Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

Objective:To compare the therapeutic efficacy and safety of local anesthesia and spinal anesthesia for the patients with varicocele(VC)who underwent microsurgical varicocelectomy(MV).Methods:We retrospectively analyzed the data of VC patients who underwent MV treatment at the Andrology Department of the Affiliated Ruikang Hospital of Guangxi University of Chinese Medicine from May 2020 to March 2023.Cases with complete clinical data and follow-up evaluation were selected and divided into a control group(spinal anesthesia)and an observation group(local anesthesia)according to different anesthesia methods.The surgical time(including anesthesia time),visual analogue scale(VAS)score for pain,hospital stay,treatment cost,sperm concentration,for-ward motile sperm rate,and normal sperm morphology rate after three months of surgery,as well as postoperative complications and re-currence rate were compared between the two groups.Results:A total of 107 eligible cases were included,with 56 cases in the con-trol group and 51 cases in the observation group.There was no significant difference in the VAS score for pain during and after four hours of surgery,as well as postoperative complications,and recurrence rate between the two groups(P＞0.05).There was an signif-icant increase in sperm concentration,forward motile sperm rate,and normal sperm morphology rate in both of two groups after three months of surgery(P＜0.05).However,there was no significant difference between the two groups three months after surgery(P＞0.05).The surgical time and hospital stay were shorter than those of the control group(P＜0.05).And the treatment cost in observa-tion group was lower than that of the control group(P＜0.05).Conclusion:Both local anesthesia and lumbar anesthesia for MV treatment of VC have good efficacy and safety.However,patients treated with MV under local anesthesia for VC have obvious advanta-ges in terms of operation time(including anesthesia time),hospital stay,and treatment cost,which is worthy of clinical promotion and application.

Objective:To assess the prognostic value of cerebrospinal fluid (CSF) neuron specific enolase (NSE) combined with protein content in predicting poor prognosis in patients with intraventricular hemorrhage after external ventricular drainage (EVD).Methods:The clinical data of 73 intraventricular hemorrhage patients underwent EVD in the Second Affiliated Hospital of Wenzhou Medical University from February 2019 to January 2022 were retrospectively analyzed. After 90 d of surgery, 37 patients (good prognosis group) had a modified Rankin score of 0 to 2, while 36 cases (poor prognosis group) had a score of 3 to 5. The baseline characteristics including gender, age, hypertension, diabetes and Glasgow coma score (GCS) upon admission were recorded. The peripheral blood samples were collected within 24 h of admission to measure C-reactive protein, white blood cell and blood potassium. The CSF samples were obtained within 24 h after EVD to measure NSE, protein content, white blood cell and red blood cell. Binary Logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with intraventricular hemorrhage after EVD. The efficacy of CSF NSE combined with protein content in predicting the poor prognosis in patients with intraventricular hemorrhage after EVD was evaluated by the receiver operating characteristics (ROC) curve.Results:There were no statistical differences in gender distribution, age, hypertension, diabetes, blood C-reactive protein, white blood cell and blood potassium between two groups ( P>0.05); the GCS upon admission in poor prognosis group was significantly lower than that in good prognosis group: (5.83 ± 0.20) scores vs. (9.54 ± 0.43) scores, the CSF NSE, protein content, white blood cell and red blood cell were significantly higher than those in good prognosis group: (377.94 ± 21.91) μg/L vs. (86.43 ± 11.96) μg/L, (16.70 ± 2.07) g/L vs. (2.92 ± 0.74) g/L, (731.61 ± 141.36) × 10 6/L vs. (302.16 ± 90.99) × 10 6/L and (410 332 ± 88 584) × 10 6/L vs. (156 075 ± 61 387) × 10 6/L, and there were statistical differences ( P<0.01 or <0.05). Binary Logistic regression analysis result showed that elevated CFS NSE and higher CSF protein content were independent risk factors of poor prognosis in patients with intraventricular hemorrhage after EVD ( OR = 1.053 and 1.270, 95% CI 1.005 to 1.103 and 1.020 to 1.581, P<0.05). ROC curve analysis result showed that the area under the curve of CFS NSE combined with protein content detection to predict the poor prognosis in patients with intraventricular hemorrhage after EVD was larger than that of CFS NSE and protein content alone detection (0.982 vs. 0.971 and 0.903), and the optimal cutoff values of CSF NSE and protein content were 233.090 μg/L and 1.425 g/L, respectively. Conclusions:CSF NSE and protein content are significantly elevated in patients with intraventricular hemorrhage after EVD. The combined detection of CSF NSE and protein content provides valuable prognostic information for prognosis in patients with intraventricular hemorrhage after EVD, and it can provide important basis for prognosis evaluation.

