TCF12 Transcriptionally Activates SPHK1 to Induce Osteosarcoma Angiogenesis by Promoting the S1P/S1PR4/STAT3 Axis.

Transcription factor 12 (TCF12) is a known oncogene in many cancers. However, whether TCF12 can regulate malignant phenotypes and angiogenesis in osteosarcoma is not elucidated. In this study, we demonstrated increased expression of TCF12 in osteosarcoma tissues and cell lines. High TCF12 expression was associated with metastasis and poor survival rate of osteosarcoma patients. Knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells. TCF12 was found to bind to the promoter region of sphingosine kinase 1 (SPHK1) to induce transcriptional activation of SPHK1 expression and enhance the secretion of sphingosine-1-phosphate (S1P), which eventually resulted in the malignant phenotypes of osteosarcoma cells. In addition, S1P secreted by osteosarcoma cells promoted the angiogenesis of HUVECs by targeting S1PR4 on the cell membrane to activate the STAT3 signaling pathway. These findings suggest that TCF12 may induce transcriptional activation of SPHK1 to promote the synthesis and secretion of S1P. This process likely enhances the malignant phenotypes of osteosarcoma cells and induces angiogenesis via the S1PR4/STAT3 signaling pathway.

Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients: A meta-analysis.

BACKGROUND: Remimazolam is characterized by rapid action and inactive metabolites. It is used as the general anesthetic for many clinical surgeries. In this study, we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients. AIM: To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults. METHODS: The PubMed, Web of Science, the Cochrane Library databases were queried for the relevant key words "remimazolam," "and propofol," "and gastrointestinal endoscopy or gastroscopy." The search scope was "Title and Abstract," and the search was limited to human studies and publications in English. Seven studies wherein remimazolam and propofol were compared were included for the meta-analysis. RESULTS: We selected seven randomized controlled trials involving 1445 cases for the analysis. Remimazolam reduced the hypotension (relative risk, RR = 0.44, 95%CI: 0.29-0.66, P = 0.000), respiratory depression (RR = 0.46, 95%CI: 0.30-0.70, P = 0.000), injection pain (RR = 0.12, 95%CI: 0.05-0.25, P = 0.000), bradycardia (RR = 0.37, 95%CI: 0.24-0.58, P = 0.000), and time to discharge [weighted mean difference (WMD) = -0.58, 95%CI: -0.97 to -0.18, P = 0.005], compared to those after propofol administration. No obvious differences were observed for postoperative nausea and vomiting (RR = 1.09, 95%CI: 0.97-1.24, P = 0.151), dizziness (RR = 0.77, 95%CI: 0.43-1.36, P = 0.361), successful sedation rate (RR = 0.96, 95%CI: 0.93-1.00, P = 0.083), or the time to become fully alert (WMD = 0.00, 95%CI: -1.08-1.08, P = 0.998). CONCLUSION: Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults. However, further studies are required to confirm these findings.

Efficacy and safety of remimazolam in bronchoscopic sedation: A meta-analysis.

BACKGROUND: Remimazolam is a new benzodiazepine used for procedural sedation and general anesthesia. Several studies have used remimazolam for bendable bronchoscopy. AIM: To assess the safety and efficacy of remimazolam for sedation in patients undergoing bendable bronchoscopy by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: We searched the EMBASE, PubMed, Cochrane Library, and Web of Science databases for RCTs on bendable bronchoscopic procedural sedation with remimazolam vs conventional sedatives (CS). RESULTS: Five studies with 1080 cases were included. Remimazolam had the same sedation success rate compared with CS [relative risk (RR): 1.35, 95%CI: 0.60-3.05, P = 0.474, I2 = 99.6%]. However, remimazolam was associated with a lower incidence of hypotension (RR: 0.61; 95%CI: 0.40-0.95, P = 0.027; I2 = 65.1%) and a lower incidence of respiratory depression (RR: 0.50, 95%CI: 0.33-0.77, P = 0.002, I2 = 42.3%). A subgroup analysis showed a higher success rate of sedation with remimazolam than midazolam (RR: 2.45, 95%CI: 1.76-3.42, P < 0.001). Compared with propofol, the incidence of hypotension (RR: 0.45, 95%CI: 0.32-0.64, P < 0.001, I2 = 0.0%), respiratory depression (RR: 0.48, 95%CI: 0.30-0.76, P = 0.002, I2 = 78.4%), hypoxemia (RR: 0.36, 95%CI: 0.15-0.87, P = 0.023), and injection pain (RR: 0.04, 95%CI: 0.01-0.28, P = 0.001) were lower. CONCLUSION: Remimazolam is safe and effective during bronchoscopy. The sedation success rate was similar to that in the CS group. However, remimazolam has a higher safety profile, with fewer inhibitory effects on respiration and circulation.

