OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Objective: To explore the longitudinal correlation between smartphone multitasking and depressive symptoms, so as to provide an evidence based basis for promoting the mental health of college students. Methods: A total of 967 college students were recruited from one university in Taiyuan, Chongqing, and Shenzhen cities, China, by using multi stage randomized cluster sampling from October to December 2021 at baseline, and a follow up survey was conducted in May 2022. Smartphone multitasking behaviors were assessed by means of the Assessment of Smartphone Multitasking for Adolescents (ASMA), and depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) among college students. Chi square tests were performed to compare the differences in depressive symptoms between different groups of demographic characteristics, and binary Logistic regression models were employed to analyze the associations between smartphone multitasking and depressive symptoms among college students. Results: The rates of depressive symptoms among college students at baseline and follow up were 35.2% and 42.3%, respectively. Compared to the low level smartphone multitasking index group at baseline, the moderate and high level groups were more likely to experience depressive symptoms at baseline (moderate level group: OR=1.74, 95%CI =1.22-2.50, high level group: OR=2.77, 95%CI =1.94-3.95) and followup (moderate level group: OR=1.41, 95%CI =1.01-1.95, high level group: OR=1.64, 95%CI =1.17-2.29) ( P <0.05). In addition, compared to the persistently low smartphone multitasking index, increased risk of depressive symptoms was associated with maintaining a moderate to high ( OR=2.94, 95%CI =1.83-4.71), and a higher ( OR=2.07, 95%CI =1.31-3.27) or lower smartphone multitasking index ( OR=2.02, 95%CI =1.27-3.19) ( P <0.05). Moreover, higher smartphone multitasking index scores were positively associated with the risk of new-onset depressive symptoms at follow up ( OR=1.87, 95%CI=1.07-3.27, P <0.05). Conclusions Smartphone multitasking behaviors are find to be associated with an increased risk of depressive symptoms in college students. There is a need to reduce smartphone multitasking in order to decrease depressive symptoms and promote students mental health.

Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods In this prospective study, adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumor tissues were detected by ADx-amplification refractory mutation system (ADx-ARMS). EGFR mutations of plasma free tumor DNA were detected by ADx-ARMS and ADx-super amplification refractory mutation system (ADx-SuperARMS) at the same time. Patients with EGFR-mutant in tumor tissues and receiving EGFR-TKIs were finally enrolled. Plasma mutation-positive patients with both methods were high abundance group.Patients with positive mutations by ADx-SuperARMS but negative by ADx-ARMS were medium abundance group. Mutation-negative patients with both methods were recognized as low abundance group. The correlation between EGFR mutation abundance and clinical response to EGFR-TKIs were analyzed. Results Among 71 patients enrolled, 42 harbored EGFR mutations in plasma were detected by ADx-ARMS, while 53 were found by ADx-SuperARMS.There were 42 patients in high abundance group, 11 in medium group while the other 18 in low group. The objective response rates (ORRs) were 69.0%,7/11 and 10/18 in high, medium and low groups, respectively. The difference was significant between high and low abundances groups (P=0.006). Median progression-free survival (PFS) in high,medium and low groups were 11.0, 8.5 and 9.0 monthes, respectively (P<0.001). In patients with tumor 19-Del, the ORRs were 70.4%,5/7 and 6/11 in high,medium and low abundance groups, respectively. The median PFS of high abundance group was significantly longer than the other two groups (12.0 monthes vs 9.0, 9.0 monthes). As to subjects with L858R mutation, the ORRs were 10/15,2/4 and 3/6,respectively, with median PFS 9.6, 5.5 and 9.5 monthes. Conclusions The relative abundance of EGFR mutations in plasma predicts clinical response to EGFR-TKIs in patients with advanced lung adenocarcinoma. The higher the mutation abundance is, the better the efficacy of EGFR-TKIs is.

