Risk Factors for Fentanyl-Induced Cough Following General Anesthesia in Adults: A Retrospective Study from a Single Center in China.

BACKGROUND Fentanyl-induced cough (FIC) during general anesthesia induction and postoperative nausea and vomiting are common complications, yet the risk factors for FIC remain controversial. This retrospective study was conducted at a single center in China and aimed to investigate the risk factors for fentanyl-induced cough following general anesthesia in adults. MATERIAL AND METHODS A total of 601 adult patients undergoing elective surgery were enrolled, and the incidence of FIC during general anesthesia induction and postoperative adverse events were recorded. The risk factors for FIC during general anesthesia induction and postoperative nausea and vomiting were assessed using multivariate logistic regression analysis. RESULTS The incidence of FIC, nausea, and vomiting were 21.8%, 6.3%, and 4.5%, respectively. The results of multivariate logistic regression analysis indicated that pharyngitis history was associated with an increased risk of FIC during general anesthesia induction (odds ratio [OR]: 2.852; 95% confidence interval [CI]: 1.698-4.792; P<0.001), whereas use of lidocaine could protect against FIC risk (OR: 0.649; 95% CI: 0.557-0.757; P<0.001). However, the characteristics of patients were not associated with the risk of postoperative nausea and vomiting. CONCLUSIONS The findings from this study showed that a history of pharyngitis increased the risk of FIC, while the use of lidocaine was associated with a reduced risk of FIC. The risk of postoperative nausea and vomiting was not affected by fentanyl use or patient characteristics.

Noncoding RNA miR-205-5p mediates osteoporosis pathogenesis and osteoblast differentiation by regulating RUNX2.

As a kind of noncoding RNAs, microRNAs (miRNAs) play important roles in disease pathogenesis by regulating gene expression. However, the molecular mechanism of miRNAs in osteoporosis remains largely unknown. In the present study, we aim to explore the genome-wide miRNAs expression profile and the regulatory mechanism of miR-205-5p in osteoporosis. A total of 72 differentially expressed miRNAs were identified in osteoporosis via microarray technology and bioinformatics analysis. We focused on one of the abnormally expressed miRNAs, miR-205-5p, which was previously unknown in osteoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that miR-205-5p was upregulated in osteoporosis samples and its expression was gradually decreased during osteogenic differentiation. Besides, miR-205-5p overexpression could inhibit the activity of osteoblast markers, including collagen, type I, α 1 (COL1A1) and alkaline phosphatase (ALP) while miR-205-5p inhibition showed the opposite results. Moreover, bioinformatics analysis identified the potential targets of miR-205-5p, including runt-related transcription factor 2 (RUNX2), SMAD1 and BCL6, etc. The dual-luciferase reporter assay confirmed RUNX2 was directly targeted by miR-205-5p. Furthermore, the rescue experiments showed that RUNX2 overexpression could significantly weaken the effect of miR-205-5p on osteoblast markers, indicating that miR-205-5p may inhibit osteogenic differentiation by targeting RUNX2.

Analysis of clinical features and outcomes of 161 patients with severe and critical COVID-19: A multicenter descriptive study.

BACKGROUND: This study aimed to investigate clinical characteristics, laboratory indexes, treatment regimens, and short-term outcomes of severe and critical coronavirus disease 2019 (COVID-19) patients. METHODS: One hundred and sixty one consecutive severe and critical COVID-19 patients admitted in intensive care unit (ICU) were retrospectively reviewed in this multicenter study. Demographic features, medical histories, clinical symptoms, lung computerized tomography (CT) findings, and laboratory indexes on admission were collected. Post-admission complications, treatment regimens, and clinical outcomes were also documented. RESULTS: The mean age was 59.38 ± 16.54 years, with 104 (64.60%) males and 57 (35.40%) females. Hypertension (44 [27.33%]) and diabetes were the most common medical histories. Fever (127 [78.88%]) and dry cough (111 [68.94%]) were the most common symptoms. Blood routine indexes, hepatic and renal function indexes, and inflammation indexes were commonly abnormal. Acute respiratory distress syndrome (ARDS) was the most common post-admission complication (69 [42.86%]), followed by electrolyte disorders (48 [29.81%]), multiple organ dysfunction (MODS) (37 [22.98%]), and hypoproteinemia (36 [22.36%]). The most commonly used antiviral drug was lopinavir/ritonavir tablet. 50 (31.06%) patients died, while 78 (48.45%) patients healed and discharged, and the last 33 (20.50%) patients remained in hospital. Besides, the mean hospital stay of deaths was 21.66 ± 11.18 days, while the mean hospital stay of discharged patients was 18.42 ± 12.77 days. Furthermore, ARDS (P < .001) and MODS (P = .008) correlated with increased mortality rate. CONCLUSION: Severe and critical COVID-19 presents with high mortality rate, and occurrence of ARDS or MODS greatly increases its mortality risk.

