MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.

Role of lumbar puncture level on the onset of epidural labor analgesia: a randomized controlled trial.

OBJECTIVE: To compare the speed of achieving painless uterine contractions in parturients undergoing epidural analgesia at different lumbar puncture levels. METHODS: This study is a randomized controlled trial at a tertiary A hospital with a history of over 80 years in Sichuan Province, China. Parturients aged 22-40 years old scheduled for vaginal delivery under epidural analgesia were recruited. Eligible patients were randomly allocated into lumbar 2-3 (L2-3) or lumbar 3-4 (L3-4) groups. Epidural analgesia was performed through the interspaces according to grouping. The primary outcome was the percentage of painless uterine contractions 15 min after the initiation of analgesia. The secondary outcomes included the percentage of painless status at 5 and 10 min, sensory block plane, motor block evaluation, adverse events of parturients, epidural analgesic consumption, Apgar score, and the parturients' evaluation of analgesia. RESULTS: Between April 2023 and August 2023, a total of 150 women were finally recruited, and 136 of them were analyzed (68 in each group). In comparison with the L3-4 groups, there was a significantly larger proportion of painless uterine contractions at 5, 10, and 15 min after analgesia initiation in the L2-3 group (20.6% vs. 7.4%, 52.9% vs. 26.5%, and 80.9% vs. 64.7%, P = .026, .002, and .034, respectively). Similarly, the pain scores were lower in the L2-3 group at 5, 10, and 15 min than that in the L3-4 group (5(4,7) vs. 6(5,7), 3(2,5) vs. 4(3,6), and 2(1,3) vs. 3(2,5), P = .006, .004, and .020, respectively). Furthermore, puncturing through the L2-3 interspace contributed to a higher evaluation of parturients to the analgesia procedure (9(8,9) vs. 8(8,9), P < .001). However, there was no significant difference in sensory block, motor block, or adverse events between the two groups. CONCLUSION: Puncturing through the L2-3 interspace is associated with faster pain relief and a better experience for parturients. These findings present a superior option for anesthesiologists when conducting epidural labor analgesia. Key messages What is already known on this topic?  Epidural analgesia is an effective way to relieve labor pain. What this study adds?  Puncturing via lumbar 2-3 interspace induces more rapid onset of epidural analgesia. How this study might affect research, practice or policy?  Lumbar 2-3 interspace is a superior option in terms of the speed of pain relief and satisfaction of parturients when conducting epidural labor analgesia.

Photoinduced Copper-Catalyzed Enantioselective Allylic C(sp3)-H Oxidation of Acyclic 1-Aryl-2-alkyl Alkenes as Limiting Substrates.

Herein, we disclose a simple copper-catalyzed method for enantioselective allylic C(sp3)-H oxidation of unsymmetrical acyclic alkenes, specifically 1-aryl-2-alkyl alkenes. The C-H substrates are used in limiting amounts, and the products are obtained with high enantioselectivity, E/Z-selectivity, and regioselectivity. The method exhibits broad functional group tolerance, and E/Z-alkene mixtures are suitable C-H substrates. The transformation is enabled by light irradiation, which sustains the enantioselective copper catalysis by photoinduced oxidant homolysis.

Vitamin D on Cardiac Function in Heart Failure: A Systematic Review and Meta-Analysis of 10 RCTs.

Background: Systematic evaluation of the effects of vitamin D supplementation in heart failure (HF) patients. Methods: Searches were conducted on National Library of Medicine, Web of Science, Cochrane Library, Google Scholar, China National Knowledge Infrastructure, and WANFANG databases. We analyzed data by using Review Manager 5.4 software. All are from the earliest records to March 2023. Outcome indicators analyzed the left ventricular ejection fraction (LVEF), the left ventricular end-diastolic internal diameter (LVEDD), the B-type brain natriuretic peptide (BNP) level and the 25-hydroxy vitamin D (25(OH)D) level. Results: Ten studies with 1099 patients were included. LVEF (mean difference (MD) = 0.74, 95% CI: -0.29 to 1.76, p = 0.41), LVEDD (MD = -0.59, 95% CI: -1.83 to 0.66, p = 0.25), BNP (MD = -0.08, 95% CI: -0.24 to 0.08, p = 0.34), 25(OH)D (MD = 0.41, 95% CI: -0.28 to 1.11, p = 0.25) are not statistically significant. And there is no heterogeneity in the results of LVEF, LVEDD and BNP indicators. Conclusions: Vitamin D supplementation may not be helpful in the clinical management of patients with HF.

