Adverse pregnancy events is an important factor affecting maternal and infant health,and the research of relative mechanisms has deepened in recent years,with particular attention given to the role of uterine artery.Hemodynamic changes in the uterine artery can directly affect blood supply to uterus and placenta as well as fetal development,which are closely related to pregnancy outcomes.As a non-invasive prenatal assessment tool,ultrasound technology have unique advantages in monitoring and evaluating changes of uterine artery blood flow.The research progresses in association between abnormal uterine artery and adverse pregnancy events were reviewed in this article.

Objective:To investigate the reparative effects and underlying mechanisms of human umbilical cord mesenchymal stem cells (hUCMSCs) in conjunction with hyperbaric oxygen (HBO) on ovarian dysfunction in mice exposed to simulated high-altitude conditions.Methods:A total of 64 six-week-old female C57BL/6 mice were randomly allocated according to random number table, assigned to control group, model group, hUCMSCs group and hUCMSCs+HBO group, with 16 mice in each group. Mice in model group, hUCMSCs group and hUCMSCs+HBO group were placed in a hypobaric oxygen chamber to simulate a high-altitude environment at an elevation of 6 500 m for 15 d, thereby establishing a model of ovarian dysfunction. Beginning on the first day following model establishment, the control and model groups received intravenous injections of 0.2 mL saline via the tail vein. In contrast, the hUCMSCs group and the hUCMSCs+HBO group received 0.2 mL hUCMSCs (1×10 6 cells) per mouse through tail vein injection, administered once a week for three weeks, with continuous intervention lasting 15 d. Furthermore, the hUCMSCs+HBO group were subjected to daily hyperbaric oxygen treatment. The recorded variables included general health status, body weight, estrous cycle changes, serum hormone levels, bilateral ovarian wet weight, ovarian index, follicular development assessment, pathological alterations of ovarian tissue, ultrastructural changes, and the expression levels of transforming growth factor beta 1 (TGF-β1) and Smad family member 3 (Smad3) detected by Western blotting in ovarian tissue. Additionally, litter size and offspring body weight were measured across all groups to evaluate the reproductive capacity of the mice. Results:1) Compared with the hUCMSCs group, the hUCMSCs+HBO group exhibited no statistically significant differences in estrous cycle, body weight, bilateral ovarian wet weight, or ovarian index (all P>0.05). Furthermore, serum levels of anti-Müllerian hormone (AMH), estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), as well as counts of various stages of follicles in hUCMSCs+HBO group, did not demonstrate statistically significant differences compared with hUCMSCs group (all P>0.05). Notably, in the hUCMSCs+HBO group, the integrity of the nuclear membrane in granulosa cells of the ovarian tissue was preserved, with only mild swelling observed in individual mitochondria, while no expansion of the rough endoplasmic reticulum or swelling of the Golgi apparatus were noted. Additionally, expression levels of TGF-β1 and Smad3 proteins in the hUCMSCs+HBO group were significantly elevated compared with the hUCMSCs group ( P=0.010, P<0.001). The conditions of the offspring and litter size showed no statistically significant differences between the two groups (all P>0.05). 2)Compared with control group, the hUCMSCs+HBO group had slightly lower values for body weight, bilateral ovarian wet weight, ovarian index, serum levels of AMH, estradiol, and progesterone, while had slightly higher serum levels of FSH and LH without statistically significant differences (all P>0.05). Importantly, the ultrastructural characteristics of granulosa cells in the ovarian tissue of the hUCMSCs+HBO group closely resembled those of control group, displaying intact structures of the nuclear membrane, mitochondria, rough endoplasmic reticulum, and Golgi apparatus. There was no significant difference in TGF-β1 protein level between hUCMSCs+HBO group and control group ( P=0.253), but Smad3 protein level in hUCMSCs+HBO group was higher than that in control group ( P<0.001). No statistically significant differences were detected in offspring body weight, litter size, or behavioral tendencies (all P>0.05). Conclusion:Both hUCMSCs and the combination of hUCMSCs with HBO intervention demonstrated a safe and effective promotion of functional repair in damaged ovarian tissue under hypoxic conditions. Notably, the combination treatment of hUCMSCs with HBO exhibited a synergistic effect compared with hUCMSCs alone. The potential mechanism underlying this enhanced functional repair may involve the upregulation of the TGF-β1/Smad3 signaling pathway, which could ultimately improve fertility outcomes in mice subjected to hypoxic environments.