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.

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.

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.

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 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.

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).

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.

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.

Huoxin Pill () Attenuates Cardiac Fibrosis by Suppressing TGF-ß1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats.

OBJECTIVE: To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats. METHODS: Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- ß 1 (TGF-ß 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay. RESULTS: HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-ß 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3. CONCLUSIONS: HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-ß 1/Smad2/3 pathway.

Comparative dose-response study of hyperbaric ropivacaine for spinal anesthesia for cesarean delivery in singleton versus twin pregnancies.

STUDY OBJECTIVE: It is controversial whether local anesthetic dose requirement for spinal anesthesia for cesarean delivery differs between patients with singleton and patients with multiple gestation pregnancies. The aim of this study was to determine and compare the ED50 and ED90 for hyperbaric ropivacaine used for spinal anesthesia for cesarean delivery in patients with singleton pregnancies versus patients with twin pregnancies. DESIGN: Prospective, randomized, comparative dose-finding study. SETTING: Operating room, Women's Hospital, Zhejiang University School of Medicine. PATIENTS: 100 patients with singleton pregnancies (Group S) and 100 patients with twin pregnancies (Group T) presenting for scheduled cesarean delivery under combined spinal-epidural anesthesia were enrolled in the study. INTERVENTIONS: Patients in Group S or Group T were randomly allocated to receive 9.5, 11, 12.5, 14 or 15.5 mg of hyperbaric ropivacaine intrathecally. A dose was considered effective when it achieved a bilateral sensory block level at the T6 dermatome or above within 10 min after intrathecal injection, there was no numerical rating scale (NRS) pain score ≥ 3 intraoperatively, and there was no requirement for epidural supplementation at any time during anesthesia and operation. Values for ED50 and ED90 for ropivacaine were determined using probit regression. The difference in ropivacaine dose requirement between patients with singleton pregnancies and patients with twin pregnancies was assessed by calculating relative median potency. MEASUREMENTS: Success rates for different intrathecal doses of ropivacaine, side effects and neonatal outcomes were recorded. MAIN RESULTS: The estimated (95% confidence interval) values for ED50 and ED90 of intrathecal ropivacaine in patients with singleton pregnancies were 11.2 (10.2 to 12.0) mg and 15.7 (14.4 to 18.3) mg, respectively. The values for ED50 and ED90 in patients with twin pregnancies were 10.5 (9.5 to 11.3) mg and 14.8 mg (13.6 to 17.0) mg, respectively. The estimate of relative median potency for ropivacaine between patients with singleton and twin pregnancies was 0.94 (95% confidence interval 0.83 to 1.04). CONCLUSION: Patients with singleton and twin pregnancies have similar dose requirement for hyperbaric ropivacaine used for spinal anesthesia for cesarean delivery in the setting of combined spinal-epidural (CSE) anesthesia, no opioids, low weight cohort, insertion with the patients in the right lateral position, and norepinephrine boluses.

Paxillin promotes the migration and angiogenesis of HUVECs and affects angiogenesis in the mouse cornea.

Neonatal vascular ophthalmopathy is a refractory ophthalmologic disease, and is a major cause of blindness. Occurrence of neonatal vascular ophthalmopathy may be associated with Paxillin, a cellular adhesion molecule which promotes the migration of endothelial cells and angiogenesis. To explore the role of PXN in corneal angiogenesis, human umbilical vein endothelial cells were divided into five groups: i) Control group; ii) Empty vector-transfected control group; iii) PXN knockdown group (shPXN group); iv) PXN-negative control (NC) group; and v) PXN over-expressed group (overExp group). PXN protein levels, migration and tube formation were assessed in the different experimental groups. Mice were divided into four groups: i) Control; ii) Model; iii) shPXN; and iv) overExp groups. Tube formation was significantly increased in the overExp group compared with the empty vector-transfected control group (P<0.01). Tube formation was significantly decreased in the shPXN group compared with the PXN-NC group (P<0.01). In mice, blood corpuscles were significantly decreased in the shPXN group. PXN promoted the migration of endothelial cells and corneal angiogenesis. The results of the present study suggest a role for PXN in corneal angiogenesis and provide a theoretical basis and potential target for the treatment of corneal angiogenesis.

