SNHG14 facilitates cell proliferation in colorectal cancer through targeting KRAS via Hippo-YAP signaling.

Accumulating evidence indicates the significant role of lncRNAs in multiple biological processes and cancer progression. However, most lncRNAs in CRC remain to be excavated. In this study, we investigated SNHG14 in CRC. SNHG14 which was generally under-expressed in normal colon specimens revealed by UCSC was uncovered as markedly highly expressed in CRC cell lines. Besides, SNHG14 was a contributor to CRC cell proliferation. Additionally, we demonstrated that SNHG14 facilitated CRC cell proliferation in a KRAS-dependent manner. Moreover, the mechanistic investigations indicated that SNHG14 interacted with YAP and therefore inactivated the Hippo pathway, so as to enhance YAP-targeted KRAS expression in CRC. Furthermore, SNHG14 was explained as transcriptionally activated by FOS, a previously identified common effector molecule of KRAS and YAP. All in all, our findings elucidated a feedback loop of SNHG14/YAP/KRAS/FOS in facilitating CRC tumorigenesis, which may help develop novel effective targets for CRC patients.

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.

The effect of low-dose esketamine on pain and post-partum depression after cesarean section: A prospective, randomized, double-blind clinical trial.

Objective: To observe and evaluate the effect of a single intravenous injection of low-dose esketamine on post-operative pain and post-partum depression (PPD) in cesarean delivery patients. Methods: A total of 210 patients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were divided into an esketamine group (Group S, n = 105) and a normal saline group (Group L, n = 105) by a random number table. At 5 min after childbirth, patients in the S group were given 0.25 mg/kg esketamine, whereas patients in the L group received an equal volume of saline. The primary outcomes included post-operative pain control according to the Numerical Rating Scale (NRS) and the incidence of PPD according to the Edinburgh Post-partum Depression Scale (EPDS). The secondary outcomes included analgesia-related adverse events and Ramsay sedation scores. Results: This clinical study was a prospective, randomized, double-blind trial. A total of 210 patients were enrolled in this study. The NRS pain (cough pain) score was lower in the S group than in the L group at 24 h after surgery (P = 0.016), and there was no significant difference in resting pain and mobilization pain at 4, 8, and 48 h after surgery or resting pain at 24 h after surgery between the two groups. There was no significant difference in the prevalence of PPD between the two groups on the day before delivery, or at the first week, the second week, or the fourth week after childbirth. At 5 min after dosing, the incidence of hallucinations (P < 0.001) and dizziness (P < 0.001) was higher in the S group than in the L group. At 15 min after dosing, the incidence of dizziness (P < 0.001) and nausea (P = 0.011) was higher in the S group than in the L group. The incidence of dizziness (P < 0.001) was higher in the S group than in the L group when leaving the operating room. The Ramsay scores in Group S were lower than in Group L at 5 min (p < 0.001), 15 min (p < 0.001) after dosing and at the time of leaving the operating room (p < 0.001). Conclusion: In this study, a single intravenous injection of 0.25 mg/kg esketamine did not reduce the incidence of depression at 1, 2, or 4 w post-partum but improved pain during exercise at 24 h post-operatively under the conditions of this clinical trial. Clinical trial registration: [www.chictr.org.cn], identifier [ChiCTR2100054332].

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.

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.