BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Objective:To investigate the effect of multi line therapy for lung adenocarcinoma transformed into small cell lung cancer (SCLC), and review and discuss the related literature.Methods:Combined with the clinical examples of lung adenocarcinoma transformed SCLC after treatment with anti epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), the diagnostic process and multi line treatment plan of transformed SCLC were analyzed, and the therapeutic effect was evaluated by imaging. At the same time, it was reviewed and discussed in combination with relevant literature.Results:Serological tumor markers were significant for the diagnosis of transformed SCLC after EGFR-TKI treatment of lung adenocarcinoma, and pathology was still the gold standard for its diagnosis. The multiline therapy of SCLC has certain effect on transformed small cell lung cancer.Conclusion:The overall prognosis of lung adenocarcinoma transformed into SCLC after EGFR TKIs treatment is poor, so it is necessary to diagnose and treat it as early as possible, evaluate the effect of imaging in time, and make treatment adjustment quickly.

Objective:To explore the value of the nursing intervention based on interaction model of Cox health behavior in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) with olfactory disorders, so as to provide reference for clinical caregivers to improve the olfactory function and quality of life of such patients and reduce negative emotions.Methods:This study was a prospective, randomized, single blind controlled trial. A convenient sampling method was used to select 50 patients with olfactory disorders of CRSwNP who were hospitalized in the Department of Otolaryngology, Second Affiliated Hospital of Kunming Medical University from February 2022 to August 2022 as the study population. According to the random number table method, 25 patients in each group were divided into a test group and a control group. The control group was given conventional perioperative nursing measures, while the test group was given nursing intervention based on interaction model of Cox health behavior. Patients in the two groups were recorded and compared in terms of olfactory function, anxiety and depression, and quality of life scores before and after the intervention. Patient satisfaction scores at the time of discharge were also compared between the two groups.Results:Finally, 24 cases were included in the control group and 23 cases in the test group. The comparison of olfactory perception threshold, recognition threshold score, anxiety-depression score and quality of life score between the two groups before the intervention was not statistically significant ( P>0.05) and was comparable. The perceptual domain scores were (-0.18 ± 1.89), (-1.30 ± 1.06) points in the test group at 2 weeks and 1 month after the intervention, respectively, which were lower than the (0.92 ± 1.65), (-0.29 ± 1.40) points in the control group. The differences were statistically significant ( t=2.09, 2.72, both P<0.05). The recognition threshold returned to its normal value (0.38 ± 1.67) points in the test group 1 month after the intervention, with a lower score than the control group′s (1.46 ± 1.77) points. The difference was statistically significant ( t=2.10, P<0.05). After the intervention, the anxiety, depression and quality of life scores in the test group were (31.93 ± 3.55), (32.31 ± 5.80), (31.30 ± 6.00) points respectively, which were lower than the (35.10 ± 5.46), (36.84 ± 6.98), (38.53 ± 9.27) points in the control group. The differences were statistically significant ( t=2.30, 2.36, 3.09, all P<0.05). In addition, the patient satisfaction score was higher in the trial group (49.31 ± 3.95) points than in the control group (44.30 ± 2.60) points, with a statistically significant difference ( t=-5.05, P<0.05). Conclusions:The nursing intervention based on interaction model of Cox health behavior can effectively improve the patients' olfactory function and quality of life, reduce the level of anxiety and depression, and improve the patients' satisfaction.

