A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

[This corrects the article DOI: 10.1016/j.apsb.2024.09.010.].

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective : To explore the polymorphism of endothelial nitric oxide synthase(eNOS) gene in umbilical cord blood of preterm infants and its relationship with major complications in preterm infants. Methods : A total of 254 preterm infants(<37 weeks) who were hospitalized were selected as the study subjects. Umbilical cord blood was collected at delivery to determine the genotypes and alleles of eNOS gene at three loci: rs61722009, rs2070744,and rs1799983. Clinical data of the preterm infants were recorded, and the relationship between eNOS gene polymorphism and major complications in preterm infants was analyzed. Results: (1) The TC+CC genotype at locus rs2070744 was an independent risk factor for bronchopulmonary dysplasia(BPD) in preterm infants, with an OR(95%CI) of 1.266(1.017-1.577).(2) The GT+TT genotype at locus rs1799983 was an independent risk factor for retinopathy prematurity(ROP), with an OR(95%CI) of 1.184(1.008-1.391).(3) The AB+AA genotype at locus rs61722009 was also an independent risk factor for ROP,with an OR(95%CI) of 1.335(1.033-1. 726).(4) There was no significant relationship between gene polymorphism and the occurrence of respiratory distress syndrome( RDS) and periventricular-intraventricular hemorrhage( PIVH). Conclusion eNOS gene polymorphism is associated with the occurrence of BPD and ROP in preterm infants. The evaluation of e NOS gene polymorphism by umbilical cord blood measurement is helpful for the prevention and correct management of some serious complications.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Glucocorticoid-induced osteoporosis(GIOP) is a serious metabolic bone disease caused by long-term application of glucocorticoids(GCs). Traditional Chinese medicine(TCM) has unique advantages in improving bone microstructure and antagonizing hormone toxicity. This paper systematically reviews the theoretical research, clinical application, and basic research progress of TCM intervention in GIOP. In terms of theoretical research, the theory of "kidney governing bone and generating marrow" indicates that the kidney is closely related to bone development, revealing that core pathogenesis of GIOP is Yin-Yang disharmony, which can be discussed using the theories of "Yin fire", "ministerial fire", and "Yang pathogen damaging Yin". Thus, regulating Yin and Yang is the basic principle to treat GIOP. In terms of clinical application, effective empirical prescriptions(such as Bushen Zhuanggu Decoction, Bushen Jiangu Decoction, and Zibu Ganshen Formula) and Chinese patent medicines(Gushukang Capsules, Hugu Capsules, Xianling Gubao Capsules, etc.) can effectively increase bone mineral density(BMD) and improve calcium and phosphorus metabolism. The combination of traditional Chinese and western medicine can reduce the risk of fracture and play an anti-GIOP role. In terms of basic research, it has been clarified that active ingredients of TCM(such as fraxetin, ginsenoside Rg_1, and salidroside) reduce bone loss and promote bone formation by inhibiting oxidative stress, ferroptosis, and other pathways, effectively improving bone homeostasis. Additionally, classical prescriptions(Modified Yiguan Decoction, Modified Qing'e Pills, Zuogui Pills, etc.) and Chinese patent medicines(Gushukang Granules, Lurong Jiangu Dropping Pills, Gubao Capsules, etc.) can improve bone marrow microcirculation, promote osteoblast differentiation, and inhibit bone cell apoptosis through multiple pathways, multiple targets, and multiple mechanisms. Through the above three aspects, the TCM research status on GIOP is elucidated in the expectation of providing reference for its diagnosis and treatment using traditional Chinese and western medicine treatment programs.
Osteoporosis/physiopathology* ; Humans ; Glucocorticoids/adverse effects* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional ; Bone Density/drug effects*

Diabetic foot ulcer (DFU) is one of the common chronic complications in diabetic patients. Its course is complex and the therapeutic effect is limited, which seriously affects the quality of life of patients. In recent years, significant progress has been made in the research on the mechanism of DFU wound repair. Studies have found that dysregulation of the inflammatory microenvironment, vascular dysfunction, obstruction of re-epithelialization, insufficient collagen deposition, and formation of wound biofilms are the core factors affecting healing. Intervention strategies targeting these mechanisms have become research hotspots. For instance, hydrogel scaffolds could provide an appropriate healing microenvironment, immune regulation strategies could promote inflammation resolution and tissue remodeling, and stem cell exosomes and growth factors have shown good potential in cell migration, angiogenesis, and matrix remodeling. Various natural compounds, such as components from Chinese herbal medicines, are also applied in diabetic foot ulcers. And it demonstrates excellent anti-inflammatory and restorative capabilities. However, existing research still faces obstacles in clinical translation, such as the immaturity of individualized treatment strategies and the difficulty of animal models in simulating complex clinical situations. By systematically summarizing the latest research progress on the repair mechanism of DFU, it is expected to provide theoretical support for precise treatment.
Humans ; Diabetic Foot/drug therapy* ; Wound Healing ; Animals

OBJECTIVES: To study the clinical characteristics of rashes induced by trimethoprim-sulfamethoxazole (TMP-SMZ) in children treated for pertussis and to inform safe medication practices. METHODS: A retrospective analysis was conducted on 238 children diagnosed with pertussis and treated with TMP-SMZ at Wuhu First People's Hospital from January to August 2024. The incidence and clinical features of rashes were summarized. RESULTS: Of 238 children, 34 (14.3%) developed rashes; 19 (55.9%) were boys, and the 5 to <10-year age group accounted for the highest proportion (70.6%, 24/34). A history of allergic disease was present in 50.0% (17/34). Rashes typically appeared on or after day 7 of therapy (82%, 28/34) and were predominantly erythematous or maculopapular eruptions (97%, 33/34); 71% (24/34) were pruritic. Fever occurred in 56% (19/34); among those who were tested for respiratory viruses, 77% (10/13) were positive for viruses such as rhinovirus and adenovirus. After discontinuation of TMP-SMZ, rashes resolved within 3 days in 97% (33/34) of patients (41% within 1 day; 56% within more than 1 but within 3 days). There was no significant difference in rash incidence between photoprotection and non-photoprotection groups (P>0.05). CONCLUSIONS TMP-SMZ for pertussis can induce rashes, particularly in children aged 5 to <10 years. The eruption is usually a pruritic erythematous or maculopapular rash, with over half of cases accompanied by fever and frequent concomitant viral infections. Most rashes resolve within 3 days after drug withdrawal. The potential association between the rash and sun exposure warrants further investigation.
Humans ; Male ; Child, Preschool ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use* ; Child ; Female ; Exanthema/chemically induced* ; Retrospective Studies ; Infant ; Whooping Cough/drug therapy* ; Adolescent

Previous studies have shown that the diversity and composition of intestinal microbiota are related to the effect of tumor immunotherapy,but the mechanism of intestinal microbiota affecting tumor immunotherapy resistance has rarely been sum-marized.This article not only expounds the current clinical sta-tus of tumor immunotherapy resistance,but also summarizes the correlation and regulatory mechanism between the composition and homeostasis of intestinal microbiota and drug resistance to different types of tumor immunotherapy,so as to provide a refer-ence for the study of potential targets for improving tumor immu-notherapy resistance based on intestinal microbiota.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.