Remimazolam has similar anesthetic effect and superior safety compared to propofol in elderly patients: A meta-analysis of randomized controlled trials.

BACKGROUND: The superiority between remimazolam and propofol for anesthesia is controversial in elderly patients (≥60 years). This meta-analysis aimed to systematically compare anesthetic effect and safety profile between remimazolam and propofol in elderly patients under any surgery. METHODS: Cochrane Library, Web of Science, and PubMed were searched until December 25, 2023 for relevant randomized controlled trials. RESULTS: Ten studies with 806 patients receiving remimazolam (experimental group) and 813 patients receiving propofol (control group) were included. Time to loss of consciousness [standard mean difference (SMD) (95% confidence interval (CI): 1.347 (-0.362, 3.055), p = 0.122] and recovery time [SMD (95% CI): -0.022 (-0.300, 0.257), p = 0.879] were similar between experimental and control groups. Mean arterial pressure at baseline minus 1 min after induction [SMD (95% CI): -1.800 (-3.250, -0.349), p = 0.015], heart rate at baseline minus 1 min after induction [SMD (95% CI): -1.041 (-1.537, -0.545), p < 0.001], incidences of hypoxemia [relative risk (RR) (95% CI): 0.247 (0.138, 0.444), p < 0.001], respiratory depression [RR (95% CI): 0.458 (0.300, 0.700), p < 0.001], bradycardia [RR (95% CI): 0.409 (0.176, 0.954), p = 0.043], hypotension [RR (95% CI): 0.415 (0.241, 0.714), p = 0.007], and injection pain [RR (95% CI): 0.172 (0.113, 0.263), p < 0.001] were lower in the experimental group compared to the control group. Postoperative nausea and vomiting was not different between groups [RR (95% CI): 1.194 (0.829, 1.718), p = 0.341]. Moreover, this meta-analysis displayed a low risk of bias, minimal publication bias, and good robustness. CONCLUSION: Remimazolam shows comparative anesthetic effect and better safety profile than propofol in elderly patients under any surgery.

Tilianin enhances the antitumor effect of sufentanil on non-small cell lung cancer.

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 µM, and the IC50 of Tilianin for H1299 cells was 44.6 µM. Functionally, 0.5 nM sufentanil and 10 µM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 µM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 µM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 µM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.

Administration of flurbiprofen axetil and dezocine for the postoperative analgesia in patients with non­small cell lung cancer: A randomized, controlled study.

Flurbiprofen axetil or dezocine monotherapy has been applied for analgesia of postoperative non-small cell lung cancer (NSCLC); however, their combination is rarely investigated. Consequently, the present study aimed to explore the effect of flurbiprofen axetil plus dezocine on postoperative pain, surgical outcomes and its safety profile in patients with NSCLC. A total of 150 patients with resectable NSCLC were enrolled and randomized into three groups: i) The flurbiprofen axetil plus dezocine group (n=50), ii) the flurbiprofen axetil group (n=51) and iii) the dezocine group (n=49). A total of 50 mg flurbiprofen axetil, 5 mg of dezocine or their combination were administered intravenously 3 h prior to surgery and subsequently every 12 h until day 3 (D3) following surgery. The postoperative pain was lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil group at 6 h (P=0.008), 12 h (P=0.003), day 1 (D1) (P=0.013), day 2 (D2) (P=0.036) and D3 (P=0.010); in addition, it was lower in the flurbiprofen axetil plus dezocine group compared with that of the dezocine group at 6 h (P=0.010), 12 h (P=0.012) and D1 (P=0.020). Patient-controlled analgesia consumption was also lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil (P=0.010) and dezocine (P=0.002) groups. Furthermore, the length of hospital stay was lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil (P=0.008) and dezocine (P=0.048) groups, while other surgical outcomes and adverse events were similar among these three groups. Moreover, the expression of tumor necrosis factor-α was lower in the flurbiprofen axetil plus dezocine group compared with that of the dezocine group at 12 h (P<0.001), D1 (P<0.001) and D3 (P=0.033). The data indicated that flurbiprofen axetil and dezocine combination was superior to monotherapy for postoperative analgesia in patients with resectable NSCLC.

Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss.

RATIONALE: Hereditary hearing loss is known to exhibit a significant degree of genetic heterogeneity. Herein, we present a case report of a novel mutation in the tenascin-C (TNC) gene in Chinese patients with nonsyndromic hearing loss (NSHL). PATIENT CONCERNS: This includes a young deaf couple and their 2-year-old baby. DIAGNOSES: Based on the clinical information, hearing test, metagenomic next-generation sequencing (mNGS), Sanger sequencing, protein function and structure analysis, and model prediction, in our case, the study results revealed 2 heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) and the TBC1 domain family member 24 (TBC1D24) gene (c.1570C>T, p.Arg524Trp). These mutations may be responsible for the hearing loss observed in this family. Notably, the heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) have not been previously reported in the literature. INTERVENTIONS: Avoid taking drugs that can cause deafness, wearing hearing AIDS, and cochlear implants. OUTCOMES: Regular follow-up of family members is ongoing. LESSONS: The genetic diagnosis of NSHL holds significant importance as it helps in making informed treatment decisions, providing prognostic information, and offering genetic counseling for the patient's family.

[Effects of electroacupuncture pretreatment on long-term postoperative cognitive dysfunction and neuron-inflammation in aged rats].

OBJECTIVE: To observe the effects of electroacupuncture pretreatment on postoperative cognitive dysfunction (POCD), neuronal apoptosis and neuron-inflammation in aged rats. METHODS: Thirty-six male SD rats aged 20 months were randomly divided into sham operation group, model group and electroacupuncture (EA) group, with 12 rats in each group. The POCD rats model was prepared by internal fixation of left tibial fracture. Five days before modeling, EA stimulation (2 Hz/15 Hz, 1 mA, 30 min) was applied to "Zusanli" (ST36), "Hegu" (LI4) and "Neiguan" (PC6) on the unaffected side of rats in the EA group, once a day for consecutive 5 d. The learning and memory abilities of rats were evaluated by water maze test 31-35 days after operation. The apoptosis of hippocampal neurons was observed by Tunel/NeuN double staining. The expressions of high mobility group protein B1 (HMGB1) and phosphorylated (p)-nuclear factor (NF)-κB in microglia cells in hippocampal dentate gyrus were detected by immunofluorescence staining. The expression levels of interleukin (IL)-6 and IL-1ß in the hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency was prolonged (P<0.05); the frequency of crossing the original platform, ratio of the swimming distance and the time in the target quadrant of the Morris water maze were significantly decreased (P<0.05); the apoptosis rate of hippocampal neurons was significantly increased (P<0.05); the expressions of HMGB1 and p-NF-κB in microglia cells in the dentate gyrus and the expression levels of IL-6 and IL-1ß in hippocampus were increased (P<0.05) in the model group. Compared with the model group, the results of the above indexes were all opposite (P<0.05) in the EA group. CONCLUSION: EA preconditioning can regulate hippocampal inflammatory response, alleviate neuronal apoptosis rate and long-term cognitive dysfunction in aged rats with POCD, the mechanisms may be related to the inhibition of microglia HMGB1/NF-κB pathway in hippocampal dentate gyrus.

Effect of Parecoxib Sodium Combined with Dexmedetomidine on Analgesia and Postoperative Pain of Patients Undergoing Hysteromyomectomy.