LCK, FOXC1 and hsa-miR-146a-5p as potential immune effector molecules associated with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a type of systemic immune disease characterized by chronic inflammatory disease of the joints. However, the aetiology and underlying molecular events of RA are unclear. Here, we applied bioinformatics analysis to identify potential immune effector molecules involved in RA. The three microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. We used the R software screen 115 overlapping differentially expressed genes (DEGs). Subsequently, we constructed a protein-protein interaction (PPI) network encoded by these DEGs and identified 10 genes closely associated with RA - LCK, GZMA, GZMB, CD2, LAG3, IL-15, TNFRSF4, CD247, CCR5 and CCR7. Furthermore, in the miRNA-hub gene networks, we screened out hsa-miR-146a-5p, which is the miRNA controlling the largest number of hub genes. Finally, we found some transcription factors that closely interact with hub genes, such as FOXC1, GATA2, YY1, RUNX2, SREBF1, CEBPB and NFIC. This study successfully predicted that LCK, FOXC1 and hsa-miR-146a-5p can be used as potential immune effector molecules of RA. Our study may have potential implications for future prediction of disease progression in patients with symptomatic RA, and has important significance for the pathogenesis and targeted therapy of RA.

Enantioselective Intermolecular Radical Amidation and Amination of Benzylic C-H Bonds via Dual Copper and Photocatalysis.

A method for direct access to enantioenriched benzylic amides and carbamate-protected primary benzylamines by C-H functionalization is reported. The C-H substrate is used as limiting reagent with only a small excess of the unactivated amide or carbamate nucleophile. The enantioselective intermolecular dehydrogenative C-N bond formation is enabled by a combination of a chiral copper catalyst, a photocatalyst, and an oxidant, and it takes place under mild conditions, which allow for a broad substrate scope. The method is compatible with late-stage C-H functionalization, and it provides easy access to 15 N-labeled amides and amines starting from cheap 15 NH4 Cl.

Enhancing Separation and Constriction of Ion Mobility Distributions in Drift Tubes at Atmospheric Pressure Using Varying Fields.

A linearly decreasing electric field has been previously proven to be effective for diffusional correction of ions in a varying field drift tube (VFDT) system, leading to higher resolving powers compared to a conventional drift tube due to its capacity to narrow distributions midflight. However, the theoretical predictions in resolving power of the VFDT were much higher than what was observed experimentally. The reason behind this discrepancy has been identified as the difference between the theoretically calculated resolving power (spatial) and the experimental one (time). To match the high spatial resolving power experimentally, a secondary high voltage pulse (HVP) at a properly adjusted time is used to provide the ions with enough momentum to increase their drift velocity and hence their time-resolving power. A series of systematic numerical simulations and experimental tests have been designed to corroborate our theoretical findings. The HVP-VFDT atmospheric pressure portable system improves the resolving power from the maximum expected of 60-80 for a regular drift tube to 250 in just 21 cm in length and 7kV, an unprecedent accomplishment.

Ion-induced nucleation of pure biogenic particles.

Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood. Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours. It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere, and that ions have a relatively minor role. Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded. Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of α-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.

Tumour necrosis factor inhibitor combined with intravenous immunoglobulin and heparin for treatment of recurrent spontaneous abortion: A two-centre, retrospective, cohort study.

