miR­3120/Hsc70 participates in forced swim stress­induced mechanical hyperalgesia in rats in an inflammatory state.

The heat shock cognate 71 kDa protein (Hsc70) is a stress­inducible ATPase that can protect cells against harmful stimuli. Transient receptor potential vanilloid 1 (TRPV1) is a well­documented nociceptor. Notably, Hsc70 can inhibit TRPV1 expression and function, suggesting that Hsc70 may have pain regulation potential. However, the role of Hsc70 in stress­induced hyperalgesia remains unclear. In the present study, the participation of Hsc70 and its regulator microRNA (miR)­3120 were investigated in forced swim (FS) stress­induced mechanical hyperalgesia in rats in an inflammatory state. Complete Freund's adjuvant (CFA) hind paw injection was performed to induce inflammatory pain in rats (CFA rats). Furthermore, in FS + CFA rats, FS stress was performed for 3 days before CFA injection. The levels of Hsc70, miR­3120 and their downstream molecule TRPV1 were measured in the dorsal root ganglion (DRG) with western blotting, immunofluorescence, reverse transcription­quantitative polymerase chain reaction and fluorescence in situ hybridization. The results revealed that FS stress significantly exacerbated CFA­induced mechanical pain. Furthermore, CFA upregulated Hsc70 and TRPV1 expression, which was partially inhibited or further enhanced by FS stress, respectively. In FS + CFA rats, intrathecal injection of a lentiviral vector overexpressing Hsc70 (LV­Hsc70) could decrease TRPV1 expression and improve the mechanical pain. Additionally, the expression levels of miR­3120, a regulator of Hsc70, were markedly upregulated on day 3 following FS stress. Finally, miR­3120 was identified to be colocalized with Hsc70 and expressed in all sizes of DRG neurons. In CFA rats, DRG injection of miR­3120 agomir to induce overexpression of miR­3120 resulted in similar TRPV1 expression and behavioral changes as those caused by FS stress, which were abolished in the presence of LV­Hsc70. These findings suggested that miR­3120/Hsc70 may participate in FS stress­induced mechanical hyperalgesia in rats in an inflammatory state, possibly via disinhibiting TRPV1 expression in the DRG neurons.

Satellite glial cell-secreted exosomes after in-vitro oxaliplatin treatment presents a pro-nociceptive effect for dorsal root ganglion neurons and induce mechanical hypersensitivity in naïve mice.

BACKGROUND: The pathophysiological mechanism underlying chemotherapy-induced neuropathic pain (CINP) remains unclear. Sensory neuronal hypersensitivity in the dorsal root ganglion (DRG) is essential for the onset and maintenance of chronic pain. Satellite glial cells (SGCs) in the DRG potentially affect the function of sensory neurons, possibly by mediating extracellular or paracrine signaling. Exosomes play an essential role in cell-cell communication. However, the role of SGC-secreted exosomes in glia-neuron communication and CINP remains unclear. METHODS: SGCs and sensory neurons were cultured from the DRG of mice. The SGCs were treated with 4 µM oxaliplatin for 24 h. Glial fibrillary acid protein (GFAP) and connexin-43 (Cx-43) expressions in the SGCs were examined with immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) detected cytokine release in the SGCs after oxaliplatin treatment. Subsequently, SGC-secreted exosomes were collected using ultracentrifugation and identified by nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Subsequently, DRG neurons were incubated with SGC-secreted exosomes for 24 h. The percentage of reactive oxygen species (ROS)-positive neurons was detected using flow cytometry, and acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) expression were examined by western blotting. SGC-secreted exosomes were intrathecally injected into naïve mice. The mechanical withdrawal threshold was assessed 24, 48, and 72 h following the injection. TRPV1 expression in the DRG was examined 72 h after intrathecal injection. Furthermore, differentially expressed (DE) miRNAs within the SGC-secreted exosomes were detected using RNA sequencing and bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses were performed to predict the function of the target genes of DE miRNAs. Finally, the DE miRNAs with pain regulation potential were identified in silico. RESULTS: After in-vitro oxaliplatin treatment, ICC showed an increase in the immunoreactivity of GFAP and Cx-43 in the SGCs. ELISA results suggested an increased release of tumor necrosis factor-α and interleukin (IL)-1ß, but a decreased release of IL-10. Oxaliplatin treatment increased the secretion of exosomes in the SGCs from 4.34 to 5.99 × 1011 (particles/ml). The exosome-specific markers CD9 and TSG101 were positive, whereas calnexin was negative for the obtained exosomes. Additionally, the SGC-secreted exosomes were endocytosed by DRG neurons after co-incubation. Moreover, after incubation with conditioned SGC-secreted exosomes (after 4 µM oxaliplatin treatment), the percentage of ROS-positive DRG neurons increased and ASIC3 and TRPV1 expressions were upregulated. After the intrathecal injection of the conditioned SGC-secreted exosomes, the mice presented with mechanical hypersensitivity and TRPV1 expression upregulation in the DRG. Notably, 25 and 120 significantly upregulated and downregulated miRNAs, respectively, were identified in the conditioned SGC-secreted exosomes. When predicting the function of target genes of DE miRNAs, certain GO terms, such as synapse organization, neurogenesis regulation, histone modification, and pain-related KEGG or Reactome pathways, including vascular endothelial growth factor A-vascular endothelial growth factor receptor 2, mammalian target of rapamycin, and mitogen-activated protein kinase signaling pathways, related to nervous system function were predicted. Finally, 27 pain regulation-related miRNAs, including miR-324-3p, miR-181a-5p, and miR-122-5p, were identified in silico. CONCLUSION: Our study demonstrates that SGC-secreted exosomes after in-vitro oxaliplatin treatment present a pro-nociceptive effect for DRG neurons and induce mechanical hypersensitivity in naïve mice, possibly via the contained miRNA cargo. Identifying the candidate miRNAs and verifying their functions in vivo are required to elucidate the exosomes mediating 'glia-neuron' communication under CINP condition.

