Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain.

Central poststroke pain (CPSP) induced by thalamic haemorrhage (TH) can be continuous or intermittent and is accompanied by paresthesia, which seriously affects patient quality of life. Advanced insights into CPSP mechanisms and therapeutic strategies require a deeper understanding of the molecular processes of the thalamus. Here, using single-nucleus RNA sequencing (snRNA-seq), we sequenced the transcriptomes of 32332 brain cells, which revealed a total of four major cell types within the four thalamic samples from mice. Compared with the control group, the experimental group possessed the higher sensitivity to mechanical, thermal, and cold stimuli, and increased microglia numbers and decreased neuron numbers. We analysed a collection of differentially expressed genes and neuronal marker genes obtained from bulk RNA sequencing (bulk RNA-seq) data and found that Apoe, Abca1, and Hexb were key genes verified by immunofluorescence (IF). Immune infiltration analysis found that these key genes were closely related to macrophages, T cells, related chemokines, immune stimulators and receptors. Gene Ontology (GO) enrichment analysis also showed that the key genes were enriched in biological processes such as protein export from nucleus and protein sumoylation. In summary, using large-scale snRNA-seq, we have defined the transcriptional and cellular diversity in the brain after TH. Our identification of discrete cell types and differentially expressed genes within the thalamus can facilitate the development of new CPSP therapeutics.

[Effects of transcutaneous electrical acupoint stimulation on quality of recovery during early period after laparoscopic cholecystectomy].

OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the quality of recovery during the early period after laparoscopic cholecystectomy and the dosage of anesthetic and analgesic. METHODS: One hundred patients who received laparoscopic cholecystectomy with gradeⅠand Ⅱ of American Society of Anesthesiologists (ASA) criteria were randomly assigned into an observation group and a control group according to random number table, 50 cases in each group. The patients in the two groups were treated with conventional endotracheal intubation anesthesia, anesthesia induction and maintenance. The patients in the observation group were treated with TEAS (2 Hz/100 Hz, 8 to 12 mA) at bilateral Hegu (LI 4) and Neiguan (PC 6), as well as Zusanli (ST 36) and the non-acupoint 2 cun outboard from Zusanli (ST 36) from 30 min before anesthesia induction to the end of operation. The patients in the control group were applied by stimulation electrode in the corresponding points without electrical stimulation. The dosage of intraoperative remifentanil and the analgesic dosage of dezocine for postoperation were recorded. The recovery time, extubation time, the changes of heart rate (HR) and mean arterial pressure (MAP) during extubation were recorded. The quality of recovery was assessed by the quality of recovery-40 questionnaire (QoR-40) 1 day before surgery (T0)，and 4 h (T1), 8 h (T2), 24 h (T3), 48 h (T4) after surgery. The patient's cognitive function was assessed by mini-mental state examination (MMSE) scale at the 5 time points. The incidences of postoperative nausea and vomiting were recorded at T1 through T4. RESULTS: The dosages of intraoperative remifentanil and dezocine in the observation group were less than those in the control group; the recovery time and extubation time were shorter than those in the control group; the HR of extubation was lower than that in the control group (all P<0.05). There was no statistic difference about MAP between the two groups (P>0.05). Compared with T0, the total scores of QoR-40 decreased in the two groups at T1, T2, T3 (all P<0.05), and the total scores in the observation group were higher than those in the control group (all P<0.05). The emotional state, physical comfort, psychological support, self-care ability, pain scores at T1 in the observation group and at T1, T2, T3 in the control group were lower than those at T0 (all P<0.05). The emotional state, physical comfort, psychological support, self-care ability, pain scores in the observation group were higher than those in the control group at T1, T2, T3 (all P<0.05). Compared with T0, the MMSE scores in the two groups decreased at T1 and T2 (all P<0.05). At T1, T2, T3, the MMSE scores in the observation group were higher than those in the control group (all P<0.05). At T1 and T2, the incidence rates of nausea and vomiting were 22.0% (11/50), 12.0% (6/50) respectively in the observation group, which were lower than 32.0% (16/50) and 24.0% (12/50) in the control group (both P<0.05). At T3 and T4, the incidence rates of nausea and vomiting were 6.0% (3/50), 2.0% (1/50) respectively in the observation group, which were not significantly different from 8.0% (4/50) and 4.0% (2/50) in the control group (both P>0.05). CONCLUSION: TEAS can improve the quality of recovery during the early period after laparoscopic cholecystectomy and reduce the dosage of anesthetic and analgesic.

