Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective:To discuss the method for establishing the rat models of irritable bowel syndrome(IBS)by chronic water avoidance stress(WAS)method,and to evaluate its feasibility.Methods:Thirty male Wistar rats were randomly divided into control group(n=10)and model group(n=20).The rats in model group were induced by WAS method for 1 h everyday,lasting for 10 consecutive days;the rats in control group underwent no interventions.After modeling,the general conditions and body weights of the rats in two groups were observed and recorded.The elevated plus maze(EPM)test was used to detect the percentages of the number of open arm entries(OE)and the time spent in open arms(OT)of the rats in two groups;the abdominal withdrawal reflex(AWR)test was used to assess the visceral sensitivity of the rats in two groups;electrocardiography was used to detect the heart rate variability(HRV)of the rats in two groups;electromyography(EMG)of the external oblique muscle was used to detect the colorectal pain sensitivity thresholds of the rats in two groups;multi-channel physiological signal recorder was used to monitor the slow wave frequency of the colon of the rats in two groups.Results:There were no death rats in both groups during the modeling period.After modeling,the rats in model group exhibited poor mental status,reduced spontaneous activity,hypoactivity,disordered and dull fur,irritability,and unclean anal areas;whereas,the rats in control group showed no significant changes in the mental state,spontaneous activity,fur,and perianal area.Compared with control group,the body weight of the rats in model group was significantly decreased(P<0.05).The EPM test results showed that compared with control group,the OE percentage and OT percentage of the rats in model group were significantly decreased(P<0.01).The AWR test results showed that 12 rats in model group scored≥3 points,indicating that the successful rate in creating the visceral pain models was 60%.Compared with control group,the low frequency(LF)signals and the ratio of LF/high frequency(HF)of the rats in model group were significantly increased(P<0.01),and the HF was significantly decreased(P<0.05).The EMG results showed that compared with control group,the coloretal pain sensitivity threshold of the colon of the rats in model group was significantly decreased(P<0.01),and the slow wave frequency of the colon was significantly increased(P<0.01).Conclusion:The WAS method for establishing the rat model of IBS effectively demonstrates the changes in behavior and mental state,increased the visceral sensitivity,accelerated colonic slow wave frequency,and autonomic nervous system imbalance;the WAS method can serve as an effective modeling approach for observing and evaluating the related drugs and interventions on treatment of IBS.

Objective Network pharmacology and molecular docking and molecular dynamics techniques were used to investigate the mechanism of action of Alhagi sparsifolia Shap.in the treatment of sepsis and to perform animal experimental verification.Methods First,we screened the effective ingredients and their action targets of Alhagi sparsifolia Shap.,meanwhile,screened relevant action targets for the treatment of sepsis,constructed a protein interaction(PPI)network,and performed topology analysis to draw a TCM disease target network diagram.Second,Kyoto Encyclopedia of genes and genomes enrichment analysis was performed for core targets in the network diagram,along with gene ontology functional enrichment analysis.This was followed by molecular docking and molecular dynamics simulation experiment validation of the core targets.Finally,mice were used for the verification of animal experiments.Results Thirty active components of Alhagi sparsifolia Shap.were screened out,and the top 5 ranked by degree value were quercetin,(-)-epigallocatechin,(-)-Epigallocatechin Gallate,genistein,kaempferol and epigallocatechin with 196 action targets;2144 disease-related targets for sepsis,105 targets for Alhagi sparsifolia Shap.-sepsis intersection,and the core targets were TNF,IL-6,AKT1,VEGFA,CASP3,IL-1β Et al.PI3K-Akt,TNF,HIF-1,AGE-RAGE,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert therapeutic effects on sepsis.Molecular docking results showed that camelina flavanoids bound equally well to each key target,among which the conformations with the lowest binding energy were(-)-Epigallocatechin Gallate-IL-6 and quercetin-IL-6.Molecular dynamics simulations were performed on the two pairs of complexes,and the results indicated that the stable binding could be achieved through a combination of electrostatic,van der Waals potential,and hydrogen bonding interactions.Animal experiments confirmed that Alhagi sparsifolia Shap.could inhibit the activation of PI3K/Akt signaling pathway,decrease the protein expression of Caspase-3,VEGF and reduced peripheral blood inflammatory factors secretion of TNF-α、IL-1βand IL-6,alleviating inflammatory injury in tissues and organs.Conclusion The therapeutic effect of Alhagi sparsifolia Shap.on sepsis is achieved through multi biological processes,multi targets,and multi pathways.It provides a certain theoretical basis for the clinical application of camel spines as well as sepsis treatment.

