OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

OBJECTIVES: To investigate the association between methylation levels of tumor suppressing subtransferable candidate 1 (TSSC1) and melanophilin (MLPH) genes in peripheral blood and coronary heart disease (CHD) in Chinese population. METHODS: This case-control study was conducted in 86 CHD patients and 95 healthy individuals, whose methylation levels of TSSC1 and MLPH genes in peripheral blood were determined using mass spectrometry. Mann-Whitney U test was used to compare the methylation levels in different subgroups. The correlation of TSSC1 and MLPH gene methylation levels with age and gender were evaluated using Spearman correlation coefficient and contingency coefficient, respectively. RESULTS: Compared with the healthy individuals, the CHD patients showed a significant correlation between MLPH hypermethylation and myocardial infarction (MI) (MLPH_CpG_2.7: P=0.045; MLPH_CpG_3/cg06639874: P=0.049; MLPH_CpG_5: P=0.019), and this correlation was even stronger in individuals below 65 years of age (MLPH_CpG_2.7: P=0.014; MLPH_CpG_4: P=0.001) and in male subjects (MLPH_CpG_2.7: P=0.004; MLPH_CpG_3/cg06639874: P=0.044). The methylation level of TSSC1 gene in peripheral blood was not found to correlate with CHD or its subtypes. CONCLUSIONS Our findings suggest a correlation of MLPH hypermethylation in peripheral blood with CHD and MI in Chinese population, especially in individuals below 65 years and in male individuals.
Humans ; DNA Methylation ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Coronary Disease/blood* ; Adult ; CpG Islands

Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1)checkpoint inhibitor combined with radiation therapy through whole-body dynamic 18 F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT)and Patlak multi-parametric analysis.Methods B16F10 mel-anoma dual-tumor mouse model was established and randomly divided into control,PD-1 monoclonal antibody,ra-diation-only,and combination groups(n=6).Whole-body 18F-FDG PET/CT imaging was performed before and 24 hours post-treatment.The changes of maximum standardized uptake value(SUVmax)and metabolic rate of FDG(MRFDG)changes were analyzed and compared.Mice were then euthanized,tumors excised and underwent histo-pathology with HE,CD8,Ki-67 staining to assess immune infiltration and proliferation.Distal tumor volumes were monitored during treatment.Results At 24 hours post-treatment,in the primary tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group(P＜0.000 1),while they decreased in the combination treatment group(P＜0.000 1),with statistically significant differences.In the distal tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group,PD-1 monoclonal antibody group,and radiothera-py-alone group.The SUVmax differences were statistically significant in the control group before and after treatment(P＜0.000 1).MRFDG values in the distal tumors showed statistically significant differences in all three groups(P＜0.01 or P＜0.000 1).In the combination treatment group,SUVmax and MRFDG values in the distal tumors de-creased significantly compared to pre-treatment(P＜0.000 1).Post-treatment comparison of SUVmax and MRFDG values in the distal tumors showed that statistically significant differences in SUVmax and MRFDG values were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(all P＜0.05).Im-munohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P＜0.001);the mean absorbance value of Ki-67 immuno-histochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P＜0.001).Conclusion The synergistic effects of combined treatment reduced distal tumor growth.Whole-body 18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma,providing reliable imaging parameters for optimizing combinatorial therapies.