The effects of fentanyl, oxycodone, and butorphanol on gastrointestinal function in patients undergoing laparoscopic hysterectomy: a prospective, double-blind, randomized controlled trial.

BACKGROUND: Perioperative opioid use is associated with postoperative bowel dysfunction, which causes longer hospital stay and higher healthcare costs. This study aimed to investigate the effect of the equivalent doses of fentanyl, oxycodone, and butorphanol on bowel function in patients undergoing laparoscopic hysterectomy. METHODS: In this randomized controlled trial, 135 patients undergoing laparoscopic hysterectomy received postoperative intravenous patient-controlled analgesia (IV-PCA) with fentanyl 8.3 µg/kg, butorphanol 0.16 mg/kg, and oxycodone 0.5 mg/kg (1: 20: 60), respectively. The primary outcome measure was the recovery of bowel function. We also evaluated and recorded the following nine indicators: pain score, sedation level, leukocyte count, percentage of neutrophils, plasma potassium levels, time to first ambulation, postoperative side effects, patients' satisfaction, and postoperative hospital length of stay. RESULTS: The mean time to flatus was significantly prolonged in Group B (45.2 ± 11.6 h) compared with Group F (33.1 ± 11.2 h, P < 0.001) and Group O (36.2 ± 10.9 h, P = 0.001). The incidence of somnolence and dizziness prove higher in Group B (P < 0.001). No statistical difference was observed in the mean time to tolerate oral diet, time to defecation, analgesic outcome, satisfaction score, time to first ambulation, and postoperative hospital length of stay. CONCLUSIONS: Compared with fentanyl and oxycodone, butorphanol prolonged the recovery of bowel function with more severe somnolence and dizziness, suggesting that butorphanol is not well suitable for IV-PCA in patients undergoing laparoscopic hysterectomy. TRIAL REGISTRATION: ClinicalTrials.gov- NCT04295109 . Date of registration: March, 2020.

Downregulation of HSPA12A underlies myotoxicity of local anesthetic agent bupivacaine through inhibiting PGC1α-mediated mitochondrial integrity.

