[Morinda officinalis how extract up-regulates the expression of SPAG11T and inhibits that of miR-210 in the testis tissue of varicocele rats].

OBJECTIVE: To investigate the effects of morinda officinalis how (MOH) on SPAG11T and microRNA-210 (miR-210) in the testis tissue of SD rats with varicocele (VC). METHODS: Forty SD rats were randomly divided into four groups of an equal number: blank control, VC model control, low-dose MOH and high-dose MOH. The rats in the former two groups were treated intragastrically with normal saline and those in the latter two with MOH extract at 200 and 400 mg/kg/d, respectively, all for 30 days. Then, the testis tissues of the rats were harvested for measurement of the levels of SOD, MDA and AI and determination of the expressions of vimentin, sperm-associated antigen 11T (SPAG11T) protein and RNA, and miR-210. RESULTS: There were no statistically significant differences in the testicular and epididymal weights among the four groups of rats (P > 0.05). Compared with the rats in the VC model control group, those in the MOH groups showed a remarkably increased SOD content (P < 0.05) but a decreased MDA level and AI in the testis tissue (P < 0.05). The expression of vimentin mRNA in the testis tissue was significantly reduced in the VC model control in comparison with that in the blank control group (0.18 ± 0.03 vs 1.00 ± 0.02), but dramatically up-regulated after treated with low-dose MOH (0.68 ± 0.07) and high-dose MOH (0.92 ± 0.08) (F = 432.901, P< 0.01). The level of SPAG11T mRNA was also remarkably decreased in the VC model control group compared with the blank controls (0.32 ± 0.04 vs 1.00 ± 0.05), but markedly elevated after treated with low-dose MOH (0.61 ± 0.09) and high-dose MOH (0.82 ± 0.13) (F = 117.423, P< 0.01). The level of testicular miR-210, however, was significantly increased in the VC model controls compared with the blank controls (1.39 ± 0.12 vs 1.00 ± 0.06), but decreased in both the low-dose MOH (1.17 ± 0.08) and high-dose MOH groups (1.09 ± 0.08) (F = 36.136, P< 0.01). CONCLUSIONS: MOH extract can up-regulate the expressions of vimentin and SPAG11T and inhibit that of miR-210 in the testis tissue of varicocele rats.

[Comparison between peel and pulp of Aurantii Fructus Immaturus by UPLC fingerprint and multicomponent quantitative analysis].

Twenty batches of Aurantii Fructus Immaturus(AFI) were collected, with their peel and pulp taken as research objects. Ultra-high performance liquid chromatography(UPLC) fingerprints of peel and pulp of AFI were established with 17 common peaks in peel and 10 in pulp. Six kinds of flavonoids were identified, i.e., narirutin, naringin, rhoifolin, hesperidin, neohesperidin and nobiletin. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine was employed for similarity analysis, which showed that the chromatographic peaks of peel and pulp were basically similar to their respective reference fingerprints, with all similarities greater than 0.90. The similarity between peel and pulp of the same batch of AFI ranged from 0.850 to 0.983. Cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were conducted on the common peaks of peel and pulp of AFI with SPSS 17.0 and SIMCA 14.1. Combined with the reference fingerprints, these analyses revealed 12 differential components regarding peel and pulp. Further, the content of the 6 flavonoids and synephrine was determined. The proposed method integrating UPLC fingerprint and multicomponent quantitative analysis is applicable to the quality evaluation of AFI. The results provide a certain basis for the scientific connotation about the appearance characteristic of AFI.

Effect of Ketamine Added to Ropivacaine in Nerve Block for Postoperative Pain Management in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Trial.

