Malignant tumor metastasis is the key factor leading to poor prognosis of patients， and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming， as a key link in the regulation of tumor metastasis activity， affects the growth， invasion， and metastasis of tumor cells by changing the metabolic pathways of intracellular substances （such as glucose， amino acids， lipids， and nucleotides）. In particular， metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ， hematogenous metastasis， and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine （TCM）， the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway， multi-target， and multi-component therapeutic characteristics， TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation （EMT） and extracellular matrix （ECM）， anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper， the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed， and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time， the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.

Objective:To investigate the efficacy and safety of different endoscopic treatment strategies for grade Ⅰ-Ⅲ internal hemorrhoids.Methods:Clinical data of 107 internal hemorrhoid patients who received endoscopic sclerotherapy or band ligation in Renmin Hospital of Wuhan University from December 2018 to December 2020 were retrospectively studied. Postoperative adverse events, efficacy, and satisfaction were followed up.Results:Among the 107 patients, there were 45 patients (42.06%) with grade Ⅰ, 55 (52.34%) with grade Ⅱ, and 6 (5.60%) with grade Ⅲ. At the same time, 94.39% (101/107) patients underwent other gastrointestinal endoscopic treatment. The postoperative follow-up time ranged from 3 to 25 months, with a median of 5 months. A total of 84 patients underwent routine endoscopic injection sclerotherapy, and 8 had adverse events after the surgery. The overall effective rate was 97.61% (82/84), and satisfaction rate was 95.24% (80/84). Nine underwent endoscopic foam sclerotherapy, and no postoperative adverse events were observed. The overall effective rate and the satisfaction rate were both 100.00% (9/9). Among the 11 patients undergoing endoscopic band ligation, 2 had adverse events after the surgery. The overall effective rate was 81.82% (9/11), and the satisfaction rate was 72.73% (8/11). Three patients underwent sclerotherapy combined with ligation, and 2 had postoperative adverse events. The overall effective rate was 100.00% (3/3), and the satisfaction rate was 66.67% (2/3). Sclerotherapy was generally superior to ligation in operation cost. Further subgroup analysis for grade Ⅰ-Ⅱ patients showed that for grade Ⅰ patients, sclerotherapy was better than band ligation in the incidence of postoperative pain ( P<0.05), and for grade Ⅱ patients, no statistically significant differences were observed in adverse events, effective rate and satisfaction rate ( P>0.05). Conclusion:Both endoscopic injection sclerotherapy and band ligation for internal hemorrhoids are safe and effective, and may not increase the risk of adverse events when simultaneously completed with other gastrointestinal endoscopic treatment.