Background: Propofol combined with remifentanil is the most common anesthesia method in laparoscopic hysteromyomectomy. However, whether the combination of the two is helpful to patients undergoing hysteromyomectomy still requires unclear. Objective: To determine the effect of parecoxib sodium combined with dexmedetomidine on analgesia and postoperative pain of patients undergoing hysteromyomectomy. Methods: Altogether, 72 patients receiving hysteromyomectomy in our hospital from February 2017 to March 2019 were enrolled. Among them, 35 patients treated with parecoxib sodium were assigned to the control group, while the rest 37 patients treated with parecoxib sodium combined with dexmedetomidine were assigned to the research group. The following items of the two groups were evaluated: visual analog scale (VAS) score, mechanical pain threshold (MPT), Riker sedation-agitation scale (RSAS) score, and expression of serum cortisol and melatonin. Results: At 12 and 24 h after operation, the VAS score of the research group was lower than that of the control group (P < 0.05), and at 6, 12, and 24 h after operation, the MPT of the research group was notably higher than that of the control group (P < 0.05). In addition, at 10 min after extubation, the research group got notably lower RSAS score than the control group (P < 0.05). Before extubation and at 20 min after extubation, the research group showed notably higher melatonin expression and notably lower serum cortisol expression than the control group (both P < 0.05). Conclusion: Parecoxib sodium combined with dexmedetomidine can effectively control the postoperative pain of patients undergoing hysteromyomectomy, reduce the incidence of agitation, and effectively control serum cortisol and melatonin in them.

Effects of Boric Acid Gel on Vaginal Candida albicans Infections and the Local Immune System in Mice.

The objective was to determine the effect of 5% boric acid gel on vaginal Candida albicans (CA) infections in mice and its effect on the local immune system (i.e., Th1, Th2, and Th17). Female mice were divided into four groups, with 10 mice in each group. Mycelial suspensions were administered into the vaginal lumen close to the cervix in groups B, F, and M. Mice in group B were given boric acid gel, and group F was treated with fluconazole gel for 30 min every 12 h. Group M was treated with sterile water, and group N was not given treatment. After the seventh day of treatment, each group was observed with the naked eye, and vaginal lavage fluid and vaginal tissue were collected. Expression levels of cytokines were measured using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. Periodic acid Schiff (PAS) staining was used to measure the fungi in vaginal tissues. There were no significant changes in group M. In groups B and F, there was less vaginal injury and less exudate, with group B doing better than group F. The numbers of CA colonies were higher in groups B, F, and M than in group N (P < 0.01). There was less vaginal colonization of CA in group B than in group F (P < 0.01). After the seventh day of treatment, levels of IFN-γ, IL-17, IL-6, TGF-ß, IL-4, and IL-10 were significantly greater in groups B, F, and M than in group N (P < 0.001); levels of IFN-γ, IL-17, IL-6, and TGF-ß in groups B and F were higher than those of group M (P < 0.01), while IL-4 and IL-10 levels were significantly lower (P < 0.001). The trends of cytokine increases and decreases were more significant in group B than in group F (P < 0.05). Immunohistochemical results were similar to ELISA results. PAS staining revealed that boric acid inhibited hyphal reproduction. The boric acid significantly reduced the symptoms associated with CA vaginal infection. It inhibited the CA growth, prevented vaginal lesions, promoted the secretion of Th1 and Th17 cytokines, and reduced Th2 cytokines.

Investigation on the Control of COVID-19 in Wuhan: Number of Infections Outside Hospitals and the Reproduction Number.

COVID-19 is erupting globally, and Wuhan successfully controlled it within a month. Infections arose from infectious persons outside hospitals. After data revision, data-based and model-based analyses were implemented, and the conclusions are as follows. The incubation period of most infected people may be 6-7 days. The number of infectious persons outside hospitals in Wuhan on January 20, 2020 was about 10000 and reached more than 20000 on the day of Lockdown; it exceeded 72000 on February 4. Both data-based and model-based analyses gave out the evolution of the reproduction number, which was over 2.5 in early January, went down to 1.62 in late January and 1.20 in early February, with a sudden drop to less than 0.5 due to the strict Stay-at-home management after February 11. Strategies of Stay-at-home, Safe-protective measures, and Ark hospitals were the main contributions to control COVID-19 in Wuhan. In Wuhan, 2 inflection points of COVID-19, exactly correspond to February 5 and February 15, the 2 days when Ark hospitals were introduced, and the complete implementation of Stay-at-home. Based on the expression of the reproduction number, group immunity is also discussed. It shows that only when the group immunization rate is over 75% can COVID-19 be under control; group immunity would be full infection and the total deaths will be 220000 for a city as big as Wuhan. Sensitivity analysis suggests that 30% of people staying at home in combination with better behavior changes, such as social-distancing and frequent handwashing, can effectively contain COVID-19. However, only when this proportion is over 60% can the controlled effect and efficiency like Wuhan be obtained.