Local anesthetics (LAs) are widely used for intraoperative anesthesia and postoperative analgesia. However, LAs (e.g. Bupivacaine) can evoke myotoxicity that closely associated to mitochondrial damage. PGC1a is a mast co-factor for mitochondrial quality control. We have recently demonstrated that PGC1a can be activated by HSPA12A in hepatocytes, suggesting a possibility that HSPA12A protects from LAs myotoxicity through activating PGC1α-mediated mitochondrial integrity. Here, we reported that HSPA12A was downregulated during Bupivacaine-induced myotoxicity in skeletal muscles of mice in vivo and C2c12 myoblast cultures in vitro. Intriguingly, overexpression of HSPA12A attenuated the Bupivacaine-induced C2c12 cell death. We also noticed that the Bupivacaine-induced decrease of glucose consumption and ATP production was improved by HSPA12A overexpression. Moreover, overexpression of HSPA12A in C2c12 cells attenuated the Bupivacaine-induced decrease of mitochondrial contents and increase of mitochondrial fragmentation. The Bupivacaine-induced reduction of PGC1α expression and nuclear localization was markedly attenuated by HSPA12A overexpression. Importantly, pretreatment with a selective PGC1α inhibitor (SR-18292) abolished the protection of HSPA12A from Bupivacaine-induced death and mitochondrial loss in C2c12 cells. Altogether, the findings indicate that downregulation of HSPA12A underlies myotoxicity of Local anesthetic agent Bupivacaine through inhibiting PGC1α-mediated Mitochondrial Integrity. Thus, HSPA12A might represent a viable strategy for preventing myotoxicity of LAs.

The Role of the Gastrointestinal System in Neuroinvasion by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most devastating pandemics in history. SARS-CoV-2 has infected more than 100 million people worldwide, leading to more than 3.5 million deaths. Initially, the clinical symptoms of SARS-CoV-2 infection were thought to be restricted to the respiratory system. However, further studies have revealed that SARS-CoV-2 can also afflict multiple other organs, including the gastrointestinal tract and central nervous system. The number of gastrointestinal and neurological manifestations after SARS-CoV-2 infection has been rapidly increasing. Most importantly, patients infected with SARS-CoV-2 often exhibit comorbid symptoms in the gastrointestinal and neurological systems. This review aims to explore the pathophysiological mechanisms of neuroinvasion by SARS-CoV-2. SARS-CoV-2 may affect the nervous system by invading the gastrointestinal system. We hope that this review can provide novel ideas for the clinical treatment of the neurological symptoms of SARS-CoV-2 infection and references for developing prevention and treatment strategies.

Proteomic analysis reveals that naturally produced citral can significantly disturb physiological and metabolic processes in the rice blast fungus Magnaporthe oryzae.

Rice blast (Magnaporthe oryzae), a major fungal disease in rice producing areas all over the world as well as in China, seriously affects the safety of rice production. Citral, a mixture of Z/E and trans isomers, is a natural acycloid monoterpene compound with good bacteriostatic effect on rice blast. To further investigate the underlying molecular mechanism, a comparative proteomics analysis was conducted between citral-treated and non-treated M. oryzae spores through two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Our analysis identified 1600-1800 proteins from M. oryzae ZB15, of which 147 were differentially expressed in 100 µg/mL citral-treated samples relative to the control group. Among these differentially expressed proteins (DEPs), 40 proteins showed significantly different expression. GO enrichment and NCBI conserved domains database analysis showed that the main groups of the cellular component were cytoplasm (23.33%), and the major molecular function categories were ion binding (31.37%), and the major categories of biological processes included small molecule metabolic process (22.22%) and transport (13.89%). Further analysis found that down-regulated proteins included the tubulin α chain, ATP synthase subunit ß and malate dehydrogenase, while the tubulin ß, enolase were upregulated. These DEPs could possibly limit the availability of energy required for many cellular processes and result in various physiological adaptions of M. oryzae. This study represents the first proteomic analysis of M. oryzae treated by citral and will help to uncover the mode-of-action of this biologically active compound against M. oryzae. These findings have practical implications with respect to the use of citral for fungal disease control.

Combination of nitrous oxide and the modified inflation-deflation method for identifying the intersegmental plane in segmentectomy: A randomized controlled trial.

