Objective: To investigate the effects and mechanisms of Astragalus Polysacharin(APS) on the proliferation and metastasis of breast cancer cells by regulating miR-107 and miR-346-mediated macrophage polarization in breast cancer-derived exosomes. Methods: Forty 8-week-old female BALB/c mice were selected and breast cancer xenograft models and 4T1 transplanted tumor models were established. The mice were divided into the control group and the APS group. The APS group mice received daily intragastric administration of APS for 25 days, while the control group mice were given the same amount of normal saline. After all treatments were completed, the mice were euthanized, and tumor tissues were isolated. Western blot and flow cytometry were used to detect the expressions of proliferating cell nuclear antigen(PCNA), Ki-67, CD206, CD163, inducible nitric-oxide synthase(iNOS), and CD86. The apoptosis of single-cell suspensions in tumor tissues was analyzed. Human breast cancer cell line MDA-MB-231 was cultured and stimulated with APS, and exosomes from the cell culture medium were collected. The proliferation, migration, and invasion of cells were detected by CCK-8 assay, scratch assay, permeability chamber cell invasion assay, and qRT-PCR. Differentially expressed genes were screened by bioinformatics. Results : By measuring the expressions of molecules related to breast cancer cell proliferation and metastasis, it was shown that APS treatment reduced the expressions of proliferation-related proteins(PCNA and Ki-67) and metastasis-related proteins(Vimentin) in MDA-MB-231 xenograft tumor tissues; and the polarization of tumor-associated macrophages was observed. APS treatment of 4T1 transplanted tumor tissues could reduce the number of M2 macrophages and increase the number of M1 macrophages, resulting in a decrease in the ratio of M2/M1 macrophages and an increase in cell apoptosis in 4T1 transplanted tumor tissues. The expressions of related proteins iNOS and CD86 increased, and CD206 and CD163 decreased. After APS treatment, the exosomes produced by MDA-MB-231 reduced the polarization of M2 macrophages and affected the expressions of miR-107 and miR-346. Conclusion APS inhibits the polarization of M2 macrophages by regulating the expression of miR-107 or miR-346 in breast cancer cell-derived exosomes, ultimately inhibiting the proliferation and metastasis of breast cancer cells.

OBJECTIVE: To explore the anti-photoaging properties of salvianolic acid B (Sal B). METHODS: The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. RESULTS: Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. CONCLUSION Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans ; Sirtuin 1/metabolism* ; Ultraviolet Rays ; Oxidative Stress/radiation effects* ; Keratinocytes/metabolism* ; Molecular Docking Simulation ; Benzofurans/pharmacology* ; Skin Aging/radiation effects* ; Reactive Oxygen Species/metabolism* ; Cell Survival/radiation effects* ; HaCaT Cells ; Hydroxyproline/metabolism* ; Glutathione Peroxidase/metabolism* ; Catalase/metabolism* ; Depsides