WHAT IS KNOWN AND OBJECTIVE: Immune disorder is a key trigger of recurrent spontaneous abortion (RSA); meanwhile, tumour necrosis factor inhibitor (TNFi) is a fundamental therapeutic for multiple immune and inflammatory diseases. Hence, this real-world study aimed to explore the efficacy and safety of TNFi combined with intravenous immunoglobin (IVIG) and heparin therapy in RSA patients. METHODS: A total of 105 RSA patients who received TNFi+IVIG+Heparin (enoxaparin) (n = 48) or IVIG+Heparin (enoxaparin) (n = 57) were retrospectively included in this two-centre cohort study. RESULTS AND DISCUSSION: The live birth rate of RSA patients in the TNFi+IVIG+heparin group was 72.9% (95% confidence interval [CI]: 69.6%-85.9%). Besides, the live birth rate in the IVIG+heparin group was 52.6% (95% CI: 42.8%-62.4%). By comparison, the live birth rate was higher in the TNFi+IVIG+heparin group compared to the IVIG+heparin group (p = 0.033). After adjustment by the multivariate logistic regression model using the enter method, TNFi+IVIG+Heparin was also superior to IVIG+Heparin regarding increased live birth rate (odds ratio [OR] = 2.941, p = 0.015). Moreover, TNFi+IVIG+Heparin (vs. IVIG+Heparin) also served as an independent factor for increased live birth rate (OR = 2.423, p = 0.035) by the forward stepwise method in the multivariate analysis. Gestational weeks at delivery (38.3 ± 1.3 vs. 37.7 ± 2.0 weeks, p = 0.155), newborn weight (3123.9 ± 332.1 vs. 3056.6 ± 287.4 g, p = 0.390), Apgar score of newborns (9.8 ± 0.5 vs. 9.7 ± 0.7, p = 0.271) were of no difference between TNFi+IVIG+Heparin and IVIG+Heparin groups. In terms of safety profile, the adverse events were of no difference between the TNFi+IVIG+Heparin and the IVIG+Heparin groups (all p > 0.05), either. WHAT IS NEW AND CONCLUSION: TNFi combined with IVIG and heparin therapy improves the live birth rate but does not elevate the adverse events compared to IVIG and heparin therapy in RSA patients.

Glossary on atmospheric electricity and its effects on biology.

There is an increasing interest to study the interactions between atmospheric electrical parameters and living organisms at multiple scales. So far, relatively few studies have been published that focus on possible biological effects of atmospheric electric and magnetic fields. To foster future work in this area of multidisciplinary research, here we present a glossary of relevant terms. Its main purpose is to facilitate the process of learning and communication among the different scientific disciplines working on this topic. While some definitions come from existing sources, other concepts have been re-defined to better reflect the existing and emerging scientific needs of this multidisciplinary and transdisciplinary area of research.

Nickel-Catalyzed Intramolecular Desulfitative C-N Coupling: A Synthesis of Aromatic Amines.

A nickel-catalyzed intramolecular C-N coupling reaction via SO2 extrusion is presented. The use of a catalytic amount of BPh3 allows the transformation to take place under much milder conditions (60 °C) than previously reported C-N coupling reactions by CO or CO2 extrusion (160-180 °C). In addition, this method displays good functional group tolerance and versatility, as it can be applied to the synthesis of dialkyl aryl amines, alkyl diaryl amines, and triaryl amines. The robustness of the desulfitative C-N coupling is demonstrated by three high-yielding gram-scale reactions.

Reduced anthropogenic aerosol radiative forcing caused by biogenic new particle formation.

The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol-cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20-100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by [Formula: see text] (27%) to [Formula: see text] Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes.

2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glycoside attenuates atherosclerosis in apolipoprotein E-deficient mice: role of reverse cholesterol transport.

The aim of this study was to evaluate the potential effects of 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) on the development of atherosclerotic plaque in ApoE-/- mice, and explore the mechanisms involved. Our data showed that after 8 weeks of treatment, TSG ameliorated serum levels of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and increased serum levels of high density lipoprotein cholesterol in ApoE-/- mice. TSG suppressed hepatic steatosis, the formation of atherosclerotic lesions, and the formation of macrophage foam cells in ApoE-/- mice. Moreover, TSG improved the expressions of hepatic SR-BI, ABCG5, and CYP7A1, and up-regulated the protein expressions of aortic ABCA1 and ABCG1. An in-vitro study showed that TSG promoted macrophage cholesterol efflux and increased the protein expressions of ABCA1 and ABCG1. Our findings provide evidence for a positive role of TSG in preventing atherosclerosis by promoting reverse cholesterol transport. These effects may be achieved by stimulating cholesterol efflux through ABCA1 and ABCG1, promoting SR-BI-mediated cholesterol uptake in the liver, increasing secretion of cholesterol into bile by ABCG5, and improving cholesterol metabolism by the CYP7A1 pathway. In addition, antioxidative and anti-inflammatory effects of TSG may also contribute to its inhibitory effects on atherosclerosis. Further study is needed to investigate whether other potential mechanisms are involved in TSG-mediated atheroprotection.