Objective: To observe the effect of internal limiting membrane peeling and transplantation on vision-related quality of life in refractory macular hole. Methods: A retrospective clinical study. Thirty patients (30 eyes) with refractory macular hole diagnosed in Ophthalmology Department of The First Affiliated Hospital of Nanjing Medical University from January to December 2016 were included in this study. There were 13 males (13 eyes) and 17 females (17 eyes), with the mean age of 57.3±6.9 years. There were 15 patients(15 eyes) with large macular diameter, 12 patients (12 eyes) with high myopia macular hole, and 3 patients (3 eyes) with secondary traumatic macular hole. The BCVA examination was performed using the Snellen visual acuity chart, which was converted into logMAR visual acuity. OCT was performed to measure the macular retinal thickness (CRT), base diameter and minimum diameter of macular hole. Then, the macular hole index(MHI) was calculated. The logMAR BCVA was 1.52±0.30, MHI was 0.51±0.19. The Chinese version of visual-related quality of life scale-25 (CVRQoL-25) was used to evaluate the vision-related quality of life of patients. The CVRQoL-25 score was 57.60±7.13. All patients underwent 23G vitrectomy combined with inner limited membrane peeling and autologous ILM transplantation. The follow-up was at least 3 months after surgery. The changes of BCVA, MHI, CRT and CVRQoL-25 score before and after surgery were comparatively analyzed. Paired t test was performed to compare the measurement data before and after surgery, and Spearman rank correlation analysis was used for the correlation analysis among the parameters. Results: At 3 months after surgery, the hole closure was detected in 28 eyes (93.3%), not detected in 2 eyes (6.7%). The logMAR BCVA was 1.16±0.33, CRT was 161.00±15.26, and CVRQoL-25 scores was 70.83±9.77. Compared with before surgery, the BCVA (t=4.386, P=0.000) and CVRQoL-25 score (t=-5.991, P=0.000) after surgery were improved. Spearman rank correlation analysis showed that CVRQoL-25 score was negatively correlated with preoperative and postoperative logMAR BCVA (r=−0.536, −0.796; P=0.002, 0.000); positively correlated with preoperative MHI (r=0.421, P=0.020) and postoperative CRT (r=0.589, P=0.001). Conclusion Internal limiting membrane peeling and transplantation for refractory macular hole can significantly improve the vision-related quality of life and visual acuity, while achieved a high hole closure rate (93.3%).

Objective To explore the effect of Jianbu-Huqian ointment combined with proximal femoral nail antirotation for the elderly patients with intertrochanteric fracture of femur with osteoporosis. Methods A total of 85 elderly patients with intertrochanteric fracture of femur with osteoporosis were randomly divided into the control group (40 patients) and the observation group (45 patients. Both groups of patients were treated with proximal femoral nail antirotation, and the observation group was added with Jianbu-Huqian ointment. The pain, fracture healing, joint function, bone mineral density and complications were compared between the two groups. Results The VAS pain score at 1st week (6.2 ± 1.6 vs. 7.9 ± 1.6; t=3.683, P<0.05), 3rd week (3.1 ± 1.1 vs. 5.4 ± 1.4; t=4.239, P<0.05) and 7th week (2.3 ± 0.9 vs. 4.0 ± 1.3; t=3.571, P<0.05) after operation of the observation group were significantly lower than those of the control group. The occurrence time (42.4 ± 5.9 d vs. 49.2 ± 6.2 d; t=4.139, P<0.05), walking time (6.9 ± 1.1 weeks vs. 8.7 ± 1.2 weeks;t=3.695, P<0.05), fracture healing time (13.9 ± 2.2 weeks vs. 16.2 ± 3.1 weeks, t=3.473, P<0.05) of the observation group were significantly lower than those of the control group. Harris hip score (89.8 ± 7.21 vs. 81.4 ± 5.93; t=3.728, P<0.05) in the observation group was significantly higher than that in the control group. The bone density of the femur (0.782 ± 0.142 g/cm2 vs. 0.691 ± 0.135 g/cm2; t=3.759, P<0.05) and the area of ward (0.628 ± 0.071 g/cm2 vs. 0.513 ± 0.059 g/cm2; t=4.386, P<0.05) of the observation group were significantly lower than those of the control group. The incidence of postoperative complications in the observation group was 15.0%(6/40), and the control group was 37.8% (17/45). The difference was statistically significant (χ2=5.567, P<0.05). Conclusions The Jianbu-Huqian ointment combined with proximal femoral nail antirotation could reduce the pain, promote fracture healing, and prevent the occurrence of postoperative complications for the elderly patients with intertrochanteric fracture of femur with osteoporosis.

Objective To explore the feasibility of novel nano-particle HIF-1 α@Fe3 O4 labeled pancreatic cancer PANC1 cells as well as the changes of signal intensity in 3.0T MRI scan.Methods Pancreatic cancer PANC1 cells were cultured in hypoxia condition,and hypoxia-inducible-factor-1 α(HIF-1 α) and stem cell markers CD133,Oct-4,Sox-2 were detected by Western blot assay.Cells cultured under hypoxia for 24 h were collected and then co-incubated with 5,15 and 45 μg/ml HIF-1α@Fe3O4 for 24 h.The number of HIF-1 α@Fe3O4 labeled PANC1 cells and cell survival rate were detected,and the signal intensity of T2 WI image for PANC1 cells was measured by a 3.0T MRI system.Results In hypoxia condition,HIF-1 α level was obviously increased compared with that of normoxic culture,which was further increased with the increase of hypoxia time(all P ＜ 0.05).Stem-cell markers CD133,Oct-4 and Sox-2 was positively correlated with HIF-1α level.Co-cultured with different concentrations of HIF-1α@Fe3O4 for 24 h,blue-stained iron particles in cytoplasm of PANC1 cells was dosage-dependently increased,and the peak was at the concentration of 45 μg/ml,which could reach 100％.The survival rate of the PANC1 cells cultured in normoxic condition,the unlabeled and labeled in hypoxic condition group were(87.0 ± 2.1) ％,(84.7 ± 2.7) ％ and (85 ± 3.8) ％,respectively,and the difference was not statistically significant (P ＞ 0.05).In 3.0T MRI scan,T2 WI signal intensity in unlabeled group and 5,15 and 45 μg/ml labeled group was 1.017 ± 0.046,0.793 ± 0.041,0.447 ± 0.032 and 0.240 ± 0.031,and the difference was not statistically significant (F =80.0,P ＞ 0.05).Conclusions Hypoxia condition could promote and maintain the stemness in PANC1 cells.HIF-1α@Fe3O4 probe could successfully label HIF-1α highly expressed PANC1 cells during hypoxia condition,and a significant decrease in T2WI signal intensity can be detected by a 3.0T MRI system.

