ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Objective:To investigate the pregnancy outcomes and cumulative live birth rate (CLBR) after in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with high basal follicle-stimulating hormone (bFSH) levels. Methods:This retrospective cohort study included clinical data from patients who underwent IVF/ICSI-ET treatment at the Reproductive Medical Center of Peking University Third Hospital from January 2018 to December 2022. Patients were divided into three groups based on the highest bFSH level during all cycles of treatment: group A (15 U/L≤bFSH<25 U/L), group B (25 U/L≤bFSH<40 U/L), and group C (bFSH≥40 U/L). After propensity score matching (PSM) based on the female body mass index, the baseline data, embryology laboratory outcomes, and assisted reproductive outcomes such as clinical pregnancy rate among the three groups of patients were compared. Binary logistic regression analysis was used to explore the impact of various factors on live birth, and the trend of CLBR across multiple cycles was also studied.Results:After PSM, 340 cycles were included in group A, 340 cycles were included in group B, 127 cycles were included in group C. There were statistically significant differences among the three groups in antral follicle count, bFSH, basal progesterone, basal luteinizing hormone, and anti-Müllerian hormone levels ( P=0.004, P<0.001, P<0.001, P<0.001, P<0.001). In the analysis of controlled ovarian stimulation (COS) protocols, groups A and B mainly used conventional COS protocol, while group C primarily used mild stimulation protocol. The duration and dosage of gonadotropin used were the highest in group A [10 (7, 12) d, 2 728 (1 650, 3 725) U], with statistically significant differences among the three groups (all P<0.001). On the day of human chorionic gonadotropin injection, there were statistically significant differences in estradiol and progesterone levels among the three groups ( P=0.022 and P=0.048, respectively). The cancellation rate of cycles did not differ significantly among the three groups ( P>0.05), while the number of oocytes retrieved ( P<0.001) and the rate of cycles with no transferable embryos ( P=0.034) showed statistically significant differences. The type of embryos transferred in all three groups was mainly cleavage-stage embryos, and there were statistically significant differences in the rate of two pronuclei and high-quality embryos among the groups ( P=0.003 and P=0.006, respectively). The rate of high-quality embryos decreased with increasing bFSH levels, and comparisons between group A and group B, as well as group A and group C, showed statistically significant differences (all P<0.016 7). The biochemical pregnancy rate and the clinical pregnancy rate in fresh cycles differed significantly among the three groups ( P=0.025 and P=0.010, respectively), while the live birth rate per initiated cycle showed marginal significance ( P=0.058). However, the miscarriage rate and the live birth rate per transfer cycle did not differ significantly among the groups (all P>0.05). Binary logistic regression analysis revealed that bFSH ( OR=0.955, 95% CI: 0.912-1.000, P=0.050) and the number of oocytes retrieved ( OR=1.104, 95% CI: 1.009-1.207, P=0.031) were independent predictors of live birth. Analysis of CLBR curves across multiple oocyte retrieval cycles showed that CLBR gradually increased with the number of oocyte retrievals and stabilized at 14.32% after the fifth retrieval. Conclusion:High bFSH levels reduce the live birth rate per initiated cycle but do not affect the live birth rate per transfer cycle. Increasing age and a low number of oocytes retrieved can both decrease the live birth rate. Multiple oocyte retrieval and transfer cycles can improve CLBR in patients with high bFSH level to some extent, but it tends to stabilize after the fifth cycle.