BACKGROUND: During thoracoscopic segmentectomy, accurately and rapidly identifying the intersegmental plane (ISP) is of great importance. This study aimed to investigate the effect and safety of a nitrous oxide (N2 O)/oxygen (O2 ) inspired mixture on the appearance time of the ISP (TISP ) via the modified inflation-deflation method. METHODS: A total of 65 participants who underwent segmentectomy were randomized into three groups: 75% N2 O (n = 24), 50% N2 O (n = 23) or 0% N2 O (n = 18). The 75% N2 O group received a gas mixture of N2 O/O2 (Fio2 = 0.25), the 50% N2 O group received N2 O/O2 (Fio2 = 0.5), and the 0% N2 O group received 100% oxygen during lung expansion. The appearance time of satisfactory and ideal planes was recorded. Furthermore, arterial blood gas at breathing room air, one-lung ventilation (OLV) before lung expansion, 5 and 15 min after lung expansion were also recorded. RESULTS: TISP was significantly shorter in the 75% N2 O group (320.2 ± 65.9 s) compared with that of the 50% N2 O group (552.4 ± 88.9 s, p < 0.001) and the 0% N2 O group (968.3 ± 85.5 s, p < 0.001), while the 50% N2 O group was shorter than that of the 0% N2 O group (p < 0.001). Arterial oxygenation was significantly improved in the 0% N2 O group only after lung expansion, before which there were no differences in mean PaO2 values among groups. CONCLUSIONS: The use of N2 O in the inspired gas mixture during lung expansion is an applicable strategy to rapidly identify the ISP via the modified inflation-deflation method without any adverse effect on OLV related arterial oxygenation during segmentectomy.

Is SARS-CoV-2 vaccination safe and effective for elderly individuals with neurodegenerative diseases?

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) poses a substantial threat to the lives of the elderly, especially those with neurodegenerative diseases, and vaccination against viral infections is recognized as an effective measure to reduce mortality. However, elderly patients with neurodegenerative diseases often suffer from abnormal immune function and take multiple medications, which may complicate the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Currently, there is no expert consensus on whether SARS-CoV-2 vaccines are suitable for patients with neurodegenerative diseases. AREAS COVERED: We searched Pubmed to conduct a systematic review of published studies, case reports, reviews, meta-analyses, and expert guidelines on the impact of SARS-CoV-2 on neurodegenerative diseases and the latest developments in COVID-19 vaccines. We also summarized the interaction between vaccines and age-related neurodegenerative diseases. The compatibility of future SARS-CoV-2 vaccines with neurodegenerative diseases is discussed. EXPERT OPINION: Vaccines enable the body to produce immunity by activating the body's immune response. The pathogenesis and treatment of neurodegenerative diseases is complex, and these diseases often involve abnormal immune function, which can substantially affect the safety and effectiveness of vaccines. In short, this article provides recommendations for the use of vaccine candidates in patients with neurodegenerative diseases.

Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

The benefits and harms of corticosteroids for patients with severe coronavirus disease 2019 (COVID-19) remain unclear. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from December 31, 2019 to October 1, 2020 to identify randomized controlled trials (RCTs) that evaluated corticosteroids in severe COVID-19 patients. The primary outcome was all-cause mortality at the longest follow-up. Secondary outcomes included a composite disease progression (progression to intubation, ventilation, extracorporeal membrane oxygenation, ICU transfer, or death among those not ventilated at enrollment) and incidence of serious adverse events. A random-effects model was applied to calculate risk ratio (RR) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of the evidence. Seven RCTs involving 6250 patients were included, of which the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial comprised nearly 78% of all included subjects. Results showed that corticosteroids were associated with a decreased all-cause mortality (27.3 vs. 31.1%; RR: 0.85; 95% CI: 0.73-0.99; P = 0.04; low-certainty evidence). Trial sequential analysis suggested that more trials were still required to confirm the results. However, such survival benefit was absent if RECOVERY trial was excluded (RR: 0.83; 95% CI: 0.65-1.06; P = 0.13). Furthermore, corticosteroids decreased the occurrence of composite disease progression (30.6 vs. 33.3%; RR: 0.77; 95% CI: 0.64-0.92; P = 0.005), but not increased the incidence of serious adverse events (3.5 vs. 3.4%; RR: 1.16; 95% CI: 0.39-3.43; P = 0.79).

The Effectiveness and Safety of Intravenous Dexmedetomidine of Different Concentrations Combined with Butorphanol for Post-Caesarean Section Analgesia: A Randomized Controlled Trial.