The Application of Artificial Neural Networks and Logistic Regression in the Evaluation of Risk for Dry Eye after Vitrectomy.

Supervised machine-learning (ML) models were employed to predict the occurrence of dry eye disease (DED) after vitrectomy in this study. The clinical data of 217 patients receiving vitrectomy from April 2017 to July 2018 were used as training dataset; the clinical data of 33 patients receiving vitrectomy from August 2018 to September 2018 were collected as validating dataset. The input features for ML training were selected based on the Delphi method and univariate logistic regression (LR). LR and artificial neural network (ANN) models were trained and subsequently used to predict the occurrence of DED in patients who underwent vitrectomy for the first time during the period. The area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate the predictive accuracy of the ML models. The AUCs with use of the LR and ANN models were 0.741 and 0.786, respectively, suggesting satisfactory performance in predicting the occurrence of DED. When the two models were compared in terms of predictive power, the fitting effect of the ANN model was slightly superior to that of the LR model. In conclusion, both LR and ANN models may be used to accurately predict the occurrence of DED after vitrectomy.

[Effects of Solid Retention Time on the Phosphorus Removal and Nitrosation Granules System].

In this paper, the low C/N ratio of domestic sewage was studied, and mature phosphorus removal granules were inoculated to investigate the effect of solid retention time(SRT)on phosphorus removal and nitrification granular sludge at middle-low temperatures (14-21℃). The test showed that at room temperature (20℃±1℃), the enrichment of AOB in the phosphorus removal granules can be achieved with 30 d SRT and 5 L·(h·L)-1 aeration intensity, while the NAR was over 90%. When the temperature was lowered to 15℃ and the SRT was 40 d, the phosphorus removal performance deteriorated, and the granule structure became loose with the formation of filamentous bacteria. Relatively sufficient oxygen destabilized nitrosation and the NAR dropped by 22.4%. NOB does not have the ability to quickly adapt to environmental changes. The 12 d anaerobic starvation and sludge removal strategy weakened the relative activity of NOB and quickly restored the performance of phosphorus removal and nitrosation. Batch experiments showed that the temperature dropped from 20℃ to 15℃, and the PAOs still maintained a high oxygen utilization rate, but the SOUR of the AOB decreased by 18%. At this time, the temperature, not the dissolved oxygen concentration, restricted the ammonia oxidation ability. Controlling the sludge age to 30 d, while reducing the aeration intensity to 4 L·(h·L)-1, achieved stable operation of phosphorus removal and nitrosation at a low temperature (15℃±1℃).

Orbital neuroblastoma metastasis: A case report and literature review.

RATIONALE: Neuroblastoma is one of the most common tumors found in children, and mostly arises in the adrenal gland and paravertebral regions. Orbital neuroblastoma metastasis is relatively rare, and is associated with poor prognosis. Since the symptoms and signs of orbital neuroblastoma are not specific, its diagnosis remains challenging. PATIENT CONCERNS: A 3-year-old girl presented with periorbital ecchymoses (raccoon eyes) and proptosis for 40 days. DIAGNOSES: Abdominal magnetic resonance imaging (MRI) and sonography analysis revealed a large mass in the left adrenal gland (primary tumor). The computed tomography and MRI further revealed multiple soft tissue masses in the skull and both orbits with erosion of the adjacent bones (the metastasis). The histological analysis of the tumor removed from the right orbit confirmed the diagnosis of neuroblastoma. INTERVENTIONS: The mass on the right face was surgically removed. OUTCOMES: The patient exhibited no deteriorative signs at the 6-month follow-up. LESSONS: Clinical manifestations, such as periorbital ecchymoses and proptosis, in combination with radiological analysis and histological findings, are important for the diagnosis of orbital neuroblastoma metastasis.

