Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: a systematic review and network meta-analysis.

This study was to compare multiple classes of medications and medication combinations to find alternatives or additives for patients not applicable to benzodiazepines (BZDs). We performed a network meta-analysis to assess the comparative effect of 11 pharmacologic treatments in patients with alcohol withdrawal syndrome. Forty-one studies were included, comprising a total sample size of 4187 participants. The pooled results from the randomized controlled trials showed that there was no significant difference in the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) reduction with other medications or medication combinations compared to BZDs. Compared to BZDs, the mean difference in ICU length of stay of anticonvulsants + BZDs was -1.71 days (95% CI = -2.82, -0.59). Efficacy rankings from cohort studies showed that anticonvulsant + BZDs were superior to other treatments in reducing CIWA-Ar scores and reducing the length of stay in the ICU. Synthesis results from randomized controlled trials indicate that there are currently no data suggesting that other medications or medication combinations can fully replace BZDs. However, synthetic results from observational studies have shown that BZDs are effective in the context of adjuvant anticonvulsant therapy, particularly with early use of gabapentin in combination with BZDs in the treatment of alcohol withdrawal syndrome, which represents a promising treatment option.

Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission.

Mitochondrial dysfunction and oxidative stress are considered to be two main drivers of diabetic myocardial ischemia-reperfusion injury (DM + MIRI). Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Dynamin-related protein 1 (Drp1) play central roles in maintaining mitochondrial homeostasis and regulating oxidative stress, but the effects of the Nrf2-Drp1 pathway on DM-MIRI have not been reported. The aim of this study is to investigate the role of the Nrf2-Drp1 pathway in DM + MIRI rats. A rat model of DM + MIRI and H9c2 cardiomyocyte injury were constructed. The therapeutic effect of Nrf2 was assessed by detecting myocardial infarct size, mitochondrial structure, levels of myocardial injury markers and oxidative stress, apoptosis, and Drp1 expression. The results showed that DM + MIRI rats had increased myocardial infarct size and Drp1 expression in myocardial tissue, accompanied by increased mitochondrial fission and oxidative stress. Interestingly, Nrf2 agonist dimethyl fumarate (DMF) could significantly improve cardiac function, mitochondrial fission, and decrease oxidative stress levels and Drp1 expression after ischemia. However, these effects of DMF would be largely counteracted by the Nrf2 inhibitor ML385. Additionally, Nrf2 overexpression significantly suppressed Drp1 expression, apoptosis, and oxidative stress levels in H9c2 cells. Nrf2 attenuates myocardial ischemia-reperfusion injury in DM rats by reducing Drp1-mediated mitochondrial fission and oxidative stress.

Resveratrol mediates the miR-149/HMGB1 axis and regulates the ferroptosis pathway to protect myocardium in endotoxemia mice.

Endotoxemia is a common complication often used to model the acute inflammatory response associated with endotoxemia. Resveratrol has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and antioxidant properties. This study explored the effect of resveratrol on endotoxemia. Lipopolysaccharide (LPS)-induced endotoxemia mouse model and endotoxemia myocardial injury cell model were established and treated with resveratrol. Cardiomyocyte activity, lactate dehydrogenase (LDH) content in cell supernatant, glutathione (GSH) consumption, lipid reactive oxygen species (ROS) production, and iron accumulation were detected. Cardiac function indexes [left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), ejection fraction (EF)%, and fractional shortening (FS)%] were measured using echocardiography. The creatine kinase muscle/brain isoenzyme (CK-MB) and CK levels in the serum were detected using an automatic biochemical analyzer. The downstream target of miR-149 was predicted, and the binding relationship between miR-149 and high mobility group box 1 (HMGB1) was verified using a dual-luciferase assay. miR-149 and HMGB1 expressions were detected using RT-qPCR and Western blot. After resveratrol treatment, cardiomyocyte viability and GSH were increased, and LDH secretion, lipid ROS production, lipid peroxidation, and iron accumulation were decreased, and cardiac function and cardiomyocyte injury were improved. Resveratrol improved LPS-induced endotoxemia cardiomyocyte injury by upregulating miR-149 and inhibiting ferroptosis. Resveratrol inhibited HMGB1 expression by upregulating miR-149. HMGB1 upregulation reversed the inhibitory effect of miR-149 on LPS-induced ferroptosis in cardiomyocytes. Resveratrol upregulated miR-149 and downregulated HMGB1 to inhibit ferroptosis and improve myocardial injury in mice with LPS-induced endotoxemia. Collectively, resveratrol upregulated miR-149, downregulated HMGB1, and inhibited the ferroptosis pathway, thus improving cardiomyocyte injury in LPS-induced endotoxemia.NEW & NOTEWORTHY Sepsis is an unusual systemic reaction. Resveratrol is involved in sepsis treatment. This study explored the mechanism of resveratrol in sepsis by regulating the miR-149/HMGB1 axis.

