Therapeutic sleep deprivation for major depressive disorder: A randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.

Genome-Wide Identification of NAC Family Genes in Oat and Functional Characterization of AsNAC109 in Abiotic Stress Tolerance.

The plant-specific NAC gene family is one of the largest transcription factor families, participating in plant growth regulation and stress response. Despite extensive characterization in various plants, our knowledge of the NAC family in oat is lacking. Herein, we identified 333 NAC genes from the latest release of the common oat genome. We provide a comprehensive overview of the oat NAC gene family, covering gene structure, chromosomal localization, phylogenetic characteristics, conserved motif compositions, and gene duplications. AsNAC gene expression in different tissues and the response to various abiotic stresses were characterized using RT-qPCR. The main driver of oat NAC gene family expansion was identified as segmental duplication using collinearity analysis. In addition, the functions of AsNAC109 in regulating abiotic stress tolerance in Arabidopsis were clarified. This is the first genome-wide investigation of the NAC gene family in cultivated oat, which provided a unique resource for subsequent research to elucidate the mechanisms responsible for oat stress tolerance and provides valuable clues for the improvement of stress resistance in cultivated oat.

Ultrasound-Assisted Extraction of Paeonol from Moutan Cortex: Purification and Component Identification of Extract.

Moutan Cortex (MC) is a traditional Chinese medicine that contains abundant medicinal components, such as paeonol, paeoniflorin, etc. Paeonol is the main active component of MC. In this study, paeonol was extracted from MC through an ultrasound-assisted extraction process, which is based on single-factor experiments and response surface methodology (RSM). Subsequently, eight macroporous resins of different properties were used to purify paeonol from MC. The main components of the purified extract were identified by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS/MS). The results indicate the optimal parameters are as follows: liquid-to-material ratio 21:1 mL/g, ethanol concentration 62%, ultrasonic time 31 min, ultrasonic temperature 36 °C, ultrasonic power 420 W. Under these extraction conditions, the actual yield of paeonol was 14.01 mg/g. Among the eight tested macroporous resins, HPD-300 macroporous resin was verified to possess the highest adsorption and desorption qualities. The content of paeonol increased from 6.93% (crude extract) to 41.40% (purified extract) after the HPD-300 macroporous resin treatment. A total of five major phenolic compounds and two principal monoterpene glycosides were characterized by comparison with reference compounds. These findings will make a contribution to the isolation and utilization of the active components from MC.

Photoprotective Effects of Epigallocatechin Gallate on Ultraviolet-Induced Zebrafish and Human Skin Fibroblasts Cells.

Background: The long-term exposure to ultraviolet radiation (UVR) raises oxidative stress and chronic inflammation levels, which in turn has a series of deleterious effects on skin health, such as sunburn, photoaging, and skin cancer. Hence, our study was determined to investigate the effects and mechanisms of epigallocatechin gallate (EGCG) in zebrafish and human skin fibroblasts (HSF) cells to alleviate ultraviolet-induced photoaging. Methods: The 4 days postfertilization (dpf) zebrafish larvae and HSF cells were treated with 10 J/cm2 UVA + 30 mJ/cm2 UVB, or 25, or 50 µM EGCG for 72 hr. The indicators involving in oxidative stress, inflammatory, and photoaging were measured by the kits, ELISA Kits and western blot methods. Results: EGCGs protect against UVR-induced skin damage in zebrafish and HSF cells. EGCG markedly decreased the reactive oxygen species (ROS), malondialdehyde, 8-OHdG levels, increased superoxide dismutase (SOD) activity, and significantly inhibited inflammatory factors levels including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-6 (IL-6) in zebrafish, and HSF cells irradiated with UVR. We found that EGCG could reduce UVR-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-κB (NF-κB), thereby reducing the protein-1 (AP-1), TNF-α, IL-1α, IL-6, and matrix metalloproteinase-1 (MMP-1) expressions, which are critical mediators of skin aging cascade causing the photoaging. Conclusion: These results validate that EGCG for protection of photoaging in zebrafish and HSF cells induced by UVR, which is closely related to the regulation of p38 MAPK/NF-κB, AP-1 signaling pathway which relieve oxidative stress, inflammation, and collagen degradation.

