1.Efficacy of intermittent theta burst stimulation therapy in treating persistent negative symptoms of schizophrenia and its relationship with changes in peripheral blood inflammatory markers
Sisi CHEN ; Shuyan TONG ; Zhu TONG ; Wanlong LI ; Hanqing SHI ; Lei YAO ; Chao ZHOU ; Xiangrong ZHANG
Sichuan Mental Health 2026;39(4):295-302
BackgroundNegative symptoms of schizophrenia impose a substantial burden on society, and the current antipsychotic drugs have limited efficacy in treating these symptoms. Intermittent theta burst stimulation (iTBS), as a novel neuromodulation technique, shows potential therapeutic promise. However, the evidence for its efficacy in treating negative symptoms of schizophrenia and its relationship with associated immuno-inflammatory changes remain to be further elucidated. ObjectiveTo investigate the efficacy of iTBS targeting the left dorsolateral prefrontal cortex (L-DLPFC) on persistent negative symptoms of schizophrenia, and to analyze its relationship with changes in peripheral blood inflammatory markers, so as to provide references for the clinical application of iTBS in treating persistent negative symptoms and to offer clues for further research into its potential biological mechanisms. MethodsA randomized, double-blind, sham-controlled clinical trial was conducted. A total of 60 patients with schizophrenia who were hospitalized at Xuzhou Oriental Peopple's Hospital from February 20, 2024 to May 10, 2025 were consecutively enrolled. All patients met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and fulfilled the criteria for persistent negative symptoms. Participants were randomly assigned into the study group and the control group, with 30 patients in each group. The two groups respectively received 20 sessions of either active iTBS or sham stimulation over a 4-week period. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at the baseline, the end of treatment, and 3 months after treatment. Peripheral blood inflammatory markers were measured at the baseline and at the end of treatment, including white blood cell count, platelet count, neutrophil count, lymphocyte count, and monocyte count, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were also calculated. A linear mixed model was used to compare PANSS scores between the two groups. Spearman correlation analysis was performed to examine the association between reductions in inflammatory markers at the end of treatment and reductions in PANSS negative symptom subscale scores, with body mass index (BMI) and chlorpromazine-equivalent dose as covariates. Results①The time-group interaction effect for the PANSS negative symptom subscale score was statistically significant (F=5.410, P<0.01). At the end of treatment and 3 months after treatment, the study group had significantly lower scores on the PANSS negative symptom subscale than the control group (P<0.01). ② At the end of treatment, group differences in reduction scores for neutrophil count, NLR, and PLR were significant (Z=-2.262, -2.048, -2.070, P<0.05). However, after FDR correction, the between-group differences in reductions in peripheral blood inflammatory markers were no longer statistically significant (P>0.05). ③ After adjusting for BMI and chlorpromazine equivalents, the reduction in PANSS negative symptom subscale scores was positively correlated with the reduction in neutrophil count in the study group (rs=0.382, P=0.045). ConclusioniTBS targeting the L-DLPFC may be beneficial in improving persistent negative symptoms of schizophrenia, and its clinical efficacy may be associated with changes in neutrophil count. [Funded by National Natural Science Foundation of China (number, 82371510); Social Development Project of Jiangsu Province (number, BE2023668). www.chictr.org.cn number, ChiCTR2500101060]
2.Clinical study of Hewei Jiangni Formula in patients with non-erosive gastroesophageal reflux disease and cold-heat complex syndrome
Shuangyuan ZHANG ; Hanqing CHEN ; Junxiang LI ; Tangyou MAO ; Lei SHI ; Zhengdao LIN ; Chuchu XUE ; Xiaohong LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1107-1114