PURPOSE: The present study aimed to determine the effectiveness of intravenous dexmedetomidine of different concentrations and to evaluate its maternal and neonatal safety when combined with butorphanol in parturients undergoing cesarean section. PATIENTS AND METHODS: A total of 114 parturients between 24 and 43 years of age, with singleton pregnancy who underwent elective cesarean section under epidural anesthesia, were randomly allocated to four groups: group C received 0.9% sodium chloride after delivery, followed by butorphanol (3 µg·kg-1·h-1); patients in groups D1, D2, and D3 received 0.5 µg·kg-1·h-1 dexmedetomidine after delivery, followed by butorphanol (3 µg·kg-1·h-1) combined with dexmedetomidine 0.03, 0.05, and 0.08 µg·kg-1·h-1, respectively. The primary outcome was the visual analogue scale (VAS) score at 6 h after delivery when patients were at rest. Secondary outcome measures included VAS after delivery when patients were on movement and uterine cramping, Ramsay sedation scale (RSS), relative infant dose (RID) of dexmedetomidine, satisfaction with analgesia after surgery and symptoms of CNS depression in neonates. RESULTS: There were no significant differences in patient characteristics among the groups (P > 0.05). The VAS at all timepoints after delivery in groups D2 and D3 were significantly lower than in groups C and D1 (P < 0.001). RSS scores were clearly higher in group D3 than in the other three groups at 6 h and 12 h (P < 0.0001). RID in groups D1, D2, and D3 was 0.171%, 0.197%, and 0.370%, respectively. Compared with group D1, RID was higher in group D3 (P = 0.0079). Degree of satisfaction with analgesia was higher in groups D2 and D3 (P < 0.005). CONCLUSION: Continuous intravenous infusion of 0.05 µg·kg-1·h-1 dexmedetomidine combined with 3 µg·kg-1·h-1 butorphanol could be safely applied in healthy parturients with satisfactory analgesia after cesarean section without changes in sedation.

Less Social Support for Patients With COVID-19: Comparison With the Experience of Nurses.

Context: Since December 2019, more than 80,000 patients have been diagnosed with coronavirus disease 2019 (COVID-19) in China. Social support status of COVID-19 patients, especially the impact of social support on their psychological status and quality of life, needs to be addressed with increasing concern. Objectives: In this study, we used social support rating scale (SSRS) to investigate the social support in COVID-19 patients and nurses. Methods: The present study included 186 COVID-19 patients at a Wuhan mobile cabin hospital and 234 nurses at a Wuhan COVID-19 control center. Responses to a mobile phone app-based questionnaire about social support, anxiety, depression, and quality of life were recorded and evaluated. Results: COVID-19 patients scored significantly lower than nurses did on the Social Support Rating Scale (SSRS). Among these patients, 33.9% had anxiety symptoms, while 23.7% had depression symptoms. Overall SSRS, subjective social support scores and objective support scores of patients with anxiety were lower than those of patients without anxiety. This result was also found in depression. In addition, all dimensions of social support were positively correlated with quality of life. Interestingly, in all dimensions of social support, subjective support was found to be an independent predictive factor for anxiety, depression, and quality of life, whereas objective support was a predictive factor for quality of life, but not for anxiety and depression via regression analysis. Conclusion: Medical staffs should pay attention to the subjective feelings of patients and make COVID-19 patients feel respected, supported, and understood from the perspective of subjective support, which may greatly benefit patients, alleviate their anxiety and depression, and improve their quality of life.

Comparison of Deep and Moderate Neuromuscular Blockade on Intestinal Mucosal Barrier in Laparoscopic Gastrectomy: A Prospective, Randomized, Double-Blind Clinical Trial.

Deep neuromuscular blockade (NMB) improves the surgical conditions and is benefit for the postoperative recovery after laparoscopic surgery. However, the mechanisms of deep NMB in promoting the recovery of intestinal function have not been completely investigated. The objective of our study was to determine the impact of the deep NMB and moderate NMB strategy on the intestinal barrier function after laparoscopic gastrectomy. We collected patients undergoing elective laparoscopic gastrectomy. Patients were randomized to deep NMB (post-tetanic count 1-2) vs. moderate NMB (train-of-four count 1-2) during the surgery. Primary outcomes were time to flatus, serum diamine oxidase (DAO) and D-lactate, and gut microbiota. Other outcomes were surgical condition scores, postoperative visual analog pain scores, and length of hospital stay. Ninety patients in deep NMB group and sixty patients in moderate NMB group completed the study. Main results showed that the time to flatus was decreased in deep NMB group (74 ± 32 h) than that in moderate NMB group (93 ± 52 h, P = 0.006). The level of serum D-lactate was statistically increased in the moderate NMB group than that in the deep NMB group (1,209 ± 224 vs. 1,164 ± 185 ng/ml, p < 0.001). But no significant differences could be detected in the level of DAO between the groups. Additionally, the 16s rRNA analysis indicated that gut microbiota were similar in Alpha diversity but distinct in Beta diversity. Furthermore, the beneficial bacteria, such as genus Lactobacillus and Bifidobacterium, were more abundant in the deep NMB group, while the potentially harmful bacteria were more abundant in the moderate NMB group. Our findings suggested that the intestinal mucosal barrier and gut microbiota were better preserved in deep NMB, which greatly improved the postoperative recovery of intestinal function after laparoscopic gastrectomy.