Sleep Deprivation and Heart Rate Variability in Healthy Volunteers: Effects of REM and SWS Sleep Deprivation.

Objective: Using PSG-guided acute selective REM/SWS sleep deprivation in volunteers, this study examined the effects of sleep deprivation on the cardiovascular and autonomic nervous systems, as well as the relationship between cardiac neuromodulation homeostasis and cardiovascular disease. Methods: An experiment was conducted using 30 healthy volunteers (male : female = 1 : 1, aged 26.33 ± 4.5 years) divided into groups for sleep deprivation of SWS and REM sleep, and then, each group was crossed over for normal sleep (2 days) and repeated sleep deprivation (1 day, 3 times). During the study period, PSG and ELECTRO ECG monitoring were conducted, and five-minute frequency domain parameters and blood pressure values were measured before and after sleep deprivation. Results: Changes in VLF, LFnu, LF/HF, HF, and HFnu after SWS sleep deprivation were statistically significant (P < 0.05), but not LF (P = 0.063). Changes in VLF, LF, HF, LF/HF, LFnu, and HFnu after REM sleep deprivation were not statistically significant (P > 0.05). Conclusions: An increase in sympathetic nerve activity results from sleep deprivation and sudden awakening from SWS sleep is associated with a greater risk of cardiovascular disease.

Depression severity partially mediates the association between thyroid function and psychotic symptoms in first-episode, drug-naive major depressive disorder patients with comorbid anxiety at different ages of onset.

BACKGROUND: Anxiety and psychotic symptoms are common in patients with major depressive disorder (MDD), with a strong association with thyroid function. Age of onset contributes to the heterogeneity of MDD patients. This study aimed to assess the prevalence of psychotic symptoms in MDD patients with comorbid anxiety and to explore the relationship between thyroid function and psychotic symptoms by ages of onset. METHODS: A total of 894 first-episode, drug-naïve Chinese Han MDD patients with comorbid anxiety were recruited. Thyroid function and psychometric measures including Hamilton Anxiety Scale, Hamilton Depression Scale, and Positive and Negative Syndrome Scale were evaluated. Patients were divided into early adulthood onset (EAO, < 45 years old) and mid-adulthood onset (MAO, ≥ 45 years old) groups. RESULTS: The MAO subgroup had a higher prevalence of psychotic symptoms compared to EAO subgroup. TSH and TPOAb levels were positively correlated with psychotic symptoms severity, with a more pronounced effect in MAO subgroup. Furthermore, MDD severity partially mediated the effects of TPOAb and TSH levels on psychotic symptoms in both subgroups. LIMITATIONS: A causal relationship could not be demonstrated with this cross-sectional study, and the results should be limited to first-episode, drug-naïve MDD patients without considering more potential confounders. Moreover, the male-to-female ratio imbalance is present. CONCLUSIONS: Our results indicated that age of onset moderated the association between thyroid function and psychotic symptom, and depression severity partially mediated the effects of thyroid function on psychotic symptoms, suggesting thyroid function may serve as a biomarker of psychotic symptoms in MDD patients with anxiety.

Associations of three thermogenic adipokines with metabolic syndrome in obese and non-obese populations from the China plateau: the China Multi-Ethnic Cohort.