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective:To investigate the pregnancy outcomes and cumulative live birth rate (CLBR) after in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with high basal follicle-stimulating hormone (bFSH) levels. Methods:This retrospective cohort study included clinical data from patients who underwent IVF/ICSI-ET treatment at the Reproductive Medical Center of Peking University Third Hospital from January 2018 to December 2022. Patients were divided into three groups based on the highest bFSH level during all cycles of treatment: group A (15 U/L≤bFSH<25 U/L), group B (25 U/L≤bFSH<40 U/L), and group C (bFSH≥40 U/L). After propensity score matching (PSM) based on the female body mass index, the baseline data, embryology laboratory outcomes, and assisted reproductive outcomes such as clinical pregnancy rate among the three groups of patients were compared. Binary logistic regression analysis was used to explore the impact of various factors on live birth, and the trend of CLBR across multiple cycles was also studied.Results:After PSM, 340 cycles were included in group A, 340 cycles were included in group B, 127 cycles were included in group C. There were statistically significant differences among the three groups in antral follicle count, bFSH, basal progesterone, basal luteinizing hormone, and anti-Müllerian hormone levels ( P=0.004, P<0.001, P<0.001, P<0.001, P<0.001). In the analysis of controlled ovarian stimulation (COS) protocols, groups A and B mainly used conventional COS protocol, while group C primarily used mild stimulation protocol. The duration and dosage of gonadotropin used were the highest in group A [10 (7, 12) d, 2 728 (1 650, 3 725) U], with statistically significant differences among the three groups (all P<0.001). On the day of human chorionic gonadotropin injection, there were statistically significant differences in estradiol and progesterone levels among the three groups ( P=0.022 and P=0.048, respectively). The cancellation rate of cycles did not differ significantly among the three groups ( P>0.05), while the number of oocytes retrieved ( P<0.001) and the rate of cycles with no transferable embryos ( P=0.034) showed statistically significant differences. The type of embryos transferred in all three groups was mainly cleavage-stage embryos, and there were statistically significant differences in the rate of two pronuclei and high-quality embryos among the groups ( P=0.003 and P=0.006, respectively). The rate of high-quality embryos decreased with increasing bFSH levels, and comparisons between group A and group B, as well as group A and group C, showed statistically significant differences (all P<0.016 7). The biochemical pregnancy rate and the clinical pregnancy rate in fresh cycles differed significantly among the three groups ( P=0.025 and P=0.010, respectively), while the live birth rate per initiated cycle showed marginal significance ( P=0.058). However, the miscarriage rate and the live birth rate per transfer cycle did not differ significantly among the groups (all P>0.05). Binary logistic regression analysis revealed that bFSH ( OR=0.955, 95% CI: 0.912-1.000, P=0.050) and the number of oocytes retrieved ( OR=1.104, 95% CI: 1.009-1.207, P=0.031) were independent predictors of live birth. Analysis of CLBR curves across multiple oocyte retrieval cycles showed that CLBR gradually increased with the number of oocyte retrievals and stabilized at 14.32% after the fifth retrieval. Conclusion:High bFSH levels reduce the live birth rate per initiated cycle but do not affect the live birth rate per transfer cycle. Increasing age and a low number of oocytes retrieved can both decrease the live birth rate. Multiple oocyte retrieval and transfer cycles can improve CLBR in patients with high bFSH level to some extent, but it tends to stabilize after the fifth cycle.

AIM:To explore the regulatory mecha-nism of pinoresinol diglucoside(PDG)on angiogen-esis during osteoporotic fracture healing in vivo and in vitro.METHODS:Fifty male C57BL/6J mice were randomly divided into five groups:normal group,model group,PDG 0.005,0.015 g/kg groups,and parathyroid hormone 1-34(PTH1-34)4×10-5 g/kg group.The osteoporotic fracture model of ovariec-tomized combined with femoral fracture was estab-lished,the PDG group was given intragastric admin-istration every other day and the PTH1-34 group was given subcutaneous injection of PTH1-34 every other day for 8 weeks.Micro-CT scanning,immunofluo-rescence and immunohistochemical staining were used to detect the related parameters and protein expressions.Human umbilical vein endothelial cells(HUVECs)were cultured,normal group,PDG 1,10,100 μmol/L groups and PTH1-341 ng/mL group were set up.CCK-8 assay,scratch experiment,tubule for-mation