Effects of an intraoperative intravenous Bolus Dose of Dexmedetomidine on postoperative catheter-related bladder discomfort in male patients undergoing transurethral resection of bladder tumors: a randomized, double-blind, controlled trial.

PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.

Clinical epidemiology and outcomes of patients with gastric intestinal metaplasia in the Los Angeles County System.

BACKGROUND: Gastric intestinal metaplasia (GIM) is a precursor to gastric adenocarcinoma (GAC). In the United States, there is no consensus on the utility of surveillance for GIM, and minority populations most affected by GAC are understudied. Our aims were to define clinical and endoscopic features, surveillance practices, and outcomes in patients with GIM in a multicenter safety-net system. METHODS: We identified patients with biopsy-proven GIM between 2016-2020 at the three medical centers comprising Los Angeles County Department of Health Services. Demographics, findings at index esophagogastroduodenoscopy (EGD) first showing GIM, recommended interval for repeat EGD, and findings at repeat EGD were abstracted. Descriptive statistics were performed to characterize our cohort. T-tests and chi-squared (χ2) tests were used to compare patients with and without multifocal GIM. RESULTS: There were 342 patients with newly-diagnosed biopsy-proven GIM, 18 (5.2%) of whom had GAC at index EGD. Hispanic patients comprised 71.8% of patients. For most patients (59%), repeat EGD was not recommended. If recommended, 2-3 years was the most common interval. During a median time to repeat EGD of 13 months and cumulative follow-up of 119 patient-years, 29.5% of patients underwent at least one repeat EGD, of whom 14% had multifocal GIM not previously detected. Progression to dysplasia or GAC was not detected in any patients. CONCLUSION: In a predominantly minority population with biopsy-proven GIM, there was a 5% incidence of GAC on index EGD. Though progression to neither dysplasia nor GAC was detected, there was significant variability in endoscopic sampling and surveillance practices.

The use of cervical cerclage in asymptomatic twin pregnancies with cervical shortening or dilation: a twelve-year retrospective cohort study.

BACKGROUND: To identify the effect and optimal time of cervical cerclage in asymptomatic twin pregnancies with cervical shortening or dilation. METHODS: This observational retrospective study enrolled all women with asymptomatic twin pregnancies who were diagnosed with asymptomatic cervical shortening or dilation at the Second Affiliated Hospital of Wenzhou Medical University between 2010 and 2022. Women included were allocated into the cerclage group (n = 36) and the no cerclage group (n = 22). The cerclage group was further divided into the cerclage group (< 24 weeks group) and the cerclage group (24-28 weeks group) according to the time of cerclage. The no cerclage group was further divided into no cerclage group (< 24 weeks group) and no cerclage group (24-28 weeks group) according to the time of ultrasound-indicated or physical exam indicated cerclage. The rates of PTB < 24, 28, 32 and 34 weeks of gestation, maternal and neonatal outcomes were compared among the groups. RESULTS: The gestational age (GA) at delivery was higher (P = 0.005) and the interval time between the presentation of the indicated cerclage and delivery was longer in the cerclage group (P < 0.001). The rates of PTB before 28, 32, and 34 weeks of gestation, caesarean section and stillbirth were lower in the cerclage group (P < 0.05). The birthweight of the twins was higher in the cerclage group (P = 0.012). Admissions to the NICU were more frequent in pregnancies with no cerclage (P = 0.008). Subgroup analysis showed that the interval time between the presentation and delivery was longer in the cerclage group (< 24 weeks) (P < 0.001). The GA at delivery and the birthweight of the twins were significantly higher in the cerclage group (< 24 weeks) (P < 0.001). No differences were found in the GA at presentation, the GA at delivery, the interval time between the presentation to delivery and birthweight between the cerclage group (24-28 weeks group) and the control group (24-28 weeks group) (P > 0.05). CONCLUSIONS: Cerclage appears to prolong the GA at delivery and the interval time between the presentation to delivery, and may reduce the incidence of PTB before 28, 32 and 34 weeks of gestation and adverse perinatal outcomes in asymptomatic twin pregnancies with cervical shortening or dilation. Cerclage before 24 weeks of gestation showed longer GA at delivery, longer interval time between the presentation to delivery and higher birthweight of the twins. The GA at presentation, the GA at delivery, the interval time between the presentation to delivery and birthweight in women with cerclage at 24-28 weeks were similar to those in women without cerclage at 24-28 weeks.

Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial.

BACKGROUND: CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma. METHODS: Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco2 <30 mm Hg, 30 mm Hg ≤ Etco2 < 40 mm Hg, and 40 mm Hg ≤ Etco2 < 45 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique. RESULTS: To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P < .001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P < .001), while no significant difference was found between group L and group N (P = 1.000). CONCLUSIONS: Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

Pregnancy outcomes and risk factors for preeclampsia in dichorionic twin pregnancies after in vitro fertilization: a five-year retrospective study.

BACKGROUND: Both in vitro fertilization (IVF) and preeclampsia (PE) were associated with placental dysfunction. Although IVF can increase the incidence of PE, the pregnancy outcomes and risk factors for preeclampsia in dichorionic twin pregnancies conceived via IVF remain unclear. This study aimed to investigate the pregnancy outcomes and the risk factors for preeclampsia in dichorionic twin pregnancies conceived through IVF compared to those conceived after natural conception (NC). METHODS: This retrospective observational study enrolled 181 dichorionic twin pregnancy women with preeclampsia from 2016 to 2020. According to the mode of conception, they were allocated into IVF (n = 117) and NC groups (n = 64). The clinical characteristics of preeclampsia and pregnancy outcomes between the two groups were compared by using Student's t test, chi-square test, and Fisher's exact test, and logistic regression models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI) for risk factors of early-onset preeclampsia. RESULTS: The incidence of early-onset PE and growth discordance in dichorionic twin pregnancies with PE is significantly higher in IVF-PE group than in NC group (78.60% vs 43.80%, P < 0.001, 11.10% vs 25.00%, P = 0.015). We found that IVF (aOR = 4.635, 95% CI: 2.130-10.084, P < 0.001) and growth discordance (aOR = 3.288; 95% CI: 1.090-9.749, P < 0.05) increased the incidence of early-onset PE. CONCLUSIONS: In preeclamptic dichorionic twin pregnancies, IVF and growth discordance were associated with the increased incidence of early-onset PE. The underlying mechanism for the relationship between IVF and early-onset PE or growth discordance may be placental dysfunction.

Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro.

BACKGROUND: Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV. METHODS: A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 µg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated. RESULTS: Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells. CONCLUSIONS: Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Effects of an Intraoperative Intravenous Bolus Dose of Dexmedetomidine on Remifentanil-Induced Postinfusion Hyperalgesia in Patients Undergoing Thyroidectomy: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Consecutive exposure to high-dose remifentanil during anesthesia may induce remifentanil-induced postinfusion hyperalgesia (RPH). Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, may have synergistic effects with opioids and aid in perioperative pain management. In this study, we hypothesized that an intraoperative bolus dose of intravenous dexmedetomidine could alleviate RPH in patients undergoing thyroidectomy under general anesthesia. METHODS: Ninety patients undergoing thyroidectomy were randomly assigned to 1 of 3 groups: placebo, normal saline (group P); low-dose dexmedetomidine 0.2 µg·kg-1 (group LD); or high-dose dexmedetomidine 0.5 µg·kg-1 (group HD). Remifentanil was infused at a rate of 0.30 µg·kg-1·minute-1. Mechanical pain thresholds were measured using an Electronic von Frey device preoperatively and at 30 minutes, 6 hours, 24 hours, and 48 hours after surgery and were analyzed with 2-way repeated-measures analysis of variance (ANOVA) followed by Bonferroni post hoc comparison. We also recorded postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 48 hours after surgery. RESULTS: The mechanical pain thresholds around the skin incision were significantly higher in group LD compared to group P 30 minutes and 6 hours after surgery (mean ± standard deviation: [65.0 ± 25.2] vs [49.6 ± 24.4] g, mean difference [95% confidence interval]: 15.4 [0.3-30.5] g, P = .045 at 30 minutes; [65.9 ± 24.5] vs [49.3 ± 26.1] g, 16.6 [1.1-32.1] g, P = .032 at 6 hours). The pain thresholds around the skin incision were significantly higher in group HD compared to group P 30 minutes and 6 hours after surgery ([67.8 ± 21.7] vs [49.6 ± 24.4] g, 18.2 [3.1-33.3] g, P = .013 at 30 minutes; [68.3 ± 22.5] vs [49.3 ± 26.1] g, 19.0 [3.5-34.5] g, P = .011 at 6 hours). The incidence of hyperalgesia around the skin incision was lower in group HD than in group P 30 minutes and 6 hours after surgery (4 [13%] vs 14 [48%], P = .012 at 30 minutes, 4 [13%] vs 12 [41%], P = .045 at 6 hours), although no significant difference was observed between group LD and group P. Postoperative pain scores, the incidence of rescue analgesic demand, and postoperative side effects were not significantly different between the groups. CONCLUSIONS: An intraoperative intravenous bolus dose of dexmedetomidine 0.5 µg·kg-1 alleviates remifentanil-induced hyperalgesia in patients undergoing thyroidectomy without a significant difference in side effects.