Objective:To develop early gastric cancer (EGC) detection system of magnifying blue laser imaging (ME-BLI) model and magnifying narrow-band imaging (ME-NBI) model based on deep convolutional neural network, to compare the performance differences of the two models and to explore the effects of training methods on the accuracy.Methods:The images of benign gastric lesions and EGC under ME-BLI and ME-NBI were respectively collected. A total of five data sets and three test sets were collected. Data set 1 included 2 024 noncancerous lesions and 452 EGC images under ME-BLI. Data set 2 included 2 024 noncancerous lesions and 452 EGC images under ME-NBI. Data set 3 was the combination of data set 1 and 2 (a total of 4 048 noncancerous lesions and 904 EGC images under ME-BLI and ME-NBI). Data set 4: on the basis of data set 2, another 62 noncancerous lesions and 2 305 EGC images under ME-NBI were added (2 086 noncancerous lesions and 2 757 EGC images under ME-NBI). Data set 5: on the basis of data set 3, another 62 noncancerous lesions and 2 305 EGC images under ME-NBI were added(4 110 noncancerous lesions and 3 209 EGC images under ME-NBI and ME-BLI). Test set A included 422 noncancerous lesions and 197 EGC images under ME-BLI. Test set B included 422 noncancerous lesions and 197 EGC images under ME-NBI. Test set C was the combination of test set A and B (844 noncancerous and 394 EGC images under ME-BLI and ME-NBI). Five models were constructed according to these five data sets respectively and their performance was evaluated in the three test sets. Per-lesion video was collected and used to compare the performance of deep convolutional neural network models under ME-BLI and ME-NBI for the detection of EGC in clinical environment, and compared with four senior endoscopy doctors. The primary endpoint was the diagnostic accuracy of EGG, sensitivity and specificity. Chi-square test was used for statistical analysis.Results:The performance of model 1 was the best in test set A with the accuracy, sensitivity and specificity of 76.90% (476/619), 63.96% (126/197) and 82.94% (350/422), respectively. The performance of model 2 was the best in test set B with the accuracy, sensitivity and specificity of 86.75% (537/619), 92.89% (183/197) and 83.89% (354/422), respectively. The performance of model 3 was the best in test set B with the accuracy, sensitivity and specificity of 86.91% (538/619), 84.26% (166/197) and 88.15% (372/422), respectively. The performance of model 4 was the best in test set B with the accuracy, sensitivity and specificity of 85.46% (529/619), 95.43% (188/197) and 80.81% (341/422), respectively. The performance of model 5 was the best in test set B, with the accuracy, sensitivity and specificity of 83.52% (517/619), 96.95% (191/197) and 77.25% (326/422), respectively. In terms of image recognition of EGC, the accuracy of models 2 to 5 was higher than that of model 1, and the differences were statistically significant ( χ2=147.90, 149.67, 134.20 and 115.30, all P<0.01). The sensitivity and specificity of models 2 and 3 were higher than those of model 1, the specificity of model 2 was lower than that of model 3, and the differences were statistically significant ( χ2=131.65, 64.15, 207.60, 262.03 and 96.73, all P < 0.01). The sensitivity of models 4 and 5 was higher than those of models 1 to 3, and the specificity of models 4 and 5 was lower than those of models 1 to 3, and the differences were statistically significant ( χ2=151.16, 165.49, 71.35, 112.47, 132.62, 153.14, 176.93, 74.62, 14.09, 15.47, 6.02 and 5.80, all P<0.05). The results of video test based on lesion showed that the average accuracy of doctors 1 to 4 was 68.16%. And the accuracy of models 1 to 5 was 69.47% (66/95), 69.47% (66/95), 70.53% (67/95), 76.84% (73/95) and 80.00% (76/95), respectively. There were no significant differences in the accuracy among models 1 to 5 and between models 1 to 5 and doctors 1 to 4 (all P>0.05). Conclusions:ME-BLI EGC recognition model based on deep learning has good accuracy, but the diagnostic effecacy is sligntly worse than that of ME-NBI model. The effects of EGC recognition model of ME-NBI combined with ME-BLI is better than that of a single model. A more sensitive ME-NBI model can be obtained by increasing the number of ME-NBI images, especially the images of EGG, but the specificity is worse.

OBJECTIVE：To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney disease-mineral and bone disorder（CKD-MBD）model rats. METHODS ：The male SD rats were randomly divided into normal group（n＝10），high phosphorus group （n＝30），model group （n＝30），calcitriol group （positive control ，0.09 μg/kg，n＝30）， Modified liuwei dihuang decoction group （10 g/kg by crude drug ，n＝30）. CKD-MBD model was established by high phosphorus and adenine diet for 6 weeks. After modeling ，normal group and model group were given normal diet/high phosphorus diet and intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution intragastrically（water as solvent ），0.1 mL/kg，once a day ，for consecutive 6 weeks. Blood sample of rats in the normal group were collected ，and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected ， and they were sacrificed at 2，4 and 6 weeks after administration. The contents of blood urea nitrogen （BUN），serum creatinine （Scr），calcium，phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum were detected in each group. The bone mineral density（BMD）of femoral was measured ，the morphological changes of renal tissue and bone tissue were observed ，and the percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS ：Compared with normal group，above indexes in high phosphorus group had no significant change at different time points （P＞0.05）. There was no abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point ，the contents of BUN ，Scr， phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in the model group were significantly increased ，while the contents of calcium in serum and the BMD of femoral were significantly decreased （P＜0.05 or P＜0.01）. The renal tissue showed diffuse fibrosis. The width of trabecular bone was increased and the number of osteoblasts was decreased. Compared with the model group at the same time point ，the contents of BUN（except for Modified liuwei dihuang decoction group after 2 weeks of administration ），Scr，serum phosphorus ，iPTH， FGF-23，RANKL and osteocalcin ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point ；serum calcium content and BMD（except for 2 weeks of administration ）were significantly increased （P＜0.05 or P＜0.01），and the pathological changes of renal/bone tissue were significantly improved ；there was no statistical significance in above indexes between Modified liuwei dihuang decoction group and calcitriol group （P＞0.05）. CONCLUSIONS ：Modified liuwei dihuang decoction can improve kidney/ bone injury of CKD-MBD model rats ，and improve BMD and regulate disorder of calcium and phosphorus metabolism.

