Upregulation of miRNA-10a-5p promotes tumor progression in cervical cancer by suppressing UBE2I signaling.

Cervical cancer (CC) is a common malignant neoplasm in gynecology. There is increasing evidence to suggest that microRNAs (miRNAs) act as crucial regulators of CC. However, whether miR-10a-5p plays a role in CC is under investigation. The aim of this stuy was to assess the miR-10a-5p expression pattern in the development of CC and investigate its downstream target. MiR-10a-5p inhibition decreased CC cell proliferation and impaired CC cell invasion and migration but enhanced apoptosis. UBE2I was a direct target of miR-10a-5p. QRT-PCR results showed a down-regulation of UBE2I in CC cells, opposing miR-10a-5p. Besides, overexpression of miR-10a-5p down-regulated UBE2I. Functional rescue experiments further indicated the miR-10a-5p-UBE2I axis was linked to CC cell growth, apoptosis and metastasis. MiR-10a-5p upregulation promotes cervical cancer development by inhibiting UBE2I. These results also predict that miR-10a-5p may be a potential target for the clinical treatment of CC.IMPACT STATEMENTWhat is already known on this subject? As a widely researched cancer-related miRNA, the overexpression of miR-10a-5p has been verified in various cancers. It has been described in a meta-analysis report that there were 42 miRNAs up-regulated and 21 miRNAs down-regulated in different stages of cervical cancer tissue versus healthy tissue.What do the results of this study add? We verified that miR-10a-5p initiates and promotes tumor cell development by decreasing UBE2I abundance. This miR-10a-5p-mediated post-transcriptional regulation of UBE2I is involved in the tumorigenesis, invasion and migration of human cervical cancer.What are the implications of these findings for clinical practice and/or further research? These findings provide mechanistic insights into how miR-10a-5p regulates cervical cancer hyper-proliferation and metastasis, as well as a new target for clinical treatment. Nevertheless, whether miR-10a-5p/UBE2I axis can be regulated by non-invasive methods need further exploration, which will be the focus of our future research.

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial.

This current phase II clinical trial was to compare the effect and safety of adamgammadex, a new cyclodextrin-based selective relaxant binding agent, with sugammadex to reverse rocuronium-induced neuromuscular block. Patients were randomised to receive adamgammadex (4 or 6 mg kg-1) or sugammadex (2 mg kg-1, as a positive control group) at the reappearance of the second twitch (T2) in response to TOF stimulation. The standard safety data were collected. The 4 mg kg-1 (n = 16) and 6 mg kg-1 (n = 20) adamgammadex- and 2 mg kg-1 (n = 20) sugammadex-induced recovery time of TOF ratio to 0.9 were 2.3, 1.6, and 1.5 min, respectively (p = 0.49). The 4 mg kg -1 adamgammadex-induced median recovery time was longer than that of 2 mg kg-1 sugammadex (p = 0.01), and there was no difference between the 6 mg kg -1 adamgammadex group and 2 mg kg-1 sugammadex group (p = 0.32). Then, the number of patients who experienced adverse events (AEs) was 6, 11, and 14 for adamgammadex at 4, 6 mg kg-1 and sugammadex at 2 mg kg-1, respectively. The treatment emergent AEs that occurred more than twice were detailed as follows: incision site pain, hypotension, emesis, fever, throat pain, blood bilirubin increase, abnormal T-wave of ECG, dizziness, incision site swelling, postoperative fever, expectoration, and nausea. For drug-related AEs, the increased urine acetone bodies and first-degree atrioventricular block were observed in two patients from sugammadex group. Then, the previously reported AEs were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block as sugammadex.

MiR-195-5p facilitates the proliferation, migration, and invasion of human trophoblast cells by targeting FGF2.

BACKGROUND: Preeclampsia (PE), the most significant adverse exposure to cardiovascular risk during pregnancy, is one of the three major factors contributing to maternal and fetal mortality and the leading cause of preterm birth. Recently, various miRNAs have been reported to participate in PE occurrence and development. Nevertheless, the regulatory impact of miR-195-5p in PE is still indistinct. METHODS: Quantitative realtime-PCR (qRT-PCR), western blot, and fluorescence in situ hybridization (FISH) assay were performed to examine miR-195-5p and FGF2 expressions in PE serum samples or HTR-8/SVneo and TEV-1 cells. CCK8, flow cytometry, wound scratch, and transwell assays were conducted to determine cell viability, cycle, apoptosis, migration, and invasion. Dual-luciferase reporter assay unveiled the relationship between miR-195-5p and FGF2. Migration-related and invasion-related protein expressions were measured by western blot assay. RESULTS: miR-195-5p was prominently downregulated while FGF2 was increased in serum samples from PE patients and hypoxia-treated human trophoblast cells. FGF2 was predicted as a downstream target of miR-195-5p and targeted association was verified by dual-luciferase reporter assay. Functional experiments elaborated that miR-195-5p could facilitate trophoblast cell proliferation and metastasis but hinder cell cycle and apoptosis. Inversely, overexpressing of FGF2 could reverse the effects of miR-195-5p on trophoblast cell growth. DISCUSSION: miR-195-5p was decreased in PE serum samples and cell lines, serving as a potential biomarker in protecting PE exacerbation by targeting FGF2.