Objective:To resolve the issue of poor automatic segmentation of the bowel in women with pelvic tumors, a Dense V-Network model was established, trained and evaluated to accurately and automatically delineate the bowel of female patients with pelvic tumors.Methods:Dense Net and V-Net network models were combined to develop a Dense V-Network algorithm for automatic segmentation of 3D CT images. CT data were collected from 160 patients with cervical cancer, 130 of which were randomly selected as the training set to adjust the model parameters, and the remaining 30 were used as test set to evaluate the effect of automatic segmentation.Results:Eight parameters including Dice similarity coefficient (DSC) were utilized to quantitatively evaluate the segmentation effect. The DSC value, JD, ΔV, SI, IncI, HD (cm), MDA (mm), and DC (mm) of the small intestine were 0.86±0.03, 0.25±0.04, 0.10±0.07, 0.88±0.05, 0.85±0.05, 2.98±0.61, 2.40±0.45 and 4.13±1.74, which were better than those of any other single algorithm.Conclusion:Dense V-Network algorithm proposed in this paper can deliver accurate segmentation of the bowel organs. It can be applied in clinical practice after slight revision by physicians.

Objective To evaluate the accuracy and validate the feasibility of auto-segmentation based on self-registration and Atlas in adaptive radiotherapy for cervical cancer using MIM-Maestro software.Methods The CT scan images and delineation results of 60 cervical cancer patients were obtained to establish the Atlas template database.The planning CT (pCT) and replanning CT (rCT) images were randomly selected from 15 patients for the contouring of clinical target volume (CTV) and organs at risk (OAR) by an experienced radiation oncologist.The rCT images of 15 patients were auto-contoured using Atlas-based auto-segmentation (Atlas group),and mapping contours from the pCT to the rCT images was performed by rigid and deformable image registration (rigid group and deformable group).The time for the three methods of auto-segmentation was also recorded.The similarity of the auto-contours and reference contours was assessed using dice similarity coefficient (DSC),overlap index (OI),the average hausdorff distance (AHD) and the deviation of centroid (DC),and the results were statistically compared among three groups by using one-way analysis of variance.Results The mean time was 89.2 s,22.4 s and 42.6 s in the Atlas,rigid and deformable groups respectively.The DSC,OI and AHD for the CTV and rectum in the rigid and deformable groups significantly differed from those in the Atlas group (all P＜0.001).In the rigid and deformable groups,the OI for the intestine significantly differed from that in the Atlas group.The mean DSC for CTV was 0.89 in the rigid and deformable groups,and 0.76 in the Atlas group.The optimal delineation of the bladder,pelvis and femoral heads was obtained in the deformable group.Conclusions AIl three methods of auto-segmentation can automatically and rapidly contour the CTV and OARs.The performance in the deformable group is better than that in the rigid and Atlas groups.