Objective To observe and analyze the clinical efficacy of Hewei Jiangni Formula in treating patients with non-erosive gastroesophageal reflux disease(NERD)and cold-heat complex syndrome and explore its regulatory mechanism on visceral hypersensitivity.Methods Sixty patients with NERD and cold-heat complex syndrome diagnosed at the Gastroenterology Clinic of Dongfang Hospital,Beijing University of Chinese Medicine from January 2021 to Decemer 2023,were randomly divided into the Hewei Jiangni Formula group and omeprazole group,with 30 patients per group.The Hewei Jiangni Formula group was treated with Hewei Jiangni Formula and omeprazole enteric-coated tablets placebo,whereas the omeprazole group was treated with omeprazole enteric-coated tablets and Hewei Jiangni Formula placebo.The treatment period was scheduled to last for 8 weeks.The primary outcome indicators(Gastroesophageal Reflux Disease Quality of Life Questionnaire(GERD-Q)scale score:response rate,total score,and single symptom score)and secondary outcome indicators(traditional Chinese medicine clinical scores scale)were recorded before and after treatment in both groups.Ten healthy individuals were recruited from the Physical Examination Center of Dongfang Hospital,Beijing University of Chinese Medicine,as the healthy control group.The expression levels of mast cell tryptase(MCT),protease-activated receptor 2(PAR2),transient receptor potential vanilloid 1(TRPV1),substance P(SP),calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and 5-hydroxytryptamine 3 receptor(5-HT3R)were recorded.These indicators were then used for the following comparisons:the NERD patients vs.the healthy group before treatment;the Hewei Jiangni Formula group vs.the omeprazole group after treatment;the intra-group comparisons within both NERD groups.Changes in serum levels of these indicators were observed before and after treatment in both NERD groups.Results According to the GERD-Q scores before and after treatment,the effective rate was 90.00%in the Hewei Jiangni Formula group and 86.67%in the omeprazole group,with no significant differences.Both groups exhibited improved symptoms of heartburn,regurgitation,upper abdominal pain,and sleep disorders caused by heartburn or regurgitation(P<0.05);however,neither group exhibited significantly improved nausea(P>0.05).Before treatment,MCT,PAR2,TRPV1,SP,CGRP,5-HT,and 5-HT3R expression levels in both NERD groups were significantly higher than those in the healthy control group(P<0.05).After treatment with Hewei Jiangni Formula or omeprazole enteric-coated tablets,the expression levels of these indicators decreased in both groups(P<0.05).The omeprazole group was superior to Hewei Jiangni Formula in reducing 5-HT3R expression(P<0.05).Conclusion Hewei Jiangni Formula significantly improves the symptoms of patients with NERD and cold-heat complex syndrome,with efficacy comparable to that of omeprazole enteric-coated tablets.It is superior to omeprazole in improving symptoms of spleen yang deficiency,such as loss of appetite,fatigue,borborygmus with loose stools,and cold extremities.Hewei Jiangni Formula reduces MCT,PAR2,TRPV1,SP,CGRP,5-HT,and 5-HT3R expression levels,regulates related signaling pathways,and alleviates visceral hypersensitivity.
3.Clinical study of Hewei Jiangni Formula in patients with non-erosive gastroesophageal reflux disease and cold-heat complex syndrome
Shuangyuan ZHANG ; Hanqing CHEN ; Junxiang LI ; Tangyou MAO ; Lei SHI ; Zhengdao LIN ; Chuchu XUE ; Xiaohong LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1107-1114
Objective To observe and analyze the clinical efficacy of Hewei Jiangni Formula in treating patients with non-erosive gastroesophageal reflux disease(NERD)and cold-heat complex syndrome and explore its regulatory mechanism on visceral hypersensitivity.Methods Sixty patients with NERD and cold-heat complex syndrome diagnosed at the Gastroenterology Clinic of Dongfang Hospital,Beijing University of Chinese Medicine from January 2021 to Decemer 2023,were randomly divided into the Hewei Jiangni Formula group and omeprazole group,with 30 patients per group.The Hewei Jiangni Formula group was treated with Hewei Jiangni Formula and omeprazole enteric-coated tablets placebo,whereas the omeprazole group was treated with omeprazole enteric-coated tablets and Hewei Jiangni Formula placebo.The treatment period was scheduled to last for 8 weeks.The primary outcome indicators(Gastroesophageal Reflux Disease Quality of Life Questionnaire(GERD-Q)scale score:response rate,total score,and single symptom score)and secondary outcome indicators(traditional Chinese medicine clinical scores scale)were recorded before and after treatment in both groups.Ten healthy individuals were recruited from the Physical Examination Center of Dongfang Hospital,Beijing University of Chinese Medicine,as the healthy control group.The expression levels of mast cell tryptase(MCT),protease-activated receptor 2(PAR2),transient receptor potential vanilloid 1(TRPV1),substance P(SP),calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and 5-hydroxytryptamine 3 receptor(5-HT3R)were recorded.These indicators