05), β-catenin (1.21±0.01 vs 0.99±0.07, t=5.47, P<0.05), N-cadherin (1.05±0.09 vs 0.90±0.03, t=2.65, P>0.05) at UA of 10 μmol/L; MMP9 (1.07±0.03 vs 0.79±0.09, t=5.26, P<0.001), β-catenin (1.21±0.01 vs 0.89±0.05, t=10.55, P<0.001), and N-cadherin (1.04±0.09 vs 0.68±0.10, t=4.59, P<0.05) at UA of 15 μmol/L; MMP9 (1.07±0.03 vs 0.52±0.07, t=12.50, P<0.001), β-catenin (1.21±0.01 vs 0.83±0.02, t=24.01, P<0.000 1) and N-cadherin (1.04±0.09 vs 0.49±0.11, t=6.70, P<0.01) at UA of 20 μmol/L. Interfering with ANXA6 inhibits the proliferation, invasion and migration of 231 cells, and overexpression of ANXA6 promotes the proliferation, invasion and migration of 231 cells. Western Blot assay showed that compared with the control group (KD-NC group), the protein expressions of MMP9 (1.07±0.01 vs 0.62±0.16, t=4.86, P<0.01), β-catenin (1.02±0.14 vs 0.64±0.15, t=3.20, P<0.05), N-cadherin (0.98±0.14 vs 0.67±0.12, t=2.85, P<0.05) were decreased expression; Compared with the control group (OE-NC group), the protein expressions of MMP9 (0.54±0.22 vs 1.06±0.08, t=3.90, P<0.05), β-catenin (0.92±0.07 vs 1.06±0.04, t=3.06, P<0.05) and N-cadherin (0.90±0.07 vs 1.06±0.01, t=3.75, P<0.05) were significantly increased. Interference with ANXA6 promoted the inhibitory effect of UA on the proliferation ability of 231 cells ( P<0.05). Overexpression of ANXA6 weakened the inhibitory effect of UA on the proliferation of 231 cells ( P<0.05).The results of immunohistochemistry assay showed that the expression level of ANXA6 in breast cancer tissue was significantly increased, and the expression of ANXA6 was related to tumor size ( P<0.05), but not to age, T stage, N stage, pathological grade, AJCC stage, ER, PR and E-cad. Conclusion:The expression level of ANXA6 in breast cancer tissues is increased, and UA can inhibit the growth, invasion and metastasis of 231 cells by down-regulating the expression of ANXA6.