The appropriate dose of propofol for anesthesia induction in morbidly obese patients.

BACKGROUND: To investigate the optimal dose of propofol in patients with morbid obesity when the anesthetic induction dosage is calculated based on lean body weight (LBW). METHODS: Forty morbid obese patients with body mass index (BMI) ≥35 kg/m2 were randomly divided into two groups: B and M. The sequential method was used in group B to study the EC50 and 95% confidence interval (CI) that met a bispectral index (BIS) value of <50 (the initial dose was set at 2.5 mg/kg). The sequential method was used in group M to obtain the EC50 and 95% CI (the initial dose was set as 3.0 mg/kg) satisfying the mean arterial pressure (MAP) fluctuation margin of >40%. The optimal dose interval of propofol was obtained by synthetically analyzing the results of the two-sequence method. RESULTS: There was no significant difference in the general condition between the two groups (P>0.05). There was no significant change in vital signs from when patients entered the operating room to when sufentanil was infused (P>0.05). The probit model of group B was Y=-5.411+2.343X, the EC50 of positive reaction with BIS <50 was 2.310 mg/kg, and 95% CI was 1.850-2.883 mg/kg. The probit model in the M group was Y=3.275 - 0.918X, the EC50 of positive reaction that reached >40% of the whole process of anesthetic induction was 3.567 mg/kg, and 95% CI was 1.233-7.165 mg/kg. CONCLUSIONS: The appropriate dosage of propofol was 2.310-3.567 mg/kg when the anesthetic induction dosage for patients with morbid obesity was calculated based on LBW. With this dose, the depth of intubation is satisfactory and the hemodynamics are stable.

Study on the correlation between OPRM1 A118G gene polymorphism(rs1799971) and dosage of opioid analgesics in patients after lumbar decompression / 中国基层医药

Objective:To study the correlation between OPRM1 A118G gene polymorphism (rs1799971) and the dosage of opioid analgesics in patients after lumbar decompression.Methods:From July 2017 to September 2018, 147 patients undergoing selective posterior lumbar decompression under general anesthesia in the People's Hospital of Xinjiang Uygur Autonomous Region were treated with sufentanil intravenous controlled analgesia(PCIA). The gene polymorphism was detected by PCR.The VAS, Ramasy sedation score, total dosage of sufentanil and adverse reactions of sufentanil in 48 h after operation were observed.Results:The genotype frequencies of AA, GA and GG were 30.6%, 55.5% and 13.9%, respectively, the difference was statistically significant(χ 2=6.324, P=0.423), and G and A allele frequencies were 41.7%, 58.3%, respectively, the difference was statistically significant(χ 2=5.559, P=0.184). There were no statistically significant differences in SpO 2, Ramasay sedation score and VAS score among the groups after operation(all P>0.05). The total dosage of sufentanil in OPRM1 mutant GG[(151.0±23.4)μg] and GA[(132.0±19.1)μg] was higher than that in AA[(123.0±16.2)μg] within 48 h of PCIA, the differences were statistically significant( t=5.206, 2.817, all P<0.05). Conclusion:The OPRM1 A118G gene polymorphism(rs1799971) is correlated with the dosage of opioid analgesics after lumbar decompression.