OBJECTIVE To study the improvement effects and potential mechanisms of water extract from Chrysanthemum morifolium on skeletal muscle atrophy in rats after ischemic stroke. METHODS Sprague-Dawley rats were randomly divided into sham operation group， model group， ATP group （10 mg/kg）， C. morifolium water extract high-dose and low-dose groups （1.08， 0.54 g/kg）. Except for sham operation group， ischemic stroke models were induced in rats from the other groups using middle cerebral artery occlusion. Starting from the first day after surgery， rats in each group were given corresponding drug/normal saline intragastrically， once a day， for consecutive 7 days. On the 7th day post-surgery， the rats’ body weights were measured， and their motor functions were evaluated， including Longa scores， exercise distance， grip strength； the electrophysiological signals of the skeletal muscles in rats were measured； the pathological morphology of the soleus muscle in rats was observed； the levels of tumor necrosis factor-α （TNF-α） in serum and soleus muscle were measured； the expressions of proteins related to TNF-α/c-Jun N- terminal kinase （JNK）/mitogen-activated protein kinase （MAPK） signaling pathway in the soleus muscle were determined. RESULTS Compared with sham operation group， the body weight， grip strength and exercise distance of rats were decreased/ shortened significantly （P＜0.01）； additionally， there was a notable reduction in the interpeak value of skeletal muscle electrophysiology （P＜0.05 or P＜0.01）. Longa score， as well as the levels of TNF-α in serum and soleus muscle， and the expression levels of TNF-α， phosphorylated JNK， phosphorylated MAPK， muscle ring-finger protein-1， and muscle atrophy Fbox- 1 protein in the soleus muscle， were all significantly elevated （P＜0.01）. The skeletal muscle cells of the soleus muscle in the model group showed significant atrophy， with a markedly decreased cross-sectional area （P＜0.01）. Compared with the model group， the levels of the aforementioned indicators were significantly reversed in C. morifolium water extract groups （P＜0.05 or P＜ 0.01）， and the skeletal muscle cells of the soleus muscle were markedly enlarged. CONCLUSIONS C. morifolium water extract can improve skeletal muscle atrophy in rats after ischemic stroke， the mechanism of which may be associated with suppressing the activation of the TNF- α/JNK/MAPK E-mail：19932015@cdutcm.edu.cn signaling pathway.

In the context of the development of transplant oncology, it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma (HCC). The antitumor effect of ginkgolic acid (GA) has been confirmed, and some studies suggest that GA may also have an immunosuppressive effect. The immunosuppressive effect of GA was evaluated by histopathology, T-cell subpopulation, and cytokine detection in rat liver transplantation and mouse cardiac transplantation models, and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect. Metabolites, activation, and ferroptosis markers of CD8⁺ T cells were detected in vivo and in vitro. Based on rat liver transplantation and mouse cardiac transplantation models, the immunosuppressive effect of GA was first confirmed by histopathology, T-cell subpopulation, and cytokine detection. In the mouse cardiac transplantation model, transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A (LDHA) expression and pyruvate metabolism in CD8⁺ T cells. It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8⁺ T cells through LDHA, inhibiting their activation and inducing ferroptosis. Overexpression of LDHA partially reversed the effect of GA on the metabolism, activation, and ferroptosis of CD8⁺ T cells in vitro. GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8⁺ T cells to exert an immunosuppressive effect, which lays an experimental foundation for the future clinical application of its immunosuppressive effect.

Objective To investigate the effect of different strand lengths of 125I seeds with the same activity on the dose of different reference points around the seeds.Methods The scanned images were transferred to the three-dimensional treatment planning system(3D-TPS)according to DICOM format.The target volume was delineated at 5 mm and 10 mm above and below the center of the phantom,and a 0.8 mCi seeds strand was simulated.The 1-20 seeds were arranged with an equal spacing of 5 mm(5 mm-100 mm).The 5 mm points above and below the center of the seeds strand were defined as point A and point A',and the 10 mm points above and below the center were defined as point B and point B'.5 mm above and below the edge of the seeds strand on the left side were defined as AL points and AL'points,and 5 mm above and below the edge of the seeds strand on the right side were defined as AR points and AR'points.Similarly,points 10 mm above the above mentioned positions were defined as BL points,BL'points,BR points,BR'points.The average dose symmetry points were measured at AL,AL',AR,and 5 mm,10 mm,15 mm and 20 mm inside AR' of the 45 mm-100 mm seeds strand.The dose at the center was compared with the dose at the end points.The dose at the center point A was compared with the average dose at the symmetry points of 5 mm,10 mm,15 mm and 20 mm inside of the end points AL,AL',AR and AR',and the dose at each point was curve fitting.The correlation between each point and seeds strands of different lengths was analyzed.Results There was a positive correlation between the dose and the length of each point.There was no statistically significant difference between the center point and the end point.There was a statistically significant difference in dosage at points 5 mm and 10 mm inside from point A,while there was no statistically significant difference in dosage at points 15 mm and 20 mm inside from point A.The dose of A,A',B and B' point increased steadily with the increase of seed chain length,and the fitting curves were obtained respectively:y=e(-0.620/x+5.28)(R2=0.992),y=e(-0.640/x+5.34)(R2=0.987),y=e(-0.82/x+4.80)(R2=0.984),y=e(-0.82/x+4.83)(R2=0.9g1).Conclusion The doses at points A,A',B,and B'are positively correlated with seeds strand length and have a high degree of stability.Point A can be used as a reference point for the target area dose of the seeds strand,and point B can be used as a reference point for the dose to critical organs.The dose at other positions is more variable and thus has a certain degree of uncertainty as a reference point for the seeds strand dose.