Effect of Inhibiting p38 on HuR Involving in ß-AChR Post-transcriptional Mechanisms in Denervated Skeletal Muscle.

Previous studies reported that RNA-binding protein human antigen R (HuR) mediates changes in the stability of AChR ß-subunit mRNA after skeletal muscle denervation; also, p38 pathway regulated the stability of AChR ß-subunit mRNA in C2C12 myotubes. However, the relationship between HuR and p38 in regulating the stability of AChR ß-subunit mRNA have not been clarified. In this study, we wanted to examine the effect of inhibiting p38 on HuR in denervated skeletal muscle. Denervation model was built and 10% DMSO or SB203580 were administered respectively follow denervation. Tibialis muscles were collected in 10% DMSO-administered contralateral (undenervated) leg, 10% DMSO-administered denervated leg, SB203580-administered contralateral (undenervated) leg, and SB203580-administered denervated leg, respectively. P38 protein, ß-AChR mRNA and protein, HuR protein, ß-AChR mRNA stability, and HuR binding with AChR ß-subunit mRNAs were measured. Results demonstrated that the administration of SB203580 can inhibit the increase of ß-AChR protein expression and mRNA expression and stability, and RNA-binding protein human antigen R (HuR) expression, in cytoplasmic and nuclear fractions in skeletal muscle cells following denervation. Importantly, we observed that SB203580 also inhibited the increased level of binding activity between HuR and AChR ß-subunit mRNAs following denervation. Collectively, these results suggested that inhibition of p38 can post-transcriptionally inhibit ß-AChR upregulation via HuR in denervated skeletal muscle.

Two Pathways Regulate Differential Expression of nAChRs Between the Orbicularis Oris and Gastrocnemius.

BACKGROUND: We previously demonstrated differential expression of nicotinic acetylcholine receptors (nAChRs) in the facial nerve-innervated orbicularis oris and somatic nerve-innervated gastrocnemius, which contribute to different sensitivities to muscle relaxants. Furthermore, the orbicularis oris exhibits less sensitivity to muscle relaxants after facial nerve injury, which is also related to upregulation of nAChRs. Here, we explored the regulatory mechanism for the different expression patterns. Because the agrin/Lrp4/MuSK/rapsyn and neuregulin1/ErbB signaling pathways are indispensable for maintaining the expression of nAChRs, we examined the activity of these two signaling pathways in gastrocnemius and orbicularis oris innervated by normal or injured facial nerves. MATERIALS AND METHODS: A quantitative analysis of these two signaling pathways was realized by immunofluorescence, and immunoprecipitation was applied to detect the level of phosphorylated MuSK in the gastrocnemius and orbicularis oris innervated by normal or injured facial nerves in adult rats. RESULTS: ErbB and the phosphorylated MuSK were expressed more in orbicularis oris than in gastrocnemius (P < 0.05). No significant difference was found in the expression of agrin/Lrp4/MuSK/rapsyn. After facial nerve injury, the level of agrin and the percentage of phosphorylated MuSK decreased significantly, although the expression levels of MuSK, rapsyn, and neuregulin1/ErbB were highly upregulated. CONCLUSIONS: Differential expression of the neuregulin1/ErbB signaling pathway may account for the different expression patterns of nAChRs at the neuromuscular junctions of the orbicularis oris and gastrocnemius. Overexpression of MuSK and rapsyn may contribute to upregulation of nAChRs after facial nerve injury.