PURPOSE: Nerve blocks are commonly used as a part of multimodal pain relief. It was previously shown that ketamine could enhance the analgesic effect of local anesthetics in nerve blocks. A literature review on adding ketamine to local anesthetics for ameliorating analgesia revealed inconsistencies in analgesic efficiency and safety. This prospective, randomized, double-blind trial was performed to evaluate the antinociceptive effect of mixing ketamine with local anesthetics in a combined femoral and sciatic nerve block (CFSNB) during anterior cruciate ligament (ACL) reconstruction. METHODS: Seventy-six patients undergoing preoperative ultrasound-guided CFSNB in ACL reconstruction were enrolled. Patients were randomly assigned to 3 groups: Group RNK received perineural administration of 40-mg ketamine plus 0.375% ropivacaine in 40-mL volume; Group RIK received 40 mL of 0.375% ropivacaine, as well as IV ketamine 40 mg; and Group R received 40 mL of 0.375% ropivacaine. Pain scores were recorded. AUC was calculated based on the pain scores at different times. Duration of CFSNB, postoperative analgesic demand, time to first analgesic demand, and adverse events were also examined. FINDINGS: Perineural ketamine decreased pain scores 20 and 24 h' postoperatively, as well as lowered AUC values (all, P = 0.001). Group RNK had a prolonged time to first analgesic request (P = 0.014), inhibited rebound pain (P = 0.001), and increased satisfactory score at 48 h' postsurgery (P = 0.001). Perineural ketamine prolonged the duration of sensory block (P = 0.001) with no effect on early mobilization. There were no significant differences between Group R and Group RIK in terms of postoperative pain scores, AUC of different time intervals (P = 0.832 or more), and time to first rescue analgesics (P = 0.585). Compared with the 2 other groups, IV ketamine had a higher incidence of hallucination after operations. IMPLICATIONS: Perineural ketamine added to the ropivacaine-enhanced analgesic efficacy of CFSNB with less rebound pain compared with the IV ketamine and control groups. IV ketamine had no effect in potentiating analgesia when a conventional multimodal approach was used in the study. Chinese Clinical Trial Registry: ChiCTR1900023867.

Edaravone Protects against Pancreatic and Intestinal Injury after Acute Pancreatitis via Nuclear Factor-κB Signaling in Mice.

Acute pancreatitis (AP) is one kind of acute surgical abdominal disease in the world. It causes intestinal damage with subsequent bacterial migration, endotoxemia and secondary pancreatic infections. In this investigation, we determined that edaravone (EDA) reduces pancreatic and intestinal injury after AP in mice. This was demonstrated by a reduction in histological score, apoptosis, interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α, along with obstructing activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NFκB). Our study results suggested that EDA exerts its protective effects against pancreatic and intestinal injury after AP via regulation of the TLR4/NFκB pathway. Our findings provide the basis for EDA to treat AP-induced pancreatic and intestinal injury, even might develop as a potential therapy for other inflammatory diseases.

A small dose of remifentanil pretreatment suppresses sufentanil-induced cough during general anesthesia induction: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Intravenous use of sufentanil can elicit cough. This study aimed to evaluate the inhibitory effect of pre-injection of a mall dose of remifentanil on sufentanil-induced cough during the induction of general anesthesia. METHODS: This prospective, randomized, controlled trial was conducted from January 10, 2019 to March 01, 2019. A total of 100 patients undergoing elective surgery under general anesthesia were enrolled, and at last 84 patients were included and randomly allocated into two equal size groups (n = 42): Patients in the Remifentanil group (R group) received an intravenous infusion of remifentanil 0.3 µg/kg (diluted to 2 ml) 1 min before sufentanil injection; patients in the Control group (C group) received 2 ml of normal saline (NS) at the same time point. Injections of patients in both groups were completed within 5 s. Then, sufentanil 0.5 µg/kg was injected within 5 s and the number of coughs that occurred within 1 min after sufentanil injection were recorded. One minute after sufentanil injection, etomidate 0.3 mg/kg and cisatracurium 0.15 mg/kg were given for general anesthesia induction irrespective of the presence or absence of cough. The mean arterial pressure (MAP) and heart rate (HR) at time points just before remifentanil pretreatment administration (T0), 3 min after administration (T1), 1 min after intubation (T2), and 3 min after intubation (T3) were recorded. RESULTS: The incidence of cough in patients in the R group and C group was 4.8 and 31%, respectively. Compared with group C, the incidence and severity of cough in group R was significantly lower (P < 0.01). No significant differences were observed in MAP and HR at the time of general anesthesia induction between the two groups (P > 0.05). CONCLUSION: Pretreatment with a small dose of remifentanil effectively and safely reduced the incidence and severity of cough induced by sufentanil during anesthesia induction and can be used as an alternative treatment to inhibit coughing caused by sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900020587, registered date: January 9, 2019), http://www.chictr.org.cn.

Quantitative Relationships between Pulmonary Function and Residual Neuromuscular Blockade.

BACKGROUND: Neuromuscular blockade is a risk factor for postoperative respiratory weakness during the immediate postoperative period. The quantitative relationships between postoperative pulmonary-function impairment and residual neuromuscular blockade are unknown. METHODS: 113 patients who underwent elective laparoscopic cholecystectomy were enrolled in this study. They all had a pulmonary-function test (PFT) during the preoperative evaluation. Predictive values based on demographic data were also recorded. The train-of-four ratio (TOFR) was recorded at the same time as the PFT and at every 5 minutes in the qualified 98 patients in the postanesthesia care unit (PACU). We analyzed the degree of PFT recovery when the TOFR had recovered to different degrees. RESULTS: There was a significant difference (P < 0.05) between the preoperative baseline value and the postoperative forced vital capacity at each TOFR point, except at a TOFR value of 1.1. There was also a significant difference (P < 0.05) between the preoperative baseline value and the postoperative peak expiratory flow at each TOFR point. CONCLUSIONS: Postoperative residual neuromuscular blockade was common (75.51%) after tracheal extubation, and pulmonary function could not recover to an acceptable level (85% of baseline value), even if TOFR had recovered to 0.90. TRIAL REGISTRATION: Chinese Clinical Trial Register is ChiCTR-OOC-15005838.

