Ionizing radiation (IR) is a genotoxic agent that can play an important role in the occurrence and development of various diseases by inducing epigenetic changes. Studies have shown that the basic mechanisms of IR-induced epigenetic changes include abnormal DNA methylation, increased oxidative stress levels, changes in histone modifications, and regulation by microRNAs. These can lead to health hazards such as malignant tumors, genetic effects, nervous system damage, circulatory system diseases, and radiation-induced cataracts. This article collected relevant literatures regarding epigenetic changes induced by IR from 2005 to 2024, and reviewed the basic mechanisms of IR-induced epigenetic changes and the associated disease risks, providing the reference for radiation protection in occupational exposure and radiotherapy.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g^-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells(VSMCs)induced by homocysteine(Hcy).Methods Human VSMCs were cultured in vitro and divided into a Control group(0 μmol/L Hey)and a Hey group(100 μmol/L Hey).After intervention,expression levels of pro Caspase-1,gasdermin D(GSDMD),N-GSDMD,and NLR family pyrin domain containing 3(NLRP3)were detected by Western blot.MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction.Interleukin(IL)-1 β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay.Cells were also transfected with control miR-22-3p(miR-22-3p-NC),miR-22-3p-mimic,and miR-22-3p-inhibitor,to observe the effects on VSMC pyroptosis induced by Hcy.Results Expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs were increased(P＜0.05),IL-1 β and IL-18 levels were increased(P＜0.01),and the relative expression level of miR-22-3p was reduced(P＜0.01)in the Hcy group compared with the Control group.Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01),and significantly decreased levels of IL-1β and IL-18(P＜0.01),while transfection with miR-22-3p-inhibitor significantly increased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01)and significantly increased the levels of IL-1β and IL-18(P＜0.05).Conclusions MiR-22-3p may delay Hcy-induced VSMC pyroptosis.

Objective:To explore the application value of preoperative high-resolution magnetic resonance imaging(MRI)enhanced examination in the preoperative diagnosis of tumor node metastases(TNM)staging of rectal tumor.Methods:A total of 80 patients with rectal tumor admitted to Guang'an People's Hospital from June 2021 to September 2022 were selected.All patients underwent high-resolution MRI enhanced examinations before surgery and they were confirmed by postoperative pathological examination.The consistency of MRI T staging,N staging and postoperatively pathological staging results was analyzed.Results:The postoperative pathological staging results showed that 14 cases were at T1 stage,and 29 cases were at T2 stage,and 25 cases were at T3 stage,and 12 cases were at T4 stage,and 28 cases were at N0 stage,and 33 cases were at N1 stage and 19 were at N2 stage in the 80 patients.The diagnostic accuracies of T staging and N staging of high-resolution MRI routine and enhanced examinations were respectively 86.25%(69/80)and 90.00%(72/80)(Kappa=0.806,0.847,P<0.05).The consistency rate between preoperative high-resolution MRI detection and postoperative pathology for metastatic lymph nodes of 80 patients was 88.75%(71/80).The analysis found that metastatic lymph nodes mostly concentrated in the diameter range of 0.8-1.0 cm,accounting for 66.41%.With the increasing of N staging and T staging,the volume transfer constant(Ktrans)of the region of interest(ROI)of tumor increased successively.The Ktrans value of metastatic lymph nodes was significantly higher than that of non-metastatic lymph nodes,and the difference was statistically significant(t=14.890,P<0.05).Conclusion:Preoperative high-resolution MRI routine and enhanced examination has highly consistency with postoperative pathological TN staging of rectal tumor.The improvement of high-resolution MRI enhanced examination is helpful to assess the progression of patients'tumors and to determine treatment plans for them.

This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.

Objective:To investigate the correlation between serum concentration of vasohibin-1 (VASH-1) and urinary albumin creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy.Methods:The clinical data of 196 patients with T2DM from February 2017 to December 2020 were analyzed retrospectively. According to whether diabetic nephropathy (DN) was combined, 33 patients without DN of T2DM were divided into the control group,and 163 patients with DN of T2DM were divided into the case group, and the case group was divided into four groups:normal albuminuria group (groupⅠ, UACR <30 mg/g, 21 cases),microalbuminuria group (groupⅡ, UACR ≥30-≤300 mg/g, 50 cases), clinical albuminuria group (group Ⅲ, UACR>300 mg/g, 43 cases), and clinical albuminuria hypertensive group (groupⅣ, UACR >300 mg/g with hypertension, 49 cases). Serum levels of VASH-1,C-reactive protein(CRP), erythrocyte sedimentation rate (ESR) and transforming growth factor β1 (TGF-β1) with other biochemical indicators were measured. T-test was used for comparison between measurement data groups in accordance with normal distribution, one-way ANOVA was used for comparison between multiple groups, q-test was used for pairwise comparison, and χ2 test was used for comparison between counting data groups. The influencing factors were analyzed by multivariate Logistic regression.Pearson correlation analysis was used to analyze the correlation between vash-1 and UACR. Results:UACR((1 175.9±120.4) mg/g), CRP((9.80±2.01) mg/L), ESR((20.61±2.20) mm/h),TGF-β1((16.75±2.05) μg/L), VASH-1((645.3±183.5) ng/L) in case group were higher than that in the control group((11.5±2.0) mg/g, (4.77±1.34) mg/L, (8.33±1.56) mm/h, (10.63±1.97) μg/L, (416.3±162.1) ng/L), and there were significant differences between the two groups ( t=123.39,13.76,30.54,15.75,6.66; all P<0.001). Multivariate logistic regression analysis showed that VASH-1 ( OR=1.881,95% CI 1.146-3.089), UACR( OR=1.511,95% CI 1.064-2.146), TGF-β1( OR=1.846,95% CI 1.135-3.001)were all risk factors for DN of T2DM ( P values were 0.009, 0.022 and 0.012). Serum VASH-1 ((693.5±201.4), (709.8±214.7) ng/L] in group Ⅲ and group Ⅳ were higher than those in group Ⅰ and group Ⅱ ((585.3±162.1), (632.9±165.5) ng/L). There was significant difference between the two groups ( F=129.46, P<0.001). The CRP ((7.08±1.36), (8.99±3.72), (10.58±3.48), (11.64±3.50) mg/L), ESR ((17.36±1.76), (19.05±4.12), (21.45±5.74), (22.69±9.13) mm/h) and TGF- β1 ((14.75±1.97), (16.50±1.90), (17.06±1.23), (18.39±1.46) μg/L) of groupⅠ, groupⅡ, groupⅢ and groupⅣ increased gradually, and there were significant differences between the four groups ( F values were 73.48, 156.61, 25.83; all P<0.001). Pearson correlation analysis showed that there was a significant positive correlation between VASH-1 and UACR ( r=0.532, P=0.008). Conclusion:The concentration of VASH-1 in serum of patients with T2DM complicated with DN increased with the increase of UACR. VASH-1 may become a new marker for predicting early DN of T2DM.

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.

Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.