Objective:To investigate the mechanism of ursolic acid (UA) in inhibiting the growth and metastasis of breast cancer MDA-MB-231 (“231”) cells by downregulating ANXA6.Methods:This study conducted relevant in vitro cytology and molecular biology experiments in the Department of Clinical Laboratory and Central Laboratory of Putuo Hospital, Shanghai University of Traditional Chinese Medicine from February 2023 to August 2024. Human breast cancer 231 cells were cultured in vitro, and the effects of different concentrations of UA on the proliferation and invasion and metastasis of 231 cells were detected by CCK-8 and Transwell assays. Western Blot was used to detect the effect of UA on the expression of ANXA6 and invasion and metastasis-related proteins MMP9, β-catenin and N-cadherin in 231 cells. The 231 cells that interfered with and overexpressed ANXA6 were constructed by lentivirus transfection to generate stable ANXA6 interfering and overexpressing 231 cells, which were divided into 231/KD-ANXA6 group, 231/KD-NC group, 231/OE-ANXA6 group, and 231/OE-NC group. CCK-8 assay and Transwell assay were used to detect the proliferation activity, invasion and metastasis ability of 231 cells after interference and overexpression of ANXA6 and the effect of UA on the proliferation ability of 231 cells after interference and overexpression of ANXA6. Western Blot and RT-PCR assays were used to detect the expression of invasion and migration biomarkers such as MMP9, β-catenin, and N-cadherin in 231 cells after interference and overexpression of ANXA6. Immunohistochemistry was used to detect the expression level of ANXA6 in breast cancer tissues, and the relationship between ANXA6 expression and clinicopathological features and prognosis of breast cancer was analyzed.Results:The CCK-8 assay results showed that compared with the control group (0 μmol/L UA, 100.00%±7.37%), the proliferative activity of 231 cells at UA concentrations of 2.5, 5, 10, 20 and 40 μmol/L (90.23%±1.76%, t=2.24, P<0.05; 85.19%±4.23%, t=3.02, P<0.05; 65.45%±0.35%, t=8.11, P<0.01; 37.79%±0.98%, t=14.50, P<0.001; 18.18%±0.15%, t=19.23, P<0.001) were significantly decreased. Furthermore, UA (10, 15, 20 μmol/L) inhibited the invasion and metastasis ability of 231 cells; Western Blot assay showed that compared with the control group (0 μmol/L UA), the protein expressions of MMP9 (1.07±0.03 vs 0.99±0.11, t=1.27, P>0.05), β-catenin (1.21±0.01 vs 0.99±0.07, t=5.47, P<0.05), N-cadherin (1.05±0.09 vs 0.90±0.03, t=2.65, P>0.05) at UA of 10 μmol/L; MMP9 (1.07±0.03 vs 0.79±0.09, t=5.26, P<0.001), β-catenin (1.21±0.01 vs 0.89±0.05, t=10.55, P<0.001), and N-cadherin (1.04±0.09 vs 0.68±0.10, t=4.59, P<0.05) at UA of 15 μmol/L; MMP9 (1.07±0.03 vs 0.52±0.07, t=12.50, P<0.001), β-catenin (1.21±0.01 vs 0.83±0.02, t=24.01, P<0.000 1) and N-cadherin (1.04±0.09 vs 0.49±0.11, t=6.70, P<0.01) at UA of 20 μmol/L. Interfering with ANXA6 inhibits the proliferation, invasion and migration of 231 cells, and overexpression of ANXA6 promotes the proliferation, invasion and migration of 231 cells. Western Blot assay showed that compared with the control group (KD-NC group), the protein expressions of MMP9 (1.07±0.01 vs 0.62±0.16, t=4.86, P<0.01), β-catenin (1.02±0.14 vs 0.64±0.15, t=3.20, P<0.05), N-cadherin (0.98±0.14 vs 0.67±0.12, t=2.85, P<0.05) were decreased expression; Compared with the control group (OE-NC group), the protein expressions of MMP9 (0.54±0.22 vs 1.06±0.08, t=3.90, P<0.05), β-catenin (0.92±0.07 vs 1.06±0.04, t=3.06, P<0.05) and N-cadherin (0.90±0.07 vs 1.06±0.01, t=3.75, P<0.05) were significantly increased. Interference with ANXA6 promoted the inhibitory effect of UA on the proliferation ability of 231 cells ( P<0.05). Overexpression of ANXA6 weakened the inhibitory effect of UA on the proliferation of 231 cells ( P<0.05).The results of immunohistochemistry assay showed that the expression level of ANXA6 in breast cancer tissue was significantly increased, and the expression of ANXA6 was related to tumor size ( P<0.05), but not to age, T stage, N stage, pathological grade, AJCC stage, ER, PR and E-cad. Conclusion:The expression level of ANXA6 in breast cancer tissues is increased, and UA can inhibit the growth, invasion and metastasis of 231 cells by down-regulating the expression of ANXA6.

Objective To explore the correlation between 5 dimensions of personality,physical activity(PA),and bone mineral density(BMD)among college students.Methods A total of 705 undergraduates(329 males and 376 females)from a sports university were recruited.Based on their sports training experience,the participants were divided into 6 major sports groups,including ball sports,skilled sports,competitive sports,track and field,leisure sports,and no sports.Students with professional sports training(ie,athletes)were categorized into ballgame,skilled,competitive,and track and field groups,while the rest(non-athletes)were placed in leisure and no sports groups.Ten-Item Personality Inventory in China(TIPI-C),or the 5-factor model of personality,was used to measure the 5 personality dimensions of openness,conscientiousness,extraversion,agreeableness,and neuroticism of the participants.Their daily level was measured with GT3X+ triaxial accelerometers over 7 continuous days.Then,parameter thresholds were established and the participants'PA was categorized as light(LPA),moderate(MPA),and vigorous(VPA).The bone mineral density(BMD)of arms,legs,and the total body was measured using dual-energy X-ray absorptiometry.The mediation effect of PA and that of the 5-factor model of personality were tested using PROCESS and Sobel tests.The correlation between the 5 personality dimensions,PA,and BMD was explored,with PA and the 5 personality dimensions as mediator variables.A comparison of PA and BMD was conducted across the 6 major sports groups.The correlation between PA of different intensities and BMD was also analyzed using Spearman's correlation.Results Although there were 90 potential relationships between PA,the 5 personality dimensions,and BMD,only 3 were significant.When conscientiousness was used as an independent variable and MPA,as a mediating variable,statistically significant differences in PROCESS results were reported(P<0.01),with MPA mediating 17.3%of arm BMD,19.4%of leg BMD,and 19.1%of total body BMD.Among male students,there was no significant difference in LPA among the 6 groups,but significant differences in MPA and VPA(P<0.05).Among female students,significant differences in LPA,MPA,and VPA were observed in all 6 groups and the differences between MPA and VPA were especially prominent(P<0.05).For both males and females,the differences in arm,leg,and total body BMD across the 6 groups were statistically significant(P<0.05),with these differences being more pronounced in females.There was no correlation between LPA and BMD in either sex.MPA and VPA were positively correlated with BMD,with MPA correlating with arm,leg,and total body BMD(males,Spearman's correlation[rs]:0.11-0.14,P<0.05;females,rs:0.20-0.23,P<0.01).VPA correlated with arm,leg,and total body BMD(males,rs:0.11-0.23,P<0.05;females,rs:0.26-0.30,P<0.01).Conclusion MPA is associated with BMD in college students scoring high in the conscientiousness dimension of personality.In addition,there is a weak positive correlation between both MPA and VPA and BMD levels,with these associations being more pronounced in females.

