Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective To observe the application effect of different doses of dexmedetomidine in thyroid surgery under recurrent laryngeal nerve monitoring.Methods A total of 60 patients with thyroid surgery un-der general anesthesia,moreover adopting recurrent laryngeal nerve monitoring during the operation,in this hospital from October 2021 to June 2023 were selected as the study subjects and divided into the control group(group A),low dose group(group B)and high dose group(group C)by the random number table method.The group B and group C respectively used dexmedetomidine 0.3 μg/kg and 0.6 μg/kg as a loading dose be-fore anesthesia induction,0.3 μg·kg-1·h-1 and 0.6 μg·kg-1·h-1 were respectively injected by mi-cropump for anesthesia maintenance,while the group A adopted the same amount of normal saline.The other anesthesia management methods were the same in the three groups.The mean arterial pressure(MAP)and heart rate after entering the room(T0),before anesthesia induction(T1),after anesthesia intubation(T2),at 1 min after anesthesia intubation(T3),immediately after surgical incision(T4),isolation of the thyroid gland(T5)and at 1 min after extubation(T6),incidence rate of adverse reactions,choking reaction score,extubation time after stopping medication and dosage of propofol and remifentanil were recorded.Results The choking reaction score,extubation time after stopping medication and propofol dosage were manifested as the group C＜group B＜group A(P＜0.05).The remifentanil dosage in group C and group B was less than that in group A(P＜0.05).MAP at T1 in the group C was lower than that in the group A and group B(P＜0.05),but there was no statistical difference between the group A and group B(P＞0.05).MAP at T2-T6 in the group B and group C was lower than that in the group A(P＜0.05),but the difference between the group B and group C had no statistical significance(P＞0.05).The heart rate at T1-T6 in the group B and group C was lower than that in the group A(P＜0.05).The heart rate at T1,T2,T4,T5 and T6 in the group C was lower than that in the group B(P＜0.05).Bradycardia during operation did not occur in various groups.The intraoperative recurrent laryngeal nerve monitoring process was smooth without appearing interference.The incidence rate of adverse reactions had no statistical difference in various groups(P＞0.05).Conclusion He-modynamics by using 0.6 μg/kg dexmedetomidine in the patients with thyroid operation under recurrent la-ryngeal nerve monitoring is more smooth and steady,which could reduce the use amounts of anesthetic drugs,decrease the occurrence of choking reaction,shorten the operation extubation time after operation,moreover does not increase the incidence rate of postoperative adverse reactions.

Objective To evaluate the efficacy of patient-controlled brachial plexus block with different concentrations of dexmedetomidine mixed with ropivacaine for analgesia after elbow joint surgery.Methods One hundred patients of both sexes,aged 18-64 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elbow joint surgedyy,were divided into 4 groups (n =25 each) using a random number table method:different concentrations of dexmedetomidine mixed with ropivacaine groups (DR1-3 groups) and ropivacaine group (group R).An analgesia pump was connected at the end of surgery and patient-controlled brachial plexus block was performed.The patient-controlled analgesia (PCA) solution contained 0.5 μg/ml dexmedetomidine and 0.2％ ropivacaine in group DR1,0.75 μg/ml dexmedetomidine and 0.2％ ropivacaine in group DR2,1 μg/ml dexmedetomidine and 0.2％ ropivacaine in group DR3 and 0.3％ ropivacaine in group R.All the drugs were diluted to 400 ml in normal saline in each group.The PCA pump was set up to deliver 3 ml bolus dose with a 20-min lockout interval and background infusion at 5 ml/h.Parecoxib 0.6 mg/kg was intravenously injected as a rescue analgesic.The visual analogue scale (VAS) scores at rest and during movement (voluntary and continuous passive movement) were recorded at the end of surgery and 12,24,36,48 and 72 h after surgery.The number of successfully delivered doses,the number of attempt and postoperative consumption of parecoxib were recorded.The elbow flexion angle during voluntary and continuous passive movement was recorded.The development of motor block and drug-related adverse reactions was also recorded.Results There was no significant difference in VAS scores at rest at each time point among the four groups (P＞0.05).Compared with group R,the VAS scores during movement,the number of attempts,the number of successfully delivered doses and parecoxib consumption