Application of a Core-Shell Structure Nano Filtration Control Additive in Salt-Resistant Clay-Free Water-Based Drilling Fluid.

When drilling into a reservoir, the drilling fluid containing bentonite is prone to solid phase invasion, causing serious damage to the reservoir, and the conventional API barite suspension stability is poor, which makes it easy to cause sedimentation and blockage. Therefore, in order to avoid accidents, we use ultrafine barite to obtain a good suspension stability. More importantly, the method of modifying zwitterionic polymers on the surface of nano-silica is used to develop a temperature-resistant and salt-resistant fluid loss reducer FATG with a core-shell structure, and it is applied to ultra-fine clay-free water-based drilling fluid (WBDF). The results show that the filtration loss of clay-free drilling fluid containing FATG can be reduced to 8.2 mL, and AV can be reduced to 22 mPa·s. Although the viscosity is reduced, FATG can reduce the filter loss by forming a dense mud cake. The clay-free drilling fluid system obtained by further adding sepiolite can reduce the filtration loss to 3.8 mL. After aging at 220 °C for 15 d, it still has significant salt tolerance, the filtration loss is only 9 mL, the viscosity does not change much, a thinner and denser mud cake is formed, and the viscosity coefficient of the mud cake is smaller. The linear expansion test and permeability recovery evaluation were carried out. The hydration expansion inhibition rate of bentonite can reach 72.5%, and the permeability recovery rate can reach 77.9%, which can meet the long-term drilling fluid circulation work in the actual drilling process. This study can provide guidance for technical research in related fields such as reservoir protection.

Propofol improves ischemia reperfusion-induced liver fibrosis by regulating lncRNA HOXA11-AS.

Liver ischemia reperfusion (IR) injury induces hepatic stellate cell (HSC) activation and liver fibrosis. Propofol (PRO) possesses a positive protective effect on liver ischemia reperfusion injury. We aimed to investigate PRO function and mechanism in IR-induced liver fibrosis. A mice model of liver IR was established. Hematoxylin-eosin (HE) staining was utilized to evaluate liver tissue's pathological changes. Masson staining was applied to evaluate liver fibrosis. The expression level of α-SMA was measured by immunohistochemical (IHC). The expressions of lncRNA HOXA11-AS (HOXA11-AS), PTBP1, HDAC4, α-SMA, COL1A1 and Fibronectin were tested by qRT-PCR or Western blot. The commercial kits detected alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in serum. Enzyme-linked immunosorbent assay (ELISA) measured TNF-α and IL-6 levels. The binding relationship between HOXA11-AS, PTBP1 and HDAC4 was verified by RNA immunoprecipitation (RIP). Our results showed that PRO alleviated liver fibrosis and the inflammation in IR-induced mice. PRO decreased the expression levels of HOXA11-AS, PTBP1 and HDAC4. Furthermore, HOXA11-AS overexpression abolished the protective effect of PRO against liver fibrosis in mice with IR-disposed. HOXA11-AS interacted with PTBP1 to regulate HDAC4 level and prevented its degradation in JS-1 cells. HDAC4 silencing eliminated the regulatory of HOXA11-AS overexpression on fibrosis and inflammation in IR-induced mice PRO inhibited HOXA11-AS expression to regulate HDAC4, thereby influencing liver fibrosis and inflammation induced by IR. It suggesting that PRO plays a protective role in liver fibrosis induced by ischemia-reperfusion in mice by regulating HOXA11-AS/PTBP1/HDAC4 axis.

Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy. / å³ç¾Žæ‰˜å’ªå®šå¯¹è€å¹´æ‚£è€ è‚å¶åˆ‡é™¤æœ¯åŽè°µå¦„å’Œæ—©æœŸæœ¯åŽè®¤çŸ¥åŠŸèƒ½éšœç¢çš„é¢„é˜²æ•ˆæžœ.

OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 µg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 µg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1ß, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1ß decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1ß at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1ß and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.

Four-factor prothrombin complex concentrate plus andexanet alfa for reversal of factor Xa inhibitor-associated bleeding: Case series.

PURPOSE: To manage factor Xa (FXa) inhibitor-associated bleeding, andexanet alfa or 4-factor prothrombin concentrate (4F-PCC) has been used to restore hemostasis. However, literature on the outcomes for patients who received both andexanet alfa and 4F-PCC is limited. SUMMARY: We report a case series of 5 patients who received andexanet alfa plus 4F-PCC for reversal of FXa inhibitor-associated bleeding. Patients were included in this case series if they received both andexanet alfa and 4F-PCC for reversal of FXa inhibitor-associated bleeding. They were followed to either discharge or death, and in-hospital complications related to concurrent use of andexanet alfa and 4F-PCC were documented. We report an incidence of thromboembolism of 40% (2 of 5 cases) and an in-hospital mortality rate of 60% (3 of 5 cases). Taking these cases together with those in the existing literature, we found a total of 23 reported cases of safety outcomes with andexanet alfa plus 4F-PCC. The overall incidence of thromboembolism was 35% (8 of 23 cases). CONCLUSION: This case series adds to the limited literature describing the outcomes for patients receiving andexanet alfa plus 4F-PCC. We encourage other institutions to report safety data on administering both agents.

Evaluation of Free Valproate Concentration in Critically Ill Patients.

Protein binding of valproate is variable in ICU patients, and the total valproate concentration does not predict the free valproate concentration, even when correcting for albumin. We sought to quantify valproate free concentration among ICU patients, identify risk factors associated with an increasing free valproate concentration, and evaluate the association between free valproate concentration with potential adverse drug effect. DESIGN: Retrospective multicenter cohort study. SETTING: Two academic medical centers. PATIENTS: Patients greater than or equal to 18 years of age with concomitant free and total valproate concentrations collected in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifty-six patients were included in the study, with a median age of 56 years (42-70) and 65% of patients were male. The median total valproate concentration was 53 µg/mL (38-70 µg/mL), the free valproate concentration was 12 µg/mL (7-20 µg/mL), and the free fraction was 23.6% (17.0-33.9%). Therapeutic discordance between the free and total valproate concentration occurred in 70% of patients. On multivariable analysis, increased free valproate concentration was associated with higher total valproate concentration (per 5 µg/mL increase, increase 1.72 µg/mL, 95% CI, 1.48-1.96) and lower serum albumin (per 1 g/dL decrease, increase 4.60 µg/mL, 95% CI, 2.71-6.49). There was no association between free valproate concentration and adverse effects. CONCLUSIONS: The valproate total and free concentration was discordant in the majority of patients (70%). Increased valproate free concentration was associated with hypoalbuminemia and total valproate concentration. Clinical decisions based on total valproate concentration may be incorrect for many ICU patients. Prospective, controlled studies are needed to confirm these findings and their clinical relevance.

Dexmedetomidine alleviates inflammation in neuropathic pain by suppressing NLRP3 via Nrf2 activation.