[Effects of ulinastatin on cognitive function in patients with coronary artery bypass grafting].

OBJECTIVE: To investigate the effects of ulinastatin(UTI) on postoperative cognitive function in patients undergoing coronary artery bypass grafting. METHODS: One hundred and twenty-seven patients undergoing elective coronary artery bypass surgery were randomly divided into three groups:high-dose UTI group(16000 U/kg i.v.), low-dose UTI group(8000 U/kg i.v.) and control group(normal saline). The levels of plasma cortisol were measured before and one day after surgery. The level of IL-6, IL-10, TNF-α and S100ß were measured before operation(T0), at open chest(T1), end of operation(T2), 6 h(T3)and 24 h(T4) after operation. A neuropsychological test scale was to evaluate the cognitive function 1 day before operation, 1 week and 3 months after operation. RESULTS: Ninety-three patients completed the study. There was no significant difference in general information of patients among three groups(P>0.05). The level of plasma cortisol one day after operation was significantly higher than that before operation in control group(P<0.01). The levels of plasma cortisol in high-dose UTI group and low-dose UTI group were lower than that of control group(P<0.01). In all groups, the level of plasma IL-6, IL-10, TNF-α and S100B increased remarkably at T2, T3, T4 compared to those at T0(all P<0.05). The level of plasma IL-6, TNF-α(at T2, T3, T4)and S100ß(at T3)in high-dose UTI group and low-dose UTI group were all lower than those of control group(P<0.05),while there were no significant differences between high-dose UTI group and low-dose UTI group(P>0.05). The incidence of postoperative cognitive dysfunction in POCD 1 week after operation in high-dose UTI and low-dose UTI groups(25.8% and 23.3%)was lower than that in control group(50.0%), while there were no significant difference 1 month after operation between high-dose UTI group(12.9%) or low-dose UTI group(16.7%)and control group(28.1%). The level of plasma S100ß at T2 of POCD patients(n=31)was higher than that of non-POCD group(n=62)(P<0.05). CONCLUSION: Ulinastatin can reduce the incidence of postoperative cognitive dusfunction 1 week after coronary artery bypass surgery, which might be associated with inhibition of inflammation and S100ß expression.

The action sites of propofol in the normal human brain revealed by functional magnetic resonance imaging.

Propofol has been used for many years but its functional target in the intact brain remains unclear. In the present study, we used functional magnetic resonance imaging to demonstrate blood oxygen level dependence signal changes in the normal human brain during propofol anesthesia and explored the possible action targets of propofol. Ten healthy subjects were enrolled in two experimental sessions. In session 1, the Observer's Assessment of Alertness/Sedation Scale was performed to evaluate asleep to awake/alert status. In session 2, images with blood oxygen level dependence contrast were obtained with echo-planar imaging on a 1.5-T Philips Gyroscan Magnetic Resonance System and analyzed. In both sessions, subjects were intravenously administered with saline (for 3 min) and then propofol (for 1.5 min) and saline again (for 10.5 min) with a constant speed infusion pump. Observer's Assessment of Alertness/Sedation Scale scoring showed that the subjects experienced conscious­sedative­unconscious­analepsia, which correlated well with the signal decreases in the anesthesia states. Propofol induced significant signal decreases in hypothalamus (18.2%±3.6%), frontal lobe (68.5%±11.2%), and temporal lobe (34.7%±6.1%). Additionally, the signals at these three sites were fulminant and changed synchronously. While in the thalamus, the signal decrease was observed in 5 of 10 of the subjects and the magnitude of decrease was 3.9%±1.6%. These results suggest that there is most significant inhibition in hypothalamus, frontal lobe, and temporal in propofol anesthesia and moderate inhibition in thalamus. These brain regions might be the targets of propofol anesthesia in human brain.