AIM: To study the effect of changing left ventricular afterload and isolated perfused rabbit heart on ventricular refractory period measured by subhthreshold conditioning train stimulation (St).METHODS:Ventricu- lar refractory pened strength- interval relation was measured by St method under the condition of changine left ven- tricular afterload and elimination action of nervous and body fluid.RESULTS: Reducing left ventricular afterload pro -longed ventricular refractory period measured by St method (P

AIM:To study the effects of changing right heart load on electrophysiologic parameters in anesthetized dogs. METHODS:Change of right atrial and ventricular load, right atrial and ventricular diastolic threshold (ADT, VDT), right atrial and ventricular relative refractory period (ARRP,VRRP) and right atrial and ventricular effective refractory period (AERP, VERP) were recorded. RESULTS: Increasing right heart load step by step(grade A and B) caused prolongation of ARRP, AERP, VRRP (grade B, P

Objective To observe the clinical results of treatment for ischemic necrosis of the femoral head with autogenous spongy bone morselized and BMP implantation after arthroscopic core decompression.Methods Retrospectively analyzing the clinical data of 23 cases(30 hips),who were treated with autogenous cancerous bone morselized and BMP implantation after arthroscopic core decompression.Results 23 patients were followed up after discharge,follow-up time was 12 to 36 months,with an average of20.4 months.X-ray demonstrate good bone restoration in femoral head.In the observation period,femoral fractured or collapsed in 1 case of stageⅡ C、1 case of stage ⅢB,the original pain symptom aggravating,so artificial joint replacement were implemented.The other cases can maintain the results obtained in postoperative 6 months.According to the comprehensive evaluation.all the cases were 40～92scores after treatment.The rate of excellent and good results Was 76.7%.The results were better in stage Ⅰ(5/5),Stage Ⅱ(12/16),and Stage Ⅲ(6/9).Hip pain disappeared or lightening obviously,function improved obviously,Xray demonstrate femoral head contour smoothly and joint clearance normal.Conclusion Autogenous spongy bone morselized and BMP implantation after arthroscopic core decompression had good clinic curative effects in treatment of inchoate ischemic necrosis of the femoral head.

Objective To study the impacts of bladder filling status on the dosimetric parameters of the target volume and organs at risk (OAR) in intensity-modulated radiotherapy (IMRT) for prostate cancer.Methods Ten localized prostate cancer patients without serious complications treated with IMRT were selected for this study.These patients underwent CT scans of the whole pelvic cavity three times in different bladder filling status (empty and injected with 150 ml and 300 ml of normal saline) to obtain three series of pelvic CT images.The three sets of CT images were transferred to the treatment planning system.The target volume and OAR such as the rectum,bladder,and femoral heads were contoured by the same doctor.The treatment planning was performed and optimized by the physicist.The dosimetric parameters of the target volume and OAR in three bladder filling status were subjected to analysis by paired t-test.Results If the bladder filling status was consistent in orientation and radiation,the bladder filling status was not associated with the dosimetric parameters of the target volume and femoral heads (P =0.077-0.998 ; P =0.219-0.969) ;it had significant impacts on the dosimetric parameters of the bladder (P =0.000-0.562) and some dosimetric parameters of the rectum (P =0.000-0.645),and bladder filling was favorable for the protection of the bladder and rectum.If the bladder filling status was not consistent in orientation and actual radiation,the calculated planning target volume,the dosimetric parameters of the bladder,and some dosimetric parameters of the rectum were different from those in actual treatment (P =0.000-0.913).Conclusions For the prostate cancer patients treated with IMRT,it is recommended to keep the bladder well and consistently filled.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

ObjectiveProteomics was used to investigate the protein differences between porcine cardiac blood（PCB） and porcine blood（PB） from Menghe medical school and to compare the effects of both on the microglial inflammation of Salviae Miltiorrhizae Radix et Rhizoma（DS）. MethodNanoliquid chromatography-quadrupole orbitrap mass spectrometry（nLC-MS/MS） and bioinformatics were utilized to compare the proteomic differences of PCB and PB in simulated gastrointestinal digestion. Furthermore， Western blot was used to verify the contents of some shared proteins and differential proteins identified in PCB and PB. In addition， BV2 neuroinflammation model constructed by corticosterone（CORT） and lipopolysaccharide（LPS） was applied to detect the intervention effects of PCB and PB on the levels of tumor necrosis factor（TNF）-α and interleukin（IL）-6 in BV2 inflammatory cells of DS. ResultA total of 69 common proteins and 68 differential proteins were identified in PCB and PB， among which the common proteins included transferrin（Tf） with brain-targeting effect， and the differential proteins in the two were 41 and 27， respectively. Western blot validation showed that the difference in the content of the same protein Tf between PCB and PB was not statistically significant， while the difference in the contents of the specific proteins of creatine kinase M and heart-type fatty acid binding protein（H-FABP） were statistically significant（P<0.05）. Moreover， in vitro experimental studies revealed that compared with the same concentration of DS group， in addition to the 100 mg·L^-1 PB-DS group， PCB-DS and PB-DS groups could significantly inhibit the levels of TNF-α and IL-6 in BV2 inflammatory cells（P<0.05， P<0.01）， and PCB-DS group had more significant anti-inflammatory effect than PB-DS group with the same concentration（P<0.05， P<0.01）. ConclusionBoth of PCB and PB can enhance the inhibitory effect of DS on the release of inflammatory factors， thus playing a neuroprotective role， and PCB promotes DS inhibition more significantly， which may be due to the existence of the two involved in energy metabolism-related differential proteins， which can lay a foundation for revealing the scientific connotation of the processing of PCB-DS and PB-DS.

