Objective To investigate the effect and mechanism of shikonin on the proliferation,migration,invasion and apoptosis of human gastric cancer MGC803 cells.Methods The MGC803 cells in the logarithmic growth phase were randomly divided into the blank control group,shikonin group,shikonin+insulin-like growth factor-1(IGF-1)group,and shikonin+LY294002 group.Cells in the blank control group were cultured in drug-free medium,cells in the shikonin group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1,cells in the shikonin+IGF-1 group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1 and IGF-1 with a final concentration of 10 μmol·L-1,and cells in the shikonin+LY294002 group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1 and LY294002 with a final concentration of 30 μmol·L-1.After 24 h of culture,the cell proliferation was detected by cell counting kit-8,the cell apoptosis was detected by flow cytometry,the cell migration was detected by scratch assay,and the cell invasion was detected by Transwell assay.The expression levels of B cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax),cytochrome C(Cyt C),cleaved caspase-3,cleaved caspase-9,phosphoinositide 3 kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(PKB),and phosphorylated PKB(p-PKB)proteins were measured by using Western blot.Results The MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin group were significantly higher than those in the blank control group(P＜0.05);the MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin+IGF-1 group were significantly lower than those in the shikonin group(P＜0.05);and the MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin+LY294002 group were significantly higher than those in the shikonin group(P＜0.05).The MGC803 cell scratch healing rate and the number of invasive cells in the shikonin group were significantly lower than those in the blank control group(P＜0.05);the MGC803 cell scratch healing rate and the number of invasive cells in the shikonin+IGF-1 group were significantly higher than those in the shikonin group(P＜0.05);and the MGC803 cell scratch healing rate and the number of invasive cells in the shikonin+LY294002 group were significantly lower than those in the shikonin group(P＜0.05).The relative expression level of Bcl-2 protein in MGC803 cells in the shikonin group was significantly lower than that in the blank control group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly higher than those in the blank control group(P＜0.05);the relative expression level of Bcl-2 protein in MGC803 cells in the shikonin+IGF-1 group was significantly higher than that in the shikonin group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly lower than those in the shikonin group(P＜0.05);and the relative expression level of Bcl-2 protein in MGC803 cells in the shikonin+LY294002 group was significantly lower than that in the shikonin group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly higher than those in the shikonin group(P＜0.05).The relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin group were significantly lower than those in the blank control group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin group and the blank control group(P＞0.05);the relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin+IGF-1 group were significantly higher than those in the shikonin group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin+IGF-1 group and the shikonin group(P＞0.05);and the relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin+LY294002 group were significantly lower than those in the shikonin group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin+LY294002 group and the shikonin group(P＞0.05).Conclusion Shikonin can inhibit the proliferation,migration and invasion and promote the apoptosis of human gastric cancer MGC803 cells,which may be related to its inhibition of the PI3K/PKB signaling pathway.

T cells play an essential role in adaptive immunity,and the specific recognition of antigens by T cell receptors(TCRs)is the key in initiating anti-tumor and antiviral immune responses.Recent studies have demonstrated that force plays an important regulatory role in T cell immune responses,laying the foundation for the emerging field of mechanoimmunology.In this review,the mechanisms by which force assists TCRs in distinguishing between specific antigens and non-specific antigens,as well as the critical role force plays in initiating TCR transmembrane signaling and triggering T cell activation are mainly discussed.The novel biophysical single-molecule tools and advanced imaging techniques that can deeply reveal the importance of mechanical forces at the molecular and/or cellular level are summarized.Based on the research results of domestic and foreign expert teams,combined with the research work of our team,this review summarizes and discusses the role of force in T cell function,so as to provide a system framework for deeply understanding the cutting-edge hotspots in the field of mechanoimunology and exploring new research directions.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To implement an intervention with community-dwelling middle-aged and elderly people through a new science promotion approach, and to evaluate changes in the level of bone health awareness.Methods:From April 2017 to June 2017, 200 community-dwelling middle-aged and elderly people aged 50 years and over were randomly included.They were divided into the intervention group receiving a new science promotion intervention(n=100, with 50 males and 50 females)and the control group(n=100, with 50 males and 50 females). Baseline and follow-up assessments of bone health awareness were performed before and after the one-year intervention.A questionnaire survey on preferences for different types of science promotion articles in WeChat accounts was conducted.Differences in scores for intervention effects before and after intervention were compared between the two groups.Potential influencing factors for the scale score were examined by a multi-factor analysis.Results:After one year of intervention, scores for intervention effects were higher in the intervention group than in the control group( P<0.001). In the intervention group, scores were higher after intervention than before intervention( P<0.001). In the control group, scores after follow-up were slightly higher than those at baseline(29.4±11.4 vs.27.9±10.1, P<0.001). The increase in scores before and after intervention was greater in the intervention group than in the control group( P<0.001). Baseline score, group designation, history of drinking and diabetes impacted the scores in middle-aged and elderly women, while other factors did not.Most middle-aged and older people preferred texts illustrated with pictures, and older people were more receptive to videos. Conclusions:The new science promotion method is beneficial to bone health management, can improve bone health awareness in middle-aged and elderly people.