Bryophytes and the symbiotic microorganisms, the pioneers of vegetation restoration in karst rocky desertification areas in southwestern China.

In karst rocky desertification areas, bryophytes coexist with algae, bacteria, and fungi on exposed calcareous rocks to form a bryophyte crust, which plays an irreplaceable role in the restoration of karst degraded ecosystems. We investigated the biodiversity of crust bryophytes in karst rocky desertification areas from Guizhou Province, China. A total of 145 species in 22 families and 56 genera were identified. According to frequency and coverage, seven candidate dominant mosses were screened out, and five drought-resistant indexes of them were measured. Hypnum leptothallum, Racopilum cuspidigerum, and Hyophila involuta have high drought adaptability. We explored the interactions between two dominant mosses (H. leptothallum, H. involuta) and the structure of microbial communities in three karst rocky desertification types. Microbial diversity and function analysis showed that both moss species and karst rocky desertification types affect microbial communities. Moss species much more strongly affected the diversity and changed the community composition of these microbial groups. Bacteria were more sensitive in the microbiome as their communities changed strongly between mosses and drought resistance factors. Moreover, several species of fungi and bacteria could be significantly associated with three drought-resistant indexes: Pro (free proline content), SOD (superoxide dismutase activity), and POD (peroxidase activity), which were closely related to the drought adaptability of mosses. Our results enforced the potential role of moss-associated microbes that are important components involved in the related biological processes when bryophytes adapted to arid habitats, or as one kind of promoters in the distribution pattern of early mosses succession in karst rocky desertification areas.

Effects of metronidazole combined probiotics over metronidazole alone for the treatment of bacterial vaginosis: a meta-analysis of randomized clinical trials.

OBJECT: To evaluate the curative effect of metronidazole combined probiotics over metronidazole alone in the treatment of BV. METHODS: We are searching randomized controlled trials on major online databases including PubMed, Science Direct, and Cochrane Database between 1990 and 2015. The primary outcome measure was the cure rate of BV. Cochran's Chi-square test (Q test) was used to test for heterogeneity among trials, and the I 2 index. We used mixed-effects modeling for parameters of the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs). RESULTS: Analysis suggests the cure rate of BV [RR = 1.12, 95% CI (0.94-1.32), p = 0.20], and the I 2 index was 83%. The value of I 2 index decreased to 16% after removing the study of Anukam et al., and Amsel 1.04 (95% CI 0.96-1.13) (p = 0.35), Nugent 1.02 (95% CI 0.94-1.11), short-term 1.01 (95% CI 0.93-1.10) (p = 0.79), long-term 1.06 (95% CI 0.98-1.14) (p = 0.13), Europe 1.06 (95% CI 0.95-1.19) (p = 0.32), Non-Europe 0.99 (95% CI 0.94-1.05) (p = 0.83). When the two same groups data were combined, respectively, the RRs for all studies were the same as 1.03 (95% CI 0.96-1.09) (p = 0.42) showing that there is not statistically significant in relevant stratums. CONCLUSION: The result has showed an overall little significance for the efficacy of metronidazole combined probiotics over metronidazole alone for the treatment of BV. We need more further studies to provide enough evidence to confirm the benefits of probiotics in the treatment of BV.