OBJECTIVE： To investigate estrogen-like effect of tetrahydroxy stilbene glucoside （TSG） and its effects on the expression of estrogen receptor （ER） in uterus of sexually immature mice. METHODS： Totally 60 sexually immature Kunming mice were randomly divided into normal group， positive control group （estradiol valerate， 0.18 mg/kg）， TSG low-dose and high-dose groups （50， 150 mg/kg）， TSG low-dose and high-dose groups+estradiol valerate groups （same dose as medication alone group）. Normal group was given constant volume of water intragastrically， and administration groups were given relevant medicine 0.2    mL/10 g， once morning and night， for consecutive 5 d. The uterus index and body weight increase of mice in each group were determined and calculated the next day after the last administration. The contents of serum estrogen （E2， LH， FSH） were determined by ELISA. HE staining was used to observe the morphology characteristics of uterus， and uterine tube diameter and endometrial thickness were detected. The expression of ER（ER-α and ER-β） in uterus was detected by immunohistochemical staining. RESULTS： The myometrium of the mice in normal group was parallel and compact， the epithelium of the uterus was columnar， and the expression of ER-α and ER-β was low. The uterine tube diameter， endometrium and epithelium of mice in each administration group increased， thickened or proliferated in varying degrees， and the expression of ER-α and ER-β changed. Compared with normal group， uterus indexes （positive control group， TSG high-dose group， TSG+estradiol valerate groups）， the increase of body weight （positive control group， TSG high-dose groups， TSG low-dose+estradiol valerate group）， uterine tube diameter and endometrial thickness （positive control group， TSG low-dose group， TSG+estradiol valerate groups）， the expression of ER-α （positive control group， TSG+estradiol valerate groups） and the expression of ER-β （postive control group， TSG high-dose+estradiol valerate group）were increased significantly， while serum contents of LH （positive control group， TSG high-dose group） and FSH （TSG low-dose+estradiol valerate group） were decreased significantly （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression in ER-α and ER-β of TSG+estradiol valerate groups， the increase of body weight and serum content of E2 in TSG low-dose+estradiol valerate group were significantly higher than same TSG dose alone groups （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression of ER-α and ER-β in TSG groups， uterine tube diameter and the expression of ER-β in TSG+estradiol valerate groups， body weight increase of mice in TSG low-dose group were significantly lower than positive control group， while serum content of LH in TSG+estradiol valerate groups were significantly higher than positive control group （P＜0.05 or P＜0.01）. CONCLUSIONS： TSG can increase uterus indexes and body weight of sexually immature mice to certain extent， regulate estrogen level， increase the diameter of uterine tube and endometrial thickness and up-regulate the expression of ER in the uterus， showing certain estrogen-like effect， which is weaker than that of estradiol valerate. Combined use of them may antagonize the effect of estradiol valerate.

OBJECTIVETo study the primary and secondary factors of the allergic history, the frequency of acupoint application and the time of acupoint application in the treatment of bronchial asthma and optimize its scheme.

METHODSEighty patients of bronchial asthma were selected as the subjects in the orthogonal trial. The herbal medicines were the empirical formula of acupoint application (prepared at the ratio as 2:2:1:1:1:1:1:1:1 of,, unprocessed,,,,,and) and used on bilateral Feishu (BL 13), Xinshu (BL 15), Geshu (BL 17) and Shenshu (BL 23). Firstly, two groups were divided according to allergic history (40 cases with allergic history and 40 cases without allergic history), and then four subgroups were divided on the basis of the two main groups, 10 cases in each one. Through studying three factors and two levels, i.e. allergic history (Factor A:A:with allergic history; A:without allergic history), the frequency of acupoint application (Factor B:B:4 times; B:10 times, in which, in the group of 4-time applications, the application was given once every 10 days; in the group of 10-time applications, the application was given once every 4 days); and the time of application (Factor C:C:4 h; C:8 h), the optimal scheme was screened on the basis of the attack frequency before and after treatment and the score of the asthma quality life questionnaire (AQLQ) before treatment and 6 months after treatment in the patients of each group.

RESULTS① The orthogonal trial indicated that the best optimal scheme was ABC, meaning the patients with allergic history were treated with acupoint application for 10 times, remained for 4 h. ②Factor B (frequency of acupoint application) and C (time of acpoint application) were the significant influential factors of AQLQ scores (both<0.05). ③The comparison of the attack frequency and AQLQ score before and after treatment in all of the patients showed that the different combinations of factor levels induced the different impacts on the asthma attack frequency and AQLQ scores. Except in the group No.1 and the group No.5, the improvements were all significant in the rest groups, indicating the significant differences (<0.05,<0.01).

CONCLUSIONSAcupoint application reduces apparently the attack frequency of asthma in the patients and improves the living quality. The primary and secondary relationship among the allergic history, the frequency of acupoint application and the time of acupoint application for the impacts on the therapeutic effects are:the frequency of acupoint application > the time of acupoint application > the allergic history. The best optimal scheme is ABC, meaning the patients with allergic history are treated with acupoint application for 10 times, remained for 4h.