Objective To explore the effect of traditional Chinese medicine enema combined with acupoint massage on postoperative intestinal function recovery.Methods A total of 80 patients with abdominal surgery admitted to First Affiliated Hospital of Huzhou University from January 2022 to June 2023 were selected and divided into study group and control group according to random number table method,with 40 cases in each group.The control group was treated with conventional Western medicine,while the study group was treated with traditional Chinese medicine enema combined with acupoint massage on the basis of conventional Western medicine treatment.The therapeutic effect,postoperative recovery time,gastrointestinal hormone level,abdominal distension pain and gastrointestinal reaction score were compared between two groups.Results Postoperative bowel sound recovery time,first anal defecation time and full-flow diet recovery time in study group were significantly shorter than those in control group(P<0.05).At 5 days after surgery,the levels of motilin(MTL),gastrin(GAS)and gastric inhibitory peptide(GIP)in two groups were significantly higher than those in this group at 1 day after surgery(P<0.05).The levels of MTL,GAS and GIP in study group were significantly higher than those in control group(P<0.05).At 5 days after surgery,abdominal distension score and gastrointestinal reaction score in two groups were significantly lower than those in this group 1 day after surgery(P<0.05),and abdominal distension score and gastrointestinal reaction score in study group were significantly lower than those in control group(P<0.05).The total effective rate of study group was significantly higher than that of control group(χ2=3.914,P=0.048).Conclusion Traditional Chinese medicine enema combined with acupoint massage can effectively shorten the recovery time of intestinal function,improve the level of gastrointestinal hormone,relieve abdominal distension pain and gastrointestinal reaction after abdominal operation,and the effect is significant,worthy of clinical application.

Objective To prepare T cell immunoglobulin domain and mucin domain 1 protein-1(TIM-1)-Fc fusion protein,and to investigate the intervention effect of TIM-1-FC fusion protein on ovabumin(OVA)-induced asthma mice as well as its po-tential mechanism.Methods Through genetic engineering,pcDNA3.1(+)-TIM-1-Fc plasmid was constructed and stably transfected into CHO cells.Cell culture supernatant was collected and purified,and TIM-1-Fc fusion protein was ob-tained.Mouse model of allergic asthma was established by intraperitoneal injection of OVA aluminum hydroxide solution.The mice were randomly divided into control group,asthma group and TIM-1-Fc intervention group.The TIM-1-Fc intervention group included TIM-1-Fc nasal drop group and TIM-1-Fc injection group.20 min before each intervention,40 μL ovalbumin sa-line solution(OVA-NS)was used for nasal drops.Protein TIM-1-Fc nasal drops group(1 μg/40 μL TIM-1-Fc nasal drops was administrated in each mouse)and TIM-1-Fc injection group(6 μg/200 μL TIM-1-Fc was injected intraperitoneally in each mouse)were interfered with TIM-1-Fc fusion,once a day for 7 days.Normal saline was used as replacement in the control group.Hematoxylin-eosin staining(HE)was used to observe the pathological changes of lung tissue.Flow cytometry was used to detect the proportion of type 2 helper T cells(Th2),type 17 helper T cells(Th17),regulatory T cells(Treg)and the levels of related cytokines in peripheral blood of mice.Results TIM-1-Fc fusion protein and OVA-induced allergic asthma mouse model was successfully constructed.Compared with asthma group,TIM-1-Fc fusion protein could significantly reduce airway inflam-matory injury and lung tissue injury in asthmatic mice.TIM-1-Fc fusion protein intervention could significantly reduce the pro-portion of TIM-1 CD4+T cells and TIM-1+Th17 cells in peripheral blood,increase the number of TIM-1+Treg cells,signifi-cantly reduce the proportion of Th2 and Th17 cells,and increase the proportion of Treg cells.It could modulate Th1/Th2 and Th17/Treg immune imbalances in asthma.Conclusion TIM-1-Fc fusion protein improves airway inflammation and lung tissue injury in OVA-induced allergic asthma mice,and its mechanism may be related to the immune regulation of Th1/Th2 and Th17/Treg by TIM-1-Fc fusion protein.

Objective:To explore the symptom management experience in young and middle-aged patients with home peritoneal dialysis.Methods:Using the descriptive phenomenological research method and purposive sampling method, 13 young and middle-aged peritoneal dialysis patients were selected for semi-structured interviews, and the interview data was analyzed and sorted out to extract themes.Results:A total of four themes were summarized, including difficulties in symptom management (lack of symptom management knowledge, insufficient symptom perception ability), effect of poor symptom management effectiveness (limited daily life behavior, weakened family roles, obstacles in returning to the workplace, withdrawal of social activities and increased economic burden), polarized symptom management coping strategies (positive and negative responses) and multifaceted symptom management needs (longing for new treatment methods, hoping for disease knowledge popularization and craving for social support in various aspects) .Conclusions:There are many obstacles and needs in the process of symptom self-management of young and middle-aged home peritoneal dialysis patients. It is suggested that medical staff should combine the characteristics and psychology of middle-aged and young peritoneal dialysis patients, implement targeted intervention measures, and improve their symptom management ability.