OBJECTIVE: To explore the relationship between physiological parameters changes and severe heatstroke induced by 5-km armed cross-country training. METHODS: A total of 521 male officers and soldiers from a special team who participated in the summer training of 5-km armed cross-country training from year 2016 to 2017 were enrolled. All trainees participated in 5-km armed cross-country training in high temperature and humidity environment of ambient temperature > 32 centigradeand (or) relative humidity > 65%. The trainees were divided into two groups according to the incidence of severe heatstroke in the course of training. The age, enlistment time, constitution score, body mass index (BMI), external environment (ambient temperature, relative humidity, wind speed, heat index) of trainees of the two groups, and the change rates of arterial blood oxygen saturation (SaO₂), body temperature, pulse and blood pressure within 5 minutes after the 5-km armed cross-country training were compared between the two groups. The risk factors of severe heatstroke were screened by two classified Logistic regression analysis, and the predictive value of various risk factors of severe heatstroke was analyzed by the receiver operator characteristic curve (ROC). RESULTS: In 521 trainees of 5-km armed cross-country training, 29 trainees suffered from severe heatstroke accounting for 5.57%. There was no significant difference in the age, enlistment time, constitution score, BMI, or external environment during 5-km armed cross-country training between severe heatstroke group and non-severe heatstroke group. Compared with those without severe heatstroke, the descending rates of body temperature, pulse, blood pressure and SaO₂ increased rate within 5 minutes after 5-km armed cross-country training of severe heatstroke trainees were significantly decreased [temperature descending rate: (0.67±0.30)% vs. (1.43±1.28)%, pulse descending rate: (7.53±5.21)% vs. (13.48±8.07)%, blood pressure descending rate: (9.28±6.84)% vs. (19.42±7.73)%, SaO₂ increased rate: (0.51±0.39)% vs. (1.50±1.43)%, all P < 0.01]. Two classification Logistic regression analysis showed that the temperature descending rate [odds ratio (OR) = 0.485, 95% confidence interval (95%CI) = 0.289-0.817], pulse descending rate (OR = 0.903, 95%CI = 0.845-0.965), blood pressure descending rate (OR = 0.841, 95%CI = 0.790-0.896), and SaO2 increased rate (OR = 0.421, 95%CI = 0.250-0.711) were the risk factors for severe heatstroke during 5-km armed cross-country training (all P < 0.01). ROC curve analysis showed that temperature descending rate [area under ROC curve (AUC) = 0.659, 95%CI = 0.604-0.714], pulse descending rate (AUC = 0.730, 95%CI = 0.762-0.900), blood pressure descending rate (AUC = 0.831, 95%CI = 0.659-0.801), SaO₂ increased rate (AUC = 0.711, 95%CI = 0.655-0.767) could be used for the incidence of severe heatstroke prediction during 5-km armed cross-country training (all P < 0.01), and the predicted value was the same. CONCLUSIONS Under the same conditions, the severe heatstroke during 5-km cross-country training is closely related to the descending rates of body temperature, pulse, and blood pressure as well as SaO₂ increased rate within 5 minutes after the training, whose predictive values for severe heatstroke were the same.
Blood Pressure ; Heart Rate ; Heat Stroke ; Hot Temperature ; Humans ; Male ; Risk Factors

Objective: To explore the relationship between physiological parameters changes and severe heatstroke induced by 5-km armed cross-country training. Methods: A total of 521 male officers and soldiers from a special team who participated in the summer training of 5-km armed cross-country training from year 2016 to 2017 were enrolled. All trainees participated in 5-km armed cross-country training in high temperature and humidity environment of ambient temperature > 32 ℃and (or) relative humidity > 65%. The trainees were divided into two groups according to the incidence of severe heatstroke in the course of training. The age, enlistment time, constitution score, body mass index (BMI), external environment (ambient temperature, relative humidity, wind speed, heat index) of trainees of the two groups, and the change rates of arterial blood oxygen saturation (SaO₂), body temperature, pulse and blood pressure within 5 minutes after the 5-km armed cross-country training were compared between the two groups. The risk factors of severe heatstroke were screened by two classified Logistic regression analysis, and the predictive value of various risk factors of severe heatstroke was analyzed by the receiver operator characteristic curve (ROC). Results: In 521 trainees of 5-km armed cross-country training, 29 trainees suffered from severe heatstroke accounting for 5.57%. There was no significant difference in the age, enlistment time, constitution score, BMI, or external environment during 5-km armed cross-country training between severe heatstroke group and non-severe heatstroke group. Compared with those without severe heatstroke, the descending rates of body temperature, pulse, blood pressure and SaO₂ increased rate within 5 minutes after 5-km armed cross-country training of severe heatstroke trainees were significantly decreased [temperature descending rate: (0.67±0.30)% vs. (1.43±1.28)%, pulse descending rate: (7.53±5.21)% vs. (13.48±8.07)%, blood pressure descending rate: (9.28±6.84)% vs. (19.42±7.73)%, SaO₂ increased rate: (0.51±0.39)% vs. (1.50±1.43)%, all P < 0.01]. Two classification Logistic regression analysis showed that the temperature descending rate [odds ratio (OR) = 0.485, 95% confidence interval (95%CI) = 0.289-0.817], pulse descending rate (OR = 0.903, 95%CI = 0.845-0.965), blood pressure descending rate (OR = 0.841, 95%CI = 0.790-0.896), and SaO₂ increased rate (OR = 0.421, 95%CI = 0.250-0.711) were the risk factors for severe heatstroke during 5-km armed cross-country training (all P < 0.01). ROC curve analysis showed that temperature descending rate [area under ROC curve (AUC) = 0.659, 95%CI = 0.604-0.714], pulse descending rate (AUC = 0.730, 95%CI = 0.762-0.900), blood pressure descending rate (AUC = 0.831, 95%CI = 0.659-0.801), SaO₂ increased rate (AUC = 0.711, 95%CI = 0.655-0.767) could be used for the incidence of severe heatstroke prediction during 5-km armed cross-country training (all P < 0.01), and the predicted value was the same. Conclusions Under the same conditions, the severe heatstroke during 5-km cross-country training is closely related to the descending rates of body temperature, pulse, and blood pressure as well as SaO₂ increased rate within 5 minutes after the training, whose predictive values for severe heatstroke were the same.