Analysis of Influencing Factors of Serum Stress Index and Prognosis of HICH Patients by Different Anesthesia Methods Combined with Small Bone Window Microsurgery.

In order to investigate the effects of sevoflurane on the serum stress index level and prognosis of patients with hypertensive cerebral hemorrhage (HICH) during small bone window microsurgery, a total of 102 HICH patients are selected for analysis. MAP values in both groups decreased significantly at T1 and T2 (P < 0.05), and the changes in MAP and HR indexes in the sevoflurane combined group were more stable than those in the control group. The time of postoperative awakening in the sevoflurane combined group decreases significantly than the control group (P < 0.001). The levels of T-AOC and GSH-Px in both groups increase significantly after operation, and those in the sevoflurane combined group increase significantly than the control group (P < 0.001). The levels of MDA and 8-OHDG in the sevoflurane combined group decrease significantly than the control group after operation (P < 0.05). Spearman correlation coefficient analysis shows that the levels of T-AOC and GSH-Px are negatively correlated with the prognosis of HICH patients, while MDA and 8-OHDG are positively correlated with the prognosis of HICH patients (P < 0.001). Sevoflurane interventional anesthesia has a high anesthetic effect in small bone window microsurgery, which has positive effects on controlling blood pressure of HICH patients, shortening postoperative recovery time and improving patients' stress response and neurological function. This paper conducts an in-depth analysis of the prognosis of HICH patients, indicating that the prognosis of HICH patients is closely related to their serum stress indicators T-AOC, GSH-Px, MDA, and 8-OHDG, providing a new direction for follow-up clinical diagnosis and treatment of HICH patients and accurate prognosis assessment.

Effects of Dexmedetomidine Combined with Intravenous Anesthesia on Oxidative Stress Index, Postoperative Sleep Quality, and Brain Function in HICH Patients.

To investigate the effects of dexmedetomidine combined with intravenous anesthesia on oxidative emergency indicators, postoperative sleep quality, and brain function in patients with hypertensive cerebral hemorrhage (HICH), a total of 285 HICH patients admitted to our hospital from February 2020 to February 2021 were selected. The combined anesthesia group (n = 142) and the control group (n = 143) were established by the random number table method. The control group received conventional intravenous anesthesia, and the combined anesthesia group received dexmedetomidine combined intravenous anesthesia. Two groups of patients before and after operation was observed vital signs, oxidative stress index difference, comparing each time, the change of the two groups of brain function index, adverse reactions occurred between observation group, and the postoperative period of Pittsburgh Sleep Quality Index Scale (PSQI) score as a result, the Pearson correlation coefficient analysis of oxidative stress level and the correlation of HICH patients sleep quality. After operation, the mean arterial pressure (MAP) and heart rate (HR) of patients in both groups decreased significantly. The MAP level in the combined anesthesia group significantly increased compared to the control group, and the HR level decreased significantly than the control group (all P < 0.05). The levels of TNF-α, IL-6 and MDA in both groups increased significantly on day 7 after operation compared with before operation, but the indexes in the combined anesthesia group significantly decreased compared with the control group (P < 0.05). The level of superoxide dismutase (SOD) in both groups significantly decreased compared to that before operation, and the index value in combined anesthesia group significantly increased compared to that in the control group (P < 0.05). After surgery, the levels of central nerve specific protein (S100-ß) and neuron specific enolase (NSE) in 2 groups increased with time, and the indexes in the combined anesthesia group significantly decreased compared to the control group (all P < 0.05). The incidence of adr in combined anesthesia group decreased significantly than that in control group (P < 0.05). After surgery, PSQI scores of the two groups showed a downward trend with time extension, and scores of the combined anesthesia group decreased significantly than those of the control group at 24 h, 48 h and 7 d after surgery (all P < 0.05). Pearson's correlation coefficient was used to analyze that TNF-α, IL-6, and MDA levels were positively correlated with PSQI score, while SOD level was negatively correlated with PSQI score (all P < 0.05). Dexmedetomidine combined with intravenous anesthesia can significantly improve the vital signs and oxidative stress response of HICH patients, effectively reduce the risk of adverse reactions, have little impact on the brain function of patients, and can improve the postoperative sleep quality of patients. This operation is worthy of clinical application. In addition, this study further analyzed the influence mechanism of postoperative sleep quality in patients with HICH and showed that TNF-α, IL-6, MDA, and SOD were all correlated with sleep quality in patients with HICH, suggesting that follow-up detection of these indicators has positive significance in improving the prognosis of patients.

Ultrasound-guided paravertebral nerve block anesthesia on the stress response and hemodynamics among lung cancer patients.

BACKGROUND: Thoracic surgery for radical resection of lung tumor requires deep anesthesia which can lead to an adverse inflammatory response, loss of hemodynamic stability, and decreased immune function. Herein, we evaluated the feasibility and benefits of ultrasound-guided paravertebral nerve block anesthesia, in combination with general anesthesia, for thoracic surgery for lung cancer. The block was performed by diffusion of anesthetic drugs along the paravertebral space to achieve unilateral multi-segment intercostal nerve and dorsal branch nerve block. AIM: To evaluate the application of ultrasound-guided paravertebral nerve block anesthesia for lung cancer surgery to inform practice. METHODS: The analysis was based on 140 patients who underwent thoracic surgery for lung cancer at our hospital between January 2018 and May 2020. Patients were randomly allocated to the peripheral + general anesthesia (observation) group (n = 74) or to the general anesthesia (control) group (n = 66). Patients in the observation group received ultrasound-guided paravertebral nerve block anesthesia combined with general anesthesia, with those in the control group receiving an epidural block combined with general anesthesia. Measured outcomes included the operative and anesthesia times, as well as the mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation (SpO2) measured before surgery, 15 min after anesthesia (T1), after intubation, 5 min after skin incision, and before extubation (T4). RESULTS: The dose of intra-operative use of remifentanil and propofol and the postoperative use of sufentanil was lower in the observation group (1.48 ± 0.43 mg, 760.50 ± 92.28 mg, and 72.50 ± 16.62 mg, respectively) than control group (P < 0.05). At the four time points of measurement (T1 through T4), MAP and HR values were higher in the observation than control group (MAP, 90.20 ± 9.15 mmHg, 85.50 ± 7.22 mmHg, 88.59 ± 8.15 mmHg, and 90.02 ± 10.02 mmHg, respectively; and HR, 72.39 ± 8.22 beats/min, 69.03 ± 9.03 beats/min, 70.12 ± 8.11 beats/min, and 71.24 ± 9.01 beats/min, respectively; P < 0.05). There was no difference in SpO2 between the two groups (P > 0.05). Postoperative levels of epinephrine, norepinephrine, and dopamine used were significantly lower in the observation than control group (210.20 ± 40.41 pg/mL, 230.30 ± 65.58 pg/mL, and 54.49 ± 13.32 pg/mL, respectively; P < 0.05). Similarly, the postoperative tumor necrosis factor-α and interleukin-6 levels were lower in the observation (2.43 ± 0.44 pg/mL and 170.03 ± 35.54 pg/mL, respectively) than control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). CONCLUSION: Ultrasound-guided paravertebral nerve block anesthesia improved the stress and hemodynamic response in patients undergoing thoracic surgery for lung cancer, with no increase in the rate of adverse events.

Application value of goal-directed fluid therapy with ERAS in patients undergoing radical lung cancer surgery.

