Objective To investigate dynamic shifts in the oral microbiota and their association with the progression and aggravation of radiotherapy-induced oral mucositis(RIOM)in patients with head and neck malignancies undergoing radiotherapy.Methods Based on 16S rRNA gene sequencing,dynamic changes of oral microbiota in patients was analyzed.Results Firmicutes,Bacteroidetes,and Actinobacteria consistently constituted the predominant bacteria in the oral cavity.While there were no significant changes in the abso-lute abundance of microbiota,there were notable alterations in their relative richness and evenness.Analyses including CCA/RDA and Kruskal-Wallis indicated a significant increase in the proportions of Streptococcus and Lactobacillus genera in the later stages post-radio-therapy,showing statistically meaningful differences.Conclusion RIOM is associated with dysbiosis of oral microbiota.Microbial dys-biosis may aggravate the severity of RIOM.Streptococcus and Lactobacillus could be closely related to the progression of RIOM,pending further validation through animal experiments.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objective: To explore the prevalence of elevated blood pressure and overweight/obesity and their comorbidities among Tibetan middle school students in Lhasa, and to analyze their association with lifestyle and other factors, so as to provide a basis for the intervention measures targeting elevated blood pressure, overweight and obesity among middle school students in high altitude area. Methods: Using a stratified cluster random sampling method in September 2021, a total of 1 488 Tibetan junior and high students from Lhasa City were investigated with blood pressure measurement, physical examination and questionnaire survey. The influencing factors of elevated blood pressure, overweight and obesity and their comorbidities association were analyzed by multivariate Logistic regression. Results: The prevalence of elevated blood pressure, overweight/obesity and their comorbidities were 17.8%, 17.4% , 5.0% respectively. Multivariate Logistic regression analysis showed that age( OR =0.81), residence, body mass inex(BMI) and gender were the influencing factors of elevated blood pressure; and the risks of elevated blood pressure in female students were higher than male students ( OR =1.89), suburban students were higher than urban students ( OR =8.06), overweight and obesity groups were higher than normal groups ( OR =2.55, 2.87) ( P <0.05). Adjusting for confounding factors such as gender, residence and school, and BMI (only for elevated blood pressure), daily screen time ≥2 h was positively correlated with elevated blood pressure, overweight/obesity and its comorbidities ( OR =1.56, 1.59 , 2.51) ( P <0.05). Conclusions The prevalence of elevated blood pressure, overweight/obesity are relatively high in Lhasa. Longer screen time is a common factor affecting with elevated blood pressure, overweight/obesity and comorbidities among Tibetan students. Measures should be taken intervene in the lifestyle of Tibetan students, in order to reduce elevated blood pressure and overweight/obesity.

BACKGROUND:In recent years,a variety of lasers have been widely used in various diseases related to stomatology,including the prevention and treatment of dental caries. OBJECTIVE:To investigate the effect of neodymium-doped:yttrium aluminum perovskite(Nd:YAP)laser combined with two remineralizers on early enamel caries in vitro. METHODS:Early enamel caries models in vitro were artificially established by 60 enamel blocks and randomly divided into 6 groups(n=10).Group A did not undergo any treatment but underwent extracorporeal pH circulation.Group B underwent remineralization of dentin(the main component of casein phosphopeptide-amorphous calcium phosphate composite)and extracorporeal pH circulation.Group C underwent remineralization treatment of Sensodyne toothpaste(the main component of bioactive glass)and then underwent extracorporeal pH circulation.Group D received Nd:YAP laser irradiation and extracorporeal pH circulation.Group E was treated with Nd:YAP laser irradiation,with remineralization of dentin,and then with extracorporeal pH circulation.In group F,Nd:YAP laser irradiation was performed,and then Sensodyne toothpaste was used for remineralization,and the extracorporeal pH circulation was performed;the remineralization treatment was conducted twice a day,and the experimental period was 20 days.Group G was a normal control group,without caries or remineralization,but only underwent extracorporeal pH circulation.After the experiment,the microhardness,morphology and Ca/P ratio of the dental enamel surface were measured in each group. RESULTS AND CONCLUSION:(1)The surface microhardness value of dental enamel in groups B,C and D was higher than that in group A(P<0.000 1);the surface microhardness value of dental enamel in groups E and F was significantly higher than that in groups B,C and D(P<0.000 1),and the surface microhardness value of dental enamel in group F was significantly higher than that in group E(P<0.000 1).(2)Scanning electron microscopy showed that there were a lot of demineralized pores on the enamel surface of group A.There were mineral deposits on the enamel surface of group B,which were uneven and loose.In group C,there were a lot of mineral deposits on the enamel surface,and demineralized pores were found between the calcified masses.The enamel surface of group D was relatively flat;the demineralized pores were significantly smaller than that of group A,and the enamel column interstitium was damaged.In group E,the mineral deposits on the enamel surface were thicker and the demineralized pores were significantly reduced.The mineralized substances deposited on the enamel surface of group F were most dense and uniform and the demineralized pores were small.(3)The Ca/P ratio on the enamel surface of groups B and C was significantly higher than that of group A(P<0.000 1);the Ca/P ratio on the enamel surface of group E was significantly higher than that of groups B,C and D(P<0.000 1),and the Ca/P ratio on the enamel surface of group F was higher than that of group E(P<0.001).(4)These findings indicate that bioactive glass,casein phosphopeptide-amorphous calcium phosphate composite,and Nd:YAP laser after enamel demineralization can promote the remineralization of early enamel caries.Nd:YAP laser combined with bioactive glass or casein phosphopeptide-amorphous calcium phosphate composite can further strengthen the remineralization of dental enamel caries,and the combination of Nd:YAP laser and bioactive glass has the best effect.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