were significantly increased in DR1 and DR2 groups,the elbow flexion angle during voluntary and continuous passive mnovement was significantly decreased in group DR1,the elbow flexion angle during continuous passive movement was significantly decreased in group DR2,and the elbow flexion angle during voluntary movement was significantly increased (P＜0.05),and no significant change was found in the other parameters in group DR3 (P＞0.05).Compared with group DR1,the VAS scores during movement were significantly decreased,the number of attempts,the number of successfully delivered doses and parecoxib consumption were decreased,and the elbow flexion angle during voluntary and continuous passive movement was increased in DR2 and DR3 groups (P＜0.05).Compared with group DR2,the VAS scores during movement were significantly decreased,the number of attempts,the number of successfully delivered doses and parecoxib consumption were decreased,and the elbow flexion angle during voluntary and continuous passive movement was increased in group DR3 (P＜0.05).No motor block was found in DR1,DR2,and DR3 groups,and the incidence of motor block was significantly higher in group R than in the other three groups (P＜0.05).The hemodynamics was stable and no drug-related adverse reactions were found in the perioperative period in the four groups.Conclusion Patient-controlled brachial plexus block with dexmedetomidine 1 μg/ml mixed with 0.2％ ropivacaine can provide satisfactory analgesia and is helpful in improving prognosis for the patients undergoing elbow joint surgery.

Objective To compare the effects of phenylephrine and norepinephrine in patients with restrictive transfusion.Methods 65 patients undergoing laparoscopic resection of rectal cancer were selected.According to the random number table method,the patients were randomly divided into 32 cases of observation group (phenylephrine composite restriction infusion) and 33 cases of control group(norepinephrine combined restrictive transfusion).The operation and hemodynamics of the two groups at different time points were compared.At T0,T1,T2,the central venous blood and arterial blood were collected,the central venous blood saturation (ScvO2),arterial blood lactate (Lac),central venous oxygen partial pressure (PcvO2),PaO2,Hb concentrations,venous oxygen content (CcvO2),arterial oxygen content(CaO2),arteriovenous oxygen content difference (Ca-cvO2) and oxygen uptake rate (ERO2) were compared between the two groups.Results The ASA levels (Ⅰ / Ⅱ grade) of the observation group and the control group were 11 cases/21 cases and 13 cases/20 cases,respectively,the difference was not statistically significant(x2 =5.298,P =0.052).The BMI of the observation group and the control group were (20.61 ± 1.65) kg/m2,(21.57 ± 1.42) kg/m2,respectively,the difference was not statistically significant (t =0.652,P =1.980).The fluid replacement of the observation group and the control group were (1 162 ± 113) mL,(1171 ± 104) mL,respectively,the difference was not statistically significant (t =1.734,P =0.065).The blood loss of the observation group and the control group were (276 ± 41) mL,(294 ± 42) mL,respectively,the difference was not statistically significant (t =0.083,P =1.023).The urine volume of the observation group and the control group were (524 ± 113) mL,(532 ± 109) mL,respectively,the difference was not statistically significant(t =1.834,P =0.053).The operation time of the observation group and the control group were (192 ± 24) min,(197 ± 21) min,respectively,the difference was not statistically significant(t =1.367,P =0.073).The MAP at T1-T2 of the two groups increased,the CVP of the two groups was significantly higher at T1,the HR of the two groups was significantly higher at T2.The MAP,CVP,HR between the two groups had no significant differences (all P ＞ 0.05).The levels of ScvO2,PcvO2 and PaO2 at T1 were significantly higher than those at T0,on the contrary,the levels of ScvO2,PcvO2 and PaO2 at T2 were significantly lower than those at T0,and the Hb in the observation group was significantly lower at T1-T2,the Hb in the control group was significantly lower at T,-T2,which in the observation group was lower than the control group,the differences were statistically significant(all P ＜ 0.05).There was no statistically significant difference in Lac between the two groups (P ＞ 0.05).There were statistically significant differences in CcvO2,CaO2,Ca-cvO2 and ERO2 between the two groups at different time points (all P ＜ 0.05).Conclusion Phenylephrine is more effective than norepinephrine in limiting infusion in elderly patients,and it has more obvious effects on tissue oxygen metabolism.