Comparison of Effects of Propofol Combined with Different Doses of Esketamine for ECT in the Treatment of Depression: A Randomized Controlled Trial Protocol.

Objective: Major depressive disorder (MDD) is a common mood disorder. Electroconvulsive therapy (ECT) has a significant effect on treatment-resistant MDD. Esketamine may have potential advantages in improving the efficacy of ECT, and the strong affinity of this compound for NMDAR renders it a viable therapeutic option for the management of depression. This study aims to compare the effects of different doses of esketamine combined with propofol anesthesia versus propofol anesthesia alone in ECT, aiming to provide further insights for optimizing ECT and enhancing comprehensive treatment outcomes for depression. Study Design and Methods: This study was a prospective, randomized, controlled, double-blind trial involving subjects and evaluators. One hundred eleven patients scheduled for ECT were randomly assigned to three groups. In Group P, propofol at 1mg/kg was administered intravenously. In Group P+E, propofol at a dosage of 0.5mg/kg and esketamine at a dosage of 0.5mg/kg was administered intravenously. Patients in Group P+SE received propofol at a dosage of 0.75mg/kg and esketamine at a dosage of 0.25mg/kg. The same anesthesia protocol was used for the same patient until the end of the last treatment. The primary outcome measures were the Hamilton depression scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the Digit symbol substitution test (DSST). Secondary outcomes included length of hospital stay, readmission rate, hemodynamic status, recovery, and adverse events. Discussion: This study aimed to compare the effects of propofol combined with different doses of esketamine for ECT. The results may provide a better choice for ECT anesthesia.

Continuous theta burst stimulation to relieve symptoms in patients with moderate obsessive-compulsive disorder: a preliminary study with an external validation.

Obsessive-compulsive disorder (OCD) is a clinically challenging and refractory psychiatric disorder characterized by pathologically hyperactivated brain activity. Continuous theta burst stimulation (cTBS) is considered a potentially non-invasive treatment for inducing inhibitory effects on the underlying cortex. Numerous studies showed an unsatisfactory efficacy of cTBS for OCD. Accordingly, it seems that cTBS is ineffective for OCD. However, the neglect of varying OCD severities, modest sample size, absence of a multicenter design incorporating inpatients and outpatients, and lack of personalized imaging-guided targeting may constrain the conclusive findings of cTBS efficacy for OCD. In the preliminary experiment, 50 inpatients with OCD were enrolled to receive cTBS (10 sessions/day for five continuous days) or sham over the personalized right pre-supplementary motor area determined by the highest functional connectivity with the subthalamic nucleus according to our prior study. In the extension experiment, 32 outpatients with OCD received cTBS to generalize the treatment effects. The Yale-Brown Obsessive-Compulsive Scale (YBOCS) was assessed before and after treatment. In the preliminary experiment, the response rates in the cTBS group were 56.52%, respectively, significantly higher than those in the sham group. Further analysis revealed significant YBOCS improvement in patients with moderate OCD symptoms than those with severe OCD symptoms. In the extension experiment, the response rates were 50.00%. Additionally, a significant decrease in YBOCS scores was only found in patients with moderate OCD symptoms. This is the first study with an external validation design across two centers to identify OCD symptoms as playing an important role in cTBS treatment effects, especially in patients with moderate OCD symptoms.

Oxidized organic molecules in the tropical free troposphere over Amazonia.

New particle formation (NPF) in the tropical free troposphere (FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules (OOMs) produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4-5 carbon atoms, in both gas-phase and particle-phase (in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NPF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

Simvastatin reduces high uric acid-induced oxidative stress and inflammatory response in vascular endothelial cells via nuclear factor E2-related factor 2 (Nrf2) signaling.

