ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog （PTEN）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups （n=8 each group）： model group， miR‑21 overexpression group， miR‑21 inhibition group， and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression， miR‑21 inhibition， and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus （50 μL， 1×10⁸ TU per mouse） once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector （LV‑NC）. The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 （480 mg/kg） once weekly for three weeks. The expressions of miR‑21， 24 h urinary protein， serum creatinine （Scr）， blood urea nitrogen （BUN）， and renal tissue levels of collagen Ⅰ， collagen Ⅲ， α‑smooth muscle actin （α‑SMA）， and PTEN protein， as well as p‑AKT/AKT and p‑mTOR/mTOR ratios， were compared among groups. HE staining was used to observe pathological changes in renal tissue， and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group， miR‑21 expression in renal tissue increased in the miR‑21 overexpression group （P<0.05） and decreased in the miR‑21 inhibition group （P<0.05）. Compared with the model group， the miR‑21 overexpression group showed increased 24 h urinary protein， Scr， BUN， and renal tissue expression of collagen Ⅰ， collagen Ⅲ， and α‑SMA （all P<0.05）， while these indicators decreased in the miR‑21 inhibition group （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein， Scr， BUN， and renal tissue expression of Collagen Ⅰ， Collagen Ⅲ， and α‑SMA （all P<0.05）. Compared with the model group， the miR‑21 overexpression group showed decreased PTEN protein expression （P<0.05） and increased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， while the miR‑21 inhibition group showed increased PTEN expression （P<0.05） and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement， capillary loop adhesion， and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure， accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis， with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1， the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased （P<0.001）. There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.

BackgroundCurrently， the incidence of depression among teenagers is on the rise， and the related academic problems are becoming increasingly serious. Short video addiction has a negative impact on teenagers' emotional issues and academic achievements. However， few studies have explored the relationship between this addiction and the learning burnout of teenagers with depression， and even fewer have focused on the role paths of impulsivity and coping disposition in this process. ObjectiveTo explore the relationship between short video addiction and learning burnout in adolescent patients with depression， as well as the pathway of impulsivity and coping disposition， so as to provide references for the intervention of learning burnout in adolescent patients with depression. MethodsA total of 191 adolescent patients who were hospitalized at The Affiliated Brain Hospital of Guangzhou Medical University from December 2024 to April 2025 and met the diagnostic criteria for depression according to the International Classification of Diseases， tenth edition （ICD-10） were selected consecutively. The Short Video Addiction Measurement Scale （SVAMS）， the Brief Barratt Impulsiveness Scale （BBIS）， the Simplified Coping Style Questionnaire （SCSQ）， and the Adolescent Student Burnout Inventory （ASBI） were used for assessment. Pearson correlation analysis was employed to examine the correlations of the scores of each scale. Model 6 of the SPSS macro Process 4.2 was employed to analyze the chained mediation pathway of impulsivity and coping disposition between short video addiction and learning burnout. ResultsA total of 173 cases （90.58%） of adolescent patients with depression completed the valid questionnaire survey. Correlation analysis showed that SCSQ coping disposition score was negatively correlated with the SVAMS score， the BBIS score， and the ASBI score （r=-0.282， -0.341， -0.431， P<0.01）， the SVAMS score was positively correlated with the BBIS score and the ASBI score （r=0.339， 0.262， P<0.01）， and the BBIS score was positively correlated with the ASBI score （r=0.486， P<0.01）. The pathway analysis showed that the direct effect of short video addiction on learning burnout was not statistically significant， but the total effect and the indirect effect were statistically significant. The effect values were 0.275 （95% CI： 0.207–0.343） and 0.193 （95% CI： 0.143–0.246）， respectively， with the indirect effect accounting for 70.18%. Impulsivity and coping disposition both played independent mediating roles between short video addiction and learning burnout， with effect values of 0.122 （95% CI： 0.090–0.156） and 0.054 （95% CI： 0.032–0.079）， accounting for 44.36% and 19.64% of the total effect， respectively. The chained mediation effect of impulsivity and coping disposition was significant， with an effect value of 0.017 （95% CI： 0.011–0.026）， accounting for 6.18% of the total effect. ConclusionAlthough short video addiction does not directly affect learning burnout in adolescent patients with depression， it may indirectly influence learning burnout through independent and chain paths of impulsivity and coping disposition. ［Funded by Guangzhou Key Clinical Specialty （Clinical Medical Research Institute）］