were then used for the following comparisons:the NERD patients vs.the healthy group before treatment;the Hewei Jiangni Formula group vs.the omeprazole group after treatment;the intra-group comparisons within both NERD groups.Changes in serum levels of these indicators were observed before and after treatment in both NERD groups.Results According to the GERD-Q scores before and after treatment,the effective rate was 90.00%in the Hewei Jiangni Formula group and 86.67%in the omeprazole group,with no significant differences.Both groups exhibited improved symptoms of heartburn,regurgitation,upper abdominal pain,and sleep disorders caused by heartburn or regurgitation(P<0.05);however,neither group exhibited significantly improved nausea(P>0.05).Before treatment,MCT,PAR2,TRPV1,SP,CGRP,5-HT,and 5-HT3R expression levels in both NERD groups were significantly higher than those in the healthy control group(P<0.05).After treatment with Hewei Jiangni Formula or omeprazole enteric-coated tablets,the expression levels of these indicators decreased in both groups(P<0.05).The omeprazole group was superior to Hewei Jiangni Formula in reducing 5-HT3R expression(P<0.05).Conclusion Hewei Jiangni Formula significantly improves the symptoms of patients with NERD and cold-heat complex syndrome,with efficacy comparable to that of omeprazole enteric-coated tablets.It is superior to omeprazole in improving symptoms of spleen yang deficiency,such as loss of appetite,fatigue,borborygmus with loose stools,and cold extremities.Hewei Jiangni Formula reduces MCT,PAR2,TRPV1,SP,CGRP,5-HT,and 5-HT3R expression levels,regulates related signaling pathways,and alleviates visceral hypersensitivity.
4.Effects of long-term exposure to ambient fine particulate matter on diabetes mellitus and the moderating effects of diet
Jinxia WANG ; Yunhao SHI ; Dongshuai WANG ; Xuehao DONG ; Hanqing ZHANG ; Sijie ZHOU ; Yi ZHAO ; Yuhong ZHANG ; Yajuan ZHANG
Journal of Environmental and Occupational Medicine 2024;41(3):259-266
Background Long-term exposure to ambient fine particulate matter (PM2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM2.5 exposure. Objective To investigate the association between long-term exposure to PM2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM2.5 was (38.10±4.67) μg·m−3. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L−1 for each 1 μg·m−3 increase in PM2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L−1 in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM2.5 concentration showed that the risks of diabetes were increased in the low PM2.5 pollution-low vegetable intake frequency group and the high PM2.5 pollution-low vegetable intake frequency group compared with the low PM2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM2.5 pollution and low fruit intake frequency than in participants with low PM2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM2.5 on diabetes. Conclusion Long-term exposure to ambient PM2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM2.5.
5.Individual and interactive effects of atmospheric PM2.5 and O3 on mortality of circulatory system diseases in Ningxia
Dongshuai WANG ; Xuehao DONG ; Jinxia WANG ; Yunhao SHI ; Hanqing ZHANG ; Sijie ZHOU ; Yajuan ZHANG
Journal of Environmental and Occupational Medicine 2024;41(1):25-33
Background The impact of atmospheric fine particulate matter (PM2.5) and ozone (O3) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM2.5 and O3 can affect population health is rarely reported and requires study. Objective To investigate the individual and interactive impacts of atmospheric PM2.5 and O3 on the mortality of circulatory system diseases in the population of Ningxia region. Methods The data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m−3) of the Ambient air quality standards. Similarly, O3 was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m−3). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM2.5 and O3 as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. Results During the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM2.5 (40.25 μg·m−3) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM2.5 exposure over previous 1 d (lag01) and O3 exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases [ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively] were found at medium PM2.5 and O3 concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM2.5 and O3 above the primary limit. As the concentrations of PM2.5 and O3 increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. Conclusion Both atmospheric PM2.5 and O3 can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.