Objectives: Increased oxidative stress and inflammatory response are risk factors for kidney and cardiovascular diseases in patients with hyperuricemia. Uric acid (UA) has been reported to cause inflammation and oxidative damage in cells by inhibiting the nuclear factor E2-related factor 2 (Nrf2) pathway. Notably, Simvastatin (SIM) can regulate the Nrf2 pathway, but whether SIM can regulate inflammatory response and oxidative stress in vascular endothelial cells induced by high UA via this pathway has not been clarified. Materials and Methods: To demonstrate this speculation, cell activity, as well as apoptosis, was estimated employing CCK-8 and TUNEL, respectively. Indicators of oxidative stress and inflammation were assessed by related kits and western blotting. Subsequently, the effects of SIM on signaling pathways were examined using western blotting. Results: The result showed that after UA exposure, oxidative stress was activated and inflammation was increased, and SIM could reverse this trend. Meanwhile, SIM could inhibit high UA-induced apoptosis. In addition, western blotting results showed that SIM reversed the down-regulation of the expression of Nrf2 pathway-related proteins caused by high UA. Conclusion: SIM alleviated the inflammatory response as well as inhibiting oxidative stress through the Nrf2 pathway, thereby attenuating high UA-induced vascular endothelial cell injury.

Recent developments for intermolecular enantioselective amination of non-acidic C(sp3)-H bonds.

Enantioenriched chiral amines are of exceptional importance in the pharmaceutical industry. Recently, several new methods for the installation of these functional groups directly from non-acidic C(sp3)-H bonds by catalytic intermolecular enantioselective amination have been reported. These methods represent significant advances of the field and most of them display high levels of enantioselectivity, utilize the C(sp3)-H substrate as the limiting reagent, feature good functional group tolerance, and show compatibility with late-stage C(sp3)-H amination of advanced substrates. This perspective provides an overview of the recent developments in this rapidly advancing field and outlines possibilities and limitations, which will help identify unsolved challenges and guide future research efforts.

The effect of vitamin D supplementation on some metabolic parameters in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 8 RCTs.

BACKGROUND: To systematically evaluate the effects of vitamin D supplementation in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science, WANFANG databases, and Google Scholar were retrieved to collect relevant randomized controlled trials, which are published from the earliest records the time the database was created to April 2023. Meta-analysis was conducted by using Review Manager 5.4 software after evaluating in terms of inclusion and exclusion criteria. The outcome indicators include 25-hydroxyvitamin D [25(OH)D] levels, insulin resistance index (homeostasis model assessment of insulin resistance), fasting blood glucose, and fasting insulin levels (FINS). RESULTS: Eight randomized controlled trials with a total of 657 patients are included. Vitamin D supplementation increased 25(OH)D levels significantly (mean difference [MD] = 2.01, 95% confidence intervals [CI]: 0.94 to 3.08, P < .05) and vitamin D supplementation had a significant effect on insulin resistance index (MD = -0.54, 95% CI: -1.28 to 0.20, P = .16), fasting glucose (MD = -0.59, 95% CI: -1.50 to 0.32, P = .20), and FINS levels (MD = -0.30, 95% CI: -0.77 to 0.17, P = .21) had no significant effect. CONCLUSION: Vitamin D supplementation improves 25(OH)D levels in patients with nonalcoholic fatty liver disease, but there is no effect on homeostasis model assessment of insulin resistance, fasting blood glucose, or FINS.

The Effects of Different Puncture Points on Labor Analgesia Onset: Study Protocol for a Randomized Controlled Trial.

Purpose: Parturients suffer severe pain during the stages of labor, especially the first and second. Epidural anesthesia is an effective method to alleviate labor pain. L2-3, L3-4 and L4-5 spaces have been reported to be the recommendable puncture points owing to the adequate analgesia effect and high safety. However, the speed of pain alleviation via the three points has hardly been determined, which is of great importance to parturients. Thus, the aim of this study is to compare the onset time of parturients' painless uterine contraction after epidural labor analgesia through different puncture points. Study Design and Methods: It is a prospective, randomized, controlled, and subject- and assessor-blinded study. Totally, 150 subjects scheduled for vaginal delivery are going to be randomly assigned into the L2-3 and L3-4 group. Puncture point in L2-3 group is lumbar 2-3 space, while in L3-4 group it is lumbar 3-4 space. Analgesia initiation and maintenance are the same between the two groups. Primary outcome will be percentage of painless uterine contraction 15 min after epidural labor analgesia initiation. Secondary outcomes will be the sensory blocking level, motor blocking score, adverse effects of parturients, drug liquid consumption in unit interval, apgar score and degree of satisfaction of the parturients. Discussion: This study estimates the onset time of parturients' painless uterine contraction after epidural labor analgesia through L2-3 or L3-4 space. The results may provide a better choice to relieve labor pain as soon as possible.