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To investigate the reparative effects and underlying mechanisms of human umbilical cord mesenchymal stem cells (hUCMSCs) in conjunction with hyperbaric oxygen (HBO) on ovarian dysfunction in mice exposed to simulated high-altitude conditions.Methods:A total of 64 six-week-old female C57BL/6 mice were randomly allocated according to random number table, assigned to control group, model group, hUCMSCs group and hUCMSCs+HBO group, with 16 mice in each group. Mice in model group, hUCMSCs group and hUCMSCs+HBO group were placed in a hypobaric oxygen chamber to simulate a high-altitude environment at an elevation of 6 500 m for 15 d, thereby establishing a model of ovarian dysfunction. Beginning on the first day following model establishment, the control and model groups received intravenous injections of 0.2 mL saline via the tail vein. In contrast, the hUCMSCs group and the hUCMSCs+HBO group received 0.2 mL hUCMSCs (1×10 6 cells) per mouse through tail vein injection, administered once a week for three weeks, with continuous intervention lasting 15 d. Furthermore, the hUCMSCs+HBO group were subjected to daily hyperbaric oxygen treatment. The recorded variables included general health status, body weight, estrous cycle changes, serum hormone levels, bilateral ovarian wet weight, ovarian index, follicular development assessment, pathological alterations of ovarian tissue, ultrastructural changes, and the expression levels of transforming growth factor beta 1 (TGF-β1) and Smad family member 3 (Smad3) detected by Western blotting in ovarian tissue. Additionally, litter size and offspring body weight were measured across all groups to evaluate the reproductive capacity of the mice. Results:1) Compared with the hUCMSCs group, the hUCMSCs+HBO group exhibited no statistically significant differences in estrous cycle, body weight, bilateral ovarian wet weight, or ovarian index (all P>0.05). Furthermore, serum levels of anti-Müllerian hormone (AMH), estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), as well as counts of various stages of follicles in hUCMSCs+HBO group, did not demonstrate statistically significant differences compared with hUCMSCs group (all P>0.05). Notably, in the hUCMSCs+HBO group, the integrity of the nuclear membrane in granulosa cells of the ovarian tissue was preserved, with only mild swelling observed in individual mitochondria, while no expansion of the rough endoplasmic reticulum or swelling of the Golgi apparatus were noted. Additionally, expression levels of TGF-β1 and Smad3 proteins in the hUCMSCs+HBO group were significantly elevated compared with the hUCMSCs group ( P=0.010, P<0.001). The conditions of the offspring and litter size showed no statistically significant differences between the two groups (all P>0.05). 2)Compared with control group, the hUCMSCs+HBO group had slightly lower values for body weight, bilateral ovarian wet weight, ovarian index, serum levels of AMH, estradiol, and progesterone, while had slightly higher serum levels of FSH and LH without statistically significant differences (all P>0.05). Importantly, the ultrastructural characteristics of granulosa cells in the ovarian tissue of the hUCMSCs+HBO group closely resembled those of control group, displaying intact structures of the nuclear membrane, mitochondria, rough endoplasmic reticulum, and Golgi apparatus. There was no significant difference in TGF-β1 protein level between hUCMSCs+HBO group and control group ( P=0.253), but Smad3 protein level in hUCMSCs+HBO group was higher than that in control group ( P<0.001). No statistically significant differences were detected in offspring body weight, litter size, or behavioral tendencies (all P>0.05). Conclusion:Both hUCMSCs and the combination of hUCMSCs with HBO intervention demonstrated a safe and effective promotion of functional repair in damaged ovarian tissue under hypoxic conditions. Notably, the combination treatment of hUCMSCs with HBO exhibited a synergistic effect compared with hUCMSCs alone. The potential mechanism underlying this enhanced functional repair may involve the upregulation of the TGF-β1/Smad3 signaling pathway, which could ultimately improve fertility outcomes in mice subjected to hypoxic environments.