Objective To explore the effect of autophagy regulator on the injury of rat hippocampal neurons induced by oxygen-glucose deprivation (OGD).Methods Rat hippocampal neurons were cultivated in primary and subjected to OGD to simulate neuronal hypoxic ischemia injury for 2 hours or 6 hours followed by reperfusion for 12 hours with or without 3-methyladenine (3-MA, 20μmol/L) or rapamycin (0.2μmol/L). The morphology of neurons was observed with optical microscope. The expression of autophagy-related protein (LC3, P62) and apoptosis-related protein (cleaved caspase-3) were assessed by Western Blot analysis. The apoptosis of neurons was detected by flow cytometry, the release rate of lactate dehydrogenase (LDH) was calculated by automatic biochemical analyzer, and the cell activity was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay.Results Compared with the control group, the expression of LC3 Ⅱ/Ⅰ (gray value: 3.091±0.160, 3.422±0.186 vs. 0.256±0.021), cleaved caspase-3 (gray value: 0.230±0.025, 0.440±0.051 vs. 0.050±0.007), neuronal apoptotic rate, LDH release rate [(38.50±4.15)%, (59.60±5.65)% vs. (12.40±1.32)%] were increased, while the expression of P62 (gray value: 0.290±0.025,0.120±0.026 vs. 0.450±0.040), neuronal activity [(71.40±7.23)%, (42.80±4.12)% vs. (100.30±2.30)%] were decreased at 2 hours or 6 hours after OGD (allP < 0.05). When the time of OGD was 2 hours and it was combined with 3-MA, the expression of LC3 Ⅱ/Ⅰ (gray value: 2.281±0.121), the neuronal activity [(51.10±5.73)%] were decreased, while the expression of P62 and cleaved caspase-3 (gray scale: 0.410±0.037, 0.330±0.027, respectively), neuronal apoptotic rate, the injury of neurons [LDH release rate: (47.30±4.43)%] were increased (allP < 0.05). When the time of OGD was 2 hours and it was combined with rapamycin, the expression of LC3 Ⅱ/Ⅰ (gray value: 3.689±0.214), the neuronal activity [(85.30±8.56)%] were increased, while the expression of P62 and cleaved caspase-3 (gray value: 0.170±0.040, 0.090±0.096, respectively), neuronal apoptotic rate, the injury of neurons [LDH release rate: (24.30±2.14)%] were decreased (allP < 0.05). On the contrary, when the time of OGD was 6 hours and it was combined with 3-MA, the expression of LC3 Ⅱ/Ⅰ and cleaved caspase-3 (gray value: 3.021±0.178, 0.240±0.017), neuronal apoptotic rate, the injury of neurons [LDH release rate: (36.60±3.45)%] were decreased, while the expression of P62 (gray value: 0.350±0.060), the neuronal activity [(59.70±6.13)%] were increased (allP < 0.05). When the time of OGD was 6 hours and it was combined with rapamycin, the expression of LC3 Ⅱ/Ⅰ and cleaved caspase-3 (gray value: 3.923±0.201, 0.590±0.062), neuronal apoptotic rate, the injury of neurons [LDH release rate:(71.20±7.81)%] were increased, while the expression of P62 (gray value: 0.070±0.008), the neuronal activity [(27.30±2.12)%] were decreased (allP < 0.05).Conclusion The enhancement of autophagy has protective effect on neurons under the condition of mild OGD, while it can aggravate the injury of neurons induced by a long-time OGD.

