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 analyze the value of diffusion tensor imaging (DTI) combined with magnetic resonance spectroscopy (MRS) in the clinical grading and prognosis assessment of brain glioma.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with brain glioma admitted to Yan'an People's Hospital from January 2010 to December 2023. The cohort included 40 males and 32 females, with ages ranging from 25 to 76 years and an average age of (40.3 ± 6.8) years. All patients underwent routine magnetic resonance imaging plain scans, contrast-enhanced ultrasound examination, DTI, and MRS prior to surgery. Measurements were conducted for fractional anisotropy (FA), N-acetyl aspartate (NAA), choline compounds (Cho), and creatinine (Cr). Additionally, the ratios of NAA/Cho, Cho/Cr, and NAA/Cr were calculated. The imaging characteristics of brain glioma were analyzed, and the clinical utility of these indicators for grading and prognosis assessment of brain glioma was evaluated.Results:DTI results of the 72 included patients revealed disruption of the white matter fiber tracts surrounding the tumors. MRS of the 72 included patients showed either approximately normal values or indicated elevated Cho and Cr levels, along with decreased NAA levels. Diffuse mild to moderate enhancement was observed in 35 patients (48.61%), presenting with a patchy pattern that suggested a higher tumor grade. When comparing low-grade gliomas (LGG) and high-grade gliomas (HGG) to the corresponding healthy tissue, significant differences were observed in FA value in the peritumoral edema region [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.62 ± 0.08) × 10 -3 mm2/s for LGG, and (0.17 ± 0.05) × 10 -3 mm2/s vs. (0.62 ± 0.09) × 10 -3 mm2/s for HGG] , NAA/Cho ratio [(0.36 ± 0.11) vs. (1.41 ± 0.33) for LGG, and (0.19 ± 0.06) vs. (1.42 ± 0.35) for HGG], Cho/Cr ratio [(2.39 ± 0.51) vs. (1.12 ± 0.26) for LGG, and (3.81 ± 0.94) vs. (1.12 ± 0.28) for HGG], and NAA/Cr ratio [(0.75 ± 0.24) vs. (1.52 ± 0.31) for LGG, and (0.38 ± 0.12) vs. (1.52 ± 0.29) for HGG]. All observed differences were statistically significant ( tLGG = 26.56, 19.09, 14.03, 12.42; tHGG = 27.64, 21.90, 17.34, 22.97, all P < 0.05). There were statistically significant differences in FA [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.17 ± 0.05) × 10 -3 mm2/s], NAA/Cho [(0.36 ± 0.11) vs. (0.19 ± 0.06)], Cho/Cr [(2.39 ± 0.51) vs. (3.81 ± 0.94)], and NAA/Cr [(0.75 ± 0.24) vs. (0.38 ± 0.12)] between LGG and HGG ( t = 2.26, 7.85, 8.17, 7.95, all P < 0.05). Follow-up conducted 6 months to 3 years postoperatively revealed that the Cho/Cr ratio in the death group was significantly higher than that in the survival group [2.172 (1.662, 2.863) vs. 2.729 (2.431, 3.689), U = 2.17, P < 0.05]. However, there were no statistically significant differences in FA, NAA/Cho, and NAA/Cr values between survival and death groups ( P > 0.05). Conclusions:Combined DTI and MRS can reveal specific imaging characteristics of brain gliomas, providing valuable information for clinical grading of brain gliomas. Furthermore, the Cho/Cr ratio is associated with prognosis and may serve as a potential imaging biomarker for predicting the outcome of brain gliomas.

PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

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 analyze the value of diffusion tensor imaging (DTI) combined with magnetic resonance spectroscopy (MRS) in the clinical grading and prognosis assessment of brain glioma.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with brain glioma admitted to Yan'an People's Hospital from January 2010 to December 2023. The cohort included 40 males and 32 females, with ages ranging from 25 to 76 years and an average age of (40.3 ± 6.8) years. All patients underwent routine magnetic resonance imaging plain scans, contrast-enhanced ultrasound examination, DTI, and MRS prior to surgery. Measurements were conducted for fractional anisotropy (FA), N-acetyl aspartate (NAA), choline compounds (Cho), and creatinine (Cr). Additionally, the ratios of NAA/Cho, Cho/Cr, and NAA/Cr were calculated. The imaging characteristics of brain glioma were analyzed, and the clinical utility of these indicators for grading and prognosis assessment of brain glioma was evaluated.Results:DTI results of the 72 included patients revealed disruption of the white matter fiber tracts surrounding the tumors. MRS of the 72 included patients showed either approximately normal values or indicated elevated Cho and Cr levels, along with decreased NAA levels. Diffuse mild to moderate enhancement was observed in 35 patients (48.61%), presenting with a patchy pattern that suggested a higher tumor grade. When comparing low-grade gliomas (LGG) and high-grade gliomas (HGG) to the corresponding healthy tissue, significant differences were observed in FA value in the peritumoral edema region [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.62 ± 0.08) × 10 -3 mm2/s for LGG, and (0.17 ± 0.05) × 10 -3 mm2/s vs. (0.62 ± 0.09) × 10 -3 mm2/s for HGG] , NAA/Cho ratio [(0.36 ± 0.11) vs. (1.41 ± 0.33) for LGG, and (0.19 ± 0.06) vs. (1.42 ± 0.35) for HGG], Cho/Cr ratio [(2.39 ± 0.51) vs. (1.12 ± 0.26) for LGG, and (3.81 ± 0.94) vs. (1.12 ± 0.28) for HGG], and NAA/Cr ratio [(0.75 ± 0.24) vs. (1.52 ± 0.31) for LGG, and (0.38 ± 0.12) vs. (1.52 ± 0.29) for HGG]. All observed differences were statistically significant ( tLGG = 26.56, 19.09, 14.03, 12.42; tHGG = 27.64, 21.90, 17.34, 22.97, all P < 0.05). There were statistically significant differences in FA [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.17 ± 0.05) × 10 -3 mm2/s], NAA/Cho [(0.36 ± 0.11) vs. (0.19 ± 0.06)], Cho/Cr [(2.39 ± 0.51) vs. (3.81 ± 0.94)], and NAA/Cr [(0.75 ± 0.24) vs. (0.38 ± 0.12)] between LGG and HGG ( t = 2.26, 7.85, 8.17, 7.95, all P < 0.05). Follow-up conducted 6 months to 3 years postoperatively revealed that the Cho/Cr ratio in the death group was significantly higher than that in the survival group [2.172 (1.662, 2.863) vs. 2.729 (2.431, 3.689), U = 2.17, P < 0.05]. However, there were no statistically significant differences in FA, NAA/Cho, and NAA/Cr values between survival and death groups ( P > 0.05). Conclusions:Combined DTI and MRS can reveal specific imaging characteristics of brain gliomas, providing valuable information for clinical grading of brain gliomas. Furthermore, the Cho/Cr ratio is associated with prognosis and may serve as a potential imaging biomarker for predicting the outcome of brain gliomas.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.