Adverse pregnancy events is an important factor affecting maternal and infant health,and the research of relative mechanisms has deepened in recent years,with particular attention given to the role of uterine artery.Hemodynamic changes in the uterine artery can directly affect blood supply to uterus and placenta as well as fetal development,which are closely related to pregnancy outcomes.As a non-invasive prenatal assessment tool,ultrasound technology have unique advantages in monitoring and evaluating changes of uterine artery blood flow.The research progresses in association between abnormal uterine artery and adverse pregnancy events were reviewed in this article.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective To explore the safety and efficacy of radiofrequency catheter ablation(RCFA)in patients with persistent atrial fibrillation(AF)/atrial flutter(AFL)and heart failure(HF)with left ventricular ejection fraction≤35％.Methods This study is a retrospective study.Patients with persistent AF/AFL and HF with left ventricular ejection fraction≤ 35％admitted to Beijing Anzhen Hospital from January 2018 to March 2024 were enrolled.The perioperative characteristics and complications changes in echocardiographic parameters,and follow-up outcomes were analyzed.Results A total of 45 patients were enrolled with a mean age of(56±13)years and a mean LVEF of(28±4)％.The ablation strategy was circumferential pulmonary vein isolation and empirical linear ablation.The operation time and fluoroscopy time were 120(120,163)min and 5(4,10)min respectively.The patients mainly underwent linear ablation including circumferential pulmonary vein isolation(38,84.4％),cavotricuspid isthmus(37,82.2％),roofline(34,75.6％),mitral isthmus(34,75.6％).21(46.7％)patients underwent ehtanol infusion into the vein of Marshall.24(53.3％)patients underwent electrocardioversion.All patients restored sinus rhythm immediately after RFCA and had no perioperative complications.After a median follow-up of 22.9(7.8,31.0)months,2 patients died of cardiovascular disease,1 patient underwent heart transplantation,14(33.3％)patients were readmitted for cardiovascular disease,and 10 patients(23.8％)had recurrence of AF.The mean LVEF of the 28 patients who obtained LVEF at the last follow-up increased from(28±4)％to(51±14)％,and the average improvement of LVEF was(23±13)％(P＜0.0001).15 of these patients had complete recovery of left ventricular systolic function(LVEF≥ 50％).Conclusions RFCA is safe and effective for patients with persistent AF/AFL and HF with LVEF ≤ 35％,and can improve patient's cardiac function and significantly increase LVEF.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective To explore the safety and efficacy of radiofrequency catheter ablation(RCFA)in patients with persistent atrial fibrillation(AF)/atrial flutter(AFL)and heart failure(HF)with left ventricular ejection fraction≤35％.Methods This study is a retrospective study.Patients with persistent AF/AFL and HF with left ventricular ejection fraction≤ 35％admitted to Beijing Anzhen Hospital from January 2018 to March 2024 were enrolled.The perioperative characteristics and complications changes in echocardiographic parameters,and follow-up outcomes were analyzed.Results A total of 45 patients were enrolled with a mean age of(56±13)years and a mean LVEF of(28±4)％.The ablation strategy was circumferential pulmonary vein isolation and empirical linear ablation.The operation time and fluoroscopy time were 120(120,163)min and 5(4,10)min respectively.The patients mainly underwent linear ablation including circumferential pulmonary vein isolation(38,84.4％),cavotricuspid isthmus(37,82.2％),roofline(34,75.6％),mitral isthmus(34,75.6％).21(46.7％)patients underwent ehtanol infusion into the vein of Marshall.24(53.3％)patients underwent electrocardioversion.All patients restored sinus rhythm immediately after RFCA and had no perioperative complications.After a median follow-up of 22.9(7.8,31.0)months,2 patients died of cardiovascular disease,1 patient underwent heart transplantation,14(33.3％)patients were readmitted for cardiovascular disease,and 10 patients(23.8％)had recurrence of AF.The mean LVEF of the 28 patients who obtained LVEF at the last follow-up increased from(28±4)％to(51±14)％,and the average improvement of LVEF was(23±13)％(P＜0.0001).15 of these patients had complete recovery of left ventricular systolic function(LVEF≥ 50％).Conclusions RFCA is safe and effective for patients with persistent AF/AFL and HF with LVEF ≤ 35％,and can improve patient's cardiac function and significantly increase LVEF.