[Effect of Influent Ammonia Concentration on a Biological Phosphorus Removal Granules System].

Mature biological phosphorus removal granules were inoculated into a SBR. The effect of the ammonia concentration on biological phosphorus removal granules system was investigated by increasing the concentration of ammonia in the influent. The ability of the system to withstand ammonia loading was determined. The results showed that when the influent ammonia concentration was below 45 mg·L-1, the biological phosphorus removal granule system showed good performance. The TP removal efficiency was above 96%, the COD removal efficiency was over 89%. The effluent TP concentration and COD concentration were 0.4 mg·L-1 and 25 mg·L-1 respectively. The particle size was above 950 µm and the SVI was below 45 mL·g-1. When the influent ammonia concentration was 60 mg·L-1, the removal efficiency of TP was more than 95%. The effluent TP concentration was below 0.5 mg·L-1, the particle size was 760 µm, and the SVI was 56 mL·g-1. Furthermore, the biological phosphorus removal granules partially disintegrated and the metabolism and growth of PAOs began to be inhibited in the system. When the influent ammonia concentration reached 70 mg·L-1, the removal efficiency of TP was 70%, the effluent TP concentration was about 3 mg·L-1, the particle size was 570 µm, the SVI was 75 mL·g-1, and the value of PN/PS was about 7.50. The biological phosphorus granules severely disintegrated and the metabolism and growth of PAOs was severely inhibited in the system. Moreover, as the influent ammonia concentration increased, the protein increased and polysaccharide decreased from the microbial secretion of biological phosphorus removal granules. Moreover, the value of PN/PS increased, the biological phosphorus removal granules disintegrated, the particle size decreased, the SVI increased, and the structure and function of the biological phosphorus removal granules were destroyed.

Torsional and burst mode phacoemulsification for patients with hard nuclear cataract: A randomized control study.

This article aims to evaluate the outcomes of torsional and burst mode phacoemulsification in hard nuclear cataracts.Eighty eyes with grade IV or V nuclear opalescence were treated with phacoemulsification and intraocular lens implantation using conventional mode (Group A, n = 40) or torsional and burst mode phacoemulsification (Group B, n = 40). For good visualization of anterior capsule, trypan blue was injected to the anterior chamber before continuous circular capsulorhexis. The mean cumulative dissipated energy and ultrasound time were recorded. The best-corrected visual acuity, endothelial cell density, and central corneal thickness were measured before and at 1 month after surgery.The cumulative dissipated energy and ultrasound time of Group B were significantly less than that of Group A. The postoperative best-corrected visual acuities of the 2 groups were comparable. At 1 month after surgery, the changes in the endothelial cell density were significantly greater in Group A than in Group B, and the changes in the central corneal thickness were not significantly different between the 2 groups.Torsional and burst mode is a safe and effective surgical method for treating hard cataracts.

[Startup and Stabilization of Nitrosation in an Anoxic-aerobic Continuous-flow Reactor with Granules].

Matured nitrosation granules were inoculated to an anoxic-aerobic continuous-flow reactor at room temperature (17-19℃). The startup and stabilization of nitrosation with granules were studied. The results show that the nitrosation of the continuous-flow was successfully achieved with an average nitrite accumulation rate (NAR) above 95%. With the increase of the dissolved oxygen (DO) content from (3±0.2) to (4.5±0.2) mg·L-1 in the aerobic zone, the NAR remained above 95%. The effect of the hydraulic retention time (HRT) of the continuous-flow reactor was investigated. The short HRT (8.4 h) sped up the circulation of the sludge particles in the continuous-flow system such that the broken granular sludge could not be integrated in time, resulting in the deterioration of granular sludge settling and the loss of sludge granules. The performance of the system was restored with the increase of the HRT to 12.2 h and the continuous-flow system stabilized. The ammonia removal efficiency and NAR were 86.7% and 96.2% on day 166, respectively.