Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop.

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H2O2-treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury.

Surface-Plasmon-Coupled Fluorescence Enhancement Based on Ordered Gold Nanorod Array Biochip for Ultrasensitive DNA Analysis.

An innovative gold nanorod (GNR) array biochip was developed to systematically investigate the localized surface plasmon resonance (LSPR)-coupled fluorescence enhancement for signal amplification in molecular beacon detection. An ordered GNR assembly in vertical standing array on a glass surface was fabricated as plasmonic substrates, resulting in dramatically intensified LSPR between adjacent nanoparticles as compared to that from an ensemble of random nanorods. We have shown that the plasmonic response of the nanoarray can be tuned by the proper choice of GNR size to overlap the fluorophore excitation and emission wavelengths greater than 600 nm. Plasmon-induced fluorescence enhancement was found to be distance-dependent with the competition between quenching and enhancement by the metal nanostructures. The augmented fluorescence enhancement by the GNR array can efficiently overcome the quenching effect of the gold nanoparticle even at close proximity. The enhancement correlates with the spectral overlap between the fluorophore excitation/emission and the plasmonic resonance of the GNR array, indicating a surface-plasmon-enhanced excitation and radiative mechanism for the amplification. From these results, the applicability of the ordered GNR array chip was extended to molecular fluorescence enhancement for practical use as a highly functional and ultrasensitive plasmonic DNA biochip in molecular beacon fashion.

Evaluation of biometry and corneal astigmatism in cataract surgery patients from Central China.

BACKGROUND: To evaluate the distribution of biometric parameters and corneal astigmatism using the IOLMaster device before phacoemulsification in cataract patients in Central China. METHODS: Consecutive cataract patients were recruited at the Central Hospital of Wuhan between January 2015 and June 2016. Ocular axial length (AL), keratometry values, anterior chamber depth (ACD) and horizontal corneal diameter (white to white [WTW]) of each cataract-affected eye were measured with the IOLMaster device. RESULTS: The study evaluated 3209 eyes of 2821 cataract patients. The mean AL, ACD, and WTW were 24.38 ± 2.47 mm, 3.15 ± 0.48 mm, and 11.63 ± 0.43 mm, respectively. Corneal astigmatism of 0.51-1.00 diopters (D) was the most common range of values (34.96%). A total of 10.56% patients exhibited a corneal astigmatism greater than 2.0 D. The flat and steep keratometry values gradually increased with age. The mean ACD and WTW showed increasing trends as the AL increased (P < 0.001). When the AL was shorter than 26.0 mm, the keratometry decreased as AL increased. The against-the-rule (ATR) astigmatism proportion increased with age and the with-the-rule (WTR) astigmatism proportion decreased with age. CONCLUSIONS: The profile of ocular biometric data and corneal astigmatism may help ophthalmologists improve their surgical procedures and make an appropriate IOL choice to gain a high quality of postoperative vision.

Changes in Retinal Nerve Fiber Layer Thickness in Obstructive Sleep Apnea/Hypopnea Syndrome: A Meta-Analysis.

PURPOSE: To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: The Cochrane Library, Medline, and Embase were screened using our key words. Results were carefully reviewed to ensure that the included studies met the inclusion/exclusion criteria, and the quality of the studies was assessed using the Newcastle-Ottawa Scale. All included studies categorized patients with OSAHS into 3 groups (mild, moderate, and severe), and measured average and 4-quadrant (temporal, superior, nasal, and inferior) RNFL thickness. All studies included a healthy control group. The weighted mean differences and 95% confidence intervals were calculated for the continuous outcomes. RESULTS: Ten case-control studies were included in the meta-analysis, consisting of a total of 811 OSAHS group and 868 healthy eyes. A meta-analysis of the data showed that the average RNFL thicknesses in the mild, moderate, and severe OSAHS groups were significantly decreased compared to healthy controls. Additionally, RNFL thickness was significantly reduced in all but the temporal quadrant in the moderate and severe OSAHS groups when compared to healthy controls. CONCLUSIONS: On the basis of these results, we suggest that peripapillary RNFL thickness as measured by optical coherence tomography could be a useful tool to monitor and assess the severity of OSAHS in patients. Further studies are required in order to differentiate these RNFL changes from glaucomatous changes. This has not been properly examined in any of the studies we were able to identify.

Multi-functional lens based on conformal mapping.