The Application of THz Spectroscopy and GA-BP in Methanol Concentration Detection.

At ambient temperature and atmospheric pressure, making use of a photoconductive-antenna terahertz time-domain spectrograph and a self-designed air chamber, the terahertz time-domain spectroscopy (THz-TDS) technique test of methanol gas in the range of 0.1~3.0 THz shows that the methanol gas has no obvious absorption peaks in the range of 0.1~3.0 THz and has obvious absorption peaks in the range of 0.1~1.0 THz. In order to improve the determination accuracy of the concentration of the methanol gas, the author detected 15 groups of methanol gas with different concentrations on the basis of the relationship between the strengths of 15 characteristic absorption peaks of different locations and the concentration of the methanol gas, and obtained the difference curve of the of the characteristic absorption peaks. Based on the function approximation of BP neural network, the author optimized the initial weights and biases of the BP neural network by using the GA the genetic algorithm, which has higher rate of convergence to prevent from getting into local optimum easily, and constructed the mathematical model with the purpose of predicting the methanol gas concentration. The test results show that the neural network is applicable to predict methanol gas in the volume concentration range of 0.028 3~0.424 6 m3·L(-1), the average relative standard deviation of the 2 sets of samples is 1.7%, the average recovery rate is 98%, the error precision of the neural network is 10(-1), and correlation coefficient of the measured values and the predicted values is 0.996 77. The test basically achieved ideal predicted results. The research results obtained experimental data of methanol gas in the terahertz frequency band and found that the method of combining terahertz time-domain spectroscopy with GA-BP neural network can effectively detect the volume concentration of methanol gas, and provided a new method for the detection of concentration of methanol gas.

Glutamate transporter type 3 regulates mouse hippocampal GluR1 trafficking.

BACKGROUND: Rapid trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) to the plasma membrane is considered a fundamental biological process for learning and memory. GluR1 is an AMPAR subunit. We have shown that mice with knockout of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, have impaired learning and memory. The mechanisms for this impairment are not known and may be via regulation of AMPAR trafficking. METHODS: Freshly prepared 300µm coronal hippocampal slices from wild-type or EAAT3 knockout mice were incubated with or without 25mM tetraethylammonium for 10min. The trafficking of GluR1, an AMPAR subunit, to the plasma membrane and its phosphorylation were measured. RESULTS: Tetraethylammonium increased the trafficking of GluR1 and EAAT3 to the plasma membrane in the wild-type mouse hippocampal slices but did not cause GluR1 trafficking in the EAAT3 knockout mice. Tetraethylammonium also increased the phosphorylation of GluR1 at S845, a protein kinase A (PKA) site, in the wild-type mice but not in the EAAT3 knockout mice. The PKA antagonist KT5720 attenuated tetraethylammonium-induced GluR1 phosphorylation and trafficking in the wild-type mice. The PKA agonist 6-BNz-cAMP caused GluR1 trafficking to the plasma membrane in the EAAT3 knockout mice. In addition, EAAT3 was co-immunoprecipitated with PKA. CONCLUSIONS: These results suggest that EAAT3 is upstream of PKA in a pathway to regulate GluR1 trafficking. GENERAL SIGNIFICANCE: Our results provide initial evidence for the involvement of EAAT3 in the biochemical cascade of learning and memory.

Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment.

OBJECTIVES: Transfusing RBCs stored for longer than 14 days (old RBC) in humans is common. This transfusion can injure organs, such as lungs and kidneys. We determined whether transfusion with old RBC injured brain. DESIGN: Prospective, controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Six-month-old Sprague-Dawley rats lost 20% total blood volume and then received RBC prepared from equal volume of the lost blood. RBC was stored for 1 day (fresh RBC) or 7 days (old RBC, storage lesions similar to those of human RBC stored for 28 d). Some rats received IV cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC transfusion. MEASUREMENTS AND MAIN RESULTS: Rats were subjected to Barnes maze and fear conditioning tests from 1 week after blood transfusion. Rats transfused with old RBC but not fresh RBC took a longer time to identify the target hole in the Barnes maze and had less context-related fear conditioning behavior than control rats. Old RBC significantly increased interleukin 6 and ionized calcium-binding adapter molecule 1 in the hippocampus at 24 hours after the transfusion. These effects were attenuated by sulforaphane and minocycline, an antibiotic with anti-inflammatory property. Old RBC solution had a higher concentration of cell-free hemoglobin. Sulforaphane increased haptoglobin, a chelator of cell-free hemoglobin. Rats that received cell-free hemoglobin had a pattern of neuroinflammation and impairment of learning and memory similar to that of rats that received old RBC. CONCLUSIONS: These results provide initial evidence to suggest that transfusion of old RBC induces neuroinflammation and impairment of learning and memory. These effects may be mediated by cell-free hemoglobin.

Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.

BACKGROUND: Patients with postoperative cognitive dysfunction have poor outcomes. Neuroinflammation may be the underlying pathophysiology for this dysfunction. We determined whether proinflammatory cytokines affect the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors to the plasma membrane, a fundamental biochemical process for learning and memory. METHODS: Four-month-old male Fischer 344 rats were subjected to right carotid exposure under isoflurane anesthesia. Some rats received intravenous lidocaine infusion during anesthesia. Rats were tested two weeks later by Barnes maze. The hippocampus was harvested six hours after the surgery for western blotting of interleukin (IL)-1ß or IL-6. Hippocampal slices were prepared from control rats or rats subjected to surgery two weeks previously. They were incubated with tetraethylammonium, an agent that can induce long term potentiation, for determining the trafficking of GluR1, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit. RESULTS: Surgery or anesthesia increased the time to identify the target box during the Barnes maze test training sessions and one day after the training sessions. Surgery also prolonged the time to identify the target box eight days after the training sessions. Surgery increased IL-1ß and IL-6 in the hippocampus. The tetraethylammonium-induced GluR1 phosphorylation and trafficking were abolished in the hippocampal slices of rats after surgery. These surgical effects were partly inhibited by lidocaine. The incubation of control hippocampal slices with IL-1ß and IL-6 abolished tetraethylammonium-induced GluR1 trafficking and phosphorylation. Lidocaine minimally affected the effects of IL-1ß on GluR1 trafficking. CONCLUSIONS: Our results suggest that surgery increases proinflammatory cytokines that then inhibit GluR1 trafficking, leading to learning and memory impairment.

Amantadine alleviates postoperative cognitive dysfunction possibly by increasing glial cell line-derived neurotrophic factor in rats.

BACKGROUND: Postoperative cognitive dysfunction is a clinical entity that is associated with poor outcome. We determined the effectiveness of amantadine in reducing surgery-induced cognitive impairment and the role of glial cell line-derived neurotrophic factor (GDNF) in this effect. METHODS: Four-month old male Fischer 344 rats were subjected to right carotid exposure under intravenous anesthesia. Some rats received intraperitoneal injection of 25 mg/kg/day amantadine for 3 days with the first dose at 15 min before the surgery or intracerebroventricular injection of GDNF or an anti-GDNF antibody at the end of surgery. One week later, rats were started to be tested by Barnes maze and fear conditioning. Hippocampus was harvested at 6 h, 24 h or 10 days after the surgery for biochemical analysis. C8-B4 cells, a microglial cell line, were pretreated with 1 ng/ml GDNF for 30 min before being exposed to 5 ng/ml lipopolysaccharide for 2 h. RESULTS: Surgery increased the time to identify the target box in the Barnes maze when tested 1 day [22 (median) (11-66) (interquartile range) of control group vs. 158 (29-180) of surgery group, n = 15, P = 0.022) or 8 days after the training sessions and reduced context-related freezing behavior in the fear conditioning test. These effects were attenuated by amantadine (25 (14-90), n = 15, P = 0.029 compared with surgery group at 1 day after the training sessions in Barnes maze) and intracerebroventricular GDNF. Amantadine increased GDNF that was co-localized with glial fibrillary acidic protein, an astrocytic marker, in the hippocampus. Intracerebroventricular injection of an anti-GDNF antibody but not the denatured antibody blocked the effects of amantadine on cognition. Surgery induced neuroinflammation that was inhibited by amantadine. Lipopolysaccharide increased interleukin 1ß production from C8-B4 cells. This effect was inhibited by GDNF. CONCLUSIONS: Our results suggest that amantadine attenuated surgery-induced learning and memory impairment. This effect may be mediated by GDNF via inhibition of neuroinflammation.