Objective To investigate the effect of senkyunolide I(SEN I)on neuronal apoptosis in sepsis-associated encephalopathy(SAE)rats via modulation of the mixed-lineage kinase 3(MLK3)/c-Jun N-terminal kinase 3(JNK3)signaling pathway.Methods Screening for a SAE model by monitoring neurobehavioral and electroencephalographic alterations in rats with sepsis induced by cecal ligation and puncture(CLP).Divided into normal control group,sham operation group,sepsis without encephalopathy group,SAE model group,SAE+MLK3/JNK3 signaling pathway inhibitor(URMC-099)group,SAE+low-dose SEN I group(36 mg/kg),and SAE+high-dose SEN I group(144 mg/kg),with 10 animals in each group.After 30 minutes of successful modeling,intraperitoneal injection was administered according to the group,and the administration was completed within 24 hours.HE staining was used to observe the pathological conditions of hippocampal tissue under a light microscope,transmission electron microscopy was used to observe changes in the morphology of neuronal nuclei,cytoplasm,and mitochondrial ultrastructure,TUNEL staining was used to detect hippocampal neuronal apoptosis,and Western blotting was used to detect the expression levels of p-JNK3,JNK3,p-MLK3,MLK3,and Fas ligand(Fas-L)proteins.Results Compared with the normal control group and sham surgery group,the sepsis without encephalopathy group showed no significant changes in neuronal structural morphology and neuronal apoptosis,and there were no significant differences in the expression of p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L proteins(P＞0.05).However,the SAE model group had aggravated neuronal structural morphology damage,increased neuronal apoptosis rate,and increased expression level of p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L proteins(P＜0.01);Compared with the SAE model group,the inhibitor URMC-099 and SEN I treatment groups showed significant improvement in neuronal structural and morphological damage,decreased neuronal apoptosis rates,and reduced p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L protein expression(P＜0.01),with the high-dose SEN I group showing more significant improvement.Conclusion SEN I effectively reduces neuronal apoptosis in SAE and exerts neuroprotective effects on SAE by inhibiting the activation of the MLK3/JNK3 signaling pathway.

Objective To investigate the effects of γ-glutamyl hydrolase(GGH)rs11545078 C＞T polymorphisms on serum concentrations,chemotherapy toxicities of methotrexate(MTX),and prognosis in children with intracranial tumors.Methods Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA.Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C＞T polymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of toxicities,relapse,and metastasis were recorded after chemotherapy with MTX.The associations of GGH rs11545078 C＞T polymorphisms with concentration-to-dose ratios(C/D ratios),chemotherapy toxicities of MTX,relapse,and metastasis of tumors were analyzed.Results A total of 75 children were included in the present study.The frequencies of rs11545078 CC and CT genotypes were 82.67％and 17.33％,respectively.The frequencies of C and T alleles were 91.33％and 8.67％,respectively.There were no statistically significant differences for these frequencies among the children with intracranial tumors,the children with acute lymphoblastic leukemia,and the health population in Beijing.Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h(25.19 and 0.14 μmol·L-1 per g·m-2,respectively),higher metastasis rates(46.77％),and lower relapse rates(17.74％)than those in CT genotype carriers(22.01 and 0.11 μmol·L-1 per g·m-2,38.46％,and 30.77％,respectively),and the differences were no statistically significant(all P＞0.05).The incidences of gastrointestinal disorders(76.92％)in children with the CT genotype were significantly higher than those in CC genotype carriers(45.16％,P＜0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype(all P＞0.05).Conclusion GGH rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.

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 investigate the effects of γ-glutamyl hydrolase(GGH)rs11545078 C＞T polymorphisms on serum concentrations,chemotherapy toxicities of methotrexate(MTX),and prognosis in children with intracranial tumors.Methods Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA.Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C＞T polymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of toxicities,relapse,and metastasis were recorded after chemotherapy with MTX.The associations of GGH rs11545078 C＞T polymorphisms with concentration-to-dose ratios(C/D ratios),chemotherapy toxicities of MTX,relapse,and metastasis of tumors were analyzed.Results A total of 75 children were included in the present study.The frequencies of rs11545078 CC and CT genotypes were 82.67％and 17.33％,respectively.The frequencies of C and T alleles were 91.33％and 8.67％,respectively.There were no statistically significant differences for these frequencies among the children with intracranial tumors,the children with acute lymphoblastic leukemia,and the health population in Beijing.Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h(25.19 and 0.14 μmol·L-1 per g·m-2,respectively),higher metastasis rates(46.77％),and lower relapse rates(17.74％)than those in CT genotype carriers(22.01 and 0.11 μmol·L-1 per g·m-2,38.46％,and 30.77％,respectively),and the differences were no statistically significant(all P＞0.05).The incidences of gastrointestinal disorders(76.92％)in children with the CT genotype were significantly higher than those in CC genotype carriers(45.16％,P＜0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype(all P＞0.05).Conclusion GGH rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.

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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.