Vicarious traumatization in the general public, members, and non-members of medical teams aiding in COVID-19 control.

Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 (COVID-19). A large number of medical staff was sent to Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public and 526 nurses (i.e., 234 front-line nurses and 292 non-front-line nurses) to evaluate vicarious traumatization scores via a mobile app-based questionnaire. Front-line nurses are engaged in the process of providing care for patients with COVID-19. The results showed that the vicarious traumatization scores for front-line nurses including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (P < 0.001). Interestingly, the vicarious traumatization scores of the general public were significantly higher than those of the front-line nurses (P < 0.001); however, no statistical difference was observed compared to the scores of non-front-line nurses (P > 0.05). Therefore, increased attention should be paid to the psychological problems of the medical staff, especially non-front-line nurses, and general public under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat vicarious traumatization in medical staff and general public are extremely necessary.

Dexamethasone and dexmedetomidine as adjuvants to local anesthetic mixture in intercostal nerve block for thoracoscopic pneumonectomy: a prospective randomized study.

BACKGROUND AND OBJECTIVES: Perineural dexamethasone or dexmedetomidine prolongs the duration of single-injection peripheral nerve block when added to the local anesthetic solution. In a randomized, controlled, double-blinded study in patients undergoing thoracoscopic pneumonectomy, we tested the hypothesis that combined perineural dexamethasone and dexmedetomidine prolonged the duration of analgesia as compared with either perineural dexamethasone or perineural dexmedetomidine after intercostal nerve block (INB). METHODS: Eighty patients were randomized to receive INB using 28 mL 0.5% ropivacaine, with 2 mL normal saline (R group), with 10 mg dexamethasone in 2 mL (RS group) or 1 µg/kg dexmedetomidine in 2 mL (RM group), or with 1 µg/kg dexmedetomidine and 10 mg dexamethasone in 2 mL (RSM group) administrated perineurally. The INB was performed by the surgeon under thoracoscopic direct vision; a total of six intercostal spaces were involved, each with an injection of 5 mL. The primary outcome was the duration of analgesia. Secondary outcomes included total postoperative fentanyl consumption, visual analog scale pain score and safety assessment (adverse effects). RESULTS: The duration of analgesia in RSM (824.2±105.1 min) was longer than that in RS (611.5±133.0 min), RM (602.5±108.5 min) and R (440.0±109.6 min) (p<0.001). Total postoperative fentanyl consumption was lower in RSM (106.0±84.0 µg) compared with RS (243.0±175.2 µg), RM (237.0±98.7 µg) and R (369.0±134.2 µg) (p<0.001). No significant difference was observed in the incidences of adverse effects between the four groups. CONCLUSION: The addition of combined perineural dexmedetomidine and dexamethasone to ropivacaine for INB seemed to be an attractive method for prolonged analgesia with almost no adverse effects. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17012183.

A Comparative Study of Bolus Norepinephrine, Phenylephrine, and Ephedrine for the Treatment of Maternal Hypotension in Parturients with Preeclampsia During Cesarean Delivery Under Spinal Anesthesia.