OBJECTIVES: High altitude exposure decreases the incidence of obesity and metabolic syndrome, but increases the expression of the thermogenic adipokines (leptin, fat cell fatty acid-binding protein (A-FABP) and visfatin). This study investigated the correlation of these adipokines with obesity and metabolic syndrome (MetS) in populations residing in a plateau-specific environment. DESIGN: Case-control study. SETTING: We cross-sectionally analysed data from the China Multi-Ethnic Cohort. PARTICIPANTS: A total of 475 obese (OB, body mass index (BMI)≥28.0 kg/m2) plateau Han people and 475 age, sex and region-matched non-obese (NO, 18.5≤BMI<24.0 kg/m2) subjects were recruited. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. PRIMARY AND SECONDARY OUTCOME MEASURES: Data with normal distributions were expressed as the mean (Stanard Deviation, SD), and data with skewed distributions were expressed as the median (Interquartile Range, IQR). The participants were grouped and the rank-sum test, χ2 test or t-tests was used for comparing groups. Spearman correlation coefficients were estimated to assess the relationships among leptin, A-FABP, visfatin and the components of MetS in each group. RESULTS: A-FABP was an independent predictor of OB (OR, 1.207; 95% CI, 1.170 to 1.245; p<0.05), ABSI (OR, 1.035; 95%CI, 1.019 to 1.052; p<0.05) and MetS (OR, 1.035; 95% CI, 1.013 to 1.057; p<0.05). Leptin was an independent predictor of MetS in the NO group. Visfatin was an independent predictor of increased ABSI, but not for OB or MetS. CONCLUSION: An abnormally elevated plasma A-FABP level, but not leptin or visfatin is a potential risk factor for MetS in high-altitude populations.

The effect of semen cuscutae flavonoid on Sertoli cells and blood-testis barrier in male infertility: integrating network pharmacology and experimental verification.

CONTEXT: Semen cuscutae is commonly used to treat male infertility (MI), and semen cuscutae flavonoid (SCF) is the main active component of semen cuscutae. The therapeutic mechanism of SCF on MI is still unclear. OBJECTIVE: To clarify the mechanisms of SCF against MI. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to predict the potential pathways of SCF against MI. Primary Sertoli cells (SCs) were extracted from testis of 60-day-old rats and divided into Control, Model, and 3 treatment groups. The Control and Model groups were given normal medium, the treatment groups were treated with various concentrations of SCF-containing medium (200, 400, and 800 µg/mL). After 24 h, the Model and treatment groups were exposed to heat stress at 43 °C for 15 min. Western blotting and immunohistochemistry were used to detect the expression of targets. RESULT: Network pharmacology indicated that the treatment of SCF on MI was closely related to PI3K-AKT signaling pathway. The in vitro experiments showed that SCF could up-regulated the expression of AKT, AR, occludin, and Ki67, and down-regulated the expression of CK-18 in SCs after heat stress. The AKT inhibitor could block this process. CONCLUSIONS: SCF can treat MI by regulating the proliferation and differentiation of SCs and the integrity of the blood-testis barrier. The study could provide experimental basis for clinical research.

Cerebellar infarction caused by vertebral artery dissection: A case report.

RATIONALE: Vertebral artery dissection is an important cause of posterior circulation ischemic stroke in young and middle-aged people. We reported a young man with cerebellar infarction caused by dissection of the right vertebral artery. PATIENT CONCERNS: A 34-year-old man presented with intermittent dizziness, blurred vision, nausea, and transient tinnitus 10 days before admission. All these symptoms were gradually aggravated and followed by vomiting and unfavorable movement of the right limbs. All these symptoms gradually aggravated. DIAGNOSIS: Neurological examination on admission showed ataxia of the right limbs. Magnetic resonance imaging of the head revealed a right cerebellar infarction. High-resolution vessel wall magnetic resonance imaging showed dissection of the right vertebral artery. Whole-brain CT digital subtraction angiography revealed occlusion of the third segment (V3) of the right vertebral artery. This supports the diagnosis of vertebral artery dissection. INTERVENTIONS: The patient received anticoagulant treatment with warfarin. OUTCOMES: After 2 weeks of treatment, the patient showed remarkably alleviated dizziness and unfavorable movement of the right limbs. After 3 months of treatment, the modified Rankin Scale score was 0. MRI of the head revealed that the original right cerebellar focus was softened, and there were no newly formed infarct foci. LESSONS: When young and middle-aged patients without atherosclerotic risk factors encounter sudden dizziness, tinnitus, and unfavorable limb movement, vertebral artery dissection may be considered. Careful inquiry into the medical history may help make a final diagnosis. Further high-resolution vessel wall magnetic resonance imaging is an effective means to find arterial dissection. Early diagnosis and treatment for vertebral artery dissection has a favorable prognosis.

