With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.
Humans ; Open Reading Frames ; Peptides ; Glucose ; Genome ; Metabolic Diseases

BACKGROUND: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
Humans ; Cohort Studies ; Longitudinal Studies ; Diabetes Mellitus, Type 2/diagnosis* ; Maillard Reaction ; Glycated Hemoglobin ; Cardiovascular Diseases

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.
Humans ; Spirulina ; Anti-Bacterial Agents/chemistry* ; Chitosan/pharmacology* ; Biofilms ; Chitin/pharmacology*

Objective:To explore the relative concentration changes of oxygenated hemoglobin (Oxy Hb) in the prefrontal cortex (PFC) and brain region activation during emotional face recognition tasks in women with perimenopausal depression.Methods:From February to April 2023, forty perimenopausal women were recruited, including 20 women with perimenopausal depression (experimental group) and 20 women with non-perimenopausal depression (control group). All participants were evaluated by the modified Kupperman score, 24-item Hamilton depression scale (HAMD-24), and patient health questionnaire (PHQ-9). Functional near-infrared spectroscopy (fNIRS) equipment was used to measure the relative concentration of Oxy-Hb in the PFC in two groups under the emotional face recognition task. Statistical analysis was performed by SPSS 26.0 software. Data were analyzed by a t-test, rank sum test, and Pearson correlation. Results:There were statistically significant differences in the results of the modified Kupperman score((23.20±3.66), (18.10±1.28)), HAMD-24((15.95±5.47), (3.35±1.84)), and PHQ-9(7.00(5.00, 10.75), 1.50(1.00, 3.00)) scales between the the experimental group and control group ( P<0.05). There was a positive correlation between the modified Kupperman score and the HAMD-24 score in the experimental group ( r=0.685, P=0.01). The reaction time of the experimental group in identifying negative and neutral emotional faces was statistically significant compared to the control group( t=4.01, 4.80, both P<0.05). Compared with identifying neutral emotions, PFC activation was stronger in the experimental group and control group when identifying negative emotions ( P<0.05). The PFC activation in the experimental group was stronger than that in the control group when identifying negative emotions ( P<0.05). There was no statistically significant difference in the activation level between the two groups when identifying neutral emotions ( P>0.05). Conclusion:Women with perimenopausal depression exhibit specificity in emotional processing, with increased PFC activation when identifying negative emotions, impaired emotional processing function of PFC, and dysfunction of aerobic metabolism.

OBJECTIVES: This population-based, prospective cohort study investigated the association between glaucoma and mortality in older adults. METHODS: Participants aged 45 years or older at baseline (47.9% male) were enrolled in 2011 for the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was observed during 7 years of follow-up. The baseline data were collected in the 2011 CHARLS, and participants were followed up for 7 years (until 2018). The risk of all-cause mortality was investigated using Cox proportional-hazards regression with age as the time scale, adjusting for significant risk factors and comorbid conditions. RESULTS: Among the 14,803 participants included, the risk of all-cause death was significantly higher among people with glaucoma than among those without glaucoma, after adjustment for other confounders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04 to 2.03). In a subgroup analysis based on the mean age of death, among those who were 75 years and older (n=1,231), the risk of all-cause death was significantly higher in patients with glaucoma than in those without glaucoma (HR, 1.89; 95% CI, 1.24 to 1.89). CONCLUSIONS Participants with glaucoma had a higher risk of all-cause mortality, especially those aged 75 years and above. Our findings revealed potential mechanisms underlying an association between glaucoma and all-cause mortality. They also highlighted the importance of glaucoma management to prevent premature death in middle-aged and older adults.

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

Lithium carbonate as a mood stabilizer ，is the first -line treatment for bipolar disorder （BD）. Due to the narrow treatment range and large individual respons e differences ，physiological and pathological states and drug interactions can affect its therapeutic effect ；as therapeutic drug monitoring （TDM），population pharmacokinetics （PPK）and pharmacogenomics play an increasingly important role in the individualized use of lithium carbonate ，how to optimize the individualized use of lithium carbonate more effectively has attracted much attention . This paper reviewed the latest research progress of TDM ，PPK and pharmacogenomics in the individualized treatment of lithium carbonate in recent years . Due to the influence of patients ’ pathophysiological status ，the target blood concentration range of lithium among different populations was slightly different . To ensure its efficacy and safety ，routine TDM was required . PPK studies conducted in different populations showed that the relevant predictors used to optimize lithium treatment included body mass ，lean body mass ，age and renal function ，etc. Pharmacogenomics research showed that the single nucleotide polymorphisms of FKBP5，ACP1，ADCY2 and other genes were related to the difference of patients ’treatment response . Therefore，on the basis of routine TDM for lithium carbonate ，the comprehensive evaluation combined with PPK and pharmacogenomics is of great significance for the individual treatment of lithium carbonate .

Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC + rLC protein had a higher activity than the hHC + hLC protein at comparable expression levels. The specific activity of hHC + rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC + rLC treatment exhibited a visibly higher activity than those treated with hHC + hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC + rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.
Animals ; Dependovirus/genetics* ; Factor VIII/metabolism* ; Genetic Therapy/methods* ; Hemophilia A/therapy* ; Humans ; Mice ; Rats

Objective: To evaluate the effects of adeno-associated virus (AAV) carrying hFⅧ by serotype 8 (AAV8/hFⅧ) on hemophilia A (HA) mice by gene therapy strategy. Methods: pAAV-CB-EGFP, pH22 (serotype 2) and pfΔ6 (adenovirus helper) were used to package AAV into HEK-293 cells in different conditions (ratios of cells to plasmids). The efficiency of transfection and infection were evaluated using immunofluorescence microscope to seek an optimized package condition. pAAV-TTR-hFⅧ, pH 28 (serotype 8) and pfΔ6 were applied to package AAV8/hFⅧ in HEK-293 cells using the optimized package condition. The purified AAV8/hFⅧ were intravenously injected into HA mice and the effects of gene therapy were estimated. Results: The efficiency of package was evaluated according to the amount and intensity of enhanced green fluorescent protein (EGFP) under immunofluorescence microscope. Four package conditions including 10 cm-dish to transfect 10 μg plasmids, 20 cm-dish to 20 μg, 30 μg and 40 μg plasmids were employed, and the condition of 20 cm-dish to transfect 20 μg plasmids reached the highest transfection efficiency at 24 h, 48 h and 72 h after transfection. The small scale AAV-EGFP was packaged using the optimized condition and an AAV crude extract was harvested by a freeze-thaw method. HEK-293 and 16095 cells were infected by the AAV crude extract, and the preferential infection efficiency was recognized in 16095 cells under immunofluorescence microscope. Then, AAV8/hFⅧ was packaged and purified based on the optimized transfection condition, and the high purity of AAV8/hFⅧ was detected by Western blot. Fractions of AAV8/hFⅧ at the dose of 8×10¹² vg/kg were injected into HA mice through tail vein, an eye-bleeding was performed at every two weeks, and the activity of FⅧ was measured by aPTT assay. Results showed that the activity of FⅧ maintained at the therapeutic level and lasted up to 12 weeks after injection. Conclusion The purified AAV8/hFⅧ based on the optimized package condition could play a role in HA mice gene therapy, and the long-term therapeutic effects of AAV8/hFⅧ were observed in vivo.

Objective:To investigate the clinical significance of the serum platelet-derived growth factor BB (PDGF-BB) level in the diagnosis and treatment monitoring of non-small cell lung cancer (NSCLC) patients.Methods:Serum samples of 111 NSCLC patients in Xuzhou Cancer Hospital of Jiangsu Province and 105 healthy controls from Outpatients Department of Nanjing Yian Medical Examination Center between October 2014 and December 2017 were collected. Luminex assay was used to determine PDGF-BB level in serum samples of NSCLC patients and the healthy controls as well as patients after platinum chemotherapy. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of serum PDGF-BB level in patients with NSCLC, and the relationship of serum PDGF-BB level with clinicopathological features of NSCLC patients and platinum chemotherapy and effect was analyzed.Results:Compared to the healthy controls, serum PDGF-BB level was decreased in NSCLC patients [(54±24) ng/ml vs. (125±61) ng/ml, t = 11.09, P < 0.01], and the area under the ROC of serum PDGF-BB level on the diagnosis of NSCLC was 0.890. There were no significant differences in serum PDGF-BB level among NSCLC patients with different gender, age or lymph node metastasis (all P > 0.05); the serum PDGF-BB level in patients with high TNM stage was lower than that in patients with low TNM stage, and the serum PDGF-BB level in patients with low differentiation degree was lower than that in patients with high differentiation degree (all P < 0.05). Serum PDGF-BB level was continued to decrease in NSCLC patients after treatment with platinum-based chemotherapy. Conclusion:Serum PDGF-BB level of NSCLC patients is decreased, and it has a certain clinical significance in the early diagnosis of NSCLC.