Objective:To evaluate the effects of quality improvement (QI) program on the incidence of bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs) [gestational age (GA)<32 weeks].Methods:From July to December 2017,VPIs admitted to the Department of Neonatology of Yancheng Maternity and Child Health Care Hospital were retrospectively enrolled and were assigned into pre-quality improvement program group (Pre-QI group).From July to December 2018, VPIs were assigned into post-quality improvement program group (Post-QI group). QI program included delayed umbilical cord clamping (DCC), early postnatal nasal continuous positive airway pressure ventilation (nCPAP) and minimally invasive pulmonary surfactant therapy (MIST). The clinical data and prognostic indicators of the two groups of VPIs and their mothers were compared. Independent sample t-test or continuity-adjusted Chi-square test (or Fisher's exact test) and Logistic regression were used for statistical analysis. Results:A total of 204 VPIs were enrolled, including 96 cases in Pre-QI group and 108 cases in Post-QI group. 1 min Apgar score and hematocrit on admission to the neonatal intensive care unit (NICU) in the Post-QI group were significantly higher than the Pre-QI group( P<0.05). The incidence of delivery room resuscitation, endotracheal intubation at birth and endotracheal intubation in NICU in the Post-QI group were significantly lower than the Pre-QI group( P<0.05). The application of pulmonary surfactant and mechanical ventilation, the incidence of neonatal respiratory distress syndrome and BPD in the Post-QI group were lower than the Pre-QI group ( P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that DCC ( aOR=0.261,95% CI 0.091~0.718, P=0.023), nCPAP ( aOR=0.284,95% CI 0.123~0.667, P=0.015), MIST ( aOR=0.276,95% CI 0.114~0.627, P=0.011) were protective factors of BPD, and MV ( aOR=2.023,95% CI 1.048~3.918, P=0.036) was risk factor of BPD. Conclusions:The QI program consisting of DCC, early nCPAP and MIST for VPIs can reduce the incidence of BPD.

Objective:To investigate the effect of using two different input functions to reconstruct 18F-FDG PET/CT Patlak multi-parameter images on the quantitative parameters of lung cancer lesions. Methods:The original whole-body dynamic 18F-FDG PET/CT scan data of lung cancer patients in the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University were retrospectively analyzed. The total scan time was 75 min. Two input functions were used for Patlak multi-parameter reconstruction: ① Image-derived input function(IDIF)using the Time-activity curve(TAC)of descending aorta from 0 min to 75 min. ② Population-based input function (PBIF) developed by Yale University. Metabolic rate of FDG (MR FDG) and Distribution volume (DV) images were obtained by Patlak multi-parameter analysis software using the above input functions. The region of interest (ROI) method was used to delineate the lesions to obtain multi-parameter quantitative information, including the max, peak and mean value of MR FDG and DV. Paired t-test was used for statistical analysis. Results:The original data of 27 lung cancer patients who received whole-body dynamic 18F-FDG PET/CT imaging were reconstructed by Patlak with two different input functions. The max, peak and mean values of MR FDG-IDIF and MR FDG-PBIF in lung cancer lesions were as follows: (0.26 ± 0.15), (0.19 ± 0.12), (0.14 ± 0.08)μmol·min -1·ml -1 and (0.26 ± 0.15), ( 0.20 ± 0.13), (0.15 ± 0.09)μmol·min -1·ml -1, with no statistically significant difference between two functions( P > 0.05). The max, peak and mean values of DV IDIF and DV PBIF were (165.56 ± 99.89)%, (117.66 ± 72.24)%, (62.16 ± 33.65)% and(170.04 ± 103.93)%, (121.91 ± 73.71)%, (65.05 ± 37.17)%, with no statistically significant difference between two functions ( P > 0.05). Conclusions:The population-based input function may be an alternative for patients who could not lie supine for long time during whole-body dynamic 18F-FDG PET/CT Patlak multi-parameter imaging.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*