A 53-year-old female patient with stage Ⅳa colon cancer received 7 cycles of standard chemotherapy regimen. Due to the progression of the condition, she was treated with fruquintinib (5 mg once daily orally on day 1-21, 28 days as one cycle). After 20 days of treatments, the patient experienced sudden consciousness disorders, accompanied by limb convulsions. Her blood pressure was 200/150 mmHg, with urinary protein (+++). Enhanced MRI showed multiple cortical and subcortical abnormal signals in the bilateral frontal, temporal, parietal, and occipital lobes. Reversible posterior leukoencephalopathy syndrome caused by fruquintinib was considered. Then the drug was discontinued. After 2 days of symptomatic treatments such as oxygen therapy, blood pressure reduction, sedation, and antiepileptic therapy, the patient′s consciousness was improved, no limb convulsions occurred and her blood pressure was 130/80 mmHg. After 8 days of treatments, the patient′s condition stabilized and fruquintinib was given again after reducing the dosage. At an one month follow-up, MRI enhancement showed no significant abnormalities.

A 53-year-old female patient with stage Ⅳa colon cancer received 7 cycles of standard chemotherapy regimen. Due to the progression of the condition, she was treated with fruquintinib (5 mg once daily orally on day 1-21, 28 days as one cycle). After 20 days of treatments, the patient experienced sudden consciousness disorders, accompanied by limb convulsions. Her blood pressure was 200/150 mmHg, with urinary protein (+++). Enhanced MRI showed multiple cortical and subcortical abnormal signals in the bilateral frontal, temporal, parietal, and occipital lobes. Reversible posterior leukoencephalopathy syndrome caused by fruquintinib was considered. Then the drug was discontinued. After 2 days of symptomatic treatments such as oxygen therapy, blood pressure reduction, sedation, and antiepileptic therapy, the patient′s consciousness was improved, no limb convulsions occurred and her blood pressure was 130/80 mmHg. After 8 days of treatments, the patient′s condition stabilized and fruquintinib was given again after reducing the dosage. At an one month follow-up, MRI enhancement showed no significant abnormalities.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

OBJECTIVE To investigate the inhibitory effects of ursolic acid on interleukin-6 （IL-6）-mediated invasion and migration of breast cancer MDA-MB-231 cells （hereinafter referred to as “231 cells”）. METHODS The effects of 20， 40， 80， 160 and 320 µmol/L ursolic acid on the proliferation rate of 231 cells were measured by CCK-8 method. The breast cancer 231 cells were divided into control group， model group and administration group. The migration and invasion abilities of cells were detected by scratch assay and Transwell assay. Real-time quantitative polymerase chain reaction （q-PCR） assay and Western blot assay were used to detect the mRNA and protein expressions of epithelial-mesenchymal transition-related makers such as E cadherin （E-cad）， matrix metalloprotein 2 （MMP2）， MMP9， vimentin （Vim）， CD44 molecule （CD44） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）. The phosphorylation levels of JAK2 and STAT3 in the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway （in terms of p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio） were detected by Western blot assay. RESULTS A low concentration of ursolic acid of 20 µmol/L （no significant inhibitory effect on cell proliferation ability） was selected as the subsequent administration concentration. Compared with the control group， the migration and invasion abilities of cells in the model group were significantly enhanced （P＜0.05）； compared with the model group， the migration and invasion abilities of cells in the administered group were significantly reduced （P＜0.05）. Compared with the control group， the relative mRNA and protein expressions of epithelial-mesenchymal transition-related markers MMP9， MMP2， Vim， ALDH1A1 and CD44 were all elevated to different extents， and the mRNA and protein expressions of E-cad were all decreased to different extents in the model group cells， and part of the differences had statistical significance （P＜0.05）， the p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were significantly increased in the model group （P＜0.05）； compared with the model group， the expressions of the above indicators were reversed to some extent in the administration group. CONCLUSIONS Ursolic acid blocks the activation of JAK2/STAT3 signaling pathwby the inflammatory factor IL-6， which ultimately interrupts the invasion and metastasis of breast cancer cells.