Objective To investigate the impact of different 125I seeds strand radian on the dose of different reference points around the seeds.Methods CT scan of self-developed radioactive particle radiation dose measurement phantom was performed,the scanned images were transferred to the three-dimensional treatment planning system(TPS).The target area at the middle level of the model was drawn.The target volume was delineated at 5 mm and 10 mm above and below the center of the phantom.125I seeds strand plans were designed with different radians,with a total length of 8 cm,seed spacing of 0 cm,activity of 0.8 mCi,and a total of 16 particles,with radians ranging from 30°to 170°,increasing by 10° increment.The point 5 mm vertically away from the center of the seeds strand towards the center was named A',and the point away from the center was named A.The point 10 mm vertically away from the center of the seeds strand towards the center was named B',and the point away from the center was named B.The doses at different radians were recorded,and the actual absorbed dose at 1-2 months after operation was calculated based on the particle activity decay formula.Results The doses at points A'and A were(218.3±23.1)and(201.5±16.0)Gy respectively(P=0.001).The actual absorbed doses at 1 month after operation were(65.5±6.9)and(60.5±4.8)Gy respectively(P=0.001),and the actual absorbed doses at 2 months after operation were(109.2±11.5)Gy and(100±7.9)Gy respectively(P=0.001).The doses at points B'and B were(95.9±11.0)Gy and(81.7±4.9)Gy respectively(P＜0.001),and the actual absorbed doses at 1 month after operation were(28.8±3.3)Gy and(24.5±1.5)Gy respectively(P＜0.001).The actual absorbed doses at 2 month after operation were(48.0±5.5)Gy and(41.0±2.4)Gy respectively(P＜0.001).The doses at points A'and A gradually decreased with the increase of the radians,reaching the minimum value at 100 degrees,and then increased gradually,showing a cubic function change.The actual absorbed dose showed the same trend.The doses at points B'and B increased gradually with the increase of the radians,showing a cubic function change.Conclusion At different radians,the point doses and absorbed doses on the centrifugal side of the seeds strand are both less than those on the centripetal side.There is a cubic function relationship between the dose at the reference points and the radian of the seeds strand.

In the context of the development of transplant oncology,it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma(HCC).The antitumor effect of ginkgolic acid(GA)has been confirmed,and some studies suggest that GA may also have an immunosuppressive effect.The immunosuppressive effect of GA was evaluated by histopathology,T-cell subpopulation,and cytokine detection in rat liver transplantation and mouse cardiac transplantation models,and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect.Metabolites,activation,and ferroptosis markers of CD8+T cells were detected in vivo and in vitro.Based on rat liver transplantation and mouse cardiac transplantation models,the immunosuppressive effect of GA was first confirmed by histopathology,T-cell subpopulation,and cytokine detection.In the mouse cardiac transplantation model,transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A(LDHA)expression and pyruvate metabolism in CD8+T cells.It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8+T cells through LDHA,inhibiting their activation and inducing ferroptosis.Over-expression of LDHA partially reversed the effect of GA on the metabolism,activation,and ferroptosis of CD8+T cells in vitro.GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8+T cells to exert an immunosuppressive effect,which lays an experimental foundation for the future clinical application of its immunosuppressive effect.

Objective:To explore the differences of microenviroment between peri-implant tissue and oral mucosal tissue.Methods:The gene chip data GSE43744 was downloaded from the GEO database,bioinformatics tools were used to analyze the differentially ex-pressed genes between the peri-implant tissue and normal oral mucosal tissue in rat.Results:1315 differentially expressed important genes,including 797 upregulated genes and 518 downregulated genes,were screened out.Gene enrichment analysis showed that com-pared with normal oral mucosal tissue,the gene expression of innate immune activity,cell activation,inflammatory response,and func-tional expression related to external and bacterial stimuli in peri-implant tissue were significantly upregulated,while that of extracellular matrix tissue,adhesion,extracellular matrix polysaccharides,response to mechanical stimuli and response to toxic substances was sig-nificantly downregulated.Meanwhile,multiple molecular functions and biological pathways related to T cells were highly expressed,which may play an important role in the peri-implant microenvironment.In addition,PPI network was constructed,and screened 7 core genes including FCER1G,TYROBP,PTPRC,ITGB2,AIF1,EMR1 and RAC2,which may be target genes for studying peri-implant microenvironment.Conclusion:There is a significant difference of microenvironment characteristics between peri-implant tissue and o-ral mucosa.The target genes screened using PPI network may be the key to future research on the peri-implant microenvironment.

Gastrointestinal stromal tumor(GIST),with a certain malignant potential,are currently the most common subepithelial tumors of the gastrointestinal tract.Early diagnosis and prediction of malignant potential are very important for the formulation of a treatment plan and determining the prognosis of GIST.Deep learning technology has made significant progress in the diagnosis of digestive tract diseases,and it can also effectively assist physicians in diagnosing GIST and predicting their malignant potential,preoperatively.The application of deep learning technology in the diagnosis of GIST includes CT,gastrointestinal endoscopy and endoscopic ultrasound.This paper aims to review the application of deep learning technology in the diagnosis and prediction of malignant potential of GIST.

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.