Long-term survival after resection of hepatocelluar carcinoma: a potential risk associated with the choice of postoperative analgesia.

BACKGROUND: Associations between anesthetic management and cancer recurrence or long-time survival remain uncertain. In this study, we compared the effects of postoperative epidural morphine analgesia with that of postoperative IV fentanyl analgesia on cancer recurrence and long-term survival in patients undergoing resection of hepatocellular carcinoma. METHODS: A retrospective cohort study was performed on patients with hepatocellular carcinoma receiving hepatic resection at this institution (n = 1846, 1997-2007). Recurrence-free survival and long-term survival were assessed using Kaplan-Meier survival estimates and compared using a multivariate Cox proportional hazards regression, adjusted with propensity scores. RESULTS: Eight hundred nineteen patients met the inclusion criteria and were divided into 2 groups: patients receiving postoperative epidural analgesia with morphine (EA, n = 451) and patients receiving postoperative IV analgesia with fentanyl (IA, n = 368). The median time of follow-up for all patients was 4.2 years (2-9). The rates of recurrence of cancer (37.7% vs 30.7%, P = 0.036) and death (40.6% vs 30.4%, P = 0.003) were higher in the EA group versus IA group. Recurrence-free survival was similar in both the EA and IA groups (hazards ratio 2.224, 95% confidence interval, 0.207-23.893, P = 0.509). Using a multivariate Cox proportional hazards regression adjusted with propensity scores, independent risk factors for long-term survival in patients after resection of hepatocellular carcinoma were ASA physical status, tumor diameter, preoperative α-fetoprotein (+) as well as postoperative epidural analgesia with morphine. CONCLUSION: Compared with postoperative IV analgesia with fentanyl, postoperative epidural analgesia with morphine was associated with increased cancer recurrence and death but had no significant effect on recurrence-free survival in patients undergoing resection of hepatocellular carcinoma.

Chemoselective Synthesis of 3-Bromomethyloxindoles via Visible-Light-Induced Radical Cascade Bromocyclization of Alkenes.

A novel visible-light-induced radical cascade bromocyclization of N-arylacrylamides has been accomplished. This reaction overcomes the overbromination at the benzene rings suffered in traditional electrophilic reactions, thus enabling the first highly chemoselective synthesis of valuable 3-bromomethyloxindoles. The combination of pyridine and anhydrous medium is identified as the key factor for the high chemoselectivity in the current photoreaction system, which might work by suppressing the in situ generation of low-concentration Br2 from N-bromosuccinimide. Moreover, the mild reaction conditions ensure the generation of a wide range of the new desired products with excellent functional group tolerance.

Association between driving pressure and postoperative pulmonary complications in patients undergoing lung resection surgery: A randomised clinical trial.

BACKGROUND: It is uncertain whether an association exists for decreases in driving pressure and the occurrence of postoperative pulmonary complications (PPCs) in patients undergoing selective lung resection surgery. Thus, we designed this study to determine whether the positive end-expiratory pressure (PEEP) titration to the lowest driving pressure compared with conventional low PEEP level during one-lung ventilation (OLV) in patients undergoing selective lung resection surgery decreases PPCs. METHODS: This single-centre, randomised trial approved by the Ethical Committee of the Sun Yat-Sen University Cancer Center involved patients who signed written consent. Patients were randomised to the PEEP titration to the lowest driving pressure group (n = 104), or to the conventional low level of PEEP group (n = 103), consisting a PEEP level of 4 cm H2O during OLV. All patients received volume-controlled ventilation with a tidal volume of 6 mL/kg of predicted body weight. The primary outcome was defined as positive if 4 or more of eight Melbourne Group Scale (MGS) variables developed within the first 3 days after surgery. The incidence of major PPCs occurring during postoperative 7 days was also recorded. RESULTS: Among 222 patients who were randomised, 207 (93%) completed the trial (109 men [53%]; mean age, 56.9 years). The primary outcome occurred in 4 of 104 patients (4%) in the PEEP titration to the lowest driving pressure group compared with 13 of 103 patients (13%) in the conventional low level of PEEP group (risk ratio, 0.32 [95% CI, 0.10-0.90]; P = 0.021). CONCLUSIONS: Among patients undergoing selective lung surgery, intraoperative OLV with PEEP titration to the lowest driving pressure compared with conventional low PEEP level (4 cm H2O) significantly reduced PPCs within the first 3 postoperative days, however, did not significantly reduce PPCs within the first 7 postoperative days.