Efficacy and safety of different doses of ropivacaine for laparoscopy-assisted infiltration analgesia in patients undergoing laparoscopic cholecystectomy: A prospective randomized control trial.

BACKGROUND: Wound infiltration analgesia provides effective postoperative pain control in patients undergoing laparoscopic cholecystectomy (LC). However, the efficacy and safety of wound infiltration with different doses of ropivacaine is not well defined. This study investigated the analgesic effects and pharmacokinetic profile of varying concentrations of ropivacaine at port sites under laparoscopy assistance. METHODS: In this randomized, double-blinded study, 132 patients were assigned to 4 groups: Group H: in which patients were infiltrated with 0.75% ropivacaine; Group M: 0.5% ropivacaine; Group L: 0.2% ropivacaine; and Group C: 0.9% normal saline only. The primary outcome was pain intensity estimated using numeric rating scale (NRS) at discharging from PACU and at 4 hours, 6 hours, 8 hours, and 24 hours after infiltration. Secondary outcomes included plasma concentrations of ropivacaine at 30 minutes after wound infiltration, rescue analgesia requirements after surgery, perioperative vital signs changes, and side effects. RESULTS: The NRS in Group C was significantly higher at rest, and when coughing upon leaving PACU and at 4 hours, 6 hours, 8 hours, and 24 hours after infiltration (P < .05) and rescue analgesic consumption was significantly higher. Notably, these parameters were not significantly different between Groups H, Group M and Group L (P > .05). Intra-operative consumption of sevoflurane and remifentanil, HR at skin incision and MAP at skin incision, as well as 5 minutes after skin incision were significantly higher in Group C than in the other 3 groups (P < .01). In contrast, these parameters were not significantly different between Groups H, Group M and Group L (P > .05). The concentration of ropivacaine at 30 minutes after infiltration in Group H was significantly higher than that of Group L and Group M (P < .05). No significant differences were observed in the occurrence of side effects among the 4 groups (P > .05). CONCLUSIONS: Laparoscopy-assisted wound infiltration with ropivacaine successfully decreases pain intensity in patients undergoing LC regardless of the doses used. Infiltration with higher doses results in higher plasma concentrations, but below the systematic toxicity threshold.

[The effect of propofol and sevoflurane on the perioperative immunity in patients under laparoscopic radical resection of colorectal cancer].

OBJECTIVE: To compare the effect of propofol and sevoflurane on perioperative immunity and surgical outcomes in patients undergoing laparoscopic radical resection of colorectal cancer. METHODS: During September 2012 to April 2014 in Sir Run Run Shaw Hospital, thirty patients scheduled for laparoscopic colorectal cancer radical resection were randomly assigned into two groups: propofol TCI anesthesia and sevoflurane inhale anesthesia. Venous blood was taken before induction, on finishing the surgery and 24 h after surgery for lymphocyte subtype study by flow cytometry. Postoperative outcomes including intestinal obstruction, urine retention, anastomotic fistula and incision healing, antibiotic using time, hospital-stay time were compared. RESULTS: In the sevoflurane group, the percentage of CD3⁺, CD4⁺ and CD19⁺ subtype were increased immediately after surgery ((64.0 ± 13.5)%, (37.5 ± 11.8)%, (12.3 ± 4.5)%) comparing to preoperative level ((59.0 ± 12.0)%, (33.0 ± 8.3)%, (9.9 ± 4.3)%) (t= 3.423, 2.543, 2.768 respectively, all P<0.05), while NK cell percentage was significantly decreased ((22.9 ± 13.2)% vs (30.7 ± 11.9)%) (t=-3.444, P<0.01). The changes of CD3⁺, CD19⁺ and NK cell remained significant at 24 h ((63.5 ± 9.3)%, (13.0 ± 4.0)%, (22.5 ± 7.2)%) (t=2.961, 3.502, -4.621 respectively, all P<0.05). In the propofol group, the levels of CD3⁺, CD4⁺, CD19⁺ and CD4⁺ /CD8⁺ ratio were significantly increased after surgery ((69.4 ± 9.7)%, (43.2 ± 9.2)%, (15.2 ± 7.4)%, 1.9 ± 0.9) comparing to the preoperative levels ((61.9 ± 13.6)%, (34.6 ± 8.9)%, (10.4 ± 4.5)%, 1.5 ± 0.7) (t= 4.732, 6.132, 3.688, 4.640 respectively, all P<0.01), and NK cell was significantly decreased ((14.7 ± 10.2)% vs (27.2 ± 14.3)%) (t=-4.935, P<0.01). These changes were similar to that of the sevoflurane group. At 24 h in the propofol group, comparing with those after surgery, CD3⁺, CD4⁺ and CD4⁺ /CD8⁺ ratio were significantly decreased ((63.6 ± 12.3)%, (36.0 ± 8.7)%, 1.5 ± 0.6) (t=-2.879, -3.682, -3.340 respectively, all P<0.05), and returned to baseline when comparing to the preoperative level (t= 0.858, 0.758, -0.074 respectively, all P>0.05). NK cell began to recover at 24 h ((22.2 ± 12.6)%) comparing to the postoperative level (t= 2.941, P<0.05), but was still lower than the baseline (t=-2.249, P<0.05). Also, for all the above data, there were no difference between the two groups at any points (all P>0.05). There were no difference in hospital-stay time, antibiotic using time, the time to anal exhaust or defecate, postoperative fever, incision infection, neither other complications such as intestinal obstruction, urine retention, anastomotic fistula or intraperitoneal infection (all P>0.05). The incision infection rate was 0 in the propofol group while 14.3% in the sevoflurane group, which was quite clinically obvious though not statistically significant. CONCLUSIONS: Propofol may have less or shorter impact on immunity. However, whether anesthesia with propofol could be superior to that with sevoflurane for patients' immune function is still undetermined and needs further study.