BACKGROUND This study aimed to compare the efficacy and safety of bolus norepinephrine, phenylephrine, and ephedrine in parturient with preeclampsia who had hypotension during cesarean delivery under spinal anesthesia. MATERIAL AND METHODS One hundred and sixty-six parturient women with preeclampsia who had a baseline systolic blood pressure (SBP) <80% during spinal anesthesia for cesarean section were divided into three treatment groups; bolus norepinephrine 4 µg (group N) (n=56), phenylephrine 50 µg (group P) (n=55), and ephedrine 4 mg (group E) (n=55). Primary outcomes included overall SBP and heart rate (HR) until delivery. Secondary outcomes included the incidence of tachycardia (HR >120 bpm), bradycardia (HR <60 bpm), hypertension (SBP >120% baseline), number of boluses of vasopressor required and episodes of hypotension, maternal side effects, and neonatal outcome. RESULTS Overall HR in group N was significantly increased compared with group P (80.5±12 vs. 76.6±6.9 bpm; P=0.04), and significantly lower compared with group E (80.5±12 vs. 84.9±7.1 bpm; P=0.02). Parturients in group N had fewer episodes of bradycardia compared with group P (3.6% vs. 21.8%; RR=0.26l; 95% CI, 0.07-0.73; P=0.004) and fewer episodes of tachycardia compared with group E (16.1% vs. 36.4%; RR 0.54; 95% CI, 0.29-0.90; P=0.02). CONCLUSIONS A bolus dose of norepinephrine showed similar efficacy to phenylephrine but improved maternal and neonatal safety in parturients with preeclampsia with hypotension during cesarean section under spinal anesthesia.

An inadvertent subarachnoid injection reversed by cerebrospinal fluid lavage for the treatment of chronic low back pain: A case report.

RATIONALE: We present a case of high spinal anesthesia after inadvertent injection of local anesthetics and corticosteroids into the subarachnoid space during attempted epidural injection. Cerebrospinal fluid (CSF) lavage is a suitable method for treatment. PATIENT CONCERNS: A 45-year-old woman presented with posterior thigh, leg, and ankle pain for >6 months and was treated with epidural injection. Five minutes after the third time of epidural injection, the patient complained loss of sensation and muscle strength in the lower extremities and abdominal area. DIAGNOSES: A high spinal anesthesia was confirmed by the patient loss of sensation and muscle strength in the lower extremities and abdominal area. INTERVENTIONS: CSF lavage was performed for treatment. OUTCOMES: After CSF lavage, the patient gradually returns to normal sensory and motor functions of lower limbs. On the fourth day, the patient sensed her physical function restoring gradually and was discharged uneventfully. At 4-month follow-up, the patient could have normal activities without obvious subsequent complications and any pain. LESSONS: We conclude that CSF lavage could be a helpful maneuver to clear lidocaine and betamethasone and avoid potential nerve damage caused by an unintentional intrathecal injection during an epidural injection for the treatment of chronic low back pain.

Efficacy and safety of norepinephrine versus phenylephrine for the management of maternal hypotension during cesarean delivery with spinal anesthesia: A systematic review and meta-analysis.

BACKGROUND: Phenylephrine is the current "gold standard' vasopressor used to treat maternal hypotension in women undergoing cesarean delivery with spinal anesthesia. Since 2015, various studies have explored the use of norepinephrine to manage maternal hypotension. We conducted this systematic review and meta-analysis of available randomized controlled trials (RCTs) to compare the efficacy and safety of norepinephrine and phenylephrine for the prevention and treatment of maternal hypotension. METHODS: A systematic literature search was conducted using electronic databases, including PubMed, MEDLINE, Embase (Embase.com), and the Cochrane CENTRAL register of controlled trials. Parturients underwent cesarean delivery with spinal anesthesia and received norepinephrine to prevent or treat hypotension were considered. Maternal outcomes, including incidences of hypotension, hypertension, bradycardia, intraoperative nausea and vomiting (IONV), maternal cardiac output (CO), and blood pressure (BP) control precision, as well as neonatal Apgar scores and umbilical cord blood analyses, were compared between groups. RESULTS: Three RCTs in 4 reports published between 2015 and 2018 were finally identified with a total of 294 parturients. We found there was no difference in effectiveness between norepinephrine and phenylephrine for the treatment of maternal hypotension (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.37-1.10, P = .11), and there was no difference in the occurrence of hypertension (OR 0.74; 95% CI 0.33-1.62, P = .45). Of note, compared to the phenylephrine group, parturients in the norepinephrine group were less likely to experience bradycardia (OR 0.29; 95% CI 0.12-0.68, P = .005) and IONV (OR 0.54; 95% CI, 0.29-0.99, P = .04). Further, we did not observe a difference between the two vasopressors in the incidence of neonatal Apgar scores < 7 at 1  and 5 minutes or in umbilical vein (UV) blood gas. However, evidence is insufficient to draw conclusions regarding the greater maternal CO and better BP control precision with the use of norepinephrine. CONCLUSION: This systematic review and meta-analysis shows norepinephrine provides similar efficacy to manage maternal hypotension compared to phenylephrine; additionally, showing advantage regarding certain side effects like bradycardia and IONV reduction. Accordingly, norepinephrine is a promising alternative to phenylephrine. However, before routine clinical application, more studies are warranted.