The role of light wavelengths in regulating algal-bacterial granules formation, protein and lipid accumulation, and microbial functions.

High value-added products recovery from algal-bacterial granular sludge (ABGS) has received great attention recently. This study aimed to explore the role of different light wavelengths in regulating granule formation, protein and lipid production, and microbial functions. Bacterial granular sludge (BGS, R0) was most conducive to forming ABGS under blue (R2) light with the highest chlorophyll a (10.2 mg/g-VSS) and diameter (1800 µm), followed by red (R1) and white (R3) lights. R0-R3 acquired high protein contents (>164.8 mg/g-VSS) with essential amino acids above 44.4%, all of which were suitable for recycling, but R2 was the best. Also, blue light significantly increased total lipid production, while red light promoted the accumulation of some unsaturated fatty acids (C18:2 and C18:3). Some unique algae and dominant bacteria (e.g., Stigeoclonium, Chlamydomonas, and Flavobacteria) enrichment and some key functions (e.g., amino acid, fatty acid, and lipid biosynthesis) up-regulation in R2 might help to improve proteins and lipids quality. Combined, this study provides valuable guidance for protein and lipid recovery from ABGS.

Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

Importance: Perioperative respiratory adverse events (PRAEs) are the most common complication during pediatric anesthesia, and they may be affected by the administration of preoperative sedatives. Objective: To investigate the effect of intranasal dexmedetomidine or midazolam used for premedication on the occurrence of PRAEs. Design, Setting, and Participants: This single-center, double-blind, randomized clinical trial was conducted among children aged 0 to 12 years undergoing elective tonsillectomy and adenoidectomy from October 2020 to June 2021 at Children's Hospital of Xuzhou Medical University, Xuzhou, China. Data analysis was performed from June to October 2021. Interventions: Children were randomly assigned to 3 groups: the midazolam group received intranasal midazolam (0.1 mg/kg), and the dexmedetomidine group received intranasal dexmedetomidine (2.0 µg/kg) for premedication. The normal saline group received intranasal 0.9% saline for control. Main Outcomes and Measures: The primary outcome was the difference in the incidence of PRAEs among the 3 groups. The secondary outcomes were the frequency of the individual PRAEs, including the incidence of such events during the induction and recovery periods, postoperative emergence delirium, postoperative pain score, sedation success rate, and heart rate values. Results: A total of 384 children (median [IQR] age, 7 [5-10] years; 227 boys [59.1%]) were enrolled and randomized; 373 data sets were available for intention-to-treat analysis (124 children in the midazolam group, 124 children in the dexmedetomidine group, and 125 children in the normal saline group). After the data were adjusted for age, sex, American Society of Anesthesiologists physical status, body mass index, obstructive sleep apnea, upper respiratory tract infection, and passive smoking, children in the midazolam group were more likely to experience PRAEs than those in the normal saline group (70 of 124 children [56.5%] vs 51 of 125 children [40.8%]; adjusted odds ratio [aOR], 1.99; 95% CI, 1.18-3.35), whereas the dexmedetomidine group had a significantly lower PRAEs incidence than the normal saline group (30 of 124 children [24.2%] vs 51 of 125 children [40.8%]; aOR, 0.45; 95% CI, 0.26-0.78). Compared with the dexmedetomidine group, the midazolam group had a higher risk of PRAEs (aOR, 4.44; 95% CI, 2.54-7.76), but no other serious clinical adverse events were observed. Conclusions and Relevance: In this randomized clinical trial, intranasal midazolam used for premedication was associated with increased incidence of PRAEs, whereas premedication with intranasal dexmedetomidine was associated with reduced incidence of PRAEs. Where clinically appropriate, anesthesiologists should consider using intranasal dexmedetomidine for sedation in children undergoing tonsillectomy and adenoidectomy. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2000038359.