Objective To compare the clinical outcomes of selective artery (SAC) with main artery (MAC) clamping of robotic partial nephrectomy (RPN) in patients with early-stage (cTiN0M0) renal masses.Methods Between October 2016 and September 2018,a total of 343 cT1 renal mass patients receiving RPN with SAC (n =21) or MAC (n =322) in our center,were retrospectively analyzed.There were 13 males and 8 females in SAC group with a mean age of (53.1 ± 10.6) years old,mean tumor size of (2.5 ±0.7)cm,and mean R.E.N.A.L.score of 6.2 ± 1.5.There were 149 males and 173 females in MAC group,with a mean age of (51.6 ± 12.3) years old,mean tumor size of(3.5 ± 1.4)cm,and mean R.E.N.A.L.score of 7.9 ± 1.6.There was statistical significance between two groups in tumor size and R.E.N.A.L score(P ＜ 0.001).The group covariates were balanced through propensity score matching (PSM) using 1:2 nearest neighbor matching method.After matching,mean age,tumor size,R.E.N.A.L.score and preoperative eGFR in the SAC and MAC groups were (3.1 ± 10.6) vs.(52.7 ± 10.2) years,(2.5 ± 0.7) vs.(2.6±0.7) cm,6.2 ±1.5 vs.6.2 ±0.9,and (101.7 ± 19.8)vs.(101.6 ±20.3) ml/(min · 1.73m2),respectively (P ＞ 0.05).Perioperative outcomes and follow-up data were compared between the two matched groups.Results There was no significant differences resulted regarding operating time [(127.0 ±54.8)min vs.(130.0 ±49.9) min],blood loss[(166.0 ± 173.5)ml vs.(124.0 ± 101.0)ml],ischemia time [(18.9 ± 6.4) vs.(18.1 ± 5.8) min],hospital stay [(8.7 ± 3.4) d vs.(8.5 ± 2.5) d],incidences of complications (28.6％ vs.19.0％),surgical conversions (0 vs.2.4％),transfusions (4.8％ vs.2.4％) or positive surgical margin(0 vs.0) and malignant pathological outcomes(95.2％ vs.92.9％).The follow-up durations ranged from 3 to 24 months with a mean duration of 9.1 and 12.4 months in SAC and MAC,respectively.At the end of follow-up,the two groups had similar decrease in estimated glomerular filtration rate [(7.5 ± 17.2) ％ vs.(12.1 ± 18.2) ％,P =0.466],but the difference was statistically significant with ECT-GFR both of function reduction in the operated kidney [(21.6 ± 14.6) ％ vs.(38.4 ± 20.7)％,P =0.001] and in two kidneys [(2.5 ±16.4)％ vs.(14.8 ±20.0)％,P =0.002].Conclusions Robotic partial nephrectomy with selective vascular control lead to better postoperative renal function compared with main vascular clamped PN techniques and does not lead to a higher surgical risk following a strict patient selection criteria.

Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To explore the clinical utilization value of regional blood flow fluorescence visualization in selective arterial clamping robotic partial nephrectomy.Methods 12 cases of robotic partial nephrectomy with indocyanine green-based regional blood flow fluorescence visualization selective arterial clamping between October 2016 and June 2017 by our team were retrospectively analyzed.There were 9 males and 3 females with age between 36-78 years,mean age(51.2 ± 11.0) years,BMI 20.1-36.2 kg/m2,mean of (25.6 ± 4.8) kg/m2,tumor diameter 2.0-5.1 cm,mean of(3.3 ± 0.9) cm,and R.E.N.A.L.score 4-10,mean(7.3 ± 2.0).Preoperative renal function status of eGFR (estimated glomerular filtration rate) was 82-133 ml/(min · 1.73 m2),mean (101.9 ± 13.7)ml/(min · 1.73 m2) and split ECT-GFR of 44.5-70.6 ml/min,mean of(53.8 ± 8.5) ml/min in operated kidney;48.2-71.1 ml/min,mean of(56.8 ±6.8) ml/min in contralateral kidney;in total,92.7-139.1 ml/min,mean of(109.8 ± 14.6)ml/min.Perioperative information including operative time,blood loss,warm ischemia time,surgical complications,pathologic outcomes and follow-up data of included patients were analyzed.Results All procedures were done smoothly without open or radical conversion,with operative time of 95-203 min,mean of (170.6 ±38.6)min,and estimated blood loss of 60-1 000 ml,mean of(178.3 ± 206.9)ml.According to the visualize uptake of fluorescence imaging perfusion area visualization after selective arterial clamping,1 case underwent unclamping robotic partial nephrectomy,1 case converted to main renal artery clamping with warm ischemia time of 18 min,10 cases performed via renal arterial branch clamping with an average ischemia time of (25.5 ± 10.5) (range 17-46)min,1 of which due to parenchymal bleeding obscuring visualization necessitated clamping of the main renal artery with 1000 ml blood loss,46 min of arterial branch occlusion and 16 min of main artery clamping.The average postoperative hospital stay was (5.8 ± 0.9) (range 5-8)days,and the duration of drainage was (3.5 ± 0.5) (range 3-4) days.No postoperative complications occurred.Postoperative pathology:all margins were all negative,11 cases of clear cell carcinoma,eosinophilic adenoma in 1 case.The average eGFR of 9 cases of renal arterial branch clamping was (94.5 ±22.5)(range 56-140)ml/(min · 1.73 m2) at discharge with a 5％ percentage decrease versus preoperative level.Among them,4 cases obtained with ECT-GFR data 1 month postoperatively had a mean of(37.6 ±13.2)(range 20.8-55.8) ml/min with 29％ percentage decrease on the surgical side,an average of (58.5 ± 6.9) (range 51.2-68.4) ml/min with 2％ compensatory increase of the contralateral side,and (98.7 ± 16.2) (range 79.3-124.3) ml/min in total with a 10.4％ overall decrease.Conclusions The visualization of blood flow imaging based on indocyanine green fluorescence can clearly and intuitively show the effect of branching arterial occlusion in robotic partial nephrectomy,guide the optimization of surgical resection strategy,and improve safety and clinical outcome.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.