Objective To investigate and analyze the occupational stress levels and influencing factors among radiation workers in China, and provide a reference for alleviating occupational stress and promoting mental health. Methods Using the general situation questionnaire, Effort-Reward Imbalance questionnaire, and radiation protection knowledge questionnaire, a convenience sampling method was adopted to investigate the occupational stress of 243 radiation workers in Liaoning, Fujian, Guangdong, and Xinjiang provinces. The independent samples t-test, one-way analysis of variance, chi-square test, and binary logistic regression were used to analyze the influencing factors. Results The average score of Effort-Reward Imbalance was 0.97 ± 0.22, and 100 (41.15%) radiation workers had occupational stress. There were significant differences in the detection rate of occupational stress among radiation workers of different ages, working years in radiation positions, monthly incomes, daily sleep durations, and daily working hours (P < 0.05). Logistic regression analysis identified daily working hours as a factor contributing to occupational stress. Conclusion The occupational stress among radiation workers in China is relatively severe. It is recommended to pay attention to the associated risks and implement targeted intervention measures to reduce the impact of occupational stress.

OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living

The plant F-box protein more axillary growth 2 (MAX2) is a key factor in the signal transduction of strigolactones (SLs) and karrinkins (KARs). As the main component of the SKP1-CUL1-FBX (SCF) complex ubiquitin ligase E3, MAX2 is responsible for specifically recognizing the target proteins, suppressor of MAX2 1/SMAX1-like proteins (SMAX1/SMXLs), which would be degraded after ubiquitination. It can thereby regulate plant morphogenesis and stress responses. There exist homologous genes of MAX2 in the important grain and oil crop soybean (Glycine max). However, its role in plant defense responses has not been investigated yet. Here, GmMAX2b, a homologous gene of MAX2, was successfully cloned from stressed soybean. Bioinformatics analysis revealed that there were two MAX2 homologous genes, GmMAX2a and GmMAX2b, with a similarity of 96.2% in soybean. Their F-box regions were highly conserved. The sequence alignment and cluster analysis of plant MAX2 homologous proteins basically reflected the evolutionary relationship of plants and also suggested that soybean MAX2 might be a multifunctional protein. Expression analysis showed that plant pathogen infection and salicylic acid treatment induced the expression of GmMAX2b in soybean, which is consistent with that of MAX2 in Arabidopsis. Ectopic expression of GmMAX2b compensated for the susceptibility of Arabidopsis max2-2 mutant to pathogen, indicating that GmMAX2b positively regulated plant disease resistance. In addition, yeast two hybrid technology was used to explore the potential target proteins of GmMAX2b. The results showed that GmMAX2b interacted with SMXL6 and weakly interacted with SMXL2. In summary, GmMAX2b is a positive regulator in plant defense responses, and its expression is induced by pathogen infection and salicylic acid treatment. GmMAX2b might exert its effect through interaction with SMXL6 and SMXL2. This study expands the theoretical exploration of soybean disease resistant F-box and provides a scientific basis for future soybean disease resistant breeding.
Glycine max/metabolism* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plant Proteins/genetics* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; F-Box Proteins/genetics* ; Arabidopsis/genetics* ; Phylogeny

Adjuvants as essential ingredients amplify the magnitude and durability of immune responses in various vaccine strategies. Polysaccharides with potent immunoenhancing effects are widely applied as promising vaccine adjuvants, however, they have rarely been licensed for use in human vaccines due to the limitation of their efficacy and safety. Moreover, nanoparticles not only act as antigen drug delivery vectors but also possess intrinsic adjuvant functions, revealing the dual effects of nanoparticles in augmenting antigen-specific immune responses. Intriguingly, nanoparticle forms can enhance the immunostimulatory potency of polysaccharide adjuvants, since polysaccharide nanoparticles exert more excellent adjuvant effects than polysaccharides in initiating humoral, cellular and mucosal immune responses. Emerging evidence has also suggested that multiple immune-related signaling pathways including cGAS-STING, NLRP3, TLRs, cell death or metabolism signaling probably participate in the immunomodulation of polysaccharide nanoparticles, but systemic investigations into the adjuvant mechanism are still inadequate. This review aims to give an updated summary and discussion on the adjuvant function and mechanism of polysaccharide nanoparticles for understanding their superior adjuvant property and effectively utilizing them as potent immune adjuvants in vaccine development.