Promoter Specific Methylation of SSTR4 is Associated With Alcohol Dependence in Han Chinese Males.

Alcohol dependence (AD), a disease can be affected by environmental factors with epigenetic modification like DNA methylation changes, is one of the most serious and complex public health problems in China and worldwide. Previous findings from our laboratory using the Illumina Infinium Human Methylation450 BeadChip suggested that methylation at the promoter of SSTR4 was one of the major form of DNA modification in alcohol-dependent populations. To investigate whether DNA methylation levels of the SSTR4 promoter influence alcohol-dependent behaviors, genomic DNA was extracted from the peripheral blood sample of 63 subjects with AD and 65 healthy controls, and pyrosequencing was used to verify the results of BeadChip array. Linear regression was used to analyze the correlation between the methylation levels of SSTR4 promoter and the scores of alcohol dependence scales. Gene expression of SSTR4 in brain tissue was obtained from the Genotype-Tissue Expression (GTEx) project and Human Brain Transcriptome database (HBT). We found the methylation levels of SSTR4 in AD group were significantly lower than healthy controls (two-tailed t-test, t = 14.723, p < 0.001). In addition, only weak to moderate correlations between the methylation levels of the SSTR4 promoter region and scale scores of Alcohol Use Disorders Identification Test (AUDIT), Life Events Scale (LES) and Wheatley Stress Profile (WSS) based on linear regression analyses (AUDIT: R 2 = 0.35, p < 0.001; LES: R 2 = 0.27, p < 0.001; WSS: R 2 = 0.49, p < 0.001). The hypomethylated status of SSTR4 may involve in the development of AD and increase the risk of AD persistence in Han Chinese males.

Yes-associated protein promotes endothelial-to-mesenchymal transition of endothelial cells in choroidal neovascularization fibrosis.

AIM: To reveal whether and how Yes-associated protein (YAP) promotes the occurrence of subretinal fibrosis in age-related macular degeneration (AMD). METHODS: Cobalt chloride (CoCl2) was used in primary human umbilical vein endothelial cells (HUVECs) to induce hypoxia in vitro. Eight-week-old male C57BL/6J mice weighing 19-25 g were used for a choroidal neovascularization (CNV) model induced by laser photocoagulation in vivo. Expression levels of YAP, phosphorylated YAP, mesenchymal markers [α smooth muscle actin (α-SMA), vimentin, and Snail], and endothelial cell markers (CD31 and zonula occludens 1) were measured by Western blotting, quantitative real-time PCR, and immunofluorescence microscopy. Small molecules YC-1 (Lificiguat, a specific inhibitor of hypoxia-inducible factor 1α), CA3 (CIL56, an inhibitor of YAP), and XMU-MP-1 (an inhibitor of Hippo kinase MST1/2, which activates YAP) were used to explore the underlying mechanism. RESULTS: CoCl2 increased expression of mesenchymal markers, decreased expression of endothelial cell markers, and enhanced the ability of primary HUVECs to proliferate and migrate. YC-1 suppressed hypoxia-induced endothelial-to-mesenchymal transition (EndMT). Moreover, hypoxia promoted total expression, inhibited phosphorylation, and enhanced the transcriptional activity of YAP. XMU-MP-1 enhanced hypoxia-induced EndMT, whereas CA3 elicited the opposite effect. Expression of YAP, α-SMA, and vimentin were upregulated in the laser-induced CNV model. However, silencing of YAP by vitreous injection of small interfering RNA targeting YAP could reverse these changes. CONCLUSION: The findings reveal a critical role of the hypoxia-inducible factor-1α (HIF-1α)/YAP signaling axis in EndMT and provide a new therapeutic target for treatment of subretinal fibrosis in AMD.

Silencing of YAP attenuates pericyte-myofibroblast transition and subretinal fibrosis in experimental model of choroidal neovascularization.