Based on conformal mapping method, a two dimensional, multi-functional lens structure is proposed and designed in this work. The lens is an infinitely-long, gradient-index dielectric cylinder with a semi-elliptic cross-section. The lens can first be considered like a flattened Luneburg lens, which produces highly-directive electromagnetic waves by adjusting the feed position along the line connecting the two foci. It also functions like an Eaton lens. When an incoming beam impinges on the same line but outside the two foci, it will be guided through the lens structure and take a U-turn. Besides, if properly shaped, the structure can also be used as a waveguide bend. The lens can be realized using non-resonant metamaterials with inhomogeneous hole arrays. Simulation results demonstrate excellent performance of the lens and agree well with theoretical prediction. The designed lens can be used in the electromagnetic control. And it is especially useful in the real optical lens system.

Optimum programmed intermittent epidural bolus interval time of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL: a randomized controlled trial.

Background: The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects (EI90), without the use of patient-controlled epidural analgesia (PCEA). Methods: A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI90 (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL was estimated using probit regression. Results: The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5-50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score > 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups. Conclusion: The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5-50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.

Comparative dose-response study on the infusion of norepinephrine combined with intravenous ondansetron versus placebo for preventing hypotension during spinal anesthesia for cesarean section: a randomised controlled trial.

BACKGROUND: Ondansetron has been reported to attenuate the incidence of spinal anaesthesia-induced hypotension (SAIH) and norepinephrine requirement during caesarean section. However, no quantitative study has evaluated the extent of this effect. This study aimed to determine the dose-response of prophylactic infusion of norepinephrine to prevent SAIH in parturients who received intravenous ondansetron or placebo before spinal anaesthesia for caesarean section. The median effective dose (ED 50 ) and 90% effective dose (ED 90 ) were compared to evaluate the effect of ondansetron versus placebo on the norepinephrine requirement. MATERIALS AND METHODS: One hundred fifty parturients undergoing caesarean section were randomized to receive either 0.1 mg/kg ondansetron (group O) or saline control (group C) 10 min before spinal anaesthesia. The parturients were randomly assigned to one of five different norepinephrine infusion groups: 0.02, 0.04, 0.06, 0.08 or 0.10 µg/kg/min. An effective infusion dose of norepinephrine was defined as non-occurrence of hypotension during the study period. The values for ED 50 and ED 90 of norepinephrine infusion were determined using probit regression. Differences between the two groups were evaluated by comparing the relative median potency with 95% CIs. RESULTS: The ED 50 values were 0.033 (95% CIs, 0.024-0.043) µg/kg/min in group C and 0.021 (95% CIs, 0.013-0.029) µg/kg/min in group O. The ED 90 values were 0.091 (95% CIs 0.068-0.147) µg/kg/min in group C and 0.059 (95% CIs 0.044-0.089) µg/kg/min in group O, respectively. The estimate of the relative median potency for norepinephrine in group C versus group O was 0.643 (95% CIs, 0.363-0.956). The incidence of side effects was comparable between groups. No significant difference in neonatal outcomes. CONCLUSION: Intravenous ondansetron 0.1 mg/kg before spinal anaesthesia significantly reduced the dose requirement of prophylactic norepinephrine infusion in parturients undergoing elective caesarean section. This finding is potentially useful for clinical practice and further research.

Comparison of lidocaine bicarbonate with fentanyl and chloroprocaine for epidural anesthesia during cesarean section: a randomized, controlled, double-blind clinical trial.

Chloroprocaine and lidocaine bicarbonate are commonly used for epidural anesthesia because of their rapid onset, particularly in the case of conversion from epidural labor analgesia to emergency cesarean section. However, it is unclear whether lidocaine bicarbonate combined with fentanyl has an advantage over chloroprocaine alone in emergency cesarean section. In this study, 102 women who underwent elective cesarean section received 15 mL 3% chloroprocaine and 1 mL saline (CP group) or 15 mL 1.73% lidocaine bicarbonate and 1 mL fentanyl 50 µg (LF group) for epidural anesthesia. Nociceptive block level was assessed by pinprick and recorded every minute. The primary outcome was the onset time to T6 block. The median onset time to T6 analgesia was 10 [10, 10] min in the CP group and 10 [7, 10] min in the LF group (COX model for CP versus LF, HR 0.47, 95% CI 0.23-0.95, p = 0.035). The median onset time to T8 analgesia was 7 [5, 9] min in CP group and 5 [4, 7] min in LF group (COX model for CP versus LF, HR 0.61, 95% CI 0.39-0.95, p = 0.027). The proportion of hypotension episodes occurring before delivery in LF group was lower than that in CP group (p = 0.011). The incidence of block level ≥ T4 after supplemental dosing in the LF group was lower than that in the CP group (p = 0.031). Compared with 3% chloroprocaine, 1.73% lidocaine bicarbonate combined with fentanyl 50 µg has a slightly faster onset time and less hypotension in epidural anesthesia for cesarean section. Clinical Trial Registration: http://www.chictr.org.cn/index.html, identifier ChiCTR2200056180.