The aim of the present study was to investigate the mechanism by which dexmedetomidine (DEX) alleviates neuropathic pain in a chronic constriction injury (CCI) model in rats. A CCI rat model was established through sciatic nerve ligation. CCI rats were treated with DEX, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385, the NLR family pyrin domain containing 3 (NLRP3) antagonist MCC950 and/or the NLRP3 activator nigericin. The mechanical withdrawal threshold (MWT) was measured to assess the pain sensitivity of CCI rats. Hematoxylin and eosin staining and TUNEL staining were used to examine spinal injury and apoptosis, respectively. ELISA was used to quantify the levels of inflammatory factors. The expression levels of Nrf2 and NLRP3 were also examined. The results indicated that a decrease in MWT and increases in spinal cord injury, apoptosis and inflammatory factors were detected in CCI rats compared with control rats. Spinal inflammation was abrogated in DEX-treated CCI rats. Compared with the model group, an increase in MWT and decreases in spinal cord injury, apoptosis and inflammatory factors were detected in rats treated with MCC950, while the opposite effects were observed in rats treated with nigericin. The opposite effects on these indicators were observed in the DEX + ML385 and MCC950 + ML385 groups compared with the DEX and MCC950 groups, respectively. MWT was increased, while spinal cord injury, apoptosis and inflammation decreased in the nigericin + DEX group compared with the nigericin group. In summary, the results of the present study indicated that DEX reduced neuropathic pain in CCI rats by suppressing NLRP3 through Nrf2 activation.

Propofol suppressed cell proliferation and enhanced apoptosis of bladder cancer cells by regulating the miR-340/CDK2 signal axis.

BACKGROUND: As widely reported, propofol can effectively inhibit tumors development. However, little is known about the molecular mechanisms. Here, we proved that propofol regulated miR-340/CDK2 axis to suppress bladder cancer progression in vitro. METHODS: MicroRNA (MiR)-340 expression in 5637 cells was examined using qRT-PCR. Cyclin-dependent kinase2 (CDK2) expression was detected using both qRT-PCR and western blot. The levels of apoptosis-related proteins and cell cycle-related proteins were evaluated using western blot. CCK-8 assay and BrdU assay were conducted to evaluate cell proliferation. Moreover, flow cytometry assay was employed to assess cell cycle and cell apoptosis. Finally, dual luciferase reporter assay was employed to verify the binding relationship between miR-340 and CDK2. RESULTS: Here we showed that propofol treatment inhibited cell proliferation of 5637 cells but enhanced cell apoptosis. Propofol upregulated miR-340 in a dose and time dependent manner. MiR-340 inhibitor could reverse the effect of propofol on the proliferation and apoptosis of 5637 cells. Next, dual luciferase reporter assay displayed that miR-340 directly bound to the 3'-UTR of CDK2. Finally, inhibition of CDK2 could partly reversed the effect of miR-340 inhibitor on cell proliferation and cell apoptosis of propofol-treated 5637 cells. CONCLUSION: In total, our results proved that targeting miR340/CDK2 axis was novel to enhance the anti-tumor effects of propofol in bladder cancer in vitro, and our study provided alternative therapeutic strategies for clinical treatment of bladder cancer.

Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review.

PURPOSE: Despite its availability for more than 70 years, many details concerning methadone remain contentious, such as the dosing equivalents for intravenous and enteral administration. A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation that an equivalent enteral dose is twice the intravenous dose. METHODS: A librarian-assisted search of the PubMed and EMBASE databases identified all English-language articles with the terms methadone and bioavailability and/or conversion in the title or abstract published from inception though December 2019. A manual search of references was also performed to identify any additional articles. Studies were included in a scoping review if they were published in English and evaluated methadone bioavailability in human subjects. RESULTS: Among 65 publications initially identified, 6 studies involving a total of 50 patients were included in the review. Bioavailability data for healthy volunteers and patients with opioid use disorder, metastatic cancer, chronic pain from malignant or nonmalignant disease were available for analysis. The pooled mean (95% confidence interval) bioavailability (F) was 85.4% (75.2%-95.6%), with heterogeneity (I2) of 0. In the 4 studies that provided individual patient-level data, F was >50% in 40 of 42 patient measurements (95.2%) and ≥75% in 33 of 42 patient measurements (78.6%). CONCLUSION: Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1.3. This scoping review underscores the need for further research to establish an effective and safe ratio when converting between intravenous and enteral dosing formulations of methadone.