Objective:To investigate the clinical efficacy of low-energy laser in the treatment of erosive oral lichen planus (OLP) and its effect on patients' pain.Methods:Eighty-six patients with erosive OLP who were treated in Shanxian Central Hospital from February 2018 to January 2020 were included in this study. They were randomly divided into control and observation groups ( n = 43/group). The control group was treated by local injection of dexamethasone, and the observation group was treated with semiconductor low-energy laser irradiation. All patients were treated for 8 weeks. Pain scores and physical sign score before and after treatment were evaluated in each group. Therapeutic effects were compared between the two groups. Area of lesion was measured in each group. Recurrence of erosive OLP was calculated at 3 and 6 months after surgery. Results:Before treatment, there were no significant differences in visual analogue scale (VAS) score and physical sign score between the two groups (both P > 0.05). At 7, 14, 28 and 56 days after treatment, VAS score and physical sign score were significantly decreased in each group compared with those before treatment, and VAS score and physical sign score in the observation group were significantly lower than those in the control group (all P < 0.05). Total response rate in the observation group was significantly higher than that in the control group [93.02% (40/43) vs. 83.72% (36/43), χ2 = 1.81, P > 0.05). Before and 1 month after treatment, there was no significant difference in area of lesion between control and observation groups (both P > 0.05). At 3 and 6 months after surgery, area of lesion in the observation group was (0.31 ± 0.14) cm 2 and (0.32 ± 0.12) cm 2, respectively, which were significantly smaller than those in the control group [(0.42 ± 0.18) cm 2, (0.48 ± 0.19) cm 2, t = 3.16, 4.67, both P < 0.05). At 3 and 6 months after treatment, recurrence of erosive OLP in the observation group was 2.33% (1/43) and 13.95% (6/43), respectively, which were significantly lower than those in the control group [13.95% (6/43), 37.21% (16/43), χ2 = 3.89, 6.11, both P < 0.05]. Conclusion:There is no significant difference in the short-term efficacy of low-energy laser versus conventional corticosteroids in the treatment of erosive OLP. However, low-energy laser has a more obvious short-term pain relief effect than conventional corticosteroids. It can accelerate the healing of injured tissue and decrease the recurrence rate of erosive OLP.

Objective:To investigate the value of transperineal ultrasound assessment of levator hiatal antero-posterior (LHap) diameter changes in the diagnosis of pelvic floor dysfunction.Methods:The clinical data of 246 patients with suspected pelvic floor dysfunction who received treatment in Yuyao People's Hospital of Zhejiang Province from October 2020 to June 2021 were retrospectively analyzed. All these patients underwent clinical examination and modified Oxford score (MOS) evaluation. They were divided into observation group (low pelvic floor muscle contractility) and control group (normal pelvic floor muscle contractility) according to MOS. All patients were subjected to ultrasound examination and LHap diameter measurement under three conditions (at rest, pelvic floor muscle contraction, and maximal Valsalva maneuver). The percentage of shortening of LHap diameter (PDC%) and the percentage of elongation of LHap diameter (PIV%) were calculated. The differences of PDC% and PIV% were compared between the observation and control groups. The receiver operating curve was used to evaluate the values of PDC% and PIV% in the diagnosis of pelvic floor dysfunction.Results:Age, body mass index, the proportion of parturient women among included patients, and the proportion of patients who underwent vaginal delivery were significantly higher in the observation group than those in the control group (all P < 0.001). LHap diameters measured when patients were at rest, pelvic floor muscle contraction, and maximal Valsalva maneuver as well as PIV% in the observation group were (45.23 ± 5.74) mm], (37.71 ± 8.44) mm, (51.03 ± 7.41) mm and (11.42 ± 4.79)%, respectively, which were significantly higher than those in the control group [(41.78 ± 4.56) mm, (29.15 ± 4.64) mm, (44.28 ± 4.87) mm, (6.05 ± 2.13)%, t = -4.62, -8.29, -7.26, -9.36, all P < 0.001]. PDC% in the observation group was significantly lower than that in the control group [(17.52 ± 5.58)% vs. (32.19 ± 4.27)%, t = 20.39, P < 0.001]. MOS was positively correlated with PDC% ( r = 0.56, P < 0.001) and it was negatively correlated with PIV% ( r = -0.49, P < 0.001). Taking PDC% < 35.36% as the cut-off value, the area under the receiver operating curve was 0.85, the sensitivity, specificity and accuracy values were 66.40%, 97.38%, and 73.90%, respectively. Taking PIV% > 5.18% as the cut-off value, the area under the curve was 0.70, and the sensitivity, specificity and accuracy values were 71.45%, 57.90% and 68.15%, respectively. When PDC% and PIV% were used together, the area under the curve was 0.73 and the sensitivity, specificity and accuracy values were 84.57%, 55.05% and 77.32%, respectively. Conclusion:Transperineal ultrasound assessment of LHap diameter changes are of certain value in the prediction of pelvic floor dysfunction and can provide objective and quantitative data support for clinicians to diagnose pelvic floor dysfunction. This study is highly innovative and scientific.