Age-related macular degeneration (AMD) is the main reason of irreversible vision loss in the elderly. The subretinal fibrosis subsequent to choroidal neovascularization (CNV) is an important feature in the late stage of wet AMD and is considered to be one reason for incomplete response to anti-VEGF drugs. Recent studies have shown that pericyte-myofibroblast transition (PMT) is an important pathological process involving fibrotic diseases of various organs. However, the specific role and mechanism of PMT in the subretinal fibrosis of CNV have not been clarified. It has been clear that the Hippo pathway along with its downstream effector Yes-associated protein (YAP) plays an important role in both epithelial and endothelial myofibroblast development. Therefore, we speculate whether YAP participates in PMT of pericytes and promotes fibrosis of CNV. In this study, experimental CNV was induced by laser photocoagulation in C57BL/6J (B6) mice, and aberrant YAP overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of the laser-injured eyes. YAP knockdown reduced the proliferation, migration, and differentiation of human retinal microvascular pericytes in vitro. It also reduced subretinal fibrosis of laser-induced CNV in vivo. Moreover, by proteomics-based analysis of pericyte conditioned medium (PC-CM) and bioinformatic analyses, we identified that the crosstalk between Hippo/YAP and MAPK/Erk was involved in expression of filamin A in hypoxic pericytes. These findings suggest that Hippo/YAP and MAPK/Erk are linked together to mediate pericyte proliferation, migration as well as differentiation, which may embody potential implications for treatment in diseases related to CNV.

Effect of selective sleep deprivation on heart rate variability in post-90s healthy volunteers.

The 5-minute frequency domain method was used to examine the effects of polysomnography (PSG)-guided acute selective sleep deprivation (REM/SWS) on the cardiovascular autonomic nervous system, heart rate, and rhythm in healthy volunteers to understand the relationship between cardiac neuro regulatory homeostasis and cardiovascular system diseases in healthy subjects. The study included 30 healthy volunteers selected through the randomized-controlled method, randomly divided into REM sleep deprivation and SWS sleep deprivation groups. PSG analyses and dynamic electrocardiogram monitoring were done at night, during slow wave sleep or REM sleep. An all-night sleep paradigm, without any interruptions, was tested 3 times for comparison. The frequency domain parameter method was further used to monitor the volunteers 5 min before and after a period of sleep deprivation. According to the characteristics of the all-night sleep scatter plot, healthy volunteers were divided into abnormal and normal scatter plot groups. When compared with the period before sleep deprivation, high frequency (HF) and normalized high-frequency component (HFnu) were found to be decreased. Normalized low-frequency component (LFnu) increased in the abnormal scatter plot group after sleep deprivation, and this difference was statistically significant (P < 0.05). The scatter plot also showed that very low frequency (VLF) increased only in the normal group after deprivation and this difference, as well, was statistically significant (P < 0.05). The increase in diastolic blood pressure in the abnormal group was statistically significant (P < 0.05), but the change in blood pressure in the normal group was not statistically significant (P > 0.05). There are 62.5% of the patients and 20% of the employees that were observed to have abnormal whole-night sleep patterns during the uninterrupted whole-night sleep regime. Patients with atrial or ventricular premature beats (more than 0.1%), and those with ST-t changes during sleep, were all ascertained as abnormal. We concluded that some healthy people could face unstable autonomic nervous functioning related to their long-term tension, anxiety, time urgency, hostility, and other chronic stress states. In the face of acute sleep deprivation selectivity, mild stress based excitability of the vagus nerve is reduced, which diminishes the protective function, making them susceptible to conditions such as premature ventricular arrhythmia.

Wuzi-Yanzong prescription alleviates spermatogenesis disorder induced by heat stress dependent on Akt, NF-κB signaling pathway.