OBJECTIVE: To explore the application value of goal-directed fluid therapy (GDFT) in the enhanced recovery after surgery (ERAS) of patients undergoing radical lung cancer surgery (RLCS). METHODS: A total of 74 patients undergoing elective RLCS based on the enhance recovery after surgery (ERAS) concept in the HanDan Central Hospital between December 2016 and December 2019 were enrolled and assigned to a group treated by regular conventional liquids (regular group, n=34) and a group treated by goal-directed fluid (GDFT group, n=40) according to the fluid infusion scheme. The two groups were compared in intraoperative fluid inflow and outflow, hemodynamic indexes at 30 min (T0) before operation, 4 h (T1) and 24 h (T2) after operation, postoperative complications, postoperative recovery, inflammatory factors at 1 day (d 0) before operation, and at 1 day (d 1) and 7 days (d 3) after operation, as well as for postoperative life quality. RESULTS: Crystalloid fluid input, fluid infusion, and urine output of the GDFT group were all significantly less than those of the regular group (all P<0.05), and the GDFT group showed significantly lower fluctuations of MAP, cardiac index, and stroke volume (SV) than the regular group (all P<0.05). Additionally, the GDFT group showed a significantly lower overall complication rate and experienced notably earlier time to flatus and getting out-of-bed time and notably shorter hospitalization time than the regular group (all P<0.05). Moreover, the GDFT group presented with less fluctuation of IL-10, IL-6, and TNF-α levels and experienced notably higher life quality scores than the regular group. CONCLUSION: GDFT is beneficial to the rapid recovery of patients after RLCS, because it can exert a positive effect on maintaining the stability of hemodynamic indexes and reducing inflammation and postoperative complications.

The local anesthetic ropivacaine suppresses progression of breast cancer by regulating miR-27b-3p/YAP axis.

Breast cancer is a prevalent malignancy with high mortality and poor prognosis. Ropivacaine is a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of ropivacaine in breast cancer development remains elusive. Here, we tried to investigate the impact of ropivacaine on breast cancer progression and the underlying mechanism. Significantly, we revealed that ropivacaine was able to reduce the proliferation and induce the apoptosis of breast cancer cells. Ropivacaine could attenuate the invasion and migration in the cells. Mechanically, ropivacaine could enhance the miR-27b-3p expression and miR-27b-3p inhibited breast cancer progression in breast cancer cells. MiR-27b-3p targeted YAP in the breast cancer cells. Ropivacaine decreased the breast cancer progression by modulating miR-27b-3p/YAP axis in vitro. Ropivacaine could inhibit tumor growth in vivo. In conclusion, we discovered that the local anesthetic ropivacaine inhibits the progression of breast cancer via the miR-27b-3p/YAP axis. Our finding presents novel insights into the mechanism of ropivacaine inhibiting the development of breast cancer. Ropivacaine may potentially serve as an anti-tumor candidate in the therapeutic strategy of breast cancer.

Isoflurane activates AMP-activated protein kinase to inhibit proliferation, and promote apoptosis and autophagy in cervical carcinoma both in vitro and in vivo.

OBJECTIVE: Isoflurane is an extensively used inhalational anesthesia, and its carcinogenic or anti-cancerous effect has been identified recently. However, the specific role of isoflurane in cervical cancer remains unclear. AIM: This study aimed to investigate the function of isoflurane in cervical cancer as well as the underlying mechanism. METHODS: After isoflurane treatment, HeLa cell viability, percentage of apoptotic cells, expression of active caspase-3/9 were examined by CCK-8 assay, Annexin V-FITC/PI double staining, and Western blot analysis, respectively. ROS generation, ratio of NAD+/NADH, and ATP level after isoflurane stimulation were determined using commercial assay kits. Afterwards, activation of AMPK and autophagy was assessed through Western blot analysis and immunofluorescence. Whether AMPK mediated the isoflurane-induced apoptosis and autophagy was explored by adding an AMPK inhibitor (Compound C). The in vivo function of isoflurane was finally investigated on a HeLa cell xenograft model. RESULTS: Isoflurane inhibited cell viability and induced apoptosis evidenced by upregulation of active caspase-3/9 in HeLa cells. Oxidative stress was triggered by isoflurane, as isoflurane elevated ROS level, and lowered ratio of NAD+/NADH and ATP level. Further results showed isoflurane activated the AMPK/mTOR pathway and induced autophagy. In addition, inhibition of AMPK led to ameliorated effects of isoflurane on apoptosis and autophagy. In vivo experiments proved isoflurane could repress tumorigenesis, activate AMPK, and induce autophagy in Xenograft mouse. CONCLUSIONS: Isoflurane activated AMPK to inhibit proliferation and promote apoptosis and autophagy both in vitro and in vivo.

