Objective To investigate the effect and potential mechanism of rat mesenchymal stem cells(MSC)on D-galactose-induced brain-tissue aging.Methods A rat brain-aging model was established by injecting D-galactose,and rats in the treatment group received MSC injections via the tail vein.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were assessed in rat brain tissue at the end of the experiment,and pathological changes in brain tissue were observed by hematoxylin-eosin(HE)staining.Expression levels of the inflammatory factors interleukin(IL)-1 and IL-6,the pathway proteins brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B(TrkB),the negative growth regulators p53 and p16,as well as vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)were observed by polymerase chain reaction(PCR)and Western Blot.Results Brain levels of SOD activity were significantly increased and MDA levels were significantly decreased in rats in the modle group compared with the treatment group(P＜0.05).The pathological state of the cerebral cortex and hippocampus were improved and the number of neurons and nucleus pulposus ratio in the brain were increased in the treatment group,as shown by HE staining.Expression levels of IL-1,IL-6,p53,and p16 were significantly decreased,while BDNF,TrkB,VEGF,and bFGF were significantly increased in the treatment group compared with the model group,as shown by PCR and Western Blot(P＜0.05).Conclusions These result suggest that MSCs potentially mitigate D-galactose-induced cerebral senescence by concurrently modulating the BDNF-TrkB axis to attenuate oxidative/inflammatory damage,while enhancing the secretion of vasculotrophic(VEGF)and neurotrophic(bFGF)factors for neuronal maintenance.

Objective To investigate the effect and potential mechanism of rat mesenchymal stem cells(MSC)on D-galactose-induced brain-tissue aging.Methods A rat brain-aging model was established by injecting D-galactose,and rats in the treatment group received MSC injections via the tail vein.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were assessed in rat brain tissue at the end of the experiment,and pathological changes in brain tissue were observed by hematoxylin-eosin(HE)staining.Expression levels of the inflammatory factors interleukin(IL)-1 and IL-6,the pathway proteins brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B(TrkB),the negative growth regulators p53 and p16,as well as vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)were observed by polymerase chain reaction(PCR)and Western Blot.Results Brain levels of SOD activity were significantly increased and MDA levels were significantly decreased in rats in the modle group compared with the treatment group(P＜0.05).The pathological state of the cerebral cortex and hippocampus were improved and the number of neurons and nucleus pulposus ratio in the brain were increased in the treatment group,as shown by HE staining.Expression levels of IL-1,IL-6,p53,and p16 were significantly decreased,while BDNF,TrkB,VEGF,and bFGF were significantly increased in the treatment group compared with the model group,as shown by PCR and Western Blot(P＜0.05).Conclusions These result suggest that MSCs potentially mitigate D-galactose-induced cerebral senescence by concurrently modulating the BDNF-TrkB axis to attenuate oxidative/inflammatory damage,while enhancing the secretion of vasculotrophic(VEGF)and neurotrophic(bFGF)factors for neuronal maintenance.

BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.

Objective:To explore the effect of combined therapy of traditional Chinese medicine on prevention of chemotherapy-related anemia in malignant tumors.Methods:Seventy-nine patients with malignant tumors diagnosed in Zibo Hospital of Traditional Chinese Medicine from January 2019 to January 2021 were selected, and the patients were divided into experimental group (40 cases) and control group (39 cases) according to the random number table method. The control group received chemotherapy and the experimental group received chemotherapy and combined therapy of traditional Chinese medicine (Wuhong Tang combined with moxibustion). The hemoglobin (Hb) level, Karnofsky score and adverse effects were recorded before and on days 7, 14 and 21 after chemotherapy in the two groups.Results:The Hb level in the experimental group was higher than that in the control group [(117±28) g/L vs. (100±31) g/L] on day 21 after chemotherapy, and the difference was statistically significant ( t = -3.08, P = 0.030). The total effective rate of the experimental group was higher than that of the control group [85% (34/40) vs. 66.7% (26/39)], but the difference was not statistically significant ( χ2 = 4.96, P = 0.084). Karnofsky scores were (77±9) points and (77±12) points before and on day 21 after treatment in the experimental group, with no statistical difference ( t = -0.50, P = 0.623); Karnofsky scores were (78±10) points and (67±9) points in the control group, with statistical difference ( t = 8.32, P < 0.001). There was no statistical difference in Karnofsky score before treatment between the two groups ( t = 1.85, P = 0.068), but the experimental group was higher than the control group on day 21 after treatment ( t = 4.88, P < 0.001). The difference in the incidence of nausea and vomiting between the two groups was not statistically significant ( P > 0.05), and no chemotherapy-related hepatic, renal or cardiac adverse reactions were observed in either group. Conclusions:Combined therapy of traditional Chinese medicine could effectively prevent chemotherapy-related anemia and improve the quality of life of patients.

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

During the epidemic of coronavirus disease 2019 (COVID-19), the infection of the elderly population will bring great challenges to clinical diagnosis and treatment, outcome and management.Combined with the characteristics of anesthesia and the pathophysiological characteristics of COVID-19 on lung function impairment in elderly patients, Chinese Society of Anesthesiology formulated the " Recommendations for anesthesia management and infection control in elderly patients with COVID-19″. This recommendation expounds preoperative visit and infection control, anesthesia management protocol, anesthesia monitoring, anesthesia induction/endotracheal intubation, anesthesia maintenance and infection control, intraoperative lung protection strategy, anti-stress and anti-inflammatory management, hemodynamic optimization, infection control during emergence from anesthesia, and postoperative analgesia in elderly patients with COVID-19, and provides the reference for the safe and effective implementation of anesthesia management in elderly patients during the prevention and control of COVID-19 epidemic.

Objective:To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer.Methods:We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model.Results:Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m 2 per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 ( OR=1.51, 95% CI: 1.07-2.15, P=0.020), APAF1 rs11296996 ( OR=0.69, 95% CI: 0.49-0.98, P=0.039) and BAX rs4645904 ( OR=0.69, 95% CI: 0.50-0.97, P=0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 ( OR=1.42, 95% CI: 1.02-2.00, P=0.040), rs74619561 ( OR=2.16, 95% CI: 1.27-3.68, P=0.005), CASP7 rs12263370 ( OR=1.67, 95% CI: 1.05-2.66, P=0.029), rs12247479 ( OR=1.85, 95% CI: 1.12-3.08, P=0.017) and TRAIL rs112822654 ( OR=0.68, 95% CI: 0.48-0.96, P=0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P>0.05). Grade≥2 myelosuppression occurred less frequently in male than in female ( P=0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P<0.001) and dermatitis (all P<0.05). Conclusions:The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.

Objective:To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer.Methods:We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model.Results:Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m 2 per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 ( OR=1.51, 95% CI: 1.07-2.15, P=0.020), APAF1 rs11296996 ( OR=0.69, 95% CI: 0.49-0.98, P=0.039) and BAX rs4645904 ( OR=0.69, 95% CI: 0.50-0.97, P=0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 ( OR=1.42, 95% CI: 1.02-2.00, P=0.040), rs74619561 ( OR=2.16, 95% CI: 1.27-3.68, P=0.005), CASP7 rs12263370 ( OR=1.67, 95% CI: 1.05-2.66, P=0.029), rs12247479 ( OR=1.85, 95% CI: 1.12-3.08, P=0.017) and TRAIL rs112822654 ( OR=0.68, 95% CI: 0.48-0.96, P=0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P>0.05). Grade≥2 myelosuppression occurred less frequently in male than in female ( P=0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P<0.001) and dermatitis (all P<0.05). Conclusions:The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.