Akt and nuclear factor kappa B (NF-κB) signaling pathways are involved in germ cell apoptosis and inflammation after testicular heat stress (THS). We observed that after THS induced by the exposure of rat testes to 43 °C for 20 min, their weight decreased, the fraction of apoptotic testicular germ cells significantly increased, and the proliferation of germ cells was inhibited. In addition, THS lowered serum testosterone (T) level, whereas the levels of follicle stimulating hormone and luteinizing hormone were not significantly changed. The ultrastructure of the seminiferous tubules became abnormal after THS, the structure of the blood-testis barrier (BTB) became loose, and the Sertoli cells showed a trend of differentiation. The level of phosphorylated Akt was reduced, whereas the amount of phosphorylated NF-κB p65 was augmented by THS. Wuzi-Yanzong (WZYZ), a classic Chinese medicine prescription for the treatment of male reproductive dysfunctions, alleviated the changes induced by THS. In order to determine the mechanism of action of WZYZ, we investigated how this preparation modulated the levels of T, androgen receptor (AR), erythropoietin (EPO), EPO receptor, and Tyro-3, Axl, and Mer (TAM) family of tyrosine kinase receptors. We found that WZYZ activated the Akt pathway, inhibited the Toll-like receptor/MyD88/NF-κB pathway, and repaired the structure of BTB by regulating the levels of T, AR, TAM receptors, and EPO. In conclusion, these results suggest that WZYZ activates the Akt pathway and inhibits the NF-κB pathway by acting on the upstream regulators, thereby improving spermatogenesis deficit induced by THS.

Effect of Wuzi Yanzong Pills on Sertoli cells and blood-testis barrier in heat-stressed rats based on Akt signalling pathway.

The blood-testis barrier (BTB) of Sertoli cells (SCs) is an important biological barrier that maintains spermatogenesis and provides a favourable microenvironment for spermatogenesis. However, heat stress can directly damage the BTB structural proteins of testicular SCs, leading to dyszoospermia. Wuzi Yanzong Pills (WYP) is a traditional Chinese medicine formula used to treat male reproductive diseases. However, whether WYP could ameliorate heat stress injury in primary SCs extracted from rat testes and BTB proteins remains unknown. Here, treatment with WYP (low, medium and high dose) increased the SC viability and the proliferation of cell antigen Ki67 significantly. Additionally, it promoted SC maturation, which presented in the form of increased androgen receptors (ARs) and decreased cytokeratin 18 (CK-18) in three WYP dose groups. WYP upregulated BTB proteins such as zonula occludens 1 (ZO-1) and occludin across all WYP groups and decreased phosphorylated Akt (p-Akt) in the middle and high-dose groups; however, ZO-1 and occludin recovery were reduced with the presence of Akt inhibitor in WYP groups. WYP improved SC viability and proliferation, and ameliorated dedifferentiation and BTB-proteins damaged by heat stress via Akt signalling. The findings present theoretical support for the effects of WYP in the management of dyszoospermia and male infertility.

Postoperative pain treatment with transmuscular quadratus lumborum block and fascia iliaca compartment block in patients undergoing total hip arthroplasty: a randomized controlled trial.

BACKGROUND: Patients often suffer moderate or even severe pain after total hip arthroplasty; such pain seriously affects early postoperative recovery. This study aimed to investigate the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block combined with fascia iliaca compartment block for elderly patients undergoing total hip arthroplasty. METHODS: Fifty-four patients scheduled for total hip arthroplasty were included in this randomized controlled study. The patients were randomly assigned to receive only transmuscular quadratus lumborum block (group Q) or transmuscular quadratus lumborum block combined with fascia iliaca compartment block (group QF) with ultrasound guidance. Postoperatively in both groups, paracetamol 1 g was regularly administered at 6 h intervals and patient-controlled intravenous analgesia was administered. The primary outcome was cumulative sufentanil consumption via patient-controlled intravenous analgesia 24 h postoperatively. The secondary outcomes included pain degree, time to the first analgesic requirement, joint range of motion, quality of recovery, and the incidence of postoperative complications. RESULTS: Fifty patients were included, and their data were analyzed. The cumulative sufentanil consumption in group QF was significantly lower during the first 24 h after surgery than that in group Q, and the cumulative sufentanil consumption in group QF was reduced at 6-12 and 12-18 h after surgery. The postoperative pain intensity was lower in group QF than in group Q (linear mixed-effects model, the main effect of treatment: P < 0.001). Compared with group Q, group QF had higher quality of recovery and joint range of movement. The time to the first analgesic requirement was longer in group QF than in group Q (log-rank, P < 0.001). There was no statistically significant difference in complications postoperatively between the two groups. CONCLUSIONS: Our study provides a multimodal, opioid-sparing analgesic regimen for elderly patients undergoing total hip arthroplasty. The combination of transmuscular quadratus lumborum block and fascia iliaca compartment block provides a significant advantage for early postoperative functional recovery. Further studies are required to confirm the minimum effective dose. TRIAL REGISTRATION: The study was registered on the 21st December 2020 (retrospectively registered) on the Chinese Clinical Trial Registry: ChiCTR2000038686 .