Analgesic effects of low-dose ketamine after spinal fusion in adults: A protocol of prospective randomized trial.

BACKGROUND: Patients with spinal fusion often have opioid tolerance and chronic pain, which makes it difficult to control postoperative pain. In this double-blind, randomized, prospective study, we assessed the safety and efficacy of intravenous low-dose ketamine for the treatment of pain in patients undergoing the lumbar spinal fusion. METHODS: This randomized, prospective, double-blind and placebo-controlled study was approved via the hospital institutional review committee. Patients were registered with signed written consent. All the floor nurses, recovery room and surgeons, patients, statisticians as well as research assistants were unaware of the grouping. The patients were randomly divided into ketamine group and control group by random number table. Nausea, vomiting or vomiting, the intensity of pain, adverse events, cumulative morphine consumption, as well as the amount of extra antiemetics or analgesics were evaluated at 6 hours, 12 hours, 24 hours, 36 hours, and 48 hours after the operation. P < .05 was considered to be the statistically significant. The Statistical Package for the software of Social Sciences 20.0 was utilized for statistical analysis. CONCLUSIONS: For the present trial, we assumed that intravenous ketamine could improve the satisfaction of patient by reducing the total consumption of morphine equivalent and the pain scores. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5896).

Early preoperative versus postoperative administration of meloxicam in pain control, patient global status improvement, knee function recovery of arthroscopic knee surgery.

BACKGROUND: This study aimed to investigate the efficacy and safety between early preoperative administration and postoperative administration of oral meloxicam in patients underwent arthroscopic knee surgery (AKS). METHODS: Totally 296 patients with the intention to undergo AKS were recruited and randomly allocated as 1:1 ratio into early preoperative analgesia (EPA) group and postoperative analgesia (POA) group. Pain visual analog scale (VAS) score and severity (at rest and at flexion), patient global assessment (PGA) score, the consumption of rescue analgesia (pethidine), and adverse events were evaluated during the perioperation. And knee range of motion (ROM), International Knee Documentation Committee (IKDC) score, and Lysholm score were assessed at baseline and at 3 months after AKS. RESULTS: Both pain VAS score and severity (at rest and at flexion) were decreased at 4, 8, and 12 hours, but similar at -24, -2, 24, 36, and 48 hours after AKS in EPA group compared with POA group. Besides, PGA score was lower at 4, 8, 12, and 24 hours, but similar at -24, -2, 36, and 48 hours after AKS in EPA group compared with POA group. As to the consumption of pethidine in perioperative period, it was decreased in EPA group compared with POA group. No difference was observed in knee ROM, IKDC score, Lysholm score, and adverse effects between EPA group and POA group. CONCLUSION: Early preoperative administration of meloxicam was a superior approach in pain control compared with postoperative administration in treating patients underwent AKS.

Spatiotemporal Distributions and Dynamics of Human Infections with the A H7N9 Avian Influenza Virus.

