Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.

Objective:To investigate the therapeutic effects and underlying mechanisms of intrauterine perfusion of umbilical cord blood mononuclear cells (UCB-MNCs) on thin endometrium.Methods:SPF-grade Kunming mice aged 6-8 weeks were selected. A mouse model of thin endometrium was established by infusing 95% ethanol into the uterine cavity for a duration of 5 min. Using a completely randomized grouping method, 40 female mice with regular estrous cycles were randomly divided into four groups: untreated group (no intervention, n=10), sham-operated group (operation without modeling, n=10), experimental group (intrauterine infusion of UCB-MNCs during estrus after one estrous cycle post-modeling, n=10) and negative control group (intrauterine infusion of saline during estrus after one estrous cycle post-modeling, n=10). Following the administration of UCB-MNCs or physiological saline, all groups' uterine tissues were collected two estrous cycles later during their respective estrus phases. Hematoxylin-eosin staining was used to assess endometrial morphology, measure thickness, and count glands. Western blotting and reverse transcription real-time quantitative polymerase chain reaction were utilized to measure the relative protein and mRNA expression levels of leukemia inhibitory factor (LIF), vascular endothelial growth factor (VEGF), integrin (ITG) α V, ITG β 3 and proliferating cell nuclear antigen (PCNA) in the endometrium across different groups for intergroup comparisons. Results:The endometrial thickness and the number of glands in the untreated group [(507.32±85.66) μm, 18.67±6.66] showed no statistically significant differences compared with those in the sham-operated group [(502.78±73.26) μm, 19.33±7.73, all P>0.05]. The experimental group showed significantly increased endometrial thickness [(347.71±82.24) μm vs. (118.85±29.19) μm, P<0.001] and gland number (15.00±2.65 vs. 2.00±2.00, P=0.030) compared with the negative control group. There was no statistically significant difference in the relative protein and mRNA expression levels of LIF, VEGF, ITG α v, ITG β 3, and PCNA in the endometrium between the untreated group and the sham-operated group (all P>0.05). The relative protein and mRNA expression levels of endometrial LIF, VEGF, ITG α V, ITG β 3 and PCNA of the experimental group were all significantly higher than those in the negative control group (all P<0.05). Conclusion:Intrauterine perfusion with UCB-MNCs may promote endometrial regeneration and repair, as well as improve endometrial receptivity, through the upregulation of the expression levels of PCNA, LIF, VEGF, and ITG α V, ITGβ 3.

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective:To investigate the outcomes of endoscopic balloon dilation laryngoplasty （EBDL） in managing acquired subglottic stenosis in children. Methods:A retrospective analysis of clinical data from patients who underwent endoscopic balloon dilation for secondary subglottic stenosis between January 2017 and January 2024 at Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai. The study included 10 children （6 males, 4 females） aged between 13 days and 3 years at the time of their first procedure, with an average age of 7 months. Subglottic stenosis was graded according to the Myer-Cotton classification, with two cases classified as grade Ⅱ and eight cases as grade Ⅲ. All patients had a history of tracheal intubation, including seven for rescue purposes and three for operations. Eight cases were complicated by other conditions: two with atrial septal defect, patent ductus arteriosus, and patent foramen ovale; two with patent foramen ovale only; one with atrial septal defect and extreme deafness in the left ear; one with a brain tumor and hydrocephalus; one with a traumatic diaphragmatic hernia and hepatic rupture; and one case complicated by type Ⅰ laryngeal cleft. Prior to surgery, all children required respiratory support-seven needed high-flow oxygen while three required CPAP. Results:All ten cases underwent endoscopic balloon dilation under spontaneous respiration and general anesthesia, totaling fourteen dilations （an average of 1.4 dilations per person） without any complications. Post-surgery air permeability tests showed that eight cases had grade Ⅰ stenosis while two had grade Ⅱ stenosis. The follow-up period ranged from six months to six years （average duration: 46 months）. Following treatment, all patients no longer required respiratory support or experienced significant mobility limitations. Conclusion:Endoscopic balloon dilation under general anesthesia is deemed safe and effective in treating secondary subglottic stenosis. Early diagnosis coupled with prompt intervention can help avoid tracheotomy procedures altogether. Standard tracheoscopy combined with breathability testing represents a crucial approach to assess normal airway diameter and effectively reduce or prevent secondary subglottic stenosis following re-intubation.
Humans ; Laryngostenosis/surgery* ; Male ; Female ; Retrospective Studies ; Laryngoplasty/methods* ; Child, Preschool ; Infant ; Dilatation/methods* ; Laryngoscopy/methods* ; Treatment Outcome ; Endoscopy

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.

Objective:To investigate the therapeutic effects and underlying mechanisms of intrauterine perfusion of umbilical cord blood mononuclear cells (UCB-MNCs) on thin endometrium.Methods:SPF-grade Kunming mice aged 6-8 weeks were selected. A mouse model of thin endometrium was established by infusing 95% ethanol into the uterine cavity for a duration of 5 min. Using a completely randomized grouping method, 40 female mice with regular estrous cycles were randomly divided into four groups: untreated group (no intervention, n=10), sham-operated group (operation without modeling, n=10), experimental group (intrauterine infusion of UCB-MNCs during estrus after one estrous cycle post-modeling, n=10) and negative control group (intrauterine infusion of saline during estrus after one estrous cycle post-modeling, n=10). Following the administration of UCB-MNCs or physiological saline, all groups' uterine tissues were collected two estrous cycles later during their respective estrus phases. Hematoxylin-eosin staining was used to assess endometrial morphology, measure thickness, and count glands. Western blotting and reverse transcription real-time quantitative polymerase chain reaction were utilized to measure the relative protein and mRNA expression levels of leukemia inhibitory factor (LIF), vascular endothelial growth factor (VEGF), integrin (ITG) α V, ITG β 3 and proliferating cell nuclear antigen (PCNA) in the endometrium across different groups for intergroup comparisons. Results:The endometrial thickness and the number of glands in the untreated group [(507.32±85.66) μm, 18.67±6.66] showed no statistically significant differences compared with those in the sham-operated group [(502.78±73.26) μm, 19.33±7.73, all P>0.05]. The experimental group showed significantly increased endometrial thickness [(347.71±82.24) μm vs. (118.85±29.19) μm, P<0.001] and gland number (15.00±2.65 vs. 2.00±2.00, P=0.030) compared with the negative control group. There was no statistically significant difference in the relative protein and mRNA expression levels of LIF, VEGF, ITG α v, ITG β 3, and PCNA in the endometrium between the untreated group and the sham-operated group (all P>0.05). The relative protein and mRNA expression levels of endometrial LIF, VEGF, ITG α V, ITG β 3 and PCNA of the experimental group were all significantly higher than those in the negative control group (all P<0.05). Conclusion:Intrauterine perfusion with UCB-MNCs may promote endometrial regeneration and repair, as well as improve endometrial receptivity, through the upregulation of the expression levels of PCNA, LIF, VEGF, and ITG α V, ITGβ 3.