Effects of Neuromuscular Blockages on Entropy Monitoring During Sevoflurane Anesthesia.

BACKGROUND There are no data available on the effects of different degrees of neuromuscular blockade on spectral entropy during sevoflurane anesthesia. This study aimed to observe the effects of different degrees of neuromuscular blockade on state and response entropy during sevoflurane anesthesia. MATERIAL AND METHODS Eighty-one female patients were randomized to 9 groups (n=9 per group) according to the concentration of sevoflurane and degree of neuromuscular blockade. Response and state entropy were monitored. The endpoints were: 1) impact of neuromuscular blockade on state entropy and response entropy, and the difference between response entropy and state entropy; and 2) the response of entropy after cutaneous tetanic electrical noxious stimulation to the ulnar nerve under different degrees of neuromuscular blockade and concentrations of sevoflurane. RESULTS These were no significant differences in response entropy or state entropy, or differences between response entropy and state entropy among the groups in the awake state (P>0.05). Without noxious stimulation, sevoflurane concentrations and neuromuscular blockade had no significant effects on response entropy or state entropy, or on the difference between response entropy and state entropy (all P>0.05), but sevoflurane concentrations showed a significant effect on state entropy (P<0.05). After noxious stimulation, sevoflurane concentrations and neuromuscular blockade had significant effects on response entropy and state entropy, and on the difference between response entropy and state entropy. CONCLUSIONS Response entropy and state entropy decreased with increasing sevoflurane concentration. Neuromuscular blockade did not affect entropy without noxious stimulation. With stimulation, muscle relaxants significantly reduced the changes in entropy, and there were significant effects of neuromuscular blockade and sevoflurane on entropy.

γ-Acetylcholine Receptor Mediating Dynamic Changes of Resistance to Rocuronium in the Denervated Skeletal Muscle.

BACKGROUND/AIMS: Denervation resulted in resistance to non-depolarizing muscle relaxants (NDMRs), the magnitude of which changed after denervation in the skeletal muscle. The aim of this study was to investigate whether changed potencies of rocuronium were due to altered γ-acetylcholine receptor (γ-AChR) expression after skeletal muscle denervation. METHODS: Innervated and denervated muscle cells were used in this study. Patch clamp and Western blotting techniques were separately applied to examine IC50 values of rocuronium and γ-AChR protein expression at different times after denervation. Then, using the linear Pearson correlation analysis, the relationship between IC50 values of rocuronium and γ-AChR expression was tested. RESULTS: Compared with the innervated control, both IC50 values of rocuronium and γ-AChR expression significantly increased at Day 4, 7, and 14 after denervation in the skeletal muscle. Furthermore, γ-AChR protein and IC50 values of rocuronium exibited a significant positive correlation (r = 0.7678, p < 0.0001). CONCLUSION: These above results indicated that dynamic changes of resistance to NDMRs may be due to altered γ-AChR expression after skeletal muscle denervation.

Respiratory dynamics and dead space to tidal volume ratio of volume-controlled versus pressure-controlled ventilation during prolonged gynecological laparoscopic surgery.