Background Choroidal neovascularization (CNV) is one of the primary causes leading to visual damage in many fundus diseases.Many evidences indicate that macrophage activation and monocyte chemoattractant protein-1 (MCP-1) play important roles in CNV.However, the dynamic expression of macrophage and MCP-1 in the initial stage of CNV is not clear.Objective This study was to investigate the dynamic changes of F4/80 and MCP-1 expressions in retina-choroid tissue with experimental CNV.Methods Laser-induced CNV models were monocularly established in 105 SPF 8-week-old male wild type C57BL/6 mice.The mice were sacrificed at 6,12,24, 48 and 72 hours after photocoagulation, respectively, and the retina-choroid tissue sections and choroidal flatmounts were prepared.The histopathological examination was carried out to observe the changes of morphology and structure as well as inflammatory response in CNV.The expression and distribution of F4/80 and MCP-1 protein in retinachoroid were detected by double immunofluorescence technique.The expression and distribution of F4/80 in choroid were examined by immunofluorescence.The relative expression levels of F4/80 mRNA and the content of MCP-1 protein in RPE-choroid complex were assayed using real-time quantitative PCR and ELISA,respectively.The use and care of the mice complied with the Regulation for the Administration of Affair Concerning Experimental Animals by Ethic Committee of Experimental Animals of Nanjing Medical University.Results The rupture of Bruch membrane, RPE, outer nuclear layer and choroid was exhibited under the optical microscope 6 hours after photocoagulation.Infiltration of inflammatory cells and tissue edema were seen as the lapse of photocoagulation time, and proliferation of vascular endothelial cells was found 72 hours after photocoagulation.F4/80 was expressed in photocoagulation area 6 hours later, and MCP-1 was expressed around the area.With the lapse of photocoagulation time,the expression intensity of MCP-1 weakened and that of F4/80 enhanced.The contents of MCP-1 protein in RPE-choroid complex were (31.25±4.73), (276.31 ±4.20), (331.95 ±5.86), (221.24±4.42), (179.89 ± 4.10) and (130.80 ± 5.90) pg/mg in the normal control group, photocoagulation 6-, 12-, 24-, 48-and 72-hour groups, respectively,with a significant difference among the groups (F=1 416.46 ,P＜0.01).The contents of MCP-1 protein peaked at 12 hours after photocoagulation and then gradually declined.The expression levels of MCP-1 protein in different time groups were higher than those in the normal control group (all at P＜0.01).A significant difference in F4/80 mRNA expression in RPE-choroid complex was also found among the groups (F =762.72, P＜0.01, and a gradually raising tendency was seen over time, showing evidently increase in comparison with the normal control group (all at P＜0.01).Conclusions Inflammatory response occurs in the early stage of experimental CNV.MCP-1 responds to the CNV at early stage,and the accumulation and activation of macrophage play an important role in the development of CNV.

Background and objectiveIncidence and mortality rates of lung cancer are rising sharply. Small cell lung cancer patients prefer chemotherapy than surgery because of the insigniifcant side effects of Chinese medicine. Studies have shown that solasonine possesses an anti-tumor property. hTe aim of this study is to investigate the effect of solasonine on the apoptosis of lung cancer cell line H446.MethodsAppropriate concentration and time were selected with a CCK8 kit. hTe drug that was used in H446 cells was divided into four different concentrations: 0 μmol/L, 3.4 μmol/L, 6.8 μmol/L and 13.6 μmol/L. hTe changes in forms and nucleus of H446 cells that were stained with DAPI were observed under an inverted optical microscope. hTe effects on H446 cell apoptosis were detected by FCM. hTe changes in apoptosis-related proteins BCL2, BAX, and CASP3 were investigated using Western blot for 24 h.Results Solasonine reduced the survival ratio of H446 cells and in-hibited the proliferation with a dose-related effect. hTe survival ratio of H446 cells could be reduced to 16.77% (P<0.001), and the highest apoptosis ratio was 44.62% (P<0.001). Apoptosis was observed in H446 cells. Moreover, Western blot showed that the apoptosis-related proteins BAX and CASP3 were upregulated (P<0.05).ConclusionhTe proliferation of H446 cells can be inhibited by solasonine, and the expression of pro-apoptotic proteins is up-regulated, and the expression of anti-apoptotic proteins is down-regulated, thereby promoting the apoptosis of cells.