6.Effects of long-term exposure to ambient PM2.5 on hypertension and role of dietary regulation
Hanqing ZHANG ; Sijie ZHOU ; Jinxia WANG ; Yunhao SHI ; Yi ZHAO ; Yuhong ZHANG ; Yajuan ZHANG
Journal of Environmental and Occupational Medicine 2023;40(5):551-558
Background The contribution of long-term ambient PM2.5 exposure to hypertension should not be ignored. However, the conclusions of whether dietary factors play a role in regulating PM2.5-related hypertension are still inconsistent. Objective To explore the correlation between long-term exposure to ambient PM2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure) in adults in Ningxia and a potential moderating effect of dietary factors. Methods A set of cross-sectional survey data from March, 2013 to May, 2018 was retrieved from the China Northwest Cohort-Ningxia, and the average ambient PM2.5 concentration in the previous three years was also collected to estimate the long-term exposure of the participants. Binary logistic regression model was used to validate the correlation between long-term exposure to ambient PM2.5 and hypertension in Ningxia, and linear model was used to study the correlation between long-term exposure to ambient PM2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure), and to explore the influence of dietary factors on ambient PM2.5-related hypertension. Results A total of 11470 participants were included in the study, 42.2% male and 57.8% female. The three-year average ambient PM2.5 concentration before the baseline survey was 37.0 μg·m−3. Each 1 μg·m−3 increase in ambient PM2.5 was associated with an increased risk of hypertension (OR=1.111, 95%CI: 1.097, 1.125), and increased systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure by 0.886 (95%CI: 0.783, 0.990), 0.570 (95%CI: 0.500, 0.641), 0.676 (95%CI: 0.600, 0.751), and 0.316 (95%CI: 0.243, 0.389) mmHg, respectively. The stratified analysis showed that the OR and 95%CI of hypertension were 1.171 (1.097, 1.254), 1.117 (1.064, 1.174), and 1.160 (1.116, 1.207) respectively for each 1 μg·m−3 increased in PM2.5 with low frequency of vegetable and fruit consumption and salty taste respectively. The OR and 95%CI of hypertension were decreased when the moderate and high frequency of vegetable and fruit intake and moderate and light taste applied, the values were 1.091 (1.062, 1.121) and 1.114 (1.097, 1.131), 1.105 (1.082, 1.129) and 1.111 (1.092, 1.13), 1.115 (1.090, 1.140) and 1.102 (1.083, 1.121) respectively. Compared with low frequency of vegetable and fruit intake and salty taste, the increase degree of ambient PM2.5 related systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure also decreased in middle and high frequency of vegetable and fruit intake and moderate and light taste. Conclusion Long-term exposure to ambient PM2.5 is significantly associated with increased risks of hypertension and blood pressure in Ningxia area. Increasing the frequency of vegetable and fruit intake and decreasing salty taste may reduce the effect of ambient PM2.5 on hypertension and blood pressure.