ObjectiveTo analyze the correlation between 11 small molecule active components and 1 protein component of characteristic processed products with porcine cardiac blood and other products of Salviae Miltiorrhizae Radix et Rhizoma（SMRR） from Menghe medical school and anti-cerebral ischemic oxidative damage， and to identify its key component markers of characteristic processed products with porcine cardiac blood for anti-cerebral ischemic oxidative damage. MethodHigh performance liquid chromatography（HPLC） was established to simultaneously determine the contents of 11 active ingredients in SMRR and its processed products［processed with porcine cardiac blood， porcine blood， wine and transferrin（Tf） in porcine cardiac blood］， and the content of Tf in different processed products of SMRR was detected by enzyme-linked immunosorbent assay（ELISA）. Furthermore， A zebrafish ischemic stroke model was constructed to evaluate the effects of different processed products of SMRR on the behavioral trajectory of cerebral ischemic zebrafish， the neuronal damage of transgenic zebrafish Tg（elavl3：eGFP） brain， as well as the levels of malondialdehyde（MDA） and superoxide dismutase（SOD） in the brain tissues. The hippocampal neurons oxygen-glucose deprivation/reoxygenation（OGD/R）-induced ischemia-hypoxia model was constructed to evaluate the effects of different processed products of SMRR on oxidative damage of neuronal cells by taking lactate dehydrogenase（LDH）， reactive oxygen species（ROS）， MDA and SOD as indexes. Finally， principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used to analyze the 11 small molecule active components and 1 protein component with efficacy indicators， in order to screen the key components of the characteristic processed products with porcine cardiac blood for cerebral ischemic oxidative damage. ResultCompared with the raw products， the contents of water-soluble and fat-soluble components in processed products of SMRR increased to different degrees， while the content of salvianolic acid A decreased. Compared with the wine-processed products， the contents of salvianolic acid B， danshensu， rosmarinic acid and other components in the porcine cardiac blood-processed products， porcine blood-processed products， Tf-processed products were increased， while the content of salvianolic acid A was decreased. ELISA results showed that there was no significant difference in Tf content between the porcine cardiac blood-processed products， porcine blood-processed products， Tf-processed products. Pharmacological results showed that different processed products of SMRR could improve the behavioral deficits， brain neuronal injury and oxidative stress after ischemic stroke in zebrafish， and the effect of the porcine cardiac blood-processed products was most pronounced. PCA results showed that salvianolic acid B， salvianolic acid A， rosmarinic acid， lithospermic acid， danshensu， tanshinone Ⅱ_A， caffeic acid， cryptotanshinone and tanshinone Ⅰ were the main contributing components of SMRR and its processed products. And the results of correlation analysis showed that the contents of cryptotanshinone， rosmarinic acid， caffeic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone Ⅱ_A and tanshinone Ⅰ were negatively correlated with MDA level in zebrafish brain tissue， while the contents of lithospermic acid， protocatechuic aldehyde， rosmarinic acid， dihydrotanshinone Ⅰ， salvianolic acid B and Tf were positively correlated with SOD level， and the contents of rosmarinic acid， caffeic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone Ⅱ_A， tanshinone Ⅰ， danshensu， Tf were positively correlated with neuronal fluorescence intensity in the zebrafish brain. And the contents of lithospermic acid， protocatechuic aldehyde， rosmarinic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone Ⅱ_A and Tf were negatively correlated with LDH， ROS and MDA levels and positively correlated with SOD level. ConclusionThere are differences in the anti-ischemic oxidative damage effects of SMRR and its different processed products， among which the porcine cardiac blood-processed products has the strongest effect on improving oxidative damage， which may be related to the content changes of salvianolic acid B， danshensu， rosmarinic acid and other components. This study can provide a basis for clarifying the quality markers of SMRR processed with porcine cardiac blood for cerebral ischemia and elucidating its processing mechanism.