Effect of Dexmedetomidine-Assisted Intravenous Inhalation Combined Anesthesia on Cerebral Oxygen Metabolism and Serum Th1/Th2 Level in Elderly Colorectal Cancer Patients.

OBJECTIVE: To observe the effect of dexmedetomidine-assisted intravenous inhalation combined anesthesia on cerebral oxygen metabolism and serum Th1/Th2 levels in elderly patients with colorectal cancer. METHOD: From April 2018 to May 2020,100 elderly patients undergoing elective laparoscopic radical resection of colorectal cancer were prospectively selected and randomly divided into observation group and control group. Before induction of anesthesia, the loading dose of dexmedetomidine was given at 0.5 µg/kg, and the infusion time was 15 min. After tracheal intubation, 0.4 µg/kg/h dexmedetomidine was continuously pumped, and the infusion was stopped 40 min before the end of the operation. In the control group, the same amount of 0.9% sodium chloride was injected intravenously in the same way. 30 min before induction of anesthesia (T0), immediately before induction of anesthesia (T1), immediately after tracheal intubation (T2), 40 min before operation (T3), and immediately after operation (T4), record the blood oxygen content of the artery and internal jugular vein Difference (D(a-jv)O2), brain oxygen uptake rate (COER%), brain oxygen saturation (rSO2) mean. VAS scale, Ramsay scale, MoCA scale were taken at 6, 12, 24, and 48 h postoperatively to evaluate analgesia, sedation, and cognitive function. And monitor the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), myelin basic protein (MBP), neuron-specific enolase (NSE) and S100ß. The occurrence of restlessness and adverse reactions during the recovery period of the two groups were compared. RESULT: The levels of D(a-jv)O2, COER%, and rSO2 in the control group and observation group were higher than the preoperative basic values at T2, T3, and T4 (P < 0.05); The levels of D(a-jv)O2, COER%, and rSO2 in the observation group were lower than those in the control group at T2, T3, and T4 (P < 0.05). The VAS score and Ramsay score of the observation group were lower than those of the control group at 6, 12, 24, and 48 h after surgery, while the MoCA score was higher than that of the control group (P < 0.05). In addition, the serum IFN-γ, MBP, NSE and S100ß levels of the observation group were lower than those of the control group (P < 0.05), and the ratio of IFN-γ/IL-4 was higher than that of the control group (P < 0.05). The overall incidence of adverse reactions in the observation group was lower than that in the control group [32.0% (16/50) vs. 12.0% (6/50), P < 0.05]. CONCLUSION: Dexmedetomidine-assisted combined intravenous and inhalation anesthesia is beneficial to reduce perioperative cerebral oxygen metabolism and improve postoperative immunosuppression in elderly patients with colorectal cancer. It has a certain protective effect on nerve injury after operation, thus improving the cognitive function of patients and reducing the occurrence of adverse reactions.

Clinical effect and safety evaluation of hydromorphone combined with sufentanil in patient-controlled intravenous analgesia for patients with hepatocellular cancer and its effect on serum immune factors.