ASSOCIATION BETWEEN MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AND FACTORS ASSOCIATED WITH ANTIHYPERTENSIVE MEDICATION ADHERENCE IN THE MELAKA TENGAH DISTRICT: A CROSS-SECTIONAL SURVEY Introduction: The burden of cardiovascular disease and early morbidity and mortality is exacerbated by hypertension. According to the 2019 National Health and Morbidity Survey, 30% of adults in Malaysia aged over 18 years had hypertension. Our study aimed to investigate the association between medication adherence and blood pressure control and the factors associated with antihypertensive medication adherence. Methods: This cross-sectional study was conducted among adult patients with hypertension who had been under treatment at public primary health clinics in the Melaka Tengah District. A self-administered questionnaire was used, and blood pressure was measured. Descriptive and multivariate logistic regression analyses were conducted using the Statistical Package for the Social Sciences (version 28). Results: A total of 1531 patients were recruited in this study. Among them, 74.1% had good antihypertensive medication adherence, and 51.4% had their blood pressure controlled. Medication adherence was significantly associated with blood pressure control (P<0.005). The multivariate analysis showed that the determinants for antihypertensive medication non-adherence were Malay ethnicity, secondary education, farther distance from the clinic, experience of side effects of antihypertensive medications, concern about long-term side effects and usage of alternative medicine (P<0.05). Taking multiple antihypertensive medications was the only factor associated with uncontrolled blood pressure (P<0.05). Conclusion: Addressing issues on medication adherence is important to ensure blood pressure control. The factors associated with non-adherence should be closely monitored to improve blood pressure control and prevent adverse health outcomes. Single-pill combination antihypertensive medications are encouraged to reduce pill burden and improve blood pressure control.

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Nucleus Accumbens/metabolism* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Sleep ; Sleep Wake Disorders ; Stress, Psychological/complications*

Relevant research in recent years has demonstrated that the atrial fibrillation occurrence rate is significantly higher in patients with cirrhosis. The most common indication for long-term anticoagulant therapy is chronic atrial fibrillation. The use of anticoagulant therapy greatly reduces the incidence rate of ischemic stroke. Patients with cirrhosis combined with atrial fibrillation have an elevated risk of bleeding and embolism during anticoagulant therapy due to cirrhotic coagulopathy. At the same time, the liver of such patients will go through varying levels of metabolism and elimination while consuming currently approved anticoagulant drugs, thereby increasing the complexity of anticoagulant therapy. This article summarizes the clinical studies on the risks and benefits of anticoagulant therapy in order to provide a reference for patients with cirrhosis combined with atrial fibrillation.
Humans ; Atrial Fibrillation/epidemiology* ; Stroke/epidemiology* ; Anticoagulants/therapeutic use* ; Hemorrhage ; Liver Cirrhosis/drug therapy* ; Risk Factors

Objective:To explore the therapeutic effect of anti-interleukin (IL)-12/IL-23 p40 antibody on experimental autoimmune uveitis (EAU) and its mechanism.Methods:Sixty-six SPF female C57BL/6N mice aged 6-8 weeks were selected.EAU model was established in 24 mice through immunization with the interphotoreceptor retinoid-binding protein (IRBP) 651-670.The 24 mice were sacrificed before immunization, and on the 3rd, 12th, and 18th day after immunization, with 6 at each time point.Flow cytometry was used to detect the proportion of IL-17A + interferon-γ (IFN-γ) + CD4 + T cells in the spleen, lymph nodes and eyeballs.Another 6 mice were selected to establish EAU model, and fundus images of the mice were taken with a small animal imaging instrument and optical coherence tomography (OCT) 18 days after immunization.The 6 mice were sacrificed after OCT examination and the eyeballs were collected.Hematoxylin-eosin staining was used to observe the retinal inflammation and morphological changes in tissue structure.Flow cytometry was employed to detect the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes.The 6 mice were divided into IL-17A + IFN-γ + highly expressed group and IL-17A + IFN-γ + lowly expressed group according to flow cytometry results, and the retinal injury was compared between the two groups.EAU model was established in another 36 mice, which were divided into anti-IL-12/IL-23 p40 group and IgG group by random number table method, with 18 mice in each group.Anti-IL-12/IL-23 p40 or IgG was injected by tail vein at a 3-day inteval according to grouping.On the 12th and 18th day after immunization, 6 mice were selected from each group to collect lymph nodes and eyeballs, and the proportion of T cell subsets was detected by flow cytometry.Eyeballs of 6 mice in each group were extracted on the 24th day after immunization and retinal damage was observed by hematoxylin-eosin staining.The induced differentiation of CD4 + T cells in vitro was assayed by flow cytometry.The expressions of IL-17 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells.The relative expression levels of Th1 transcription factor T-bet and Th17 transcription factor retinoid acid-related orphan nuclear receptor γt (ROR-γt) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells were detected by real-time quantitative PCR.The use and care of animals followed the ARVO statement and this study protocol was approved by an Ethics Committee of Experimental Animals of Tianjin Medical University Eye Hospital (No.TJYY2019111019). Results:There were significant differences in the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes, spleen and eyeballs between wild-type mice and EAU mice at the 3rd, 12th and 18th day after immunization ( H=9.642, 16.531, 10.385; all at P<0.05). Compared with before immunization, the proportion of IL-17A + IFN-γ + CD4 + T cells was significantly increased in lymph nodes of EAU mice on the 12th day following immunization and was significantly increased in spleen and lymph nodes on day 18 after immunization (all at P<0.05). Severe retinal exudation, retinal detachment, severe inflammatory cell infiltration and extensive retinal folds were detected in IL-17A + IFN-γ + highly expressed mice.Mild retinal edema, focal inflammatory cell infiltration and mild retinal folds were found in IL-17A + IFN-γ + lowly expressed mice.The proportion of CD3 and IL-17A + IFN-γ + CD4 + T cells in the eyeballs of anti-IL-12/IL-23 p40 group was lower than that in IgG group at the 18th day after immunization, and the differences were statistically significant ( t=15.304, 8.080; both at P<0.05). On day 12 after immunization, the percentage of IL-17A + IFN-γ + CD4 + T cells in anti-IL-12/IL-23 p40 group was (0.33±0.18)%, which was significantly lower than (4.83±0.45)% in IgG group ( t=15.974, P<0.001). Compared with IgG group, the percentage of Th1, Th17, IL-17A + IFN-γ + CD4 + T cells and the expression levels of IL-17, IFN-γ, T-bet, ROR-γt in anti-IL-12/IL-23 p40 group were significantly decreased, with statistical significances (all at P<0.05). Conclusions:Anti-IL-12/IL-23 p40 has a therapeutic effect on EAU by inhibiting IL-17A + IFN-γ + CD4 + T cells.

