Anti-nociceptive Effects of Dexmedetomidine Infusion Plus Modified Intercostal Nerve Block During Single-port Thoracoscopic Lobectomy: A Double-blind, Randomized Controlled Trial.

BACKGROUND: Multimodal general anesthesia based on modified intercostal nerve block (MINB) has been found as a novel method to achieve an intraoperative opioid-sparing effect. However, there is little information about the effective method to inhibit visceral nociceptive stress during single-port thoracoscopic surgery. OBJECTIVE: To investigate whether a low-dose dexmedetomidine infusion followed by MINB might be an alternative method to blunt visceral stress effectively. STUDY DESIGN: Double-blind, randomized control trial. SETTING: Affiliated hospital from March 2020 through September 2020. METHODS: Fifty-four patients were randomized (1:1), 45 patients were included to receive dexmedetomidine with a 0.4 microgram/kg bolus followed by 0.4 microgram/kg/h infusion (group Dex) or saline placebo (group Con). During the operation, an additional dose of remifentanil 0.05-0.25 microgram/kg/min was used to keep mean arterial pressure (MAP) or heart rate (HR) values around 20% below baseline values. The primary outcome was to evaluate remifentanil consumption. Secondary outcomes included intraoperative hemodynamics, the first time to press an analgesia pump, and adverse effects. RESULTS: Remifentanil consumption during surgery was markedly decreased in the Dex group than in the Con group (0 [0-0] versus 560.0 [337.5-965.0] microgram; P = 0.00). MAP and HR in the Con group during the first 5 minutes after visceral exploration was significantly higher than in the Dex group (P < 0.05). Time to first opioid demand was significantly prolonged (P = 0.04) and postoperative length of stay was shortened slightly in the Dex group (P = 0.05). LIMITATIONS: This study was limited by the measurement of nociception. CONCLUSIONS: This study demonstrates that low-dose dexmedetomidine infusion combined with MINB might be an effective alternative method to blunt visceral stress in patients undergoing single-port thoracoscopic lobectomy. Furthermore, the analgesic effect of MINB was significantly prolonged after dexmedetomidine infusion.

The expanded effects of sevoflurane on the nervous system: the harmful effect of residual concentration of sevoflurane on the respiratory system through neurogenic inflammation.

Background: Neurogenic inflammation caused by sevoflurane may not only limite to the nervous system, but also expand to the respiratory system. The purpose of this study was to investigate the expression changes of transient receptor potential vanilloid 1 (TRPV1), neurokinin A (NKA), neurokinin B (NKB), calcitonin gene related peptide (CGRP) and substance P (SP) in 14, 21 and 42-day-old rats after inhaling 0.4% sevoflurane, in order to evaluate whether the residual sevoflurane be harmful to the respiratory system through neurogenic inflammation. Methods: The anesthetic inhalation device was designed to allow 14, 21 and 42-day-old rats inhale 0.4% sevoflurane, while rats in the control group inhaled 40% O2 for 1h. Rats in the antagonist group inhaled 0.4% sevoflurane or 40% O2 for 1 h after Capsazepine (CPZ) pretreatment. The expression of TRPV1 in lung tissue was detected by western blot, and the expression of NKA, NKB, CGRP and SP in trachea was detected by immunohistochemistry. Results: After inhaling 0.4% sevoflurane, the expression of TRPV1 in lung tissue of 14 and 21-day-old rats was significantly higher than that of the control group, as well as increased the expression of CGRP and SP in the trachea of 14-day-old rats and NKA, NKB, CGRP and SP in the trachea of 21-day-old rats. CPZ pretreatment could antagonize these effects. Conclusion: Residual sevoflurane during resuscitation of inhalation anesthesia could induce neurogenic inflammation by activating TRPV1, which damaged to the developing respiratory system, but has no significant effect on the respiratory system in adulthood.

Bioequivalence of two esomeprazole magnesium enteric-coated formulations in healthy Chinese subjects.