The present study aimed to explore the clinical efficacy and safety of hydromorphone combined with sufentanil in patient-controlled intravenous analgesia (PCIA) for patients with hepatocellular carcinoma (HCC) and its effect on serum immune factors in serum. Data from 385 patients with HCC, admitted to the Hunan Provincial People's Hospital (Changsha, China) from February 2015 to September 2018, were retrospectively analyzed. Laparoscopic hepatectomy was performed in all patients. A total of 180 patients who received PCIA were treated with sufentanil (control group), and 205 patients who received PCIA were treated with hydromorphone and sufentanil (study group). PCIA was used after hepatocellular cancer operation. In the control group, the analgesic pump was filled with sufentanil (2 µg/kg) and tropisetron (5 mg), whereas in the study group, the analgesic pump was filled with sufentanil (2 µg/kg), tropisetron (5 mg) and hydromorphone (5 mg). Both groups of drugs were diluted into 100 ml with normal saline and the loading dose was 5 ml; the continuous dose was 2 ml/h and the single PCIA amount was 2 ml. The visual analogue scale (VAS) and numeric sedation scale (NSS) scores at 12 and 24 h after operation, as well as and satisfaction score at 24 h after operation, were recorded. The levels of CD3+, CD4+, CD8+ lymphocytes and NK cells in the peripheral blood of patients were detected by flow cytometry. The postoperative hospitalization time, first flatulence time, first defecation time and first ambulation time, as well as the adverse reactions, were recorded. The results revealed that the satisfaction score of the patients at 24 h after operation was significantly higher in the study group than that in the control group (P<0.05). Additionally, there were no serious adverse reactions in either group. In conclusion, PCIA with hydromorphone and sufentanil can provide safe and effective analgesia, may improve the levels of immune factors and enhance the recovery ability of the patients.

The Impact of a Clonidine Transition Protocol on Dexmedetomidine Withdrawal in Critically Ill Pediatric Patients.

OBJECTIVES: This study describes our experience with a clonidine transition protocol to prevent dexmedetomidine (DEX) withdrawal in critically ill pediatric patients. METHODS: Retrospective review of electronic medical records of patients in the pediatric intensive care unit of a single tertiary children's hospital. All patients up to 19 years of age, who received concomitant DEX infusion and enteral clonidine between June 1, 2016, and May 31, 2018, were included. RESULTS: Two of 24 encounters had DEX restarted for withdrawal (8.3%). Five of 14 encounters who were transitioned to clonidine 2 mcg/kg every 6 hours required an increased dose, and 1 of 10 encounters transitioned to clonidine 4 mcg/kg every 6 hours required an increased dose (36% vs 10%, p = 0.21). For encounters with clonidine dose increases, 5 of 6 had improvements in Withdrawal Assessment Tool-1 (WAT-1) scores. Of these 5 encounters, 4 had decreasing or stable opioid and sedative requirements and 1 was transitioned to methadone. No encounters required discontinuation of clonidine owing to adverse events. Two of 24 encounters met our safety endpoint. One received a fluid bolus during the clonidine transition with no change in clonidine dosing, while the other had clonidine dose decreased for asymptomatic bradycardia. CONCLUSIONS: The 24 encounters in our retrospective study add to the limited literature available to describe dosing, initiation time, and duration of clonidine to prevent withdrawal from DEX in critically ill pediatric patients. Further research is needed to clarify the optimal dosing and duration of clonidine to prevent DEX withdrawal in pediatric patients.

Role of Metallothionein-1 and Metallothionein-2 in the Neuroprotective Mechanism of Sevoflurane Preconditioning in Mice.

This study investigated the protective effects and mechanisms of sevoflurane preconditioning (SPC) on neurons in ischemic mice. After SPC, mice were subjected to middle cerebral artery occlusion (MCAO). Cerebral infarction area, cell apoptosis, and metallothionein-1 (MT-1) and metallothionein-2 (MT-2) expressions in MCAO mice were analyzed. Mouse primary neurons were isolated and cultured to determine the location of metallothioneins (MTs) using immunofluorescence. Neurons transfected with MT-siRNA, exogenous MTs, or sh-MTF-1 were subjected to SPC and/or oxygen-glucose deprivation (OGD), and MT-1/MT-2 expression and neurotoxin release were assayed. Meanwhile, neurons were treated with the nitric oxide donor SNAP, degraded SNAP, or the peroxide initiator paraquat, and alterations in MT-1/MT-2 expression and neurotoxicity release were observed. SPC attenuated neuronal injury and apoptosis in MCAO mice. SPC could protect neurons against OGD injury and resulted in upregulated MT-1/MT-2 expression. MT-siRNA transfection led to the downregulated expression of MT-1/MT-2 and increased neurotoxicity, and the expression patterns of these neurons were different from those of neurons transfected with exogenous MTs. The knockdown of MTs could hinder the protective effect of SPC against OGD. Pretreatment with SNAP or paraquat could increase MTF-1 expression in the nucleus of neurons, protecting against OGD injury. The inhibition of nitric oxide and peroxide inhibited the protective role of SPC in OGD by downregulating MTF-1 expression. sh-MTF-1 transfection downregulated MT-1/MT-2 expression and enhanced neurotoxicity in neurons. SPC confers neuroprotection in focal cerebral ischemia mouse models by upregulating the expression of MT-1 and MT-2 by activating NO and peroxide and increasing MTF-1 expression in the nucleus.