Objective To investigate the differences in eNOS gene expression,activity and its metabolites before and after human bone marrow mesenchymal stem cells (hBMSCs) are induced into vascular endothelial cells.Methods hBMSCs were induced into vascular endothelial cells.The morphological changes of the cells were observed under inverted microscope.Transwell assay was used to detect the cells' migration ability.The protein expression of eNOS was detected by immunofluorescence and Western blot.The activity of eNOS was detected by ELISA and the content of NO in cell culture supernatant was determined by nitrate reduction method.Results Compared with those in the undifferentiated group,the morphological changes of the differentiated cells were obvious.Cell migration ability increased by 238.10％ (73.000±7.002 vs.21.000±4.359,P＜0.05).The expression of eNOS protein increased by 114.72％ (0.423±0.011 vs.0.197±0.079,P＜0.05).The activity of eNOS was enhanced by 157.49％ (4.967±0.073 vs.1.929±±0.103,P＜0.05).The synthesis and release of NO increased by 155.67％ (184.909±1.853 vs.72.323±0.426,P＜0.05).Conclusion After hBMSCs are induced into endothelial cells,the expression of eNOS gene increases,their activities increase,synthesis and release of the metabolite NO increase.It may provide a basis for prevention and treatment of cardiovascular diseases with stem cells.

BACKGROUND/AIMS: Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. METHODS: The effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. RESULTS: Low concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. CONCLUSIONS: Neurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions.
Absorption ; Animals ; Baths ; Colon* ; In Vitro Techniques ; Interstitial Cells of Cajal ; Lidocaine ; Myenteric Plexus ; Neural Conduction ; Neurotensin* ; Peristalsis ; Rats* ; Receptors, Neurotensin ; Video Recording

Objective: To investigate the effects of miR-24 on endothelial nitric oxide synthase (eNOS) gene expression with regulation and endothelial cell proliferation, migration, tube formation in human umbilical vein endothelial cells (HUVECs). Methods: Constructed high expression plasmid of miR-24 and miR-24 antisense sequence were introduced into HUVECs and the cells included in 3 groups: Control group, miR-24 group and miR-24 inhibitor group. HUVEC proliferation was detected by MTT test, migration was measured by Scratching and Transwell methods, tube formation was examined by Matrigel assay; mRNA and protein expressions of eNOS and Sp1were determined by RT-PCR and Western blot analysis respectively. Results:①Compared with Control group, miR-24 group had decreased cell proliferation by 45.45% as (0.36 ± 0.04) vs (0.66 ± 0.08),P<0.05; miR-24 group had lower speed of cell migration, decreased number of cell migration by 74.75% as (30.25±3.78) vs (119.80±10.94),P<0.01 and there was no obvious tube formation.②Compared with Control group, miR-24 group showed reduced eNOS mRNA expression by 46.2% as (0.49±0.02) vs (0.91±0.01),P<0.05, reduced protein expression by 49.07% as (0.55±0.05) vs (1.08±0.05),P<0.05; meanwhile, decreased Sp1 mRNA expression by 44.9% as (0.49±0. 01) vs (0. 89±0.02)P<0.05, decreased protein expression by 54.90% as (0.46±0.02) vs (1.02±0.04),P<0.05. In miR-24 inhibitor group, the above indexes were lower than Control group but higher than miR-24 group, the amount of tube formation and the length of tubes were similar between Control group and miR-24 inhibitor group. Conclusion: MiR-24 may inhibit HUVECs proliferation, migration, tube formation and suppress eNOS expression; Sp1 might be one of the important regulators.

Objective To observe the clinical efficacy of acupuncture at Xinming points (Extra) plus strong rein-forcing mani- pulation in treating optic atrophy.Methods Forty (56 eyes) optic atrophy patients were randomly allocated to a treatment group of 20 cases (29 eyes) and a control group of 20 cases (27 eyes). The control group received conventional medications, and the treatment group received acupuncture at Xinming points (Extra) plus strong reinforcing manipulation in addition. The visual acuity, the mean visual sensitivity (MS) of visual field and the P100 wave latency of P-VEP were recorded in the two groups before and after the treatment. The clinical therapeutic effects were compared between the two groups.Results The visual acuity, the MS of visual field and the P100 wave latency of P-VEP were significantly changed after treatment in both two groups (P<0.05). After the treatment, there were statistically significant differences in the visual acuity, the MS of visual field and the P100 wave latency of P-VEP between the two groups (P<0.05). The total efficacy rate was 75.0% in the treatment group versus 35.0% in the control group, and the difference was statistically significant (P<0.05).Conclusions Acupuncture at Xinming points (Extra) plus strong reinforcing manipulation is an effective method for optic atrophy.