Epidural dexmedetomidine or esketamine versus fentanyl to decrease ropivacaine use for labor analgesia: A randomized non-inferiority study.

Background: Epidural nonopioid adjuvants also reduce local anesthetic use. We aimed to test the hypothesis that, compared with the present standard fentanyl, the hourly consumption of local anesthetic was at least as good when dexmedetomidine or esketamine was combined with local anesthetic for patient-controlled epidural analgesia (PCEA). Methods: A total of 120 laboring nulliparous subjects requiring labor analgesia were recruited for the final statistical analysis. Subjects were randomized to receive 0.075 % ropivacaine added with one of three equivalent adjuvants: 0.4 µg/mL fentanyl, 0.4 µg/mL dexmedetomidine, or 1.0 mg/mL esketamine. The primary outcome was hourly ropivacaine consumption. Compared with the fentanyl group, a 20 % difference in hourly local anesthetic consumption between the dexmedetomidine and esketamine groups was considered a clinical difference (non-inferiority margin). Results: The hourly ropivacaine consumption of the fentanyl group was 12.4 (95 % confidence interval CI 11.2 to 13.6) ml/h, so the prespecified non-inferiority limit was 2.5 ml/h. The hourly ropivacaine consumption of the fentanyl group was not inferior to that of the dexmedetomidine group (12.4 ml/h vs. 11.9 ml/h, risk difference, 0.5; 95 % confidence interval CI, -1.0 to 2.0, meeting criteria for non-inferiority). However, the hourly ropivacaine consumption of the esketamine group was 14.3 ml/h, and that of the fentanyl group was 12.4 ml/h (risk difference, 1.9, 95 % CI, 0.2 to 3.6), failing to confirm non-inferiority with a non-inferiority margin of 20 %. The incidence of pruritus was highest in the fentanyl group, whereas the occurrence of mild dizziness was highest in the esketamine group. Conclusions: In setting of the conditions of this study, epidural dexmedetomidine was non-inferior compared with epidural fentanyl in combination with ropivacaine for PCEA during labor. Meanwhile, we failed to establish the non-inferiority of epidural esketamine compared with epidural fentanyl in combination with ropivacaine for labor analgesia.

Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.

Experiments on active cloaking and illusion for Laplace equation.

In recent years, invisibility cloaks have received a lot of attention and interest. These devices are generally classified into two types: passive and active. The design and realization of passive cloaks have been intensively studied using transformation optics and plasmonic approaches. However, active cloaks are still limited to theory and numerical simulations. Here, we present the first experiment on active cloaking and propose an active illusion for the Laplace equation. We make use of a resistor network to simulate a conducting medium. Then, we surround the central region with controlled sources to protect it from outside detection. We show that by dynamically changing the controlled sources, the protected region can be cloaked or disguised as different objects (illusion). Our measurement results agree very well with numerical simulations. Compared with the passive counterparts, the active cloaking and illusion devices do not need complicated metamaterials. They are flexible, in-line controllable, and adaptable to the environment. In addition to dc electricity, the proposed method can also be used for thermodynamics and other problems governed by the Laplace equation.

ED90 of epidural esketamine with 0.075% ropivacaine for labor analgesia in nulliparous parturients: a prospective, randomized and dose-finding study.

Background: Because it has been reported that racemic ketamine had a local anesthetic-sparing effect when used for epidural analgesia this would suggest the likelihood of a potential advantage (less pruritus) over opioid drugs. Esketamine has greater analgesic efficacy than racemic ketamine, but the optimum dosage regimen for epidural use is undetermined. The aim of this study was to determine the ED90 of epidural esketamine when coadministered with 0.075% ropivacaine for labor analgesia. Methods: A total of 65 laboring nulliparous patients were enrolled in this study from 16 March 2022 to 15 October 2022. The patients were randomly assigned to receive 0, 0.25, 0.5, 0.75 or 1.0 mg/mL esketamine with 0.075% ropivacaine epidurally. An effective response to the epidural loading dose was defined as numerical rating scale pain score ≤3 at 30 min after the end of the epidural loading dose (10 mL of the ropivacaine 0.075% solution with the added esketamine). The ED90 of epidural esketamine coadministered with 0.075% ropivacaine with 95% confidence intervals for labor analgesia was determined using probit regression. Secondary outcomes and side effects were recorded. Results: The estimated value of ED90 with 95% CIs for epidural esketamine with 0.075% ropivacaine was 0.983 (0.704-2.468) mg/mL. The characteristics of sensory and motor block, consumption of ropivacaine per hour, duration of first or second stage, Apgar scores did not differ among the five groups. The incidence of mild dizziness in Group esketamine 1.0 mg/mL was significantly higher than that in other groups (p < 0.05). No statistical differences were found in other side effects among groups. Conclusion: The ED90 value of epidural esketamine coadministered with 0.075% ropivacaine for labor analgesia in nulliparous parturients was about 1.0 mg/mL. Furthermore, our results suggested that epidural esketamine would cause dose-dependent mild dizziness especially at doses up to 1.0 mg/mL. As a single epidural additive, esketamine may not be suitable for labor analgesia. Future studies may investigate the appropriate dosage of esketamine at slightly higher concentrations of local anesthetics or larger initial volume of analgesia, or explore other potential advantages of esketamine. Clinical Trial Registration: (https://www.chictr.org.cn/bin/project/edit?pid=159764), identifier (ChiCTR2200057662).