Chronic prenatal hypoxia impairs cochlear development, a mechanism involving connexin26 expression and promoter methylation.

Chronic prenatal hypoxia is a damaging to fetal development and may have various consequences, including hearing loss. Connexin 26 (Cx26) is one of the major protein subunits required for gap junction formation, and has an important role in maintaining homeostasis in the cochlea and normal hearing. Cx26 mutation and expression abnormality are closely associated with inherited nonsyndromic deafness, but the association between Cx26 and prenatal hypoxia is less established. The present study aimed to examine Cx26 expression and aberrant methylation the Cx26 promoter region in the cochlea from rats exposed to chronic prenatal hypoxia. Hematoxylin and eosin staining demonstrated that the number of hair cells in the organ of Corti were less in the hypoxia group. Reverse transcription­quantitative polymerase chain reaction and western blot analysis revealed that protein and mRNA levels of Cx26 were decreased in the hypoxia group compared with the control group. Further bisulfite sequencing analysis revealed that prenatal hypoxia significantly increased the methylation status of the promoter region of the Cx26 gene. These results demonstrate that chronic prenatal hypoxia caused hearing impairment, and suggest that promoter region hypermethylation and expression downregulation of Cx26 underlie the mechanism of action.

Randomized comparison of sevoflurane versus propofol-remifentanil on the cardioprotective effects in elderly patients with coronary heart disease.

BACKGROUND: It is skeptical about cardioprotective property of sevoflurane in patients undergoing noncardiac surgery, especially in the elderly patients with coronary heart disease. We hypothesized that long duration of sevoflurane inhalation in noncardiac surgery could ameliorate myocardial damage in such patients. METHODS: This was a randomized, prospective study. One hundred twenty-one elderly patients with coronary heart disease were randomly allocated into two groups. Maintenance of anesthesia was achieved by sevoflurane inhalation (Group S) or propofol-remifentanil respectively (Group PR). Serum cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) were measured before anesthesia induction (T0), 8 h (T1) and 24 h (T2) after anesthesia respectively. The perioperative cardiac output, complications and postoperative 3-month follow-up from end of surgery were recorded. RESULTS: Between the two groups, there were no statistical differences in the values of cTnI and BNP during the study. However, The area under the curve of cTnI values over 24 h after operation was less in Group S. Group PR had lower cardiac output and consumed more amount of phenylephrine during the study (P < 0.05). CONCLUSIONS: Compared with the group PR, sevoflurane had no benefit in the myocardial protection for the elderly patients with CHD. However, Sevoflurane showed advantage in maintaining hemodynamic stability during the operative period. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008871 , 21 July 2016.

Analgesic effect of perineural magnesium sulphate for sciatic nerve block for diabetic toe amputation: A randomized trial.

BACKGROUND AND OBJECTIVES: High concentrations of local anesthetics may be neurotoxic for diabetic patients. Additive perineural administration of magnesium was reported to decrease the consumption of local anesthetics for nerve block. It was hypothesized that MgSO4 added to dilute ropivacaine was equianalgesic to more concentrated ropivacaine for toe amputations in diabetic patients. METHODS: Seventy diabetic patients were allocated into 3 groups: 1) perineural 200 mg MgSO4 added to 0.25% ropivacaine, 2) 0.25% ropivacaine alone, and 3) 0.375% ropivacaine alone. All patients underwent popliteal sciatic nerve block that was guided by ultrasonography using the respective regimens. Time of onset, duration of motor and sensory block were recorded. Spontaneous and evoked pain score, worst pain score, additional analgesic consumption, satisfaction score and initial time of analgesic requirement of each patient were documented up to 48 hours postoperatively. RESULTS: In comparison with 0.25% ropivacaine alone, magnesium supplement prolonged the duration of sensory block (p = 0.001), as well as better evoked pain score at 6 hour postoperatively (p = 0.001). In comparison with evoked pain score (1.6/10) in group of 0.375% ropivacaine, magnesium plus 0.25% ropivacaine presented a little higher score (2.5/10) at 6 hour postoperatively (p = 0.001), while lower worst pain score (p = 0.001) and less postoperative total analgesic consumption (p = 0.002). CONCLUSIONS: The regimen of adding 200mg MgSO4 to 0.25% ropivacaine for sciatic nerve block yields equal analgesic effect in comparison with 0.375% ropivacaine. These findings have suggested that supplemental MgSO4 could not improve analgesic quality except reducing the total amount of local anesthetics requirement in diabetic toe amputations with sciatic nerve blocks.