BACKGROUND: Laparoscopic operations have become longer and more complex and applied to a broader patient population in the last decades. Prolonged gynecological laparoscopic surgeries require prolonged pneumoperitoneum and Trendelenburg position, which can influence respiratory dynamics and other measurements of pulmonary function. We investigated the differences between volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) and tried to determine the more efficient ventilation mode during prolonged pneumoperitoneum in gynecological laparoscopy. METHODS: Twenty-six patients scheduled for laparoscopic radical hysterectomy combined with or without laparoscopic pelvic lymphadenectomy were randomly allocated to be ventilated by either VCV or PCV. Standard anesthesic management and laparoscopic procedures were performed. Measurements of respiratory and hemodynamic dynamics were obtained after induction of anesthesia, at 10, 30, 60, and 120 min after establishing pneumoperitoneum, and at 10 min after return to supine lithotomy position and removal of carbon dioxide. The logistic regression model was applied to predict the corresponding critical value of duration of pneumoperitoneum when the Ppeak was higher than 40 cmH2O. RESULTS: Prolonged pneumoperitoneum and Trendelenburg position produced significant and clinically relevant changes in dynamic compliance and respiratory mechanics in anesthetized patients under PCV and VCV ventilation. Patients under PCV ventilation had a similar increase of dead space/tidal volume ratio, but had a lower Ppeak increase compared with those under VCV ventilation. The critical value of duration of pneumoperitoneum was predicted to be 355 min under VCV ventilation, corresponding to the risk of Ppeak higher than 40 cmH2O. CONCLUSIONS: Both VCV and PCV can be safely applied to prolonged gynecological laparoscopic surgery. However, PCV may become the better choice of ventilation after ruling out of other reasons for Ppeak increasing.

Observation of ventilation effects of I-gel™, Supreme™ and Ambu AuraOnce™ with respiratory dynamics monitoring in small children.

The shortcomings of laryngeal mask airway (LMA™), such as upper airway obstruction and gastric distension or airway leakage, may limit its application in small children. The I-gel™ (I-gel), LMA-Supreme™ (LMA-S), and Ambu AuraOnce™ (Ambu) are three improvements upon these shortcomings. This study adopted respiratory dynamic monitoring to observe the ventilation parameters of the three laryngeal masks in small children. A total of 105 children were randomized into Ambu (n = 35), I-gel (n = 35), and LMA-S (n = 35) groups. Primary outcomes included leak pressure and respiratory dynamic data. Secondary outcomes included hemodynamic data and bispectral index values after induction (T0), time after successful laryngeal mask insertion (T1) and at three recording points every 10 min after insertion (T2, T3, and T4), as well as laryngeal mask related adverse reactions. The inspiratory/expiratory tidal volume per kilogram of body weight in the Ambu group was significantly different from those in the other groups (P < 0.05), while the leak pressure in the Ambu group was significantly lower (P < 0.05). At T3 and T4, the expiratory resistance values in the Ambu group were significantly lower than those in the LMA-S group (P < 0.05). We have shown that the three laryngeal masks provided secure ventilation in children <6 years of age by using continuous respiratory dynamic monitoring. We concluded that the I-gel presented a better sealing effect and fewer adverse reactions.

Neuroprotective effects of HTR1A antagonist WAY-100635 on scopolamine-induced delirium in rats and underlying molecular mechanisms.

BACKGROUND: Limited surveys have assessed the performance of 5-hydroxytreptamine receptor 1A and its antagonist WAY-100635 in pharmacological manipulations targeting delirium therapies. The purpose of this paper was to assess the central pharmacological activity of WAY-100635 in a rat model of scopolamine-induced delirium and its underlying mechanism. RESULTS: A delirium rat model was established by intraperitoneal injection of scopolamine and behavioral changes evaluated through open field and elevated plus maze experiments. Concentrations of monoamines in the hippocampus and amygdalae were detected by high performance liquid chromatography. The effect of WAY-100635 on the recovery of rats from delirium was assessed by stereotactic injection of WAY-100635 and its mechanism of action determined by measuring mRNA and protein expression via real time PCR and western blotting methods. The total distance and the number of crossing and rearing in the elevated plus maze test and the time spent in the light compartment in the dark/light test of scopolamine-treated rats were significantly increased while the percentage of time spent in the open arms was decreased, showing the validity of the established delirium rat model. The measurement of the concentrations of noradrenaline, 3,4-dihydroxyphenylacetic acid, the homovanillic acid, 5-hydroxy-3-indoleacetic acid and serotonin concentrations in the cerebrospinal fluid (CSF) of scopolamine-induced delirium rats were significantly increased. The intra-hippocampus and intra-BLA injections of WAY-100635 improved the delirium-like behavior of rats by significantly reducing the expression of NLRP3 inflammasome and the release of IL1-ß and IL8 into CSF. CONCLUSIONS: Taken together, these findings indicate that WAY-100635 may exert a therapeutic effect on post-operative delirium by controlling neurotransmission as well as suppressing neuroinflammation in the central nervous system.