Obstructive sleep apnea (OSA) may induce chronic intermittent hypoxia, which may lead to the disorders of multiple systems and organs and even sudden cardiac death in severe cases. Besides respiratory, cardiovascular, endocrine, and metabolic diseases, OSA is also closely associated with nonalcoholic fatty liver disease (NAFLD). This article briefly describes the current status of OSA and NAFLD, introduces the impact of OSA on NAFLD, and reviews the mechanisms of OSA in NAFLD. It is pointed out that clarifying the mechanisms of OSA in affecting NAFLD and discovering potential prevention and treatment targets for NAFLD from the aspect of OSA are of great significance in delaying and even blocking the progression of NAFLD.

Objective: To investigate the clinical efficacy of uterine arterial embolization combined with hysteroscopy in the treatment of cesarean scar pregnancy. Methods: From September 2016 to March 2018, 68 patients with cesarean scar pregnancy in the People's Hospital of He'nan Province were collected.According to different treatment methods, the patients were divided into observation group and control group.The observation group (42 cases) firstly received bilateral uterine artery embolization, then hysteroscopy pregnancy lesion was resected after 2-3 days.The control group (26 cases) directly received hysteroscopy endoscopic pregnancy lesion resection. Results: There were 42 cases in the observation group, 2 cases(all of them III type)failed, of which 1 case was treated with laparoscopy, and 1 case was converted to transvaginal focus clearance.In the control group, 26 cases of cesarean scar pregnancy were treated directly by hysteroscopy, and 6 cases were failed(1 case of type I, 4 cases of type II, 1 case of type III), among which 3 cases were treated with uterine artery embolization.Then hysteroscopic surgery was performed in 2 cases, combined with laparoscopy for pregnancy focus debridement.One case of severe hemorrhage occurred in III type operation, which was immediately converted to open operation.The operation time, intraoperative blood loss, surgical success rate, length of hospital stay, blood β-HCG return to normal time, menstrual recovery time, postoperative vaginal bleeding, postoperative vaginal bleeding time in the observation group were (17.09±3.62)min, (32.6±5.6)mL, 95.2%(40/42), (4.76±1.63)d, (18.00±6.62)d, (30.28±4.23)d, (32.75±8.32)mL, (3.26±1.06)d, respectively, which in the control group were (49.51±3.41)min, (60.3±13.6)mL, 76.9%(20/26), (7.23±1.96)d, (22.00±6.91)d, (36.41±7.62)d, (46.23±11.73)mL, (6.42±2.45)d, respectively, the differences between the two groups were statistically significant(t=36.68, 14.09, χ²=5.189, t=5.62, 2.30, 4.27, 5.54, 7.35, all P<0.05). Conclusion Bilateral uterine artery embolization combined with hysteroscopy in the treatment of cesarean scar pregnancy has some advantages including high successful rate, short operation time, less bleeding, hospitalization time and postoperative recovery, etc.It is a safe and effective treatment especially for type I and type II scar pregnancy.

Objective · To detect the vitamin D2 and D3 levels in the patients with moderate and severe depression. Methods · Eighty-five patientswho met the criteria for major depressive disorder were recruited (53 patients with moderate depression, 32 patients with severe depression). Fifty agematchedhealthy volunteers were recruited as controls. Serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels were detected by using liquidchromatography-tandem mass spectrometry (LC-MS/MS). The risk factors which might influence the severity of depression were screened by Logisticregression analysis. Results · The serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels in the case group was lower than those in the controlgroup (P=0.012, P=0.000, P=0.000). The patients with moderate depression presented significantly lower serum 25 (OH) D3 and total 25 (OH) D2/D3 levelsthan the controls did (P=0.000), although no significant difference in serum 25 (OH) D2 levels was found between these two groups. As well, the serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels in patients with severe depression were significantly lower than those in patients with moderate depression and controls (P<0.05). The body mass index of severe depression group was much higher than that of moderate depression group and control group (P=0.002). Both overweight/obesity and the concentration of vitamin D may be the major influencing factors of depression severity (P=0.034, P=0.011). Conclusion · Vitamin D2 and D3 deficiency in depressive patients, particularly in those patients with severe depression, was shown in the present study. In addition, overweight/obesity as well as the concentration of vitamin D may exert the significant influence on the severity of depression. Vitamin D supplementation and weight control may be needed to be considered in making therapeutic strategies of major depressive disorder.