Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.

Objective To investigate the effects and related molecular mechanisms of esket-amine on the proliferation,epithelial-mesenchymal transition(EMT),and stem cell properties of colorectal cancer(CRC)cells.Methods CRC cell line SW480 was cultured with varying concentra-tions of esketamine,and the cells were divided into blank group(0 μmol/L),low-concentration group(1 μmol/L),medium-concentration group(5 μmol/L)and high-concentration group(10 μmol/L).Cell proliferation activity was assessed using the EdU proliferation assay,cell spheroid-forming ability was evaluated via the spheroid formation assay,cell migration capacity was measured using the scratch assay,cell invasion ability was determined through the transwell assay,and the expression levels of tumor stem cell property markers[NANOG homeobox(NANOG),SRY-box transcription fac-tor(SOX)2,SOX4],the neurogenic locus Notch homolog protein 1(Notch1)receptor and the Notch1 intracellular domain(Notch1 ICD)were detected by western blot.A recovery test was con-ducted by adding the Notch1 receptor agonist Jagged1 to the culture groups with different concentra-tions of esketamine.Results Compared with the blank group,esketamine significantly inhibited the proliferation activity,spheroid-forming ability,migration ability,and invasion ability of CRC cells in a concentration-dependent manner.The intracellular expression levels of SOX2,SOX4,NANOG,and Notch1 ICD proteins were significantly decreased,while the expression level of the Notch1 recep-tor was significantly increased in the esketamine groups(P＜0.05).After the addition of Jagged1,the inhibitory effects of esketamine on the proliferation activity,metastatic ability,and stem cell properties of CRC cells were alleviated.Conclusion Esketamine inhibits CRC cell proliferation,metastasis,EMT,and stem cell properties by reducing the activation level of the Notch1 receptor,demonstrating a potential for clinical anti-tumor applications.

Objective:To observe the hemodynamic change and inhibitory effect on stress response of oxycodone during induction, maintenance and resuscitation period of general anesthesia in patients undergoing gastric cancer surgery.Methods:60 patients with general anesthesia undergoing elective gastric cancer from March 2018-March 2019 in No.904 Hospital were selected. According to the random number table method, they were randomly divided into two groups ( n=30): Oxycodone group (group O) and Fentanyl group (group F). The anesthesia was induced by intravenous oxycodone 0.3 mg/kg (group O) or fentanyl 3 μg/kg (group F), propofol 2 mg/kg and cisatracurium 0.25 mg/kg. Oxycodone (group O) or fentanyl (group F) with sevoflurane were used for maintenance of general anesthesia. The mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia induction (T 0), immediately intubation (T 1), 1 min (T 2) and 5 min (T 3) after intubation, immediately skin incision (T 4), surgery for 1 h (T 5), the end of operation (T 6) and 1 min (T 7) and 5 min (T 8) after extubation. The concentration of glucose (Glu), cortisol (Cor), epinephrine (E) and norepinephrine (NE) were detected in time T 0,T 2, T 4,T 5 and T 7. The time of extubation and the visual analogue scale (VAS) scores after extubation and 30 min after entering postanesthesia care unit (PACU) were recorded. The incidence of cough during induction, dysphoria during extubation and the adverse effects such as nausea, vomit and respiratory depression during PACU were also observed. Results:There were no significant difference between two groups in MAP and HR at the time point from T 0 to T 8 ( P>0.05); there were no significant difference about concentrations of Glu, Cor, E and NE at the time point of T 0,T 2,T 4,T 5 and T 7 ( P>0.05). Extubation time and VAS scores of 30 min after entering PACU in group O were significantly lower than those of group F ( P<0.05). Meanwhile, the incidences of cough during induction, dysphoria during extubation and respiratory depression in group O were significantly lower than in group F ( P<0.05). There was no significant difference in the incidence of nausea and vomiting ( P>0.05). Conclusions:Oxycodone can be safely and effectively used for induction and maintenance of general anesthesia in gastric cancer surgery, inhibit intraoperative stress response, and improve the quality of recovery period.