BACKGROUND:Matrigel is the best material for the culture of tumor organoids,but matrigel alone is not enough to simulate the mechanical environment of tumor growth in vitro.Although the introduction of sodium alginate material can improve the stiffness of the hydrogel based on matrigel,its mechanical properties of hydrogel are difficult to maintain stability in long-term culture.OBJECTIVE:To introduce a small amount of calcium ions into the medium of breast cancer organoids and to observe its maintenance effect on the long-term mechanical properties of the matrigel-sodium alginate hydrogel.METHODS:(1)Sodium alginate composite hydrogels with low,medium,and high stiffness were prepared by introducing different mass concentrations(0,2.5,and 5 mg/mL)of sodium alginate into the constant mass concentration(5 mg/mL)of matrigel.The mechanical properties of hydrogels were measured regularly by rheometer.(2)Human triple negative breast cancer cells MDA-MB-231 were resuspended in hydrogel pre-gels with different stiffness.After gelling,breast cancer organoid factor medium containing(or without)calcium ions was added for breast cancer organoid culture.At a set time point,rheometer was used to regularly measure the effect of calcium ion introduction on the mechanical properties of hydrogel.The morphologic changes of breast cancer organoids were observed under optical microscope.Rate of breast cancer organoids forming into pellets was calculated on day 13.After 7 days of breast cancer organoid culture,different concentrations of the chemotherapy drug docetaxel(0.1,1,10,and 100 nmol/L)were added for intervention for 6 days.Cell viability was detected and the semi-inhibitory concentration of docetaxel,IC50,was calculated.RESULTS AND CONCLUSION:(1)The introduction of sodium alginate effectively improved the mechanical strength of the composite hydrogel.(2)With the extension of breast cancer organoid culture time,the mechanical strength of hydrogels decreased.On day 13 of culture,the mechanical properties of medium and high stiffness hydrogels in the culture environment containing calcium ions were significantly higher than those in the culture environment without calcium ions(P<0.05).There was no significant change in the mechanical properties of low stiffness hydrogels in the two cultures(P>0.05).In long-term culture(13 days),breast cancer organoids changed from round to spindle shape with the decrease of hydrogel mechanical properties in the medium and high stiffness hydrogel groups.After the introduction of calcium ions,the morphology of breast cancer organoids did not change with the extension of culture time in the two groups.The introduction of calcium ions in the culture environment had no effect on the pellet formation rate of breast cancer organoids in the low stiffness hydrogel group,but could improve the pellet formation rate of breast cancer organoids in the medium and high stiffness hydrogel groups.(3)In the culture environment without calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration,and there was no significant difference in IC50 among the three hydrogel groups(P>0.05).In the culture environment containing calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration.The cell viability of breast cancer organoids in the medium and high stiffness hydrogel groups was stronger than that in the low stiffness hydrogel group,and the IC50 was higher than that in the low stiffness hydrogel group(P<0.05).(4)The results showed that the mechanical properties of the matrigel-sodium alginate hydrogel could be maintained by introducing calcium ions into the breast cancer organoid culture system.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, causing a significant socioeconomic burden. This article reviews the effects of influenza vaccination on COPD and finds that influenza vaccine can significantly reduce the risk of influenza infection, reduce the number of acute exacerbations, and reduce the hospitalization rate in patients with COPD. The vaccine has a favorable safety profile and significant economic benefits, which can reduce medical costs. Currently, influenza vaccination mainly faces challenges such as insufficient patient awareness, insufficient support from the medical system, and socio-cultural and economic factors. Efforts should be focused on reducing the acute exacerbation of COPD patients and providing a scientific basis for the prevention and management of COPD patients.