experiment,immunofluorescence and Western blot were used to detect the related pa-rameters and protein expressions.RESULTS:In vivo experiments found,compared with the normal con-trol group,a small amount of bone callus volume of fracture site were increased in the model control group,while BMD of non-callus site of femur,tra-becular bone fraction(BV/TV),trabecular thickness(Tb.Th)and trabecular number(Tb.N)were de-creased(P＜0.01),and trabecular separation(Tb.Sp)was increased(P＜0.01).The positive expression of vascular endothelial marker vascular endothelial markers(CD31)was decreased(P＜0.01).Compared with mice in the model control group,bone callus volume,index of BMD and BV/TV were increased in the PDG 0.005 g/kg group(P＜0.05),index of BMD,BV/TV,Tb.Th,Tb.N were increased,and index of Tb.Sp was decreased in the PDG 0.015 g/kg group(P＜0.05),the positive expression of CD31 was in-creased in the PDG administration groups(P＜0.01),the protein expressions of vascular endothelial growth factor(VEGF-A)(P＜0.01),Yes-associated protein 1(YAP1)(P＜0.01),PDZ-binding motif(TAZ)(P＜0.05)and TEA domain transcription factor 2(TEAD2)(P＜0.01)were increased in callus in the PDG 0.015 g/kg groups.Cell experiments found,compared with the normal control group,PDG groups promoted the proliferation,migration and tubule formation activity of HUVECs to varying de-grees(P＜0.05),at the same time,the expression of endothelial cadherin(E-cadherin)was decreased(P＜0.01),and VEGF-A,TEAD2,TAZ and YAP1 protein expression were increased(P＜0.05).CONCLUSION:PDG may accelerate osteoporotic fracture healing by promoting bone angiogenesis through regulat-ing Hippo signal pathway.

Objective:To investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.

AIM:To explore the regulatory mecha-nism of pinoresinol diglucoside(PDG)on angiogen-esis during osteoporotic fracture healing in vivo and in vitro.METHODS:Fifty male C57BL/6J mice were randomly divided into five groups:normal group,model group,PDG 0.005,0.015 g/kg groups,and parathyroid hormone 1-34(PTH1-34)4×10-5 g/kg group.The osteoporotic fracture model of ovariec-tomized combined with femoral fracture was estab-lished,the PDG group was given intragastric admin-istration every other day and the PTH1-34 group was given subcutaneous injection of PTH1-34 every other day for 8 weeks.Micro-CT scanning,immunofluo-rescence and immunohistochemical staining were used to detect the related parameters and protein expressions.Human umbilical vein endothelial cells(HUVECs)were cultured,normal group,PDG 1,10,100 μmol/L groups and PTH1-341 ng/mL group were set up.CCK-8 assay,scratch experiment,tubule for-mation experiment,immunofluorescence and Western blot were used to detect the related pa-rameters and protein expressions.RESULTS:In vivo experiments found,compared with the normal con-trol group,a small amount of bone callus volume of fracture site were increased in the model control group,while BMD of non-callus site of femur,tra-becular bone fraction(BV/TV),trabecular thickness(Tb.Th)and trabecular number(Tb.N)were de-creased(P＜0.01),and trabecular separation(Tb.Sp)was increased(P＜0.01).The positive expression of vascular endothelial marker vascular endothelial markers(CD31)was decreased(P＜0.01).Compared with mice in the model control group,bone callus volume,index of BMD and BV/TV were increased in the PDG 0.005 g/kg group(P＜0.05),index of BMD,BV/TV,Tb.Th,Tb.N were increased,and index of Tb.Sp was decreased in the PDG 0.015 g/kg group(P＜0.05),the positive expression of CD31 was in-creased in the PDG administration groups(P＜0.01),the protein expressions of vascular endothelial growth factor(VEGF-A)(P＜0.01),Yes-associated protein 1(YAP1)(P＜0.01),PDZ-binding motif(TAZ)(P＜0.05)and TEA domain transcription factor 2(TEAD2)(P＜0.01)were increased in callus in the PDG 0.015 g/kg groups.Cell experiments found,compared with the normal control group,PDG groups promoted the proliferation,migration and tubule formation activity of HUVECs to varying de-grees(P＜0.05),at the same time,the expression of endothelial cadherin(E-cadherin)was decreased(P＜0.01),and VEGF-A,TEAD2,TAZ and YAP1 protein expression were increased(P＜0.05).CONCLUSION:PDG may accelerate osteoporotic fracture healing by promoting bone angiogenesis through regulat-ing Hippo signal pathway.

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors