Overexpression of miR-96 leads to retinal degeneration in mice.

Double knockout of miR-183 and miR-96 results in retinal degeneration in mice; however, single knockout of miR-96 leads to developmental delay but not substantial retinal degeneration. To further explore the role of miR-96, we overexpressed this miRNA in mouse retinas. Interestingly, we found that overexpression of miR-96 at a safe dose results in retinal degeneration in the mouse retina. The retinal photoreceptors dramatically degenerated in the miR-96-overexpressing group, as shown by OCT, ERG and cryosectioning at one month after subretinal injection. Degenerative features such as TUNEL signals and reactive gliosis were observed in the miR-96-overexpressing retina. RNA-seq data revealed that immune responses and microglial activation occurred in the degenerating retina. Further qRT‒PCR and immunostaining experiments verified the microglial activation. Moreover, the number of microglia in the miR-96-overexpressing retinas was significantly increased. Our findings demonstrate that appropriate miR-96 expression is required for mouse retinal homeostasis.

The safety of preoperative carbohydrate drinks in extremely elderly patients assessed by gastric ultrasonography: a randomized controlled trial.

BACKGROUND: Modern perioperative guidelines encourage drinking oral carbohydrates 2 h before management. Nevertheless, research on the safety of preoperative carbohydrate drinks, particularly in extremely elderly patients is lacking. We aimed to evaluate the safety of carbohydrate drinks 2 h before surgery in extremely elderly patients (≥ 80 years) using gastric ultrasonography. METHODS: We conducted a randomized prospective comparative study of 70 patients aged over 80 years who were scheduled for total knee arthroplasty, hip fracture or humerus fracture surgery. These patients were randomly assigned to the carbohydrate group (n = 35), which fasted from midnight, except for drinking 355 mL of a carbohydrate-containing fluid 2 h before surgery, or the fasting group (n = 35), which fasted from midnight and drank no fluid before surgery. The primary outcome of the study was the cross-sectional area (CSA) of the gastric antrum in the right lateral decubitus position (RLDP) before surgery. The secondary outcomes included CSA in the supine position, intraoperative blood glucose levels and their variability coefficients, Perlas grade, and the visual analog scale of subjective feelings. RESULTS: The CSA in the RLDP and supine positions revealed no differences between the carbohydrate and fasting groups at 0 h preoperatively (P > 0.05). In the qualitative assessment, preoperative 0-h Perlas grading did not differ significantly between the groups (P > 0.05). From 2 h before surgery to transfer out of the post-anesthesia care unit, the average blood glucose level of patients in the carbohydrate group was significantly higher than that in the fasting group (P < 0.001) but remained within the normal range. Moreover, the blood glucose variability coefficient was significantly lower in the carbohydrate group than in the fasting group (P = 0.009). Oral intake of 355 mL carbohydrates before surgery significantly relieved patients' feelings (P < 0.001). CONCLUSION: Preoperative consumption of carbohydrate drinks 2 h before surgery is safe in "healthy" extremely elderly patients. In addition, preoperative drinking has potential value in maintaining ideal blood glucose levels and stable blood glucose fluctuations perioperatively and improving subjective perceptions of preoperative preparation. This finding warrants further investigation in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number ChiCTR1900024812), first registered on 29/07/2019.

Time interval between alfentanil and rocuronium administration necessary to prevent rocuronium-induced withdrawal movement.

BACKGROUND: We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (TimeAR50). METHODS: A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 µg/mL. Then, alfentanil 15 µg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon's up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection. RESULTS: The TimeAR50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the TimeAR50 was 4.7 s (95% confidence interval [CI], 1.2-7.6 s) and 20.3 s (95% CI, 7.7-26.1 s) in the male and female patients, respectively. The TimeAR95 was 10.6 s (95% CI, 7.7-25.3 s) and 35.0 s (95% CI, 28.1-95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups. CONCLUSION: The TimeAR50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL: http://www.chictr.org.cn . Registry number: ChiCTR2100045137 ) .

Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial.

Importance: In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness. Objective: To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. Design, Setting, and Participants: A randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018. Interventions: Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474). Main Outcomes and Measures: Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. Results: Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). Conclusions and Relevance: In patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia. Trial Registration: ClinicalTrials.gov Identifier: NCT02213380.

Preoperative assessment of cognitive function and risk assessment of cognitive impairment in elderly patients with orthopedics: a cross-sectional study.

BACKGROUND: Preexisting cognitive impairment is emerging as a predictor of poor postoperative outcomes in seniors. Nevertheless, cognitive impairment in a large proportion of geriatric patients has not been well identified and diagnosed. METHODS: This is a cross-sectional study. Mini-mental state examination scale was used to assess the cognitive function of elderly patients aged ≥65 years undergoing orthopedic surgery preoperatively. The baseline, living habits and laboratory examination results of two groups were compared, and a multivariable logistic regression model was used to identify independent predictors of preoperative cognitive impairment. RESULTS: A total of 374 elderly patients with orthopedic surgery indications met the inclusion criteria, and 28.61% of them had preoperative cognitive impairment. Multivariable logistic regression analysis showed that age (OR = 1.089, P < 0.001), subjective sleep disorders (OR = 1.996, P = 0.021), atherosclerosis (OR = 2.367, P = 0.017), and high cholesterol level (OR = 1.373, P = 0.028) were independent risk factors for preoperative cognitive impairment, while high education level performed as a protective factor (compared with the illiterate group, primary school group: OR = 0.413, P = 0.009; middle school or above group: OR = 0.120, P < 0.001). CONCLUSIONS: The prevalence of preoperative cognitive dysfunction in geriatric elective orthopedic surgical patients was high. Our study identified venerable age, low level of education, subjective sleep disorders, atherosclerosis, and high cholesterol level as risk factors for preoperative cognitive impairment in these patients. Understanding these risk factors contributes to assisting in prevention and directed interventions for the high-risk population.

Improvements in blood transfusion management: cross-sectional data analysis from nine hospitals in Zhejiang, China.

BACKGROUND: Since 2008, updated perioperative blood management (PoBM) guidelines have been implemented in Zhejiang, China. These guidelines ensure that the limited blood resources meet increasing clinical needs and patient safety requirements. We assessed the effects of implementing updated PoBM guidelines in hospitals in Zhejiang, China. METHODS: We performed a retrospective multicenter study that included adult patients who received blood transfusions during surgical care in the years 2007 and 2011. The volume of allogeneic red blood cells or autologous blood transfusions (cell salvage and acute normovolemic hemodilution [ANH]) for each case was recorded. The rates of performing appropriate pre-transfusion assessments during and after surgery were calculated and compared between the 2 years. RESULTS: We reviewed 270,421 cases from nine hospitals. A total of 15,739 patients received blood transfusions during the perioperative period. The rates of intraoperative allogeneic transfusion (74.8% vs. 49.9%, p <  0.001) and postoperative transfusion (51.9% vs. 44.2%, p <  0.001) both decreased from 2007 to 2011; the rates of appropriate assessment increased significantly during (63.0% vs. 78.0%, p <  0.001) and after surgery (70.6% vs. 78.4%, p <  0.001). The number of patients who received cell salvage or ANH was higher in 2011 (27.6% cell salvage; 9.3% ANH) than in 2007 (6.3% cell salvage; 0.1% ANH). CONCLUSION: Continuing education and implementation of updated PoBM guidelines resulted in significant improvements in the quality of blood transfusion management in hospitals in Zhejiang, China.

Effect of Intermittent Thoracic Paravertebral Block on Postoperative Nausea and Vomiting Following Thoracoscopic Radical Resection of the Lung Cancer: A Prospective Randomized Trial.

Purpose: To explore the benefits of ultrasound-guided intermittent thoracic paravertebral block (TPVB) combined with intravenous analgesia (PCIA) in alleviating postoperative nausea and vomiting (PONV) during video-assisted thoracic surgery (VATS). Patients and Methods: 120 patients with lung carcinoma undergoing VATS were included and divided into three groups: group S (single TPVB+PCIA), group I (intermittent TPVB+PCIA), and group P (PCIA). The patients' NRS scores, postoperative hydromorphone hydrochloride consumption, and intramuscular injection of bucinnazine hydrochloride were recorded. The incidence of PONV and complications were documented. Results: Compared with the group P, both group I and group S had significantly lower static NRS scores from 1-48 hours after the operation (P <0.05), and the dynamic NRS score of group I at the 1-48 hours after the operation were significantly decreased (P <0.05). Compared with the group P, the proportion of patients with PONV in group I was significantly lower (P <0.05), while there was no significant difference in group S. Moreover, the hospitalization period of patients in group I was significantly reduced compared with the other two groups (P <0.01), and the patient satisfaction was significantly increased compared with the group P (P <0.05). Conclusion: Intermittent TPVB combined with PCIA can reduce the postoperative pain and the occurrence of PONV.

Olanzapine for the prevention of postoperative nausea and vomiting after gynecologic laparoscopic surgery: a randomized controlled trial.

Purpose: This study was designed to investigate the prophylactic effect of oral olanzapine in postoperative nausea and vomiting after gynecologic laparoscopic surgery. Methods: ASA I-II, aged 18-75 years, planned to undergo gynecologic laparoscopic surgery with general anesthesia in adult female patients. Using the randomized numbers table, the patients were placed in two groups. Oral olanzapine 5 mg or placebo was given 1 h before anesthesia. All patients received standard antiemetic prophylaxis with dexamethasone and granisetron. The primary outcome was nausea and/or vomiting in the 24 h after the postoperative. Results: A total of 250 patients were randomized, and 241 were analyzed. The primary outcome occurred in 10 of 120 patients (8.3%) in the olanzapine group and 23 of 121 patients (19.2%) in the placebo group (p = 0.014). According to Kaplan-Meier analysis, the probabilities of nausea and/or vomiting in the 24 h after the postoperative in the olanzapine group were lower than in the placebo group (log-rank p = 0.014). In a multivariate Cox analysis, the variables of use of olanzapine [hazard ratio (HR): 0.35, 95% confidence interval (CI): 0.16-0.79; p = 0.012] and use of vasoactive drugs (HR: 2.48, 95% CI: 1.07-5.75; p = 0.034) were independently associated with nausea and/or vomiting in the 24 h after the postoperative. Conclusion: Our data suggest that olanzapine relative to placebo decreased the risk of nausea and/or vomiting in the 24 h after gynecologic laparoscopic surgery. Trial registration: The trial was registered prior to patient enrollment at The Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj=166900, link to registry page, Principal investigator: Nanjin Chen, Date of registration: 25 April 2022).

Preventing nausea and vomiting after laparoscopic gynecological surgery: the benefits of using olanzapine Why was this study done? Despite the use of antiemetics, postoperative nausea and vomiting remain prevalent. Furthermore, patients who undergo gynecological laparoscopic surgery are at an increased risk. Therefore, this study investigated whether oral Olanzapine could reduce the incidence of nausea and vomiting after gynaecological Laparoscopy? What did the researchers do? The research team examined patients who underwent gynecological laparoscopic surgery under general anesthesia. They observed the occurrence of nausea and vomiting within 24 hours after surgery in patients who either received or did not receive Olanzapine treatment. The goal was to assess the effectiveness of Olanzapine in reducing postoperative nausea and vomiting. What did the researchers find? The addition of Olanzapine, when combined with granisetron and dexamethasone, resulted in a decreased risk of nausea and/or vomiting within the 24 hours following gynecologic laparoscopic surgery, as compared to the placebo. Administering oral Olanzapine at a dosage of 5 mg reduced the incidence of nausea and vomiting after gynecological laparoscopy from 19.2% to 8.3%. What do the findings mean? This study has identified a safe and effective medication for preventing postoperative nausea and vomiting. Implementing Olanzapine as a preventive measure can significantly reduce the incidence of nausea and vomiting following surgery, thereby enhancing the overall medical experience for patients.

LncRNA HCG18 loaded by polymorphonuclear neutrophil-secreted exosomes aggravates sepsis acute lung injury by regulating macrophage polarization.

Polymorphonuclear neutrophils (PMNs) exert significant roles in septic acute lung injury (ALI). Accumulating evidence suggests that PMN-derived exosomes (PMN-exo) are a novel subcellular entity that is the fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-exo in septic ALI and the underlying mechanisms remain unclear. Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in septic ALI, was used to induce PMN activation in vitro. Using an in vitro co-culture system, the rat alveolar macrophage cell line NR8383 was co-cultured with TNF-α-stimulated PMN-released exosomes (TNF-α-exo) to further confirm the results of the in vitro studies and explore the underlying mechanisms involved. A septic lung injury model was established by cecal ligation and puncture surgery, and PMN-exo were injected into septic mice through the tail vein, and then lung injury, inflammatory release, macrophage polarization, and apoptosis were examined. The results reported that TNF-α-exo promoted the activation of M1 macrophages after i.p. injection in vivo or co-culture in vitro. Furthermore, TNF-α-exo affected alveolar macrophage polarization by delivering HCG18. Mechanistic studies indicated that HCG18 mediated the function of TNF-α-exo by targeting IL-32 in macrophages. In addition, tail vein injection of si-HCG18 in septic mice significantly reduced TNF-α-exo-induced M1 macrophage activation and lung macrophage death, as well as histological lesions. In conclusion, TNF-α-exo-loaded HCG18 contributes to septic ALI by regulating macrophage polarization. These findings may provide new insights into novel mechanisms of PMN-macrophage polarization interactions in septic ALI and may provide new therapeutic strategies for patients with sepsis.

Estimation of the median effective dose and the 95% effective dose of alfentanil required to inhibit the bronchoscopy reaction during painless bronchoscopy with i-gel supraglottic airway device: an Up-and-Down Sequential Allocation Trial.

Background: In practice, the optimal dose of alfentanil that should be used when painless bronchoscopy is performed is unknown. The purpose of this study was to investigate the effective dose of alfentanil in suppressing bronchoscopy responses to painless bronchoscopy with an i-gel supraglottic airway device. Methods: Patients aged 18-70 years, with American Society of Anesthesiologists (ASA) physical status I-II, who planned to undergo painless bronchoscopy were recruited for this study. Alfentanil was administered intravenously 2 minutes before propofol administration. The response to bronchoscopy was measured, including oxygen saturation (SPO2) and changes in respiratory rhythm. The median effective dose of alfentanil (ED50) required to alleviate responses to the bronchoscopy was calculated using Dixon's up-and-down method in the female and male groups. Probit analysis was used to generate a dose-response curve in each group. Results: A total of 48 patients were recruited for the study including 25 females and 23 males. The ED50 of alfentanil for suppressing responses to painless bronchoscopy in females and males was 13.68±4.75 and 17.96±3.45 µg/kg, respectively. The difference was not statistically significant between the two groups (P=0.078). Probit analysis showed the ED50 of alfentanil in female bronchoscopy was 12.4 µg/kg [95% confidence interval (CI): 4.5 to 17 µg/kg]. In men, the ED50 of alfentanil was 16.4 µg/kg (95% CI: 12.1 to 20.1 µg/kg). According to the probit analysis, the 95% effective dose (ED95) of alfentanil was 22.4 µg/kg (95% CI: 17.5 to 67.3 µg/kg) in female bronchoscopy. In men, the ED95 of alfentanil was 23.3 µg/kg (95% CI: 19.8 to 46.2 µg/kg). Conclusions: Our data suggest that there were no obvious differences between men and women in the effective dose of alfentanil in painless bronchoscopy.

Ultrasound-Guided Oblique Sagittal Anterior Quadratus Lumborum Block in Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: The anterior quadratus lumborum block (QLB) is gaining popularity in total hip arthroplasty (THA) surgeries for postoperative pain management and this technique rarely results in lower limb muscle weakness. However, no studies have described the range of its blockade. OBJECTIVES: The aim of the study was to confirm the range of cold temperature sensory blockades, observe the opioid consumption after THA surgery, assess the pain of the patients, and assess the safety of this technique. STUDY DESIGN: Randomized controlled study. SETTING: Taizhou Hospital of Zhejiang Province. METHODS: Patients who underwent primary THAs were randomized to take an oblique sagittal anterior QLB with 30 mL of 0.375% ropivacaine (QLB+G group) or with 30 mL of 0.9% saline (G group). The main purpose of the study was to confirm the range of cold hypoesthesia. The other aim included the average blood pressure, heart rate, surgical pleth index, and bispectral index values fluctuation during the intraoperative period of expanding the medullary cavity, the sufentanil, and remifentanil consumption during the operation, the amount of time the patients stayed in the Postanesthesia Care Unit, the 8 hours, 16 hours, and 24 hours total dosage of oxycodone, the resting and exercise Visual Analog Scale (VAS) pain scores at 8 hours, 16 hours, and 24 hours after surgery, postoperative adverse events, and safety. RESULTS: The QLB+G group identified areas  of cold hypoesthesia after the block, but there were no areas of cold hypoesthesia in the G group. The consumption of oxycodone in the 8 hours, 16 hours, and 24 hours after the surgery and the consumption of sufentanil during the surgery were significantly smaller in the QLB+G group (P < 0.05). The QLB+G group have lower pain scores at the resting 8 hours and exercise 8 hours, 16 hours, and 24 hours after the surgery (P < 0.05). The 2 groups have comparable safety in the study. LIMITATIONS: This study only tested the areas of cold hypoesthesia after the QLB, but not tested the area of sensory loss. Using ice to test for hypoesthesia is subjective, and may not reflect the actual area of the block. CONCLUSIONS: Ultrasound-guided oblique sagittal anterior QLB can reduce the analgesics required after and during THA and the postoperative VAS pain scores, but it rarely affects muscle strength.

Silencing the expression of lncRNA SNHG15 may be a novel therapeutic approach in human breast cancer through regulating miR-345-5p.

Background: Long noncoding RNA (lncRNA) short nucleolar RNA host gene 15 (SNHG15) has been found to have an oncogenic function in numerous malignancies. Nevertheless, the biological function and regulatory mechanisms of SNHG15 in breast cancer have not been fully elucidated. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of SNHG15 and in MDA-MB-231 breast cancer cells. The expression of SNHG15 was silenced using small interfering RNA (siRNA) technology. The proliferation and migration of the cells were examined by colony formation assays, cell counting kit 8 (CCK-8) assays, and transwell assays. For the zebrafish xenograft injection experiments, cultured cells labelled with the fluorescent dye CM-DiI were injected into the perivitelline space of the larvae. Results: This present study revealed that the expression of lncRNA SNHG15 (lnc-SNHG15) was significantly upregulated in breast cancer cells, and its overexpression was associated with the tumor. The relative expression of lnc-SNHG15 could be downregulated using siRNAs, and silencing lnc-SNHG15 inhibited the proliferation and the migration of MDA-MB-231 cells. In vivo experiments using the zebrafish xenograft model showed similar results. Mechanistically, the knockdown effect of lnc-SNHG15 could be restored by inhibiting the expression of the miR-345-5p, confirming the negative regulation between lnc-SNHG15 and miR-345-5p. Interestingly, cisplatin treatment combined with SNHG15 knockdown effectively inhibited MDA-MB-231 cell proliferation and migration in the zebrafish xenograft compared to negative controls. Conclusions: In conclusion, lnc-SNHG15 knockdown increased miR-345-5p expression and negated cisplatin resistance in breast cancer cells, and thus, lnc-SNHG15 may be a potential novel target for breast cancer therapy.

TRPV1, Targeted by miR-338-3p, Induces Neuropathic Pain by Interacting with NECAB2.

A variety of studies have proposed that transient receptor potential vanilloid 1 (TRPV1) is involved in the progression of multiple diseases, including neuropathic pain. Although increased expression of TRPV1 in chronic constriction injury was described earlier, the underlying regulatory mechanisms of TRPV1 in neuropathic pain remain largely unknown. In our study, we constructed a chronic constriction injury (CCI) rat model to deeply analyze the mechanisms underlying TRPV1. RT-qPCR-indicated TRPV1 mRNA and protein expression were extremely upregulated in CCI rat dorsal spinal cord tissues. Then, TRPV1 was corroborated to interact with N-terminal EF-hand Ca2+-binding protein 2 (NECAB2). The mRNA and protein levels of NECAB2 were increased in CCI tissues. Moreover, TRPV1 and NECAB2 together regulated nociceptive procession-associated protein metabotropic glutamate receptor 5 (mGluR5), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and Ca2+ in isolated microglia of CCI rats. Moreover, TRPV1 upregulation apparently increased mechanical allodynia and thermal hyperalgesia as well as the expression of inflammation-associated genes (COX-2, TNF-α, and IL-6). In addition, downregulation of NECAB2 significantly decreased mechanical allodynia and thermal hyperalgesia as well as the expression of COX-2, TNF-α, and IL-6. Furthermore, TRPV1 was confirmed to be a downstream target of miR-338-3p. TRPV1 overexpression abolished the inhibitory effect by miR-338-3p elevation on neuropathic pain development. In summary, this study proved TRPV1, targeted by miR-338-3p, induced neuropathic pain by interacting with NECAB2, which provides a potential therapeutic target for neuropathic pain treatment.

The Analgesic Efficacy of Erector Spinae Plane Blocks in Patients Undergoing Posterior Lumbar Spinal Surgery for Lumbar Fracture.

OBJECTIVE: To investigate the postoperative analgesic efficacy of ultrasound-guided lumbar erector spinae plane (ESP) blocks in patients undergoing posterior lumbar spinal surgery for lumbar spinal fractures. METHODS: A total of 80 patients who were scheduled for posterior internal fixation for lumbar spinal fractures were divided into a patient-controlled analgesia (PCA) group or a combined ESP-PCA group. Numeric rating scale at rest and during movement, postoperative sufentanil consumption, and accumulative and effective bolus presses of PCA were recorded at 6, 12, 24, and 48 hours postoperatively. Numeric rating scale at rest and during movement was the primary outcome. Incidence of postoperative nausea and vomiting during the first 24-48 hours, pruritus and chronic postoperative pain, and dose of pethidine for rescue analgesia were also recorded. RESULTS: Numeric rating scale at rest and during movement at 6, 12, and 24 hours was lower in the ESP-PCA group (P < 0.001, P < 0.001, P = 0.0016 at rest; all P < 0.001 during movement). Lumbar ESP blocks diminished accumulative bolus presses and effective bolus presses of PCA at 6, 12, 24, and 48 hours postoperatively. Besides, patients in the ESP-PCA group had fewer demands for sufentanil and pethidine. The incidence of postoperative nausea and vomiting in the ESP-PCA group was lower than that in PCA group. CONCLUSIONS: PCA combined with lumbar ESP blocks provided superior postoperative analgesia for patients with lumbar spinal fractures treated with posterior internal fixation. Lumbar ESP blocks decreased postoperative opioid consumption and incidence of postoperative nausea and vomiting, thereby enhancing postoperative recovery.

Changes of Opioid Consumption After Lumbar Fusion Using Ultrasound-Guided Lumbar Erector Spinae Plane Block: A Randomized Controlled Trial.

BACKGROUND: The erector spinae plane block (ESPB) is gaining popularity in lumbar fusion for postoperative pain management. OBJECTIVES: The aim of this study was to investigate the changes of opioid consumption after surgery, the range of cold temperature sensory blockade, pain, and safety. STUDY DESIGN: Randomized controlled study. SETTING: Single center. METHODS: Patients who were randomized to ESPB with 0.375% ropivacaine (ropivacaine group) and mock ESPB with saline (saline group) and underwent posterior lumbar fusion surgery. The primary endpoint was the total dosage of oxycodone. Secondary endpoints included remifentanil consumption, postoperative pain scores, postoperative adverse events, safety, and range of cold hypoesthesia. RESULTS: Oxycodone consumption in the first 48 hours after surgery was significantly lower in the ropivacaine group than in the saline group (P < 0.05). Remifentanil consumption was significantly lower in the ropivacaine group compared with the saline group during the surgery (0.69 ± 0.03 mg vs. 0.85 ± 0.04 mg, P < 0.05). The areas of cold hypoesthesia were identified in the ropivacaine group after the block, but not in the saline group. Rest and exercise pain scores after surgery were significantly lower in the ropivacaine group than in the saline group (P < 0.05). The overall safety of the ropivacaine group were generally comparable to that of the saline group. LIMITATIONS: The areas of cold hypoesthesia were tested at different time points after ESPB, but the area of sensory loss was not tested, and the recovery of postoperative sensation was not recorded. In addition, we tested only temperature sensation, but not acupuncture pain. CONCLUSIONS: Ultrasound-guided lumbar ESPB reduces the amount of analgesics required during and after lumbar fusion and reduces the postoperative Visual Analog Scale pain score.

Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study.

AIMS: Dexmedetomidine (Dex) has been noted to have neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the effect of Dex in diabetic hyperglycemia-exacerbated cerebral I/R injury and its underlying mechanism remain unclear. MAIN METHODS: The infarct volume and brain edema were evaluated by 2,3,5-triphenyltetrazolium chloride staining and standard wet-dry method. Modified neurological severity score was utilized to assess the neurological deficits. The oxidative stress and inflammation were evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and cell count kit-8 were applied to measure cell apoptosis and viability. KEY FINDINGS: Dex treatment reduced infarct volume, decreased brain water content and improved neurological deficit in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Dex treatment reduced the levels of ROS, MDA, TNF-α and IL-1ß in the entire middle cerebral artery territory of diabetic mice subjected to MCAO/R, as well as in primary culture of mouse hippocampal neurons stimulated with 50 mM glucose and oxygen glucose deprivation/reperfusion. Dex treatment inhibited neuronal apoptosis induced by diabetic hyperglycemia-exacerbated cerebral I/R injury. Dex upregulated nuclear factor of activated T-cells 5 (NFAT5) and Sirtuin 1 (SIRT1) expression, induced NF-E2-related factor 2 (Nrf2) translocation from cytoplasm to nucleus and inhibited the acetylation of Nrf2. However, these changes triggered by Dex treatment were abrogated by NFAT5 knockdown. SIGNIFICANCE: Dex protects against diabetic hyperglycemia-exacerbated cerebral I/R injury through attenuation of oxidative stress, inflammation and apoptosis. The underlying mechanism is at least the NFAT5/SIRT1/Nrf2 signaling pathway dependent.

MicroRNA-137 and its downstream target LSD1 inversely regulate anesthetics-induced neurotoxicity in dorsal root ganglion neurons.

PURPOSE: Anesthetic reagents, such as bupivacaine (Bv), induce significant neurotoxicity in dorsal root ganglion neurons (DRGNs). In this study, we investigated the expression, function and cross-association of microRNA-137-3p (miR-137-3p) and lysine (K)-specific demethylase 1A (LSD1) in a murine model of Bv-induced neural injury in DRGNs. METHODS: Murine DRGNs were culture in vitro and treated with Bv. QPCR was used to evaluate miR-137-3p expression in Bv-injured DRGNs. MiR-137-3p was genetically downregulated to evaluate its rescuing effect on Bv-induced DRGN apoptosis and neurite retraction. The association of miR-137-3p on its downstream target, LSD1 coding gene KDM1A, was evaluated by dual-luciferase activity assay and qPCR. In miR-137-3p-downregulated DRGNs, KDM1A was inhibited to evaluate its involvement in miR-137-3p-mediated modulation on Bv-induced DRGN neurotoxicity. Furthermore, KDM1A expression in Bv-injured DRGN was evaluated by qPCR, and LSD1 was overexpressed in DRGN to evaluate its direct effect on Bv-induced neurotoxicity. RESULTS: MiR-137-3p was upregulated in Bv-injured DRGNs. MiR-137-3p downregulation rescued Bv-induced DRGN apoptosis and neurite retraction. LSD1 was demonstrated to be downstream to, and inversely modulated by miR-137-3p in DRGN. In Bv-injured DRGNs, LSD1 downregulation reversed miR-137-3p-downregualtion-induced neural protection. Furthermore, LSD1 upregulation directly rescued Bv-induced apoptosis and neurite retraction in DRGNs. CONCLUSIONS: MiR-137-3p and its downstream target LSD1 are inversely associated to regulate anesthetics-induced neurotoxicity in DRGN. This signaling pathway may be a therapeutic candidate to reduce anesthetics-induced neurological damage in human patients.

Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells.

Dicyclohexyl phthalate (DCHP) is one of the phthalate plasticizers. The objective of the present study was to investigate the effects of DCHP on fetal Leydig cell distribution and function as well as testis development. Female pregnant Sprague Dawley dams orally received vehicle (corn oil, control) or DCHP (10, 100, and 500 mg/kg/day) from gestational day (GD) 12 to GD 21. At GD 21.5, testicular testosterone production, fetal Leydig cell number and distribution, testicular gene and protein expression levels were examined. DCHP administration produced a dose-dependent increase of the incidence of multinucleated gonocytes at ≥ 100 mg/kg. DCHP dose-dependently increased abnormal fetal Leydig cell aggregation and decreased fetal Leydig cell size, cytoplasmic size, and nuclear size at ≥ 10 mg/kg. DCHP reduced the expression levels of steroidogenesis-related genes (including Star, Hsd3b1, and Hsd17b3) and testis-descent related gene Insl3 as well as protein levels of 3ß-hydroxysteroid dehydrogenase 1 (HSD3B1) and insulin-like 3 (INSL3) at ≥ 10 mg/kg. DCHP significantly inhibited testicular testosterone levels at ≥ 100 mg/kg. The results indicate that in utero exposure to DCHP affects the expression levels of fetal Leydig cell steroidogenic genes and results in the occurrence of multinucleated gonocytes and Leydig cell aggregation.

Comparison of the Effects of Dibutyl and Monobutyl Phthalates on the Steroidogenesis of Rat Immature Leydig Cells.

Dibutyl phthalate (DBP) is a widely used synthetic phthalic diester and monobutyl phthalate (MBP) is its main metabolite. DBP can be released into the environment and potentially disrupting mammalian male reproductive endocrine system. However, the potencies of DBP and MBP to inhibit Leydig cell steroidogenesis and their possible mechanisms are not clear. Immature Leydig cells isolated from rats were cultured with 0.05-50 µM DBP or MBP for 3 h in combination with testosterone synthesis regulator or intermediate. The concentrations of 5α-androstanediol and testosterone in the media were measured, and the mRNA levels of the androgen biosynthetic genes were detected by qPCR. The direct actions of DBP or MBP on CYP11A1, CYP17A1, SRD5A1, and AKR1C14 activities were measured. MBP inhibited androgen production by the immature Leydig cell at as low as 50 nM, while 50 µM was required for DBP to suppress its androgen production. MBP mainly downregulated Cyp11a1 and Hsd3b1 expression levels at 50 nM. However, 50 µM DBP downregulated Star, Hsd3b1, and Hsd17b3 expression levels and directly inhibited CYP11A1 and CYP17A1 activities. In conclusion, DBP is metabolized to more potent inhibitor MBP that downregulated the expression levels of some androgen biosynthetic enzymes.

Response to the Svingen Comments on Li et al. Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells. Int. J. Environ. Res. Public Health, 2016, 13, 246.

Referring to the comments of Svingen [1] on our latest publication about Effects of in utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells [2], we would like to give some comments.[...].