Objective:To investigate the prognostic value of aldosterone synthase (CYP11B2) immunohistochemical expression in adrenal specimens for surgical outcomes of primary aldosteronism (PA).Methods:The clinical data of 99 patients who underwent total unilateral adrenalectomy from June 2022 to January 2023 at Beijing Anzhen Hospital was retrospectively analysed. The clinical data of 99 patients who underwent unilateral total adrenalectomy at Beijing Anzhen Hospital from June 2022 to January 2023 were retrospectively analyzed.There were 59 patients in the PA group, age (53.02±10.56) years, body mass index (BMI) (26.28±4.33) kg/m 2, preoperative aldosterone 29.0(15.9, 61.5)ng/dl, plasma renin 1.3(0.6, 2.8)μIU/ml, aldosterone renin ratio (ARR) 19.3(9.1, 59.2) μg/μIU, preoperative potassium (3.60±0.69) mmol/L, and systolic blood pressure (156.54±21.39) mmHg (1 mmHg=0.133 kPa).There were 40 cases in the nonfunctioning adenoma (NFA) group, age (57.23±9.39) years, BMI (27.07±3.46) kg/m 2, preoperative aldosterone 9.0(7.2, 14.1) ng/dl, plasma renin 18.0(5.2, 47.6)μIU/ml, ARR 0.6(0.2, 1.4) μg/μIU, preoperative potassium (4.17±0.41) mmol/L, and systolic blood pressure (157.97±26.87) mmHg. The differences between the two groups were statistically significant for potassium ( P<0.01), aldosterone ( P=0.012), renin ( P<0.01), and ARR ( P<0.01).Surgical outcomes were assessed using the Consensus on the Outcome of Surgery for Primary Aldosteronism (PASO) (complete/partial/no success for clinical and biochemical outcomes). CYP11B2 expression was evaluated by immunohistochemistry using the 2022 World Health Organization's histopathology of primary aldosteronism (HISTALDO) criteria. The correlation between the expression of CYP11B2 and surgical outcomes was assessed. Results:The mean follow-up of 99 patients was (11.73±4.92) months. Of these, 36 out of 59 PA patients had positive CYP11B2 expression in their adrenal specimens, while 23 were negative; all 40 NFA patients were negative for CYP11B2. Among the 36 CYP11B2-positive PA patients, there were 19 cases of aldosterone-producing adenomas, 3 aldosterone-producing nodules, 4 aldosterone-producing micronodules, 8 multiple aldosterone-producing micronodules, and 2 aldosterone-producing diffuse hyperplasia. 36 cases of CYP11B2-positive PA patients had complete clinical success in 15 cases, partial success in 20 cases, and no success in 1 case, and complete biochemical success in 24 cases, partial success in 11 cases, and no success in 1 case; 23 CYP11B2-negative PA patients had complete clinical success in 4 cases, partial success in 15 cases, and no success in 4 cases, and complete biochemical success in 6 cases, partial success in 15 cases, and no success in 2 cases. Adrenal specimens from CYP11B2-positive PA patients had significantly better clinical ( P=0.038) and biochemical ( P=0.008) success rates than CYP11B2-negative PA patients. Patients with aldosterone-producing adenomas had complete clinical success in 8 cases, partial success in 11 cases, and no success in 0 cases, and biochemical success was completely achieved in 16 cases, partially achieved in 2 cases, and not successful in 1 case. They also had significantly higher clinical ( P=0.028) and biochemical ( P<0.01) success rates compared to CYP11B2-negative PA patients. Conclusions:Patients with PA who had immunohistochemical staining for CYP11B2 positivity and high expression in adrenal specimens had a better postoperative clinical and biochemical prognosis. Patients with aldosterone-producing adenomas had the greatest postoperative outcome of all pathological subtypes of PA.

Objective:To establish a flow cytometric assay for myeloid-derived suppressor cells (MDSC) in human peripheral whole blood and reference intervals for healthy adults in Shanghai region.Method:A whole blood eight-color and twelve-parameter flow cytometric assay was designed, utilizing fluorescently labeled antibodies against CD45, CD3, CD19, CD123, CD56, CD16, HLA-DR, CD33, CD11b, CD14, CD15 and CD20.A total of 246 healthy participants who met the health standards from the health check-ups conducted at the Tongji University Affiliated Shanghai East Hospital between May 8 to December 2, 2024 were enrolled. Peripheral venous whole blood was collected using EDTA-K 2 anticoagulant vacuum tubes for MDSC detection. A single-platform flow cytometry based relative count technique was used to quantify the percentage of each MDSC subpopulation. Kolmogorov Smirnov (K-S) test was used to test the distribution of specimens. Mann-Whitney U test and Kruskal-Wallis (K-W) test were used to evaluate whether reference intervals should be established separately based on gender or age. According to the clinical significance of MDSC, bilateral reference intervals were taken. Non parametric methods were used to take the percentile P2.5 and P97.5 to represent the rank of the lower and upper reference limits, respectively. Results:The results showed that a gating strategy was designed to exclude granulocytes, lymphocyte lineage cells, and natural killer cells. The K-S test results showed that the MDSC in each group of healthy individuals were distributed in a skewed manner. The U test showed significant gender differences ( P0.05) in the distribution of total myeloid-derived suppressor cells (T-MDSC) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). The K-W test showed no significant differences in MDSC among different age groups (21-30 years old, 30-40 years old, 40-50 years old, and 50-60 years old). T-MDSC reference interval is 0.056%-0.485%, PMN-MDSC reference interval is 0.035%-0.406%, Monocytic myeloid-derived suppressor cells (M-MDSC) reference interval is 0.000%-0.221%, early-stage myeloid-derived suppressor cells (E-MDSC) reference interval is 0.004%-0.125%. Reference interval verification was conducted on 20 healthy individuals, with a pass rate of 100%. Conclusion:A whole blood eight-color and twelve-parameter flow cytometric assay was established in this experiment. Based on the flow cytometry single platform method, reference intervals for healthy adults in Shanghai region were established.