5-HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation-induced NLRP3 activity.

Postoperative delirium is a common complication that often results in poor outcomes in surgical and elderly patients. Accumulating evidences suggest that the pathophysiology of delirium results from multiple neurotransmitter system dysfunctions. To further clarify the effects of the selective serotonin (5-HT) (1A) antagonist WAY-100635 on the behaviors in scopolamine induced-delirium rats and to explore the molecular mechanism, in this study, we investigated the change of monoamine levels in the cerebrospinal fluid (CSF) and different brain regions using high-performance liquid chromatography and assessed the behavioral retrieval of delirium rats treated with WAY-100635. It was found that 5-hydroxy-3-indoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid, and homovanillic acid concentrations in the CSF of scopolamine-induced delirium rats were significantly increased, among which 5-HIAA was also increased in hippocampus and basolateral amygdala (BLA), and 5-HT(1A) receptor was significantly higher in the hippocampuses and BLA than other brain regions. Furthermore, intrahippocampus and intra-BLA stereotactic injection of WAY-100635 improved the delirium-like behavior of rats. Mechanistically, after WAY-100635 treatment, significant reduction of IL-1ß release into CSF and NOD-like receptor family, pyrin domain containing 3 (NLRP3) expression, phosphorylated phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and S6K was observed. Altogether, these results suggest that delirium rats induced by scopolamine may be correlated with an increased cerebral concentration of 5-HT and dopamine neurotransmitters system; the selective 5-HT(1A) antagoniszts can reverse the delirium symptoms at some extent through tendering PI3K/Akt/mammalian target of rapamycin complex 1 (mTOR) activation-induced NLRP3 activity and then reducing IL-1ß release.

Relationship Between Respiratory Dynamics and Body Mass Index in Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA) and Comparison Between Lithotomy and Supine Positions.

BACKGROUND This study aimed to compare respiratory dynamics in patients undergoing general anesthesia with a laryngeal mask airway (LMA) in lithotomy and supine positions and to validate the impact of operational position on effectiveness of LMA ventilation. MATERIAL AND METHODS A total of 90 patients (age range, 18-65 years) who underwent general anesthesia were selected and divided into supine position (SP group) and lithotomy position groups (LP group). Vital signs and respiratory dynamic parameters of the 2 groups were measured at different time points and after implantation of an LMA. The arterial blood gas was monitored at 15 min after induction. The intraoperative changes of hemodynamic indexes and postoperative adverse reactions of LMA were recorded. The possible correlation between body mass index (BMI) and respiratory dynamic indexes was analyzed. RESULTS With prolonged duration of the operation, the inspiratory plateau pressure (Pplat), inspiratory resistance (RI), and work of breathing (WOB) gradually increased, while chest-lung compliance (Compl) and partial pressure of carbon dioxide in end-expiratory gas (PetCO2) gradually decreased (all P value <0.05). The mean airway pressure (Pmean), Pplat, and expiratory resistance (Re) in the LP group were significantly higher than in the SP group (P<0.05), while the peak inspiratory flow (FImax), peak expiratory flow (FEmax), WOB, and Compl in the LP group were significantly lower than in the SP group (P<0.05). BMI was positively correlated with peak airway pressure (PIP/Ppeak), Pplat, and airway resistance (Raw) and was negatively correlated with Compl; the differences among patients in lithotomy position were more remarkable (P<0.05). CONCLUSIONS The inspiratory plateau pressure and airway resistance increased with prolonged duration of the operation, accompanied by decreased chest-lung compliance. Peak airway pressure and airway resistance were positively correlated with BMI, and chest-lung compliance was negatively correlated with BMI. Changes among patients in lithotomy position were more remarkable than those in supine position.

Resistance to rocuronium of rat diaphragm as compared with limb muscles.