A 69-year-old male patient with peripheral T-cell lymphoma received chemotherapy with intravenous doxorubicin liposome. In the first chemotherapy cycle, no obvious adverse reactions appeared. In the second chemotherapy cycle, the patient developed transient muscle soreness during the IV infusion of doxorubicin liposome. In the third chemotherapy cycle, dexamethasone and chlorphenamine were given to prevent anaphylaxis before doxorubicin liposome treatment and the infusion rate was controlled in a standardized way. However, at about 20 minutes of infusion, the patient developed nausea and vomiting. The infusion of doxorubicin was stopped immediately and replaced by IV infusion of 0.9% sodium chloride injection 250 ml. Then the patient developed facial numbness, laryngeal pain, neck discomfort, and multiple parts of skin rash with pruritus. The electrocardiogram monitoring showed heart rate 130 times/min, blood pressure 80/50 mmHg, and oxygen saturation 0.98. The patient was given oxygen inhalation and in half-lying position following the doctor′s advice, but the patient developed dyspnea, hoarseness, and slurred speech 20 minutes later. Physical examination showed the patient′s tongue was hypertrophic, his neck was swollen and thickened. Acute laryngeal edema induced by doxorubicin liposome was considered. Intravenous injection of dexamethasone 10 mg, IV infusion of 10% calcium gluconate, and aerosol inhalation of budesonide inhalation aerosol were given immediately and about 3 hours later, the symptoms gradually improved. Two days later, the allergic symptoms disappeared.

A 69-year-old male patient with peripheral T-cell lymphoma received chemotherapy with intravenous doxorubicin liposome. In the first chemotherapy cycle, no obvious adverse reactions appeared. In the second chemotherapy cycle, the patient developed transient muscle soreness during the IV infusion of doxorubicin liposome. In the third chemotherapy cycle, dexamethasone and chlorphenamine were given to prevent anaphylaxis before doxorubicin liposome treatment and the infusion rate was controlled in a standardized way. However, at about 20 minutes of infusion, the patient developed nausea and vomiting. The infusion of doxorubicin was stopped immediately and replaced by IV infusion of 0.9% sodium chloride injection 250 ml. Then the patient developed facial numbness, laryngeal pain, neck discomfort, and multiple parts of skin rash with pruritus. The electrocardiogram monitoring showed heart rate 130 times/min, blood pressure 80/50 mmHg, and oxygen saturation 0.98. The patient was given oxygen inhalation and in half-lying position following the doctor′s advice, but the patient developed dyspnea, hoarseness, and slurred speech 20 minutes later. Physical examination showed the patient′s tongue was hypertrophic, his neck was swollen and thickened. Acute laryngeal edema induced by doxorubicin liposome was considered. Intravenous injection of dexamethasone 10 mg, IV infusion of 10% calcium gluconate, and aerosol inhalation of budesonide inhalation aerosol were given immediately and about 3 hours later, the symptoms gradually improved. Two days later, the allergic symptoms disappeared.

Objective To explore the relationship among psychological flexibility,coping style and job burnout of nurses.Methods A total of 694 nurses from one district level grade A tertiary general hospital in Yunnan were assessed using acceptance and action questionnaire 2nd edition (AAQ-Ⅱ),simplified coping style questionnaire (SCSQ) and nursing burnout scale (NBS).The relationship among psychological flexibility,coping style and job burnout of nurses was analyzed using structural equation model and Bootstrap test.Results (1) Correlation analysis showed that the total scores of AAQ-Ⅱ (21.81 ± 8.23),job burnout (22.71 ± 6.60) and its three dimensions including emotional exhaustion (8.93 ± 2.87),depersonalization (6.64±2.30)as well as reduced personal accomplishment(7.14±2.52) were positively correlated with negative coping dimension of coping style (10.86±4.99) (r=0.324-0.510,all P＜0.01),while negatively correlated with positive coping dimension(26.44±5.86) (r=-0.102--0.143,all P＜0.01).(2) Structural equation model analysis showed that positive and negative coping dimension had partial mediating effects on the relationship between psychological flexibility and job burnout (x2/df=2.30,GFI =0.91,AGFI =0.90,NFI=0.90,IFI=0.93,TLI=0.92,CFI=0.93,RMSEA=0.04).(3) Bootstrap test showed that the mediating effect sizes for positive and negative coping were 3.8％ and 8.9％ respectively and totally mediating effect size of coping style was 12.7％.Psychological flexibility had much larger effects on job burnout,and the direct effect size was 87.3％.Conclusion Coping style plays a mediating role in the relationship between psychological flexibility and job burnout,but its effect is less important.Psychological flexibility plays a major role and more directly influences on job burnout.