Comparison of Dural Puncture Epidural, Epidural and Combined Spinal-Epidural Anesthesia for Cesarean Delivery: A Randomized Controlled Trial.

Purpose: Catheter-based techniques such as combined spinal-epidural (CSE) anesthesia which are sometimes indicated for obstetric anesthesia have a complex mechanism of action. The application of the dural puncture epidural (DPE) anesthesia for cesarean section (CS) has not been well investigated. The present study compared the relatively novel DPE technique with epidural (EA) and CSE anesthesia. Patients and Methods: We randomly assigned 150 parturients who underwent elective CS to receive DPE, EA or CSE anesthesia. The primary outcome was the onset of sensory anesthesia to the T5 dermatome assessed using the Cox proportional hazards model. Secondary outcomes included median time to sensory block, quality of block, patient and surgeon satisfaction, APGAR scores and other side effects. Results: For DPE anesthesia versus EA anesthesia, the onset of anesthesia was faster (hazard ratio 2.47 [95% CI 1.56 to 3.90], adjusted P < 0.001) and the median time to surgical level was shorter (16 [IQR 14-18] min versus 19 [15.5-21] min, adjusted P < 0.001); the incidence of intraoperative pain was lower (7/48 versus 17/47, adjusted P = 0.046) and the median patient satisfaction score was higher (9 [IQR 9-10] versus 8 [8-9.5], adjusted P = 0.004). In the CSE group, the onset of anesthesia was faster than in the other two but the incidence of hypotension was higher (P < 0.001) and the phenylephrine requirement was greater (P < 0.001). Conclusion: DPE anesthesia had a faster onset and better quality of block than EA anesthesia and provided less influence to maternal hemodynamic parameters than CSE anesthesia for CS. These results suggest that the dural puncture plays a significant role in enhancing the effectiveness of epidural top-ups during CSE anesthesia and indicates enlightenment that contributes to the satisfaction of anesthetic effect in DPE technique labor analgesia transferred to CS.

pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide.

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (ß-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of âˆ¼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the "ELVIS" effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the "proton sponge" effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 µg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA.

A dc carpet cloak based on resistor networks.

We propose, design, and implement a two-dimensional dc carpet cloak for steady electric field using the transformation optics (TO) method. Based on the circuit theory, we introduce a resistor network to mimic the resulting anisotropic conducting medium. The experimental prototype is fabricated using metal film resistors, and the measured results agree perfectly well with theoretical predictions. This study gives the first experimental verification of a dc carpet cloak, which expands the application of TO theory, and has potential applications in related areas.

dc electric invisibility cloak.

We present the first experimental demonstration of a dc electric cloak for steady current fields. Using the analogy between electrically conducting materials and resistor networks, a dc invisibility cloak is designed, fabricated, and tested using the circuit theory. We show that the dc cloak can guide electric currents around the cloaked region smoothly and keep perturbations only inside the cloak. Outside the cloak, the current lines return to their original directions as if nothing happens. The measurement data agree exceptionally well with the theoretical prediction and simulation result, with nearly perfect cloaking performance. The proposed method can be directly used to realize other dc electric devices with anisotropic conductivities designed by the transformation optics. Manipulation of steady currents with the control of anisotropic conductivities has a lot of potential applications, such as electric impedance tomography, graphene, natural resource exploration, and military camouflage.

Comparative Dose-Response Study of Phenylephrine Bolus for the Treatment of the First Episode of Spinal Anesthesia-Induced Hypotension for Cesarean Delivery in Severe Preeclamptic versus Normotensive Parturients.