7.Role of sclerostin in the occurrence and development of uveal melanoma and its biological mechanism
Hanqing WANG ; Xiaoming HUANG ; Tong WU ; Shuangshuang SHI ; Jianfeng WAN ; Sidi ZHAO ; Dongrun TANG ; Fengyuan SUN
Chinese Journal of Experimental Ophthalmology 2023;41(7):630-640
Objective:To investigate the effects of sclerostin (SOST) and WNT/CTNNB1 signaling pathway on the cell cycle, migration and invasion of human uveal melanoma (UM) cells and its related mechanism.Methods:UM tissues from 20 cases of epithelioid UM and 16 cases of spindle cell type UM were collected.The contents of SOST, Wnt-1 and Catenin beta-1 proteins in the collected tissues were detected by immunohistochemical staining.Three human UM tissue derived cell lines OCM-1 (primary spindle cell type), Mum-2B (metastatic epithelioid) and Mum-2C (metastatic spindle cell type) were selected and divided into three groups, blank control group not transfected, empty vector group transfected with SOST negative control vector and SOST siRNA group transfected with SOST siRNA.After 24-hour transfection, the mRNA and protein expression levels of SOST, CTNNB1, WNT protein family 1 (WNT1), CCND1, matrix metalloproteinase (MMP)2 and MMP9 were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The invasion and migration ability of the transfected cells were measured by transwell method, and the cell cycle distribution was detected by flow cytometry.Another 9 female BALB/c nude mice were selected and randomized into OCM-1 group, OCM-1 empty vector group and SOST shRNA group, inoculated with OCM-1 without lentivirus infection, OCM-1 with blank lentivirus infection and OCM-1 with SOST shRNA lentivirus infection, respectively.Six weeks after inoculation, the in situ formation of tumor was observed.The interaction between SOST and low density lipoprotein receptor related protein(LRP)-5/6 in OCM-1 cells was explored by co-immunoprecipitation assay.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2018KY[L]-20).Results:Immunohistochemical staining results showed that the SOST expression level was higher and the expression levels of Wnt-1 and Catenin beta-1 were lower in spindle cell type UM tissues than in epithelioid UM tissues, and the differences were all statistically significant (all at P<0.01). The real-time fluorescence quantitative PCR results showed that the relative expression of SOST mRNA was significantly lower and the relative expressions of CCND1, WNT1 and MMP9 mRNA were significantly higher in SOST siRNA groups than in corresponding empty vector groups in the three cell lines (all at P<0.05). In OCM-1 and Mum-2C cell lines, the relative expressions of CTNNB1 mRNA were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Western blot results showed that the relative expression of SOST protein was significantly lower and the relative expressions of Wnt-1, Catenin beta-1, cyclin-D1, MMP2 and MMP9 proteins were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Transwell assay showed that the cell invasion and migration ability of SOST siRNA group was significantly higher than that of blank control group and empty vector group in the three cell lines (all at P<0.01). Flow cytometry showed that the proportion of G1-phase cells and the G1/S-phase ratio were significantly lower in SOST siRNA group than in blank control groups and empty vector groups (all at P<0.01). The eyeball volume of OCM-1 group, OCM-1 empty vector group and SOST shRNA group was (42.7±4.6), (49.0±22.9) and (135.2±32.7)mm 3, respectively, showing a significant overall difference ( F=19.963, P<0.01). The eyeball volume of SOST shRNA group was larger than that of OCM-1 group and OCM-1 empty vector group, and the differences were statistically significant (both at P<0.05). Co-immunoprecipitation results showed that SOST could interact with LRP-5 and LRP-6 by binding to them, respectively. Conclusions:Silencing SOST can promote the invasion and migration of UM cells, and increase the proportion of UM cells in the division phase.Silencing SOST can promote tumor growth in eyes of nude mice.SOST may play this function by interacting with the membrane receptor LRP-5/LRP-6 and then regulating the WNT/CTNNB1 signal pathway.
8.Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway.
Shuhua SHAN ; Jinping NIU ; Ruopeng YIN ; Jiangying SHI ; Lizhen ZHANG ; Caihong WU ; Hanqing LI ; Zhuoyu LI
Acta Pharmaceutica Sinica B 2022;12(3):1254-1270
Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.