BACKGROUND: Skeletal muscles are composed of different muscle fiber types. We investigated the different potency to rocuronium among diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the differences of acetylcholine receptors (AChRs) among these three typical kinds of muscles. MATERIALS AND METHODS: The isolated left hemidiaphragm nerve-muscle preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations were established to evaluate the potency to rocuronium. Concentration-response curves were constructed and the values of IC50 were obtained. The density of AChRs at the end plate and the number of AChRs per unit fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated. RESULTS: The concentration-twitch tension curves of rocuronium were significantly different. The curves demonstrated a shift to the right of the DIA compared with the EDL and SOL (P < 0.01), whereas no significant difference was observed between EDL and SOL (P > 0.05). IC50 was significantly largest in DIA, second largest in SOL, and smallest in EDL (P < 0.05). The number of AChRs per unit fiber CSA was largest in DIA, second largest in EDL, and smallest in SOL (P < 0.01 or P < 0.05). The DIA showed the lowest affinity of the AChRs, whereas the SOL showed the highest affinity. CONCLUSIONS: The resistance to rocuronium of DIA compared with EDL and SOL was verified. The DIA was characterized by the largest number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although compared with SOL, EDL was proved to have larger number of AChRs per unit fiber CSA and the lower affinity of the AChRs. These findings may be the mechanisms of different potency to rocuronium in DIA, EDL, and SOL. The results of the study could help to explain the relationship between different composition of muscle fibers and the potency to muscle relaxants. Extra caution should be taken in clinical practice when monitoring muscle relaxation in anesthetic management using different muscles.

Controlled ventilation or spontaneous respiration in anesthesia for tracheobronchial foreign body removal: a meta-analysis.

BACKGROUND: Either controlled ventilation or spontaneous respiration is commonly used in general anesthesia for inhaled foreign body removal via rigid bronchoscopy. Controversy in the literature exists concerning which form of ventilation is optimally suited for bronchoscopy. We performed a meta-analysis to compare controlled ventilation and spontaneous respiration with respect to complications, operation time, and anesthesia recovery time. METHODS: We searched MEDLINE (1946-2013) and the Cochrane Central Register of Controlled Trials, EMBASE. The articles were evaluated for validity, and the data on complications, including desaturation, laryngospasm, laryngeal edema, bucking and coughing, body movement, breath holding, operation time, and anesthesia recovery time, were extracted by the authors and summarized using odds ratios, mean differences, and 95% confidence intervals (CIs). RESULTS: From the included studies, 423 subjects received controlled ventilation, whereas 441 subjects received spontaneous respiration. There was no significant difference in the incidence of desaturation between controlled ventilation and spontaneous respiration (odds ratio, 0.70; 95% CI, 0.30-1.63). However, the incidence of laryngospasm was lower when controlled ventilation was performed (OR, 0.27; 95% CI, 0.10-0.76). The operation time (mean difference, -9.07 min; 95% CI, -14.03 to -4.12) was shorter in the controlled ventilation group. CONCLUSIONS: Current evidence does not show a preference for either controlled ventilation or spontaneous respiration, although laryngospasm has a lower incidence when controlled ventilation is performed. Additional clinical studies are required to substantiate this issue.

Serum progesterone, glycosylated hemoglobin and insulin levels with the risk of premature rupture of membranes in gestational diabetes mellitus.

OBJECTIVE: To discuss the correlation between serum progesterone, glycosylated Hemoglobin (HbA1c), and insulin levels in pregnant women with Gestational Diabetes Mellitus (GDM) and the risk of Premature Rupture of Membranes (PROM). METHODS: A retrospective analysis was conducted on 52 patients diagnosed with GDM who also presented with PROM (Observation group) and compared with 89 patients diagnosed with GDM but not complicated with PROM (Control group). Progesterone, insulin, and HbA1c were detected. Risk factors for PROM in GDM patients were analyzed. RESULTS: The observation group had higher HbA1c and fasting blood glucose levels. Poor blood glucose control and GWG are risk factors for PROM in GDM patients. PROM increases adverse pregnancy outcomes in GDM. HbA1c, insulin, and HOMA-IR can predict the risk of PROM in GDM. CONCLUSIONS: The effective prediction of preterm PROM can be achieved through the monitoring of serum HbA1c, insulin levels, and insulin resistance in patients with GDM.