Influence of progestational stress on BDNF and NMDARs in the hippocampus of male offspring and amelioration by Chaihu Shugan San.

BACKGROUND: Progestational stress has been proven to be a risk for the neural development of offspring, especially in the hippocampus. However, whether Chaihu Shugan San (CSS) can ameliorate hippocampal neural development via the regulation of brain-derived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptors (NMDAR) 2A (NR2A) and 2B (NR2B), and the mechanism of such action remains unclear. METHODS: Thirty-six female rats were randomly allocated into control, chronic immobilization stress (CIS) and CSS groups according to the random number table, respectively. The male offspring were fed for 21 days after birth then randomly divided into the same three groups (6 rats/group) as the female rats. Female rats, except for the control group, underwent 21-day CIS to established a progestational stress anxiety-like model which was evaluated by body weight, the elevated plus-maze (EPM) test and serum dopamine (DA) measured using an enzyme-linked immunosorbent assay (ELISA). The expression levels of estrogen receptors (ERα/ERß) and progesterone receptor (PR) in female rat ovaries were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The hippocampal tissue in the 21-day offspring was observed by hematoxylin-eosin (HE) staining. The concentration of BDNF, NR2A, and NR2B were measured by RT-qPCR and immunohistochemistry in the CA3 and dentate gyrus (DG) regions of offsprings' hippocampus. RESULTS: Compared with the female control group, significant differences in body weight, EPM test and DA concentration were observed in the CIS group, meanwhile, the concentration of ERα (P < 0.05), PR (P < 0.05) and ERß in the ovaries were decreased. In the offsprings' hippocampus of the CIS group, the chromatin of the nucleus was edge set and with condensed and irregular morphology nucleus, and the cytoplasm was unevenly stained with spaces around the cells, moreover, the expression levels of BDNF, NR2A, and NR2B were also declined (P < 0.05). However, Chaihu Shugan San reversed these changes, especially the BDNF in the DG region (P < 0.05), and NR2A and NR2B in the CA3 and DG region (P < 0.05). CONCLUSIONS: CSS could ameliorate the neural development of the hippocampus in offspring damaged by anxiety-like progestational stress in female rats via regulating the expression levels of ERα, ERß, and PR in female rat ovaries and BDNF, NR2A, and NR2B in the hippocampus of their offspring.

[Extracellular vesicles and male reproduction: Advances in studies].

The transportation of extracellular vesicles (EV) is a newly discovered mechanism of cellular communication, which plays a biological role by interacting with cell surface receptors, endocytosis and direct fusion with target cell membranes. In the field of reproduction, experimental studies have found that EVs can influence the phenotypes and functions of receptor cells related to male reproduction and affect male reproductive health via transferring biological information carriers such as functional proteins and non-coding RNAs. This review focuses on the relationship between EVs and male reproduction from the perspectives of the testis, epididymis, semen, seminal vesicle and prostate, which are closely related to male reproduction, and discusses the new mechanisms affecting male reproductive health from the perspective of EVs.