BACKGROUND: The pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well studied. AIM: To evaluate the pharmacokinetic characteristics of esomeprazole magnesium (Eso) enteric- coated capsule in the healthy subjects in China and the bioequivalence of the two formulations. METHODS: This study was conducted in the Phase I Clinical Trial Unit of the Affiliated Hospital of Changchun University of Chinese Medicine. A total of 64 healthy subjects were enrolled in the study. Thirty-two subjects fasted or fed, took the test or reference formulation Eso enteric-coated capsule by a four-cycle, two-sequence crossover of fasting/fed, self-controlled method. The liquid chromatography-mass spectrometry was performed to determine the drug plasma concentration at 16 different time points within 12 h after drug administration. The pharmacokinetic parameters Cmax, area under the curve (AUC)0-t, and AUC0-inf were calculated to evaluate the bioequivalence. RESULTS: Pharmacokinetic parameters were evaluated after subjects took the test formulation and control formulation under fasting status. The ratio of geometric means of Cmax was 104.15%, with a confidence interval (CI) of 98.20-110.46%. The ratio of geometric means of AUC0-t was 105.26%, with a CI of 99.80-111.01%. The ratio of geometric means of AUC0-inf was 105.37%, with a CI of 99.97-111.06%. The pharmacokinetic parameters were also evaluated after subjects took the reference formulation of Eso enteric-coated capsule after eating. The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state Cmax was -0.1689, and the point estimate was 0.9509 (0.80-1.25). The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-t was -0.1015 (≤ 0) , and the point estimate was 0.9003 (0.80-1.25). The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-inf was -0.0593 (≤ 0), and the point estimate was 0.8453 (0.80-1.25). The results indicated that the two formulations were bioequivalent under both fasting and fed states. CONCLUSION: The two types of esomeprazole tablets were bioequivalent under both fasting and fed states, and both were generally well tolerated.

Spatiotemporal dynamics and impacts of socioeconomic and natural conditions on PM2.5 in the Yangtze River Economic Belt.

The determination of the spatiotemporal patterns and driving factors of PM2.5 is of great interest to the atmospheric and climate science community, who aim to understand and better control the atmospheric linkage indicators. However, most previous studies have been conducted on pollution-sensitive cities, and there is a lack of large-scale and long-term systematic analyses. In this study, we investigated the spatiotemporal evolution of PM2.5 and its influencing factors by using an exploratory spatiotemporal data analysis (ESTDA) technique and spatial econometric model based on remote sensing imagery inversion data of the Yangtze River Economic Belt (YREB), China, between 2000 and 2016. The results showed that 1) the annual value of PM2.5 was in the range of 23.49-37.67 µg/m3 with an inverted U-shaped change trend, and the PM2.5 distribution presented distinct spatial heterogeneity; 2) there was a strong local spatial dependence and dynamic PM2.5 growth process, and the spatial agglomeration of PM2.5 exhibited higher path-dependence and spatial locking characteristics; and 3) the endogenous interaction effect of PM2.5 was significant, where each 1% increase in the neighbouring PM2.5 levels caused the local PM2.5 to increase by at least 0.4%. Natural and anthropogenic factors directly and indirectly influenced the PM2.5 levels. Our results provide spatial decision references for coordinated trans-regional air pollution governance as well as support for further studies which can inform sustainable development strategies in the YREB.

Sevoflurane Prevents Airway Remodeling via Downregulation of VEGF and TGF-ß1 in Mice with OVA-Induced Chronic Airway Inflammation.

Asthma is characterized by chronic airway inflammation, which is the underlying cause of airway remodeling featured by goblet cell hyperplasia, subepithelial fibrosis, and proliferation of smooth muscle. Sevoflurane has been used to treat life-threatening asthma and our previous study shows that sevoflurane inhibits acute lung inflammation in ovalbumin (OVA)-induced allergic mice. However, the effect of sevoflurane on airway remodeling in the context of chronic airway inflammation and the underlying mechanism are still unknown. Here, female C57BL/6 mice were used to establish chronic airway inflammation model. Hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Sirius red (SR) staining were used to evaluate airway remodeling. Protein levels of α-SMA, VEGF, and TGF-ß1 in lung tissues were detected by western blotting analyses and immunohistochemistry staining. Results showed that inhalation of sevoflurane inhibited chronic airway inflammation including inflammatory cell infiltration and pro-inflammatory cytokine production in BALF of the OVA-challenged mice. Meanwhile, sevoflurane suppressed airway thickening, goblet cell hyperplasia, smooth muscle hyperplasia, collagen deposition, and fiber hyperplasia in the lung tissues of the mice with airway remodeling. Most notably, sevoflurane inhibited the OVA-induced expressions of VEGF and TGF-ß1. These results suggested that sevoflurane effectively inhibits airway remodeling in mouse model of chronic airway inflammation, which may be due to the downregulation of VEGF and TGF-ß1in lung tissues. Therefore, our results indicate a potential role of sevoflurane in inhibiting airway remodeling besides its known suppression effect on airway inflammation, and support the use of sevoflurane in treating severe asthma in ICU.

C-kit gene mutation in human gastrointestinal stromal tumors.

AIM: To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST). METHODS: Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%), and no mutation was found in benign tumors. The mutation rate showed significant difference (chi2=14.39, P<0.01) between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 malignant peripheral nerve sheath tumors, 2 intra-abdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas. CONCLUSION: C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.