To clarify the genetic diversity and structure of the nucleus population of F1-generation Litopenaeus vannamei, this study utilized 15 pairs of highly polymorphic microsatellite primers to analyze the simple sequence repeat (SSR) markers and genetic diversity in 15 full-sib families of L. vannamei. A total of 112 alleles (N_a) and 60.453 effective alleles (N_e) were identified among the selected 15 SSR loci, with the average polymorphic information content (PIC) of 0.648. The average N_e, observed heterozygosity (H_o), and expected heterozygosity (H_e) in the 15 F1 families varied from 1.925 to 2.626, 0.425 to 0.783, and 0.403 to 0.572, respectively. The 15 full-sib families were primarily clustered into three categories in the phylogenetic analysis, with the genetic distance between families ranging from 0.252 to 0.574. Additionally, the genetic differentiation coefficient (F_st) among the families varied from 0.112 to 0.278, indicating substantial genetic differentiation. Overall, this study suggested that the genetic diversity of the 15 full-sib families was moderate, providing valuable genetic insights for the subsequent breeding initiatives aimed at enhancing the tolerance of L. vannamei to high levels of soybean meal.
Penaeidae/classification* ; Microsatellite Repeats/genetics* ; Animals ; Genetic Variation ; Polymorphism, Genetic ; Phylogeny ; Alleles ; Genetic Markers

Acute myeloid leukemia (AML) is a group of highly-heterogeneous clonal diseases. Chemotherapy and hematopoietic stem cell transplantation are considered as effective treatment for AML. For high-risk AML patients, allogeneic hematopoietic stem cell transplantation is an effective therapeutic option. However, some AML patients may still face the problem of disease recurrence after hematopoietic stem cell transplantation. A majority of recurrent patients cannot be effectively treated by chemotherapy or secondary transplantation, which is the main cause of death after allogeneic hematopoietic stem cell transplantation. Therefore, it is of significance to strengthen follow-up of AML patients after allogeneic hematopoietic stem cell transplantation and implement appropriate measures to prevent postoperative recurrence. In this article, the monitoring, drug prevention and cell therapy of recurrence after allogeneic hematopoietic stem cell transplantation in high-risk AML patients were reviewed, aiming to provide reference for improving clinical prognosis of high-risk AML patients undergoing allogeneic hematopoietic stem cell transplantation.

Artemisinin is a sesquiterpene lactone containing a peroxide group isolated from the plant Artemisia annua. It has antimalarial activity and is effective for the treatment of malaria. With the deepening of research on artemisinin， the pharmacological effects of artemisinin and its derivatives in other systems have gradually become a research hotspot. This article reviews the research progress of artemisinin and its derivatives in the prevention and treatment of cardiovascular diseases. Artemisinin and its derivatives in the prevention and treatment of cardiovascular disease have shown anti-atherosclerosis， lipid- lowering， inhibition of vascular remodeling， reducing vascular pressure， improving ventricular remodeling， anti-arrhythmia， protection of vascular endothelium， prevention and treatment of diabetic cardiovascular complications and protection of myocardial cells and other pharmacological effects. It provides a new treatment strategy for common cardiovascular diseases such as hypertension， arrhythmia， coronary heart disease complications after stent implantation， hyperlipidemia， etc. However， there are few studies on the antiplatelet aggregation and antithrombotic effects of artemisinin and its derivatives， the molecular mechanisms behind many pharmacological effects have not yet been clarified， and there is little clinical application. A large number of basic studies and clinical trials are still needed to answer these questions.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

The normal ventilatory function is severely impaired by tracheal traumas, stenoses, tumors and some congenital diseases, which could result in tissue hypoxia and endangering the life of the patient. Resection and reconstruction of tracheal lesions is the most effective way to treat these diseases. At present, there is still no long-term safe and reliable method to achieve the reconstruction of long-segment trachea injury in clinical practice, and tissue-engineered trachea may be the solution to this situation. Cartilage, as one of the most important parts of tissue engineered trachea, plays a key role in providing mechanical support and maintaining the integrity of trachea. Tracheal tissue engineering cartilage regeneration process consists of several important parts, including the source of the cartilage cells, tissue engineering scaffold construction strategy and hydrogel composite scaffold material preparation, and the affecting factors of biological activity and application. This article reviews the new strategies of tissue engineered tracheal cartilage regeneration and the existing obstacles in order to provide reference for clinical practice.