Doxorubicin Loaded Silica Nanoparticles with Dual Modification as a Tumor-Targeted Drug Delivery System for Colon Cancer Therapy.

In the following study, we describe the preparation and characterization of poly(ethylene glycol) (PEG) and biotin modified, doxorubicin (DOX) loaded silica nanoparticles (Dox/SLN-PEG-Biotin), which was employed as a drug delivery system for colon cancer therapy. The DOX/SLN-PEG-Biotin exhibited small particle size and low cytotoxicity in vitro. Moreover, the Dox releases from DOX/SLN-PEG-Biotin followed a redox-sensitive behavior. Biotin functionalized Dox/SLN-PEG-Biotin demonstrated tumor-targeted delivery of their payload, resulting in enhanced cellular uptake in HCT116 tumor cells and potentiated tumor accumulation in HCT116 tumor-bearing mice. In particular, in vivo anti-cancer assay confirmed that DOX/SLN-PEG-Biotin as a tumor-targeted delivery system exerted strong anti-cancer efficacy. Altogether, DOX chemotherapy using DOX/SLN-PEG-Biotin might be an effective strategy for improved treatment in colon cancer.

The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia.

Maternal hypotension commonly occurs during spinal anesthesia for cesarean delivery, with a decrease of systemic vascular resistance recognized as a significant contributor. Accordingly, counteracting this effect with a vasopressor that constricts arterial vessels is appropriate, and the pure α-adrenergic receptor agonist phenylephrine is the current gold standard for treatment. However, phenylephrine is associated with dose-dependent reflex bradycardia and decreased cardiac output, which can endanger the mother and fetus in certain circumstances. In recent years, the older, traditional vasopressor norepinephrine has attracted increasing attention owing to its mild ß-adrenergic effects in addition to its α-adrenergic effects. We search available literature for papers directly related to norepinephrine application in spinal anesthesia for elective cesarean delivery. Nine reports were found for norepinephrine use either alone or compared to phenylephrine. Results show that norepinephrine efficacy in rescuing maternal hypotension is similar to that of phenylephrine without obvious maternal or neonatal adverse outcomes, and with a lower incidence of bradycardia and greater cardiac output. In addition, either computer-controlled closed loop feedback infusion or manually-controlled variable-rate infusion of norepinephrine provides more precise blood pressure management than equipotent phenylephrine infusion or norepinephrine bolus. Thus, based on the limited available literature, norepinephrine appears to be a promising alternative to phenylephrine; however, before routine application begins, more favorable high-quality studies are warranted.

Fentanyl-induced respiratory depression is attenuated in pregnant patients.

BACKGROUND: Respiratory depression is a complication of intravenous fentanyl administration. The effect of pregnancy on respiratory depression following opioid administration is unclear. This study investigated the effect of pregnancy on fentanyl-induced respiratory depression. PATIENTS AND METHODS: Female patients were divided into three groups (n=20 per group): control group (non-pregnant and scheduled for laparoscopic surgery), early pregnancy group (pregnant for 45-60 days and scheduled for abortion), and postpartum group (5-7 days postpartum scheduled for complete curettage of uterine cavity). All patients received an intravenous infusion of fentanyl 2 µg/kg. Respiratory rate (RR), end-tidal pressure of carbon dioxide (PETCO2), and pulse oxygen saturation (SpO2) were recorded continuously from just before fentanyl infusion to 15 min after commencing infusion. Plasma levels of progesterone were measured. RESULTS: SpO2 levels in the early pregnancy and postpartum groups were significantly higher and the levels of RR and PETCO2 were significantly lower than the control group. RR and SpO2 levels were significantly decreased in all groups, whereas PETCO2 was significantly increased after fentanyl infusion. The rates of RR increase and SpO2 decrease were significantly faster in the control group than in the other groups. The lowest SpO2 after intravenous fentanyl administration was significantly positively correlated with plasma progesterone levels. CONCLUSION: Pregnancy improves fentanyl-induced respiratory depression, which may be associated with the increased levels of plasma progesterone.