Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Objective To investigate the impact of different kinds of laparoscopic surgery including conventional blunt elimination and modified acute elimination on sex hormone, antral follicle count and ovarian volume of patients with endometriosis (EMs). Methods 100 patients with EMs were chosen from January 2013 to April 2016 and randomly divided into control group (50 patients) with conventional blunt elimination and observation group (50 patients) with modified acute elimination; and the thickness of elimination lesion, the removal rate of ovary cortex, the thickness of ovarian cortex, the level of serum sex hormones, the AFC number of affected side and the volume of ovary before and after operation of the two groups were compared. Results There was no significant difference in the thickness of lesion elimination, the removal rate and removed thickness of ovarian cortical between the two groups (P > 0.05). The thickness of lesion elimination and the thickness of ovarian cortex in middle position of observation group were significantly lower than that in control group (P < 0.05). The thickness of lesion elimination, removed thickness of ovarian cortical and the removal rate of ovary cortex in hilus ovarii in observation group were significantly lower than that in control group (P < 0.05). There was no significant difference in the levels of serum sex hormones before and after treatment between the two groups (P > 0.05). There was no significant difference in the levels of AFC number of affected side before and after treatment (P > 0.05). The levels of AFC number of affected side in hilus ovarii of control group after treatment were significantly lower than that before treatment (P < 0.05). The volume of ovary of both groups after treatment were significantly lower than that before treatment (P < 0.05). The volume of ovary of observation group after treatment were significantly higher than that in control group (P < 0.05). Conclusion Compared with conventional blunt elimination, modified acute elimination in the treatment of patients with EMs can efficiently shorten the operation time, reduce the surgical trauma degree, speed up the recovery process after operation, regulate the level of FSH and AMH and be helpful to protect the ovarian reserve function.

Objective:To investigate the correlation between the plasma sphingomyelin (SM ) levels and the severity of coro‐nary artery disease in patients with coronary atherosclerotic heart disease(CAD) on admission .Methods:Clinical data of 464 pa‐tients undergoing coronary angiography were retrospectively analyzed ,which included 345 male cases and 119 female cases with mean age of 62 .71 ± 0 .46 .The patients were divided into stenosis group (n=327) and normal group (n=137) according to the results of coronary angiography .The severity of coronary artery stenosis was calculated according to Gensini score .The SM levels of all patients were measured on admission .Results:SM levels in control group and stenosis group were 39 .45 ± 0 .91 mg/dL ,45 .05 ± 0 .78 mg/dL ,respectively ,and the difference between the two groups was statistically significant (P<0 .001) .SM levels were positively correlated with Gensini scores(r=0 .155 ,P=0 .001) .The Gensini scores according to their tertiles of SM levels were 6(0‐38) ,18(2‐50) ,19(0‐49) ,respectively .The differences regarding Gensini scores among the three groups were statistically significant (P=0 .035) .After multiple related risk factors had been corrected ,the multivariate linear regression analysis showed that plasma SM levels were independently associated with Gensini scores (β=0 .143 ,95% CI 0 .148~0 .654 ,P=0 .002) .Conclusions:SM level was significantly associated with coronary angiography Gensini score ,and its level might be an independent risk factor for predicting the degree of coronary stenosis .SM might provide novel therapeutic tar‐get for the treatment of CAD .

Objective To explore the predictive values of the levels of blood lipids ,liver function and estrogen for the fetal dis‐tress in intrahepatic cholestasis of pregnancy (ICP) patients .Methods The indicators of blood lipids ,liver function and estrogen of mild IPC group ,severe ICP group and control group were detected respectively ,and the results were analyzed .Results The levels of triglycerides ,total cholesterol and low‐density lipoprotein were positively related to estradiol levels .Multivariate logistic regres‐sion analysis showed that cholyglycine (OR=8 .24 ,P=0 .01) and estradiol(OR=4 .46 ,P=0 .02) were significant for prediction of fetal distress in ICP patients .Conclusion Estradiol and cholyglycine levels may be better indicators for the prediction of fetal dis‐tress in ICP patients .

Twenty-five hybrid dogs were injected intravenously with oleic acid of the dose 0.3 ml/kg of body weight to prepare a model of respiratory distress syndrome (RDS) . The animals were killed 24 hours after injection. PaO2, PaCO2 and pH of the arterial and mixed venous blood were determined before and immediately, 0.5, 1?2, 4, 6, 22 and 24 hours after injection. The average pulmonary arterial pressure was measured hourly. The chest x-ray films were taken 2,4, 6 and 24 hours after injection. The electrolytes T3, T4, the hematocrit and RBC count, and the serum corticosteroid level were measured before and 24 hours after injection.25 dogs were divided into two groups; the control group consisted of 8 dogs and the therapeutic group consisted of 17 dogs, among which nine were treated with hyosine hydrobromide and 8 with dexamethasone. The histologic specimens of the animals of the control group and hyosine hydrobromide treated group were examined with both light and electron microscopes but the specimens of the animals of dexamethasone treated group were examined with light microscope only.It was found that dexamethasone is effective in the treatment of RDS produced with oleic acid injection while hyosine hydrobromide is of no value.