In 2013 in mainland China, a novel avian influenza virus H7N9 began to infect humans and had aroused severe fatality in the infected humans, followed by the annual outbreaks. By methods of GIS and kriging interpolation, we get the geographical distributions. We obtain the longitudinal characteristics of these outbreaks based on statistics and diagrams. After these spatiotemporal distributions, an eco-epidemiological model is established and analyzed. In this model, the general incidence functions, the factor of fully killed infected poultry, and the virus in environment are taken into account. Theoretical analysis shows that the endemic will be formed to a large extent once the H7N9 avian influenza virus exists in poultry. On the basis of dynamics, we explore the possible disease control measures by numerical simulations. Simulations indicate that measures of vaccination in poultry and stopping live poultry transactions are the primary choices for disease control in humans, and strengthened inhibition effects and environmental disinfections can effectively control the outbreak.

Beta-adrenergic activation induces cardiac collapse by aggravating cardiomyocyte contractile dysfunction in bupivacaine intoxication.

In order to determine the role of the adrenergic system in bupivacaine-induced cardiotoxicity, a series of experiments were performed. In an animal experiment, male Sprague-Dawley (SD) rats under chloral hydrate anesthesia received intravenous bupivacaine, followed by an intravenous injection of adrenalin or isoprenalin, and the electrocardiogram (ECG), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of rise of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease (-dP/dtmax) were continually monitored. In a cellular experiment, freshly isolated adult SD rat ventricular myocytes were perfused with bupivacaine at different concentrations in the presence or absence of isoprenalin, with or without esmolol. The percentage of the sarcomere shortening (bl% peak h), departure velocity (dep v) of sarcomere shortening and time to 50% of the peak speed of myocyte contraction (Tp50) was assessed by a video-based edge-detection system. In an additional experiment, Swiss mice pretreated with saline, isoprenalin, esmolol or dexmedetomidine received bupivacaine to determine the 50% lethal dose (LD50) of bupivacaine. Electron microscopy of myocardial mitochondria was performed to assess damage of these structures. To test mitochondrial reactive oxygen species (ROS) production, freshly isolated SD rat ventricular myocytes were incubated with bupivacaine in the presence of isoprenalin, with or without esmolol. First, our results showed that bupivacaine significantly reduced the LVSP and +dP/dtmax, as well as enhanced the LVEDP and -dP/dtmax (P < 0.05, vs. control, and vs. baseline). Adrenalin and isoprenalin induced a further reduction of LVSP and +dP/dtmax (P < 0.05, vs. before adrenalin or isoprenalin delivery, and vs. control). Second, bupivacaine induced a dose-dependent cardiomyocyte contractile depression. While 5.9 µmol/L or 8.9 µmol/L of bupivacaine resulted in no change, 30.0 µmol/L of bupivacaine prolonged the Tp50 and reduced the bl% peak h and dep v (P < 0.05, vs. control and vs. baseline). Isoprenalin aggravated the bupivacaine-induced cardiomyocyte contractile depression, significantly prolonging the Tp50 (P < 0.05, vs. bupivacaine alone) and reducing the dep v (P < 0.05, vs. bupivacaine alone). Third, esmolol and dexmedetomidine significantly enhanced, while isoprenalin significantly reduced, the LD50 of bupivacaine in mice. Fourth, bupivacaine led to significant mitochondrial swelling, and the extent of myocardial mitochondrial swelling in isoprenalin-pretreated mice was significantly higher than that compared with mice pretreated with saline, as reflected by the higher mitochondrial damage score (P < 0.01). Meanwhile, esmolol pretreatment significantly reduced the mitochondrial damage score (P < 0.01). Fifth, bupivacaine significantly increased the ROS in freshly isolated cardiomyocytes, and added isoprenalin induced a further enhancement of ROS production (P < 0.05, vs. bupivacaine alone). Added esmolol significantly decreased ROS production (P < 0.05, vs. bupivacaine + isoprenalin). Our results suggest that bupivacaine depressed cardiac automaticity, conductivity and contractility, but the predominant effect was contractile dysfunction which resulted from the disruption of mitochondrial energy metabolism. ß-adrenergic activation aggravated the cellular metabolism disorder and therefore contractile dysfunction.