Magnesium sulphate attenuate remifentanil-induced postoperative hyperalgesia via regulating tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord.

BACKGROUND: Remifentanil induced hyperalgesia (RIH) is characterized by stimulation evoked pain including allodynia and thermal hyperalgesia after remifentanil infusion. N-methyl-D-aspartate (NMDA) receptor was reported to be involved in the progress of RIH. We hypothesized that intrathecal MgSO4 could relieve hyperalgesia after remifentanil infusion via regulating phosphorylation of NMDA receptor NR2B subunit activity in this study. METHODS: Thirty two rats were randomly allocated into control group, model of RIH group, RIH plus 100ug MgSO4 group, RIH plus 300ug MgSO4 group. Mechanical and thermal hyperalgesia were tested at -24th h, 2nd h, 6th h, 24th h, 48th h after remifentanil infusion. Following sacrifice of rats after the last behavioral test, we performed the western blot to detect the expression of spinal phosphorylated NMDA receptor NR2B subunit (pNR2B) in the L4-L5 segments. RESULTS: Intrathecal MgSO4 (100, 300 µg) dose-dependently reduced thermal and mechanical hyperalgesia from 2 h to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of pNR2B. Nevertheless, the increased amount of pNR2B by RIH was dose-dependently suppressed by intrathecal infusion of MgSO4 in rats. CONCLUSIONS: Remifentanil induced hyperalgesia/allodynia could be ameliorated by Mg-mediated blockade targeting the NR2B subunit in NMDA receptors.

The hippocampal cyclin D1 expression is involved in postoperative cognitive dysfunction after sevoflurane exposure in aged mice.

AIMS: Increasing evidence has suggested cognitive impairment and neuronal apoptosis induced by anaesthetics are due to abnormal hyperphosphorylation of tau protein, but the detailed mechanism remains unknown. MAIN METHODS: Aged mice and neurons were both exposed to 2.5% sevoflurane for 2h. Spatial learning ability of the aged mice was tested with Morris water maze. The changes of neuroapoptosis, tau protein and cell-cycle-related factors (cyclin D1, p27) were determined using Western blot analysis. The effect of sevoflurane exposure on DNA synthesis was tested with immunofluorescent staining. KEY FINDINGS: We found that sevoflurane significantly impaired spatial learning ability in aged mice. In addition, total tau protein. phosphorylated tau protein, Caspase-3 and cyclin D1, but not p27Kip1 were drastically increased in the hippocampus. Consistent with the results from in vivo study, sevoflurane significantly increased the expression of cyclin D1 and Brdu positive neurons in cultured hippocampal neurons. The enhancement of cyclin D1 was partially reversed by the pharmacological inhibition of hyperphosphorylation of tau. SIGNIFICANCE: Our results suggested that cyclin D1 overexpression may result in the neuronal apoptosis through cell cycle re-entry and the deficits in postoperative cognitive dysfunction after sevoflurane exposure. Our research will improve the current understanding of the mechanisms underlying the postoperative cognitive dysfunction by anaesthetics exposure.

Magnesium Sulfate Plus Lidocaine Reduces Propofol Injection Pain: A Double-blind, Randomized Study.

PURPOSE: Propofol injection can cause distressing pain, and no method can inhibit it completely. Neither lidocaine nor magnesium sulfate (MgSO4) was sufficient to prevent pain from the injection of propofol. This prospective, double-blind, placebo-controlled study was designed to investigate the efficacy of the MgSO4 plus lidocaine on suppressing propofol injection pain. METHODS: Three hundred women received 300 mg MgSO4 (Group M), 40 mg lidocaine (Group L), or 300 mg MgSO4 plus 40 mg lidocaine (Group M+L). This was followed by administration of 50 mg propofol. Pain scores, behavior-related responses, and diameter of the vein were recorded following the injection of propofol. FINDINGS: Patients in Group M + L had lower pain scores. Patients' behavior-related responses in Group M + L were also better compared with the other groups. There were no differences in pain scores between Group L and Group M. The target vein diameter change in Group M and Group M + L was more obvious than in Group L. IMPLICATIONS: Administration of 300 mg MgSO4 plus 40 mg lidocaine reduces propofol injection pain very well. No complications were observed in the treatment groups.