Objective To investigate the optimal injury time point of cardiac arrest (CA) induced electrically, and establish a reproducible prolonged CA and cardiopulmonary resuscitation (CPR) model in pigs. Methods Forty healthy domestic male pigs were randomly divided into four groups, which were ventricular fibrillation (VF) 8, 10, 11, and 12 minutes groups, each group for 10 animals. In these groups, VF was induced by alternating current delivered to right ventricular endocardium and untreated for 8, 10, 11, and 12 minutes, respectively, followed by 6 minutes of CPR procedure. The resuscitation and survival outcomes were recorded. Hemodynamic parameters and arterial blood gases of animals after successful resuscitation were measured and recorded for 6 hours. Those successful resuscitation animals were regularly evaluated for the neurological deficit score (NDS) and survival outcomes every 24 hours till 96 hours after resuscitation. Results The shortest duration of CPR (minute: 6.9±1.3) and the highest successful ratio of the first defibrillation (7/10) were observed in group VF 8 minutes, and the ratio of successful resuscitation was 100%. The best coronary perfusion pressure (CPP) during the CPR, less neurological impairment, longer survival time, more stable hemodynamics, and shorter time for arterial pH and lactate level restoring to the original state after CPR were also observed in group VF 8 minutes, and no severe damage was found in those animals. The longest duration of CPR (minute:10.3±2.9) and the lowest successful ratio of the first defibrillation (1/10) were observed in group VF 12 minutes, and only 4 animals achieved restoration of spontaneous circulation (ROSC), and no animal survived to CPR 96 hours. The worst CPP during CPR and the highest NDS after resuscitation were also found in VF 12 minutes animals compared to those animals in the other groups. The injuries caused by ischemia and hypoxia in groups VF 10 minutes and VF 11 minutes were in between those of the groups VF 8 minutes and VF 12 minutes, and the duration of CPR were (7.0±2.1) minutes and (8.2±2.6) minutes. There were 9 and 7 animals achieved ROSC in groups VF 10 minutes and VF 11 minutes correspondingly, and 6 and 4 animals survived to 96 hours respectively. Obviously unstable hemodynamics was observed during the period of CPR 2 hours in the two groups. At CPR 1 hour, the heart rates (HR, beats/min) in groups VF 10 minutes and VF 11 minutes increased to 172 (155, 201) and 168 (136, 196) respectively, and the mean arterial pressures (MAP, mmHg, 1 mmHg = 0.133 kPa) declined to 97 (92, 100) and 81 (77, 100), the cardiac output (CO, L/min) decreased to 5.0 (4.0, 5.8), 3.7 (3.0, 5.4) correspondingly. Distinct injuries were found in the two groups [CPR 24-96 hours NDS in groups VF 10 minutes and VF 11 minutes: 180 (110, 255)-20 (0, 400) and 275 (223, 350)-240 (110, 400)], and the arterial pH of the two group decreased to 7.26±0.09 and 7.23±0.09 respectively, and the level of lactate (mmol/L) increased to 9.17±1.48 and 12.80±2.71 correspondingly at CPR 0.5 hour. Significantly lower pH was observed in group VF 11 minutes compared to group VF 8 minutes at CPR 0.5 hour (7.23±0.09 vs. 7.33±0.04, P < 0.05). The highest level of lactate (mmol/L) was also found at the same time point in group VF 11 minutes, which recovered to normal slowly, and was still significantly higher than groups VF 8, 10, 12 minutes (7.58±3.99 vs. 2.55±1.53, 2.13±2.00, 3.40±2.30, all P < 0.05) at CPR 4 hours. Conclusions The longer duration of CA was, the more severe damage would be, the longer CPR time would be required, and the harder of the animals to achieve ROSC. In this prolonged CA and CPR porcine model, 10-11 minutes for untreated VF, was an optimal time point with appropriate successful rate of resuscitation, survival outcomes, and post-resuscitation injuries. Therefore, we recommended 10-11 minutes might be the rational length of no-flow time in this model.