Objective To establish a blast injury experimental model using a shock tube at lateral lying position of C57BL/6 mice, investigate biomechanical responses of macrophages/microglia cells in the heart, lung and brain tissues to mechanical damage by shock wave within 24 hours. Methods Shock tube was employed to generate a shock wave to C57BL/6 mice. Firstly, the weight changes of mice were measured at different time points after the shock. Then the cardiac, pulmonary and whole brain tissue samples were dissected after anesthesia. Pathological sections were stained with HE staining to detect structural damage; the TUNEL staining method was used to mark and count the proportion of dead cells in each tissue. Microglial cells were labeled with fluorescent antibody, while responses and changes of macrophages/microglia after shock loading were analyzed. Results The shock tube exerted 179 kPa overpressure shock wave upon sideway of the mouse, and lethal rate of the mouse was 3.33%. Compared with normal control group, the mice in experimental group had a significant weight loss within 24 hours after loading shock. Pathological sections showed rupture of lung tissues after shock, accompanied by alveolar protein deposition, pulmonary bulla and other diseases. Fluorescence staining showed that lung tissue was recruited and activated in a large amount within 24 hours. The proportion of dead cells cleared rebounded to normal level within 24 hours. The heart was highly tolerant to shock, and macrophages appeared near the large blood vessels. The brain showed unilateral aggregation of microglia due to the impact posture, mainly due to prolonged inflammation and a higher proportion of dead cells at the junction of gray and white matter. Conclusions A blast shock model at lateral lying position of the mouse was established. Within 24 hours, macrophages/microglia were recruited quickly to the injury site after being impacted, which mediated strong immune stress, and might participate in the immune response to trigger a second long-term inflammatory injury. The results of the study provide experimental basis for the evaluation of primary impact injury, such as dose-effect relationship and tissue damage difference.

Objective:To investigate the efficacy of microsurgical treatment in cavernous sinus tumors.Methods:The clinical data of 87 patients with cavernous sinus tumor treated by microsurgery from January, 2010 to August, 2019 were analysed retrospectively. The surgical approaches and microsurgical skills for common tumors in Cavernous Sinus region were discussed. The follow-up included outpatient and telephone follow-ups, and the follow-up results were evaluated by KPS score.Results:Among the 87 cases, 57 were totally resected (65.5%), 14 were subtotal resected (16.1%) and 16 were major resected (18.4%). Hospitalisation ranged from 14 to 98 days, with an average of 29 days. Postoperative complications occurred in 30 cases with cranial nerve injury, 2 brain stem injury, 4 postoperative bleeding, 5 cerebrospinal fluid leakage, 4 infection, 1 Pituitary damage and 1 death. Prognosis and follow-up analysis showed 68 cases with KPS>60 and 66 with KPS>80 at 1 month after surgery; 74 with KPS>70 and 72 with KPS>80 at 3 months after surgery; 78 with KPS>80 by 12 months after surgery. During the follow-up period of 6-120 months, 3 cases died. Recurrence: 6 of incomplete resection of meningioma, were in 1-6 years after the surgery, 4 of incomplete resection of schwannoma in 1-8 years, 2 of pituitary adenoma respectively in 13 and 16 months after the surgery. There was no recurrence after reoperation. Two cases of chondrosarcoma, 3 of chordoma and 3 of germinoma were treated with radiotherapy, and during the follow-up, there was no progress of the focus. No tumor progression or recurrence was found in other cases during follow-up.Conclusion:Surgery of cavernous sinus tumor is difficult due to frequent postoperative complications. Reasonable preoperative plan, surgical approach and precise microsurgical techniques are the keys in reduction of postoperative complications and in the improvement of prognosis.