Background: It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED50 and ED90 of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension. Methods: Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 µg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 µg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed. Results: The ED50 and ED90 (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) µg and 107 (95.9-128.6) µg in parturients with normotension. The ED50 and ED90 values in parturients with severe preeclampsia were 47.6 (41.3-52.7) µg and 70.7 (62.9-86.7) µg. The relative median potency was 1.51 (1.16-2.61). Conclusion: Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED50 of phenylephrine dose compared with normotensive parturients.

Determination of the Dose-Response Relationship of Epidural Dexmedetomidine Combined with Ropivacaine for Labor Analgesia.

Background: The safety and efficacy of dexmedetomidine for epidural labor analgesia have been reported in numerous literatures, but the optimal dose has not been fully determined. The objective of this study was to determine the dose-response relationship of epidural dexmedetomidine (combined with ropivacaine) for labor analgesia. Methods: A total of 120 full-term laboring parturients requesting epidural labor analgesia were enrolled in the study from July 5, 2020 to September 22, 2021. The parturients were randomly assigned to receive 0, 0.1, 0.2, 0.3, 0.4 or 0.5 µg/mL dexmedetomidine combined with 0.075% ropivacaine epidurally. An effective dose was defined as numerical rating scale (NRS) pain score ≤3 at 30-minutes of epidural drug injection. The dose-response relationship of dexmedetomidine (with ropivacaine) for epidural labor analgesia was performed using probit regression. The median effective dose (ED50) and the 95% effective dose (ED95) values for epidural dexmedetomidine combined with 0.075% ropivacaine with 95% confidence intervals (CIs) were derived by interpolation. Results: The estimated values of ED50 and ED95 with 95% CIs for epidural dexmedetomidine (combined with 0.075% ropivacaine) were 0.085 (0.015 to 0.133) µg/mL and 0.357 (0.287 to 0.493) µg/mL, respectively. No differences were found among groups for sensory block level, number of parturients with Bromage score >0, total dosage of analgesics, cesarean delivery rate, fetal birth weight, Apgar score at 1-minute, Apgar score at 5-minutes and adverse effects. Compared with other groups, group dexmedetomidine 0.5 µg/mL had a longer duration of the first stage of labor. Conclusion: The ED50 and ED95 values of dexmedetomidine for epidural labor analgesia was 0.085 and 0.357 µg/mL under the conditions of this study. Dexmedetomidine is a suitable adjuvant for epidural labor analgesia.

Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia.

OBJECTIVE: To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models. METHODS: Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested. RESULTS: KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels. CONCLUSION: KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Identification of the risk factors in perioperative respiratory adverse events in children under general anesthesia and the development of a predictive model.

BACKGROUND: This study explored the risk factors of perioperative respiratory adverse events in children under 12 years old undergoing general anesthesia surgery. A prediction model was constructed according to the related risk factors to provide a basis for timely clinical intervention and decision-making. METHODS: Children under 12 years old who underwent general anesthesia in our hospital between January 2016 and December 2020 were included in this study. The clinical data, including age, gender, weight, American Society of Anesthesiologists (ASA) grade classification, operation season, preoperative hospital stay, anesthesia time, and postoperative pain score, were collated. Continuous variables were converted to categorical variables. Logistic regression analysis was used to screen independent risk factors and a nomogram was constructed to predict the probability of adverse events. Fitting curves and receiver operating characteristic (ROC) curves were utilized to verify the model. RESULTS: Logistic regression analyses demonstrated that age [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.08 to 1.49], body weight (OR =1.49, 95% CI: 1.21 to 1.84), anesthesia time (OR =1.61, 95% CI: 1.32 to 1.78), and surgery season (OR =1.12, 95% CI: 1.07 to 1.39) were independent risk factors for respiratory adverse events in children undergoing general anesthesia (P<0.05). The risk of respiratory-related adverse events increased in children with grade II ASA classification compared to children with grade I ASA classification (P<0.05). Similarly, the risk of respiratory adverse events increased in children with level III pain scores compared to children with level I pain scores (P<0.05). The calibration curve showed that the predicted curve was consistent with the actual curve. The area under the ROC curve (AUC) was 0.707, indicating that model showed great predictive ability. CONCLUSIONS: Age, weight, anesthesia time, operation season, ASA grade, and pain score were identified as independent risk factors for respiratory adverse events in children undergoing general anesthesia. Using the above risk factors, a nomogram was established to predict the risk of respiratory system-related adverse events. The predicted results were highly consistent with the actual risk, and the false positive rate was within a reasonable range.