Objective To investigate the effects of remifentanil in painless bronchoscopic examination of elderly panents.Methods One hundred and twenty elderly patients undergoing painless bronchoscopic examination were randomly divided into 4 groups (n=30),the group A was administered with propofol and the groups B,C and D were administered with propofol and remifentanil(remifentanil dose:0.05 μg · kg-1 · min-1 in the group B,0.10μg · kg-1 · min-1 in the group C and 0.15 μg · kg-1 · min-1 in the group D).The body moving response,hemodynamic changes,propofol dose,examination time,wake-up time,departure time and adverse reactions in each group were observed during the examination process.Results During the examination process,the body moving response and bucking of the group A were significantly higher than those of the other three groups(P＜0.05);in hemodynamics,the group A fluctuated greatly,while the group B,C and D were relatively stable,but the incidence rate of hypotension,bradycardia and transient respiratory depressionof the group D were higher than those of the other three groups(P＜0.05);propofol dose of the group A was significantly higher than that of the other three groups (P＜0.05)and the group B was higher than the group C and D(P＜0.05).In wake-up time and departure time,the groups B,C,D were significantly better than the group A(P＜0.05),while the group C and D were better than the group B(P＜0.05).Conclusion Remifentanil can be used in painless bronchoscopic examination for elderly patients,and the effect is better by using propofol combined with remifentanil at a dose of 0.1 μg · kg-1 · min-1.

Objective To observe effect of intra-and post-operative mild hypothermia using an ice blanket on patients with severe traumatic brain injury (sTBI).Methods Twenty sTBI patients with Glasgow Coma Scale (GCS) of 3-8 points were included and were assigned to either ice bag cooling (Bag group) or ice blanket cooling (Blanket group) (n =10 each) according to random number table.Patients in Bag group had temperature reduction by placing ice bag over great vessels,whereas in Blanket group an ice blanket (temperature was set as the nasopharyngeal temperature of 33℃-34℃) was employed to have temperature reduction.Hypothermia therapy in the two group groups was initiated from the beginning of operation and continued for 48 hours after operation.Intracranial pressure,cerebral perfusion pressure (CPP) and GCS in both groups were recorded respectively at 10 minutes before operation (T0) and at 8,12,24,48 and 72 hours after operation (T1,T2,T3,T4 and T5).Venous blood of the two groups was harvested to assay the serum concentration of neuronspecific enolase (NSE),myelin basic protein (MBP)and S-100β at T0,T3,T4,-Ts and at 96 hours after operation (T6) by ELISA method.Glasgow Outcome Scale (GOS) was evaluated at postoperative six months.Results In Bag group,body temperature (T1-T5) of the patients had no significant decrease (P ＞ 0.05) and NSE (T3-T6),S-100β (T3-T6) and MBP (T4-T6) were increased (P ＜ 0.05 or 0.01) when compared with those in T0 ; intracranial pressure (T2-T5) was increased (P ＜ 0.05) and CPP (T3-T5) was lowered (P ＜ 0.05) when compared with those in T1.In Blanket group,body temperature (T1-T6) of the patients presented was decreased significantly (P ＜ 0.01) and NSE (T3-T6),MBP (T5-T6) and S-100β (T4-T6) were increased (P ＜ 0.05 or 0.01) when compared those in T0 ; intracranial pressure (T2-T6) was increased (P ＜ 0.05) and CPP had no significant changes (P ＞0.05) when compared with those in T1.By contrast with those in the same time points in Bag group,lower body temperature (T1-T5) (P ＜ 0.001),lower intracranial pressure (T2-T5),higher CPP (T3-T5) as well as lower NSE (T4-T6),MBP (T4-T6) and S-100β(T6)were observed in Blanket group (P ＜0.05 or 0.01).Changes of GCS and GOS in the two groups were no significance (P ＞0.05).Conclusion Intraoperative and postoperative mild hypothermia therapy using an ice blanket may alleviate the degree of brain injury in sTBI patients.

Objective To study the changes of biochemical markers of bone turnover and bone mineral density (BMD) in mid- and old-aged women.Methods A total of 408 female volunteers aged 40 to 86 years were enrolled.Serum bone alkaline phosphatase (BAP),osteoealtin and urine type I collagen N-telopeptide(uN'TX) were measured using ELISA,and BM D at anteroposterior lumbar spine 1-4(L1-4)and femoral neck (FN) was detected by dual energy X-ray absorptiometry (QDR4500A).Results (1) Serum BAP,osteocaltin and uNTX levels were positively correlated with age,parity,number of births and duration of menopause (all P

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel,which can be activated by multiple pathways during the course of the diseases.Recent studies indicate that primary sensory neurons of the pancreas express TRPV1 receptor and the activation of TRPV1 receptor promotes pancreatic inflammation.Moreover,blockade of these transient receptor potential channels can greatly ameliorate the pain response in experimental pancreatitis.