[Effects of postoperative analgesia of ultrasound-guided transversus abdominis plane block in hemicolectomy patients].

OBJECTIVE: To investigate the effect of postoperative analgesia of ultrasound-guided transversus abdominis plane block in hemicolectomy patients. METHODS: After obtaining approval from the Hospital Ethics Committee and informed written consent from all patients, fourty hemicolectomy patients were randomly divided into two even groups. After anesthesia induction and intubation, patients received ultrasound-guided bilateral transversus abdominis plane block with 0.25% ropivacaine 60 ml (group A) or saline (group B). Post-operative patient-controlled intravenous analgesia with sufentanil was provided to all patients. RESULTS: Compared with group B, group A had less BP, HR changes at skin incision and needed less intraoperative sufentanil ((0.25 ± 0.16)µg/kg vs (0.35 ± 0.21)µg/kg) (P < 0.05) to maintain anesthesia. Group A had lower VAS than group B at 1, 4, 8, 12, 24 h after surgery (P < 0.05), less PCA demand (2.9 ± 1.6 vs 9.1 ± 1.8) (P < 0.05) and less PCA sufentanil consumption((69.1 ± 5.8)µg vs (92.6 ± 6.9)µg) (P < 0.05), thus less post-operative nausea or vomiting and higher satisfaction (P < 0.05). No complications associated to transversus abdominis plane block were found. CONCLUSION: Ultrasound-guided transversus abdominis plane block provided safe and effective post-operative analgesia for hemicolectomy patients.

[Effect of optimizing anesthetic injecting sequence during induction on fentanyl-induced coughing].

OBJECTIVE: To observe the effect of optimizing anesthetic injecting sequence during induction on fentanyl-induced coughing. METHODS: One hundred and twenty ASA I or II elective patients undergoing general anesthesia were randomly allocated to optimized group or control group: the optimized group induced with midazolam 0.06 mg/kg, followed by fentanyl 1 mg/kg at 1 min later, vecuronium 0.1 mg/kg at 1 min 55 s, propofol 1.5-2 mg/kg at 2 min, a second dose of 3 mg/kg fentanyl at 2 min 20 s, intubated at time 5 min; the control group was induced with the same medication but all the fentanyl (4 mg/kg) was injected at time 1 min. Coughing after fentanyl injection was observed and hemodynamic parameters were recorded. RESULTS: Hemodynamic changes were identical between the two groups indicated similar intubation response suppression. The incidence of fentanyl-induced coughing was significantly lower in the optimized group (4/60) than in the control group (23/60) (P < 0.01). CONCLUSION: Optimizing anesthetic injecting sequence during induction by separate fentanyl into two boluses significantly reduce fentanyl-induced coughing without affecting intubation response suppression.

[Effect of long-term sevoflurane anesthesia on markers of myocardial damage].

OBJECTIVE: To investigate the effect of long-term sevoflurane anesthesia on markers of myocardial damage or toxicity. METHODS: Forty adult patients scheduled for upper abdominal surgery with general anesthesia for 4 hours or more were randomly divided into Group S and PR (n=20 each). After anesthesia induction, patients of Group S were maintained with only sevoflurane, and patients of Group PR with target-controlled infusion of propofol 2-4 microg/ml and remifentanil 4-8 ng/ml. Anesthesia was titrated to control blood pressure and heart rate change at less than 20 percent of baseline values. Blood samples were draw at pre-induction, 4 h and 24 h post-induction respectively. Serum level of cardiac troponin I, creatine kinase MB and myoglobin were analyzed. RESULTS: There were no significant changes of troponin I, creatine kinase MB and myoglobin in Group S between pre-induction and 4 h or 24 h post-induction (P > 0.05). And there was also no significant differences as compared with Group PR (P > 0.05). CONCLUSION: At the concentration range of 1.6%-3%, long-term sevoflurane anesthesia does not cause detectable changes of markers of myocardial damage or toxicity.

The effect of 2-methoxyestradiol, a HIF-1 alpha inhibitor, in global cerebral ischemia in rats.

Global cerebral ischemia is an important clinical problem with few effective treatments. The hippocampus, which is important for memory, is especially vulnerable during global ischemia. Brain-specific knockout of hypoxia inducible factor-1 alpha (HIF-1 alpha) has been shown to be protective in focal ischemia in vivo. 2-methoxyestradiol (2ME2) is a natural metabolite of estrogen that is known to inhibit HIF-1 alpha. We tested 2ME2 in a rat model of global cerebral ischemia. Global ischemia was induced with the two-vessel occlusion model (2VO) which entailed hemorrhagic hypotension to a mean arterial pressure of 38-42 mmHg with simultaneous bilateral common carotid artery occlusion for 8 minutes. Sprague-Dawley rats (male, 280-350 g) were randomly assigned to three groups: global ischemia (GI, n=17), global ischemia with 2ME2 treatment (GI + 2ME2, n=17) and sham surgery (sham, n=12). 2ME2 treatment (15 mg/kg in 1% DMSO) was rendered 10 minutes after reperfusion. Rats in the GI and sham groups received similar doses of the DMSO solvent. Rats were killed 24 hours, 72 hours and 7 days after reperfusion. Quantitative CA1 hippocampal cell counts demonstrated significantly lower cell survival in the GI + 2ME2 group compared to either the GI or sham groups, in spite of a statistically significant reduction in HIF-1 alpha by Western blotting analysis of the GI + 2ME2 group. We conclude that 2ME2 worsens outcomes after global ischemia in rats.

[Comments on anesthesia machines' and monitors' designs].

From a view point of an anesthesiologist, the article points out some design issues of modern monitors and anesthesia machines. User interface problems such as auto-adjusted amplitude display, excessively complicated menus, unreasonable switch arrangement, unsuitable alarm settings or identical cylinder connectors, may affect patient safety and increase anesthesiologists' workload or mental burden.

[Protective effects of hydroxyethyl starch (130/0.4) against ischemia reperfusion injury of kidney: experiment with rats].

OBJECTIVE: To explore the protective effects of hydroxyethyl starch (HES)(130/0.4) against ischemia reperfusion injury of kidney and its impact on the expression of intercellular adhesion molecule-1 (ICAM-1). METHODS: Forty SD rats underwent resection of the right kidney and clamping of the left renal artery for 60 min to establish renal ischemia reperfusion model, and then were randomly divided into 4 equal groups: Group S, undergoing infusion of normal saline 20 mg/kg 20 min before the reopening of the renal artery, Group W1, undergoing infusion of HES 5 mg/kg 20 min before the reopening of the renal artery, Group W2, undergoing infusion of HES 10 mg/kg, and Group W3, undergoing infusion of normal saline 20 mg/kg. Ten rats underwent sham operation and were used as controls (Group C). 24 h after reperfusion arterial blood samples were collected to detect 6 the levels of serum creatinine (Cr) and blood urea nitrogen (BUN), and then the rats were killed with their kidneys taken out to undergo pathological examination and calculation of Paller's score. Immunohistochemistry was used to detect the expression of intercellular adhesion molecule-1 (ICAM-1). RESULTS: The levels of BUN and Cr of Group S were 152 +/- 22 and 3.17 +/- 1.00 mmol/L respectively, both significantly higher than those of Group C, and the levels of BUN and Cr of Groups W2 and W3 were 99 +/- 23 and 1.82 +/- 0.86 mmol/L and 92 +/- 28 and 1.57 +/- 0.70 mmol/L respectively, all significantly lower than those of Group S (P < 0. 05 or P < 0.01). The Paller's scores of W2 and W3 were 33.6 +/- 16.6 and 29.2 +/- 12.3 respectively,both significantly lower that of Group S (43.2 +/- 15. 8, both P < 0.05). The absorption levels of ICAM-1 of Groups W2 and W3 were 182 +/- 22 and 161 +/- 25 respectively, both significantly lower than that of Group S (212 +/- 32, P < 0.01). CONCLUSION: Infusion of 10-20 ml/kg HES (130/0.4) significantly alleviates the ischemia-reperfusion injury, probably by reducing the ICAM-1 expression.