[The concept of minimally invasive first aid and its position in emergency treatment of critical illness].

With the development of society and economy, people's requirements for emergency rescue technology and emergency services are gradually increasing. Building and improving the emergency of critical care system is an important issue currently facing. Controlling medical injuries is the goal of medical development. At present, people's requirements for first aid measures have shown a trend from invasive to minimally invasive even non-invasive. It is a new requirement for emergency medicine in the new era to establish a minimally invasive emergency system and apply the minimally invasive technology in the first-aid and critical care area, to help the patients with acute and critical illness overcome difficulties, improve outcome, and enhance the quality of life.

[Application of stroke volume variation-guided liquid therapy in laparoscopic precision hepatectomy].

OBJECTIVE: To observe the safety and impact on the short-term prognosis for patients of stroke volume variation (SVV) goal-directed fluid therapy (GDFT) in laparoscopic precision hepatectomy.
 Methods: A total of 120 patients (18-65 years old) undergoing laparoscopic precision hepatectomy were randomly divided into the fluid therapy group (group S) guided by SVV and the fluid therapy group (group C) guided by central venous pressure group (CVP), with 60 cases in each group. Mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time: at home calm (T0), the operation started (T1), began to cut the liver (T2), the hepatectomy was acheived (T3), and in the end (T4). The lactic acid was measured at T0 to T4 and 1 day after surgery (T5). The amount of blood loss, urine output and fluid supplement, the incidence of intraoperative hypotension, and the use of neophryn were recorded. The recovery of liver function, Hb, and so on were also recorded.
 Results: Compared with the group C, the number of hypotension cases, the amount of blood loss and the amount of neophryn in the group S were decreased during the operation (P<0.05), while the lactic acid values in the group S were not significantly increased than those in the group C at T3 and T4 (P<0.05) and the elevation of AST, ALT, DBIL and TBIL in the group S was significantly decreased than those in the group C at 1 and 2 d after the operation (P<0.05). Hb and Hct in the group S were higher than those in the group C at 1 d after the surgery (P<0.05). Compared with the group C, the postoperative exhaust time and hospitalization time were shortened in the group S (P<0.05), and the infection rate and ICU admission rate were decreased in the group S (P<0.05).
 Conclusion: SVV-guided GDFT in laparoscopic precise hepatectomy is safe and effective. It reduces intraoperative blood loss and benefits the short-term prognosis of patients after operations. High SVV value (13%-17%) is adopted at the liver resection stage, and SVV value with 8%-12% at the end of trans-section may be used as one of intraoperative liquid therapy in laparoscopic precise hepatectomy.

Effects of propofol combined with remifentanil anesthesia on the NO, endothelin and inflammatory cytokines in the plasma of patients with liver cirrhosis during the perioperative period.

