ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

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 study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis(UC).Methods Acer1 knockout mice(Acer1 KO)were constructed,and the UC model was induced by continuous drinking water of sodium dextran sulfate(DSS)for 7 days,and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared.The expression levels of intestinal mucosal barriers(ZO-1,Occludin,Claudin,JAMA)were detected by RT-PCR and immunohistochemistry.Systemic immune response levels(IL-1b、IL-6、IL-23、IL-17、IL-10,and TNF-a)were assessed by ELISA and intestinal inflammatory infiltration levels(TNF-a、IL-1b、IL-6、IL-17、IL-21,etc.)were assessed by RT-PCR.Results There was no significant difference between C57 and Acer1 KO mice in free drinking water.In the DSS induced UC model,compared with C57 mice,the survival rate of Acer1 KO mice decreased,the weight decreased significantly,the mechanical barrier and mucus barrier protein expression levels decreased significantly,the intes-tinal epithelial barrier was seriously damaged,the inflammatory response was strong,and the cytokine infiltration was obvious,with statistical differences(P<0.05).Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier,preventing endotoxin,and delaying the progression of UC.

Objective To investigate the value of whole lung CT radiomics combined with clinical and conventional CT features for differentiating non-tuberculous mycobacterial pulmonary disease(NTM-PD)and pulmonary tuberculosis(PTB).Methods Fifty-three NTM-PD(NTM-PD group)and 111 PTB(PTB group)patients diagnosed by mycobacteria culture were retrospectively collected.The patients were divided into training set(n=115,including 37 cases of NTM-PD and 78 cases of PTB)and test set(n=49,including 16 cases of NTM-PD and 33 cases of PTB)at the ratio of 7∶3.Patients'clinical and pulmonary CT manifestations of lesions were analyzed using univariate and multivariate logistic regression,and the independent impact factors for differentiating NTM-PD and PTB lesions were screened.The best radiomics features were extracted and screened based on whole lung CT.Based on independent impact factors,the best radiomics features and their combination,clinical-CT,radiomics and combined models were constructed with random forest,and the differential efficacy of each model was evaluated.Results Patients'age(OR=0.264),gender(OR=0.956),immunoglobulin G(OR=3.416),C reactive protein(OR=3.418)and bronchiectasis shown on CT(OR=0.285)were all independent impact factors for differentiating NTM-PD and PTB.Twelve best radiomics features were screened based on whole lung ROI.The AUC of combined model in training set and test set was 0.915 and 0.901,respectively,both higher than that of clinical model(AUC=0.832,0.801,Z=1.340,3.710,both P＜0.05)and radiomics model(AUC=0.877,0.821,Z=-2.520,-5.240,both P＜0.05).Conclusion Whole lung CT radiomics combined with clinical and conventional CT features could effectively distinguish NTM-PD and PTB.

Objective:To compare the short-term outcomes and cost-effectiveness of laparoscopic and open ileostomy reversal.Methods:A retrospective cohort study was adopted. Clinical data of patients who underwent loop ileostomy reversal at the department of Colorectal Tumor Surgery of Shengjing Hospital Affiliated with China Medical University from January 2021 to November 2023 were reviewed. After excluding those who did not undergo reversal within 3 to 6 months of the initial surgery, patients with complications such as parastomal hernia requiring additional procedures, and those who underwent laparoscopic-to-open conversion, 150 were included for analysis. Patients were grouped according to type of reversal: open surgery (92 patients) and laparoscopic (58 patients). The primary outcome was cost-effectiveness. The success rate of ileostomy reversal was used as the health outcome. Hospitalization costs were collected via the hospital information system. The willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product. Differences in cost and success rates between open and laparoscopic procedures were compared. Incremental cost per successful reversal of ileostomy reversal and incremental cost-effectiveness ratios (ICER) were calculated (ICER < WTP indicates that laparoscopic ileostomy reversal is more cost-effective than open).Results:Compared with open reversal, the intraoperative blood loss volume was lower[ (35.5±12.6) ml vs.(57.7±19.0) ml, t=7.874, P<0.001] ; adhesion release rate was higher [82.8%(48/58) vs.46.7%(43/92), χ 2=19.341, P<0.001]; time to first flatus [(99.4±32.4) hours vs.(115.0±35.3) hours, t=2.734, P=0.007] and time to unassisted ambulation [42(18-71) hours vs. 51(25-78) hours, Z=-6.440, P<0.001] were earlier; postoperative hospitalization was shorter [(12.0±3.4) days vs.(15.0±3.6) days, t=5.010, P<0.001] ; visual analog scale pain score on postoperative day 2 was lower [3(3-4) vs. 4(4-4), Z=-6.488, P<0.001;3(2-3) vs. 3(3-4), Z=-4.810, P<0.001]; and incidence of postoperative complications was lower [8.6%(5/58) vs. 21.7%(20/92), χ 2=4.408, P=0.036] in the total laparoscopic group. The ICER of the total cost of the laparoscopic group relative to the open group was 38 221.89 CNY. Univariate sensitivity analysis showed that the success rate of laparoscopic reversal had the greatest impact on the results. The cost-effectiveness acceptability curve showed that when the WTP was 257 094 CNY, the probability of laparoscopic reversal being economical was 84.9%. Conclusion:Laparoscopic ileostomy reversal is more cost-effective than open and has superior short-term outcomes.

Primary liver cancer,particularly hepatocellular carcinoma,is one of the most common malignancies in China,and hepatectomy remains the primary curative treatment.However,the efficacy of hepatectomy is significantly limited due to the heterogeneity of liver cancer,its high recurrence rate,and the fact that most patients are diagnosed at advanced stages.In recent years,the development of precision medicine has brought new hope to liver cancer treatment,especially with notable advancements in preoperative assessment,systemic therapy,minimally invasive surgery,and personalized treatment strategies.Preoperative assessment,including imaging technologies such as three-dimensional visualization and molecular imaging,helps physicians accurately evaluate tumor characteristics and liver function,guiding the choice of treatment plan.The combined application of immunotherapy and targeted therapy has significantly improved survival rates for patients with advanced liver cancer.The strategy of combining systemic therapy with local treatment has provided new pathways for translational therapy,expanding the indications for hepatectomy.The optimal selection of patients based on tumor biological characteristics,especially molecular subtyping and liver function status,to maximize patient benefit still requires further exploration.The"seven-step"modular laparoscopic hepatectomy,by achieving scientific hepatectomy,demonstrates the clinical practice of maximizing patient benefit,further elucidating a multidisciplinary,personalized treatment model centered on surgical therapy.