Objective To develop a new automatic detection algorithm of the diaphragm motion based on Canny edge detection and wavelet transform.Methods On-line fluoroscopic images under free breathing were enhanced by using the wavelet transform.After the wavelet transform,edge detection was carried out for the enhanced image.Canny edge detection algorithm was used to achieve the diaphragm edge.Programs were written in Matlab to track the position of the diaphragm.The diaphragm movement curves were derived to evaluate the characteristics of patients respiratory motion.Results Under calm free breathing,the amplitude and period of diaphragm motion acquired by means of the wavelet transform and Canny edge detection were in good agreement with manual measurement.There were six to seven respiratory cycles in a XVI MotionViewTM.The magnitude of diaphragm movement was not exactly the same in the cranio-caudal (CC) direction.The magnitude was from 6.7 mm to 8.0 mm with an average of 7.4 mm.The movements of the respiratory motion cycles had little variations in amplitude and period for the same patient between fractions except emotional excitement or cough.Conclusions The automatic diaphragm detection methods developed in this paper are precise,and can effectively reflect the characteristics of the respiratory motion.The method can save much time and improve the measure precision greatly compared with the manual measurement.

is a famous ancient medical book of China. This article made a deep analysis on compatibility of acupoints in this book from four aspects: ① Acupoints compatibility of mother-son reinforcing-reducing method; ②Acupoints compatibility of reducing heart-fire and reinforcing kendy-watre method; ③Acupoints compatibility of needling jing-point reducing xing-point method, and ④ Acupoints compatibility of four-seasions wu-zang and wushu-point method.

Objective To calculate the mean absorbed doses at celluar and subcellular levels for uniformly and non-uniformly distributed Auger electron emitters. Methods The energy deposited in cell or nucleus by Auger electrons was analytically calculated using the polynomial representation of energy loss.S-values were subsequently computed for several target-source combinations.The absorbed dose and dose distribution were calculated for spherically symmetric radionuclide distributions depending linearly and exponentially on the radial position.The dose profile as a function of the source radial coordinate was also evaluated for typical cell sizes.The contributions of photon radiation to absorbed dose in cells were ignored. Results The mean absorbed dose and dose distribution depend largely on the size of target cells,the radiation spectrum and intracellular localization and distribution of radionuclides.The contribution of intranuclear radionuclides to mean absorbed dose was larger than that of extranuclear ones. Conclusion Auger electrons can produce high local energy deposition in cells because of their very low energies and extremely short ranges.Our dose calculation method is simple.The results are reliable and can be used in many fields.