The effects of propofol combined with remifentanil on the nitric oxide (NO), endothelin (ET-1) and inflammatory cytokines in the plasma of patients with liver cirrhosis were investigated. A retrospective analysis of 68 patients with liver cirrhosis who underwent hepatectomy in the Hunan Provincial People's Hospital from March 2016 to July 2018 was made. According to different anesthesia methods, 30 patients anesthetized with propofol were enrolled into Group A. The other 38 patients anesthetized with propofol combined with remifentanil were enrolled into Group B, and the operation time, amount of bleeding during operation and postoperative awake time of the two groups were recorded. At three separate time-points T1 (30 min before the anesthesia), T2 (after the portal triad clamping), T3 (3 days after the operation), aspartate transaminase (AST) and alanine transaminase (ALT) levels in the plasma were measured by rate method, and the levels of NO, ET-1, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The plasma NO levels at the T2 time-point were significantly lower than those at the T1 and T3 time-points (P<0.05); at the T2 time-point, the concentrations of AST, ALT, ET-1, IL-6 and TNF-α in the plasma in Group A were significantly higher than those of Group B (P<0.05), while the levels of plasma NO in Group A were the opposite (P<0.05). The anesthesia of propofol combined with remifentanil could contribute to the balance of NO/ET-1 and the inhibition of inflammatory factors during the hepatectomy operation in patients with liver cirrhosis, and help to protect the liver function of patients, reducing the incidence of liver ischemia-reperfusion injury in patients.

Dilemma of healthcare reform and invention of new discipline of health fiscalogy.

BACKGROUND: China's Reform and Open up Policy in 1980s has brought rapid economic development to Chinese society. With the deepening of economic reform, the withdrawal of the state in China has had visible and worrisome consequences for health and for the functioning of health services. The new round of healthcare reform after 2009 has made significant achievements on improving fundamental health and bringing back the nature of welfare of health. However, the financing mechanism of health system has not been established, and the underlying reason behind the healthcare reform dilemma and the theoretical solution need to be found. METHODS: This study used the methods of literature review, theoretical research and comparative research to summarize and analyze the reasons and solutions of current dilemma in healthcare reform, and created the new discipline of health fiscalogy through theoretical analysis and vertical and horizontal comparison of healthcare system, especially health financing. RESULTS: Dilemma in healthcare system emerged from the circumstances of rapid process of industrialization, urbanization and population aging, including the profit-driven phenomena, tendency of excessive marketization in public hospitals, strained doctor-patient relationship, high disease burden on individuals and families, and so on. It can be concluded that the theoretical basis of healthcare system and the nature of health resources are crucial in solving the dilemma of healthcare reform. The theoretical basis of healthcare reform should be health fiscalogy focusing on government as the main body of health care responsibility rather than health economics focusing on anti-monopoly. There are two key differences between health economics and health fiscalogy: responsible person/department of disease and health welfare, and nature of resource. The new discipline of health fiscalogy has universal and important implications on both China's healthcare reform and the healthcare reform in the world. CONCLUSIONS: China's healthcare reform should return from the paradigm of health economics and marketization financing model to the paradigm of health fiscalogy and government-led financing model, which is reflected in the main position of government and social welfare.

Heparin-free continuous vena-venous hemofiltration as a veno-venous bypass in inferior vena cava reconstruction.

OBJECTIVE: This paper investigated the effects of continuous vena-venous hemofiltration on inferior vena cava reconstruction. METHOD: Totally, 11 patients were observed, vascular access in right internal jugular vein and femoral vein catheterization was established guided by ultrasound, and heparin-free continuous vena-venous hemofiltration was used to substitute for extracorporeal veno-venous bypass. Furthermore, blood pressure, central venous pressure, urine volume, blood platelet, serum albumin, renal function, serum cystatin C, CRP, TBil, AST, ALT, serum amylase, serum lipase, PLT, PT, APTT, Fig, D-mier, and adverse events were determined. RESULTS: All operations were completed successfully. Average time of continuous vena-venous hemofiltration was 2.96 ± 0.76 h. No hematoma and blood leakage was occurred when catheters were inserted, and no luminal stenosis and catheter-related infections were observed. Visceral congestion was observed when the inferior vena cava was clamped, but significantly improved immediately after the continuous vena-venous hemofiltration was begun. No hemofilter was changed due to clotting during continuous vena-venous hemofiltration therapy. Blood pressure, central venous pressure, and urine volume of the patients maintained stable. No significant change was observed in blood platelet, serum albumin, and serum creatinin. Serum cystatin and hsCRP increased after operation, but still in normal level. CONCLUSION: Heparin-free continuous vena-venous hemofiltration was an effective mode as veno-venous bypass in the treatment of inferior vena cava interruption and reconstruction.