Comparison of Mirena and Liletta levonorgestrel intrauterine devices for the treatment of endometrial intraepithelial neoplasia and grade 1 endometrioid endometrial cancer.

Objective: Current standard nonsurgical management of endometrial intraepithelial neoplasia (EIN) and grade 1 endometrioid endometrial cancer (g1EEC) is the Mirena levonorgestrel intrauterine device (M-IUD). This retrospective study was designed primarily to determine noninferiority of the Liletta IUD (L-IUD) for pathologic regression of EIN and g1EEC compared to the M-IUD at 6 months of continuous use. Secondary objectives include to determine noninferiority as above at 3, 9, and 12 months of continuous use and to identify factors including DNA mismatch repair (MMR) status associated with pathologic regression after LNG-IUD use. Methods: A retrospective observational study was performed with patients treated for EIN or g1EEC and managed continuously with M- or L-IUD. Patients with recent (within 6 months) or concurrent progesterone use were excluded. For the EIN group, the noninferiority margin of odds ratio was predetermined to be 0.58, and for the g1EEC group it was 0.64. Results: 62 patients from an academic center and a safety-net hospital were identified with continuous M-IUD (n = 44) or L-IUD (n = 18) use for EIN or g1EEC. 85% of patients treated with L-IUD were from a safety-net hospital, which had 63% with public insurance. At 3/6/9 months, 54/71/73% of patients with M-IUD and 80/83/100% with L-IUD had pathologic regression of EIN (95% confidence interval of estimated odds ratio 1.00-2.07/0.84-2.03/0.69-2.10). Lifetime smoking status, not MMR status, was significantly associated with pathologic regression. Conclusions: L-IUD is an effective fertility-sparing treatment for EIN. L-IUD is noninferior to M-IUD for pathologic regression of EIN after 3,6, and 9 months. Further larger studies are warranted to validate findings in EIN and g1EEC.

Effects of S-ketamine on Postoperative Recovery Quality and Inflammatory Response in Patients Undergoing Modified Radical Mastectomy.

INTRODUCTION: S-ketamine plays an important role in reducing postoperative pain, but its impact on the quality of recovery in breast cancer has not been clarified. We designed this trial to explore the effects of s-ketamine on the quality of postoperative recovery and inflammatory response in modified radical mastectomy. METHODS: A total of 138 patients were randomly assigned to group C (group control), group K1 (group of s-ketamine dose 1) and group K2 (group of s-ketamine dose 2). Groups K1 and K2 were given 0.1 mg/kg, 0.2 mg/kg s-ketamine intravenous (IV) after induction, followed by 0.1 mg/kg/h or 0.2 mg/kg/h continuous intravenous infusion, respectively. Group C received the same volume of saline. A 40-item Quality of Recovery Questionnaire (QoR-40) was used to assess the quality of recovery at 24 h postoperatively. Changes in inflammatory markers, nociceptive thresholds, and the occurrence of adverse events were recorded at 24 h postoperatively. RESULTS: The QoR-40 scores at 24 h postoperatively were higher in group K2 [182.00 (179.00-185.00)] compared to group K1 [174.00 (169.50-180.50)] and group C [169.00 (163.75-174.25)] (group K2 vs. group K1, P < 0.001; group K2 vs. group C, P < 0.001). At 24 h postoperatively, the neutrophil count, NLR (neutrophil-lymphocyte ratio), and CRP (C-creative protein) were all significantly lower in group K2 than group C(P < 0.05), no differences were observed between group K1 and C(P > 0.05), group K1 and K2(P > 0.05), respectively. There was no significant difference in the incidence of adverse effects among the three groups (P > 0.05). CONCLUSIONS: A high dose of s-ketamine improved the quality of recovery at 24 h after surgery, as well as alleviated the inflammatory response without increasing the incidence of adverse effects.