9.Establishment and volume estimation of three-dimensional digital model of osteoarthrosis of the femoral head
Hongbin LIU ; Hanqing ZHAO ; Yue SHI ; Lijun HOU ; Zhongxun WANG
Chinese Journal of Tissue Engineering Research 2016;20(44):6629-6635
BACKGROUND:Core decompression and autogenous bone grafts are widely used in treatment of early avascular necrosis of femoral head. According to the report, the success rate of this therapy has obvious difference;the reasons may be related to inaccurate puncture location and secondary damnification of repeated puncture. OBJECTIVE:To reconstruct three-dimensional model of femoral head necrosis by Mimics software for reappearance of lesions in the necrotic area to realize measurement of necrotic area of the femoral head and estimation of its volume. METHODS:We restructured images by using multi-slice spiral CT Syngommvvp VE23A workstation, Inspace software and NeuroDSA software. Hip CT data in DICOM format were imported into Mimics 13.0 software systems. Necrotic area of the femoral head was reconstructed with Mimics SimuIation software to truly reproduce the integrated form, scope and stereochemical structure of the necrotic area so as to achieve the measurement of the necrotic area of the femoral head and the volume estimation. We designed the best core decompression channel, simulated core decompression surgery, so that the patients could refer to the best simulated decompression path in the operation of core decompression. RESULTS AND CONCLUSION:(1) Among 36 patients (48 hips) with avascular necrosis of femoral head, there were phase I in 8 hips, accounting for 17%, phase II in 28 hips, accounting for 58%, and phase III in 12 hips, accounting for 25%. (2) The volume of necrotic area was (1 475.48±647.342) mm3 in the phase I, (4 571.77±2 344.55) mm3 in the phase II, and (4 836.46±2 969.33) mm3 in the phase III. (3) We simulated the core decompression based on the radius of the sphere of the necrotic area as parameter in the Mimics Simulation software module, and then completely cleared the necrotic area. (4) Surgery can more clearly understand information and stereochemical structure of the necrotic area with Mimics software to simulate the core decompression. It is the theoretical basis of operation.
10.Study on the therapeutic effects of an extract of herb medicines, YiGanQingDuKeLi, in combination with adefovir dipivoxil on the rebound of duck hepatitis B virus multiplication
Xin PAN ; Yujing SHI ; Qinghua ZHANG ; Hanqing XIAO ; Fengxian MENG ; Ya TU ; Yutong FEI ; Xiaolan CUI
Chinese Journal of Microbiology and Immunology 2015;(2):106-111
Abstract] Objective To investigate the in vivo therapeutic effects of an extract of herb medi-cines, YiGanQingDuKeLi, in combination with adefovir dipivoxil (ADV) on the rebound of duck hepatitis B virus ( DHBV) multiplication after withdrawal of ADV treatment.Methods Peking ducks were infected with DHBV positive serum samples for 7 days and then screened by SYBR Green real-time PCR.The ducks positive for DHBV were randomly divided into five groups including the model control group, the ADV treat-ment group, the herb treatment group, the high-dose combination therapy group and the low-dose combina-tion therapy group.The ducks in the ADV treatment and the herb treatment groups were respectively treated with distilled water and YiGanQingDuKeLi (1.2 g/ml) for 14 days after the treatment of ADV (0.25 mg/ml) for 21 days.The ducks in the high-dose group were treated with YiGanQingDuKeLi (1.2 g/ml) for 14 days after the combined treatment with high-dose YiGanQingDuKeLi (1.2 g/ml) and ADV (0.25 mg/ml) for 21 days.The ducks in the low-dose group were treated with YiGanQingDuKeLi (0.6 g/ml) for 14 days after the combined treatment with YiGanQingDuKeLi (0.6 g/ml) and ADV (0.125 mg/ml) for 21 days.Blood samples were collected from each duck via leg vein after 0, 7, 14 and 21 days of drug adminis-tration and after 7 and 14 days of drug withdrawal.The levels of DHBV-DNA, alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) in blood serum samples were detected.Results Compared with the model group, the levels of DHBV-DNA, ALT and AST in ducks from the herb treatment group and combined treatment groups were decreased before the discontinuation of ADV treatment ( P<0.05 or P<0.01).Moreover, the titers of DHBV-DNA in ducks treated with high doses of drugs were much lower than those from ADV treatment group.The levels of DHBV-DNA, ALT and AST in ducks treated with herb medi-cine and high doses of drugs remained at relatively low levels after the cessation of ADV treatment, but re-bounded significantly in ducks with ADV treatment.The levels of DHBV-DNA and ALT rebounded slightly in ducks treated with low doses of drugs as compared with those of ADV treatment group ( P<0.01 or P<0.05).Conclusion The treatment of YiGanQingDuKeLi in combination with ADV could inhibit not only the in vivo replication of DHBV, but also the rebound of DHBV multiplication after ADV withdrawal.

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