Influence of Transverse Abdominis Plane Block on Intraoperative Diaphragmatic and Respiratory Functions in Patients Receiving Laparoscopic Colorectal Surgery.

Background: The positive roles of deep muscle relaxation in abdominal surgeries and transversus abdominis plane block (TAPB) in the postoperative analgesia. This study aimed to discuss the effects of TAPB on abdominal muscle relaxation, the intraoperative diaphragmatic, and the respiratory functions. Methods: The patients were randomly divided into the TAPB group who received single-shot TAPB bilaterally (n=30), and the control group who did not receive TAPB (n=30). Both groups keep the same steps for other procedures in the surgeries and anesthesia. Four time points for monitoring were defined: The moment when pneumoperitoneum pressure stabilized following endotracheal intubation and anesthetic induction (T0), appearance of the first incisure in the pressure-volume (P-V) loop (T1), appearance of the second incisure in the P-V loop (T2), and the moment with single stimulation (SS) =20% (T3). Primary observation parameters were SS1 measured by muscle relaxation monitoring at T1, and SS2 at T2. Secondary observation parameters included surgeon's satisfaction with surgical field and respiratory dynamics at the four time points. Results: The two groups were comparable in age, gender, BMI, ASA grade, and operation time. The TAPB group had a dramatic reduction in the total dose of intraoperative sufentanil (0.73±0.21 ug/kg) compared with the control group (0.87±0.18 ug/kg) (P=0.023); Other use of drug did not differ between the two groups. The two groups did not differ significantly in SS at either T1 (SS1) or T2 (SS2). In either group, surgeon's satisfaction with surgical field at T1 and T2 decreased dramatically compared with T0 and T3 (all P<0.05). At each time point, the respiratory dynamics and the surgeon's satisfaction with surgical field did not differ significantly between the two groups. Conclusion: TAPB reduced the use of intraoperative analgesics without altering the degree of abdominal relaxation, or affecting surgeon's satisfaction with surgical field in the patients receiving laparoscopic colorectal surgery.

Kaempferol attenuates cyclosporine-induced renal tubular injury via inhibiting the ROS-ASK1-MAPK pathway.

Cyclosporine (CSA) is a widely used immunosuppressive medication. CSA nephrotoxicity severely limits its application. Kaempferol (KPF), a naturally occurring phenolic compound, has a promising protective effect in reducing CSA-induced renal tubular injury, but the mechanism remains unknown. Our study aimed to determine the protective role of KPF against CSA-induced renal tubular injury. C57/B6 mice and the NRK-52E cell line were employed. CSA worsened renal function in mice, causing detachment and necrosis of tubular cells, leading to tubular vacuolation and renal interstitial fibrosis. CSA caused the detachment, rupture, and death of tubular cells in vitro, resulting in cell viability loss. KPF mitigated all these injurious alterations. KPF hindered CSA-induced ROS generation and protected renal tubular epithelial cells, similar to the antioxidant NAC. CSA lowered SOD activity and GSH levels while increasing MDA levels, and KPF ameliorated these changes. CSA caused phosphorylation of ASK1, JNK, and p38, similar to H2O2, whereas KPF significantly inhibited these changes. In conclusion, KPF reduces CSA-induced tubular epithelial cell injury via its antioxidant properties, inhibits the phosphorylation of ASK1, and inhibits the phosphorylation of p38 and JNK, implying that the synergistic use of KPF in CSA immunotherapy may be a promising option to reduce CSA-evoked renal injury.

MiR-31-5p regulates the neuroinflammatory response via TRAF6 in neuropathic pain.

BACKGROUND: Neuropathic pain is chronic pain and has few effective control strategies. Studies have demonstrated that microRNAs have functions in neuropathic pain. However, no study has been conducted to demonstrate the role and mechanism of microRNA (miR)-31-5p in neuropathic pain. Accordingly, this study sought to determine the pathological role of miR-31-5p in chronic constriction injury (CCI) -induced neuropathic pain mouse models. METHODS: We used CCI surgery to establish mouse neuropathic pain model. Behavioral tests were performed to evaluate pain sensitivity of mice. Expressions of miR-31-5p and inflammatory cytokines in dorsal root ganglion (DRG) were examined by polymerase chain reaction. Animals or cells were received with/without miR-31-5p mimic or inhibitor to investigate its role in neuropathic pain. The mechanism of miR-31-5p was assayed using western blotting, immunofluorescence staining and dual-luciferase reporter assay. RESULTS: We found that CCI led to a significant decrease in miR-31-5p levels. Knockout of miR-31-5p and administration of miPEP31 exacerbated pain in C57BL/6 mice. Meanwhile, miR-31-5p overexpression increased the paw withdrawal threshold and latency. TRAF6 is one of the target gene of miR-31-5p, which can trigger a complex inflammatory response. TRAF6 was associated with pain and that reducing the DRG expression of TRAF6 could alleviate pain. In addition, miR-31-5p overexpression inhibited the TRAF6 expression and reduced the neuroinflammatory response. CONCLUSIONS: All the results reveal that miR-31-5p could potentially alleviate pain in CCI mouse models by inhibiting the TRAF6 mediated neuroinflammatory response. MiR-31-5p upregulation is highlighted here as new target for CCI treatment.

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats.

INTRODUCTION: We investigated a novel application of phrenic nerve stimulation (PNS) in diaphragm dysfunction induced by mechanical ventilation (MV). METHODS: Twenty-one Sprague-Dawley rats were assigned randomly to 3 groups: spontaneous breathing, 18-h controlled MV, and 18-h controlled MV with PNS. Upon completion of the experimental protocol, diaphragm contractility, gene expression of insulin-like growth factor-1 (IGF-1) and ubiquitin ligases, and serum IGF-1 levels were analyzed. RESULTS: Compared with the spontaneously breathing rats, impaired diaphragm contractile function, including force-related properties and force-frequency responses, were pronounced with MV. Furthermore, MV suppressed IGF-1 and induced muscle ring finger 1 mRNA expression in the diaphragm. In contrast, PNS counteracted MV-induced gene expression changes in the diaphragm and restored diaphragm function. CONCLUSIONS: PNS exerted a protective effect against MV-induced diaphragm dysfunction by counteracting altered expression of IGF-1 and ubiquitin ligase in the diaphragm.

Evoked electromyography to rocuronium in orbicularis oris and gastrocnemius in facial nerve injury in rabbits.

BACKGROUND: Muscles innervated by the facial nerve show different sensitivities to muscle relaxants than muscles innervated by somatic nerves, especially in the presence of facial nerve injury. We compared the evoked electromyography (EEMG) response of orbicularis oris and gastrocnemius in with and without a non-depolarizing muscle relaxant in a rabbit model of graded facial nerve injury. METHODS: Differences in EEMG response and inhibition by rocuronium were measured in the orbicularis oris and gastrocnemius muscles 7 to 42 d after different levels of facial nerve crush injuries in adult rabbits. RESULTS: Baseline EEMG of orbicularis oris was significantly smaller than those of the gastrocnemius. Gastrocnemius was more sensitive to rocuronium than the facial muscles (P < 0.05). Baseline EEMG and EEMG amplitude of orbicularis oris in the presence of rocuronium was negatively correlated with the magnitude of facial nerve injury but the sensitivity to rocuronium was not. No significant difference was found in the onset time and the recovery time of rocuronium among gastrocnemius and normal or damaged facial muscles. CONCLUSIONS: Muscles innervated by somatic nerves are more sensitive to rocuronium than those innervated by the facial nerve, but while facial nerve injury reduced EEMG responses, the sensitivity to rocuronium is not altered. Partial neuromuscular blockade may be a suitable technique for conducting anesthesia and surgery safely when EEMG monitoring is needed to preserve and protect the facial nerve. Additional caution should be used if there is a risk of preexisting facial nerve injury.