Objective: The aim of the study is to validate whether the Recognition Of Stroke In the Emergency Room (ROSIER) scale can be used by general practitioners (GPs) in an emergency medical service (EMS) protocol to transfer stroke patients from primary care center to advanced hospital with acute stroke center. Methods: GPs prospectively performed the ROSIER scale and the Cincinnati Prehospital Stroke Scale (CPSS) on suspected stroke patients as a transfer protocol. All patients were immediately transferred to the Level-II hospital for further treatment. Results: 468 of the 512 suspected stroke patients met the inclusion criteria in this study. The ROSIER scale showed a diagnostic sensitivity of 83.13% (95% confidence intervals [CI] 79.74-86.52%) and specificity of 80.88% (95% CI 77.32- 84.44%). The CPSS showed a diagnostic sensitivity of 78.01% (95% CI 74.26-81.76%) and specificity of 70.59% (95% CI 66.46-74.72%). The Kappa statistic value of the ROSIER scale and the CPSS were 0.601 and 0.454, respectively. The area under the curve (AUC) of ROSIER scale was large than the CPSS (AUC 0.855 vs. 0.791). However, the difference was not significantly different. Conclusions: This study suggest that ROSIER and CPSS could be used in an EMS protocol to transfer stroke patients from a primary care center to an advanced hospital offering thrombolysis service
Stroke

Objective To explore the effect of Ulinastatin on blood brain barrier (BBB) and apoptosis of neural cells in septic rats.Methods Fifty-two clean level male Sprague-Dawley rats were randomly (random number table) divided into six groups:Sham groups at 6 h and 24 h,each group with six rats.Sepsis groups (CLP) and Ulinastatin treated groups (UTI) at 6 h and 24 h,each group with ten rats.In CLP and UTI groups,cecal ligation and puncture (CLP) were performed to induce sepsis.Sham group was only opened and closed abdomen.Ulinastatin (50 000 U/kg) was administered via femoral vein 1 h after CLP.The same volume of saline instead of Ulinastatin was administered in Sham and CLP groups.The neurological status was assessed by Neurological Deficit Scale Scores (NDSS) at 6 h and 24 h after CLP.Then the brain was harvested for HE staining and weighing water content.The BBB permeability was assayed by Evans Blue dye extravasations.Apoptosis of neural cells were detected by TUNEL immune fluorescence.Statistical analysis was performed with SPSS version 13.0,ANOVA was used for multiple groups comparison and t-test for paired comparison.Results The Neurological Deficit Scale Scores of UTI group was lower than Sham group (P ＜ 0.05) but higher than that of CLP group (P ＜ 0.05).Swelling,degeneration and edema were observed in cerebral cortex and hippocampal neurons in CLP group through light microscope,and were more serious than those in UTI group.Compared with UTI 24 h group,BBB permeability of CLP 24 h group significantly rose (P ＜ 0.05).The number of apoptosis of neural cells increased more in CLP group than it did in UTI group (P ＜ 0.05).Conclusions Ulinastatin could protect the cerebral tissue in septic rats by alleviating the damage of BBB and reducing the apoptosis of neural cells.

Objective To investigate immunological dysfunction of intestine mucosa barrier in a rat model of sepsis. Method Sixty Sprague-Dawley rats were assigned randomly(random number) into sepsis group (n = 45)and control group (n = 15). The animals in sepsis group were subjected to cecal ligation and puncture (CLP), whereas rats of control group underwent a sham surgery. The ileac mucosa and segments were harvested 3 h, 6 h and 12 hours after CLP, and the blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3(TFF_3) mRNA, lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected. Results In the septic animals, in-testinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of the lamina propria, hemorrhage and ulceration. Compared with control, the expression of TFF_3 mRNA and level of RD-5 pro-tein were decreased and the mucosal lymphocyte apoptosis increased (P < 0.05) in sepsis group. Compared with control group, the significant differences in RD-5 and TFF_3 mRNA appeared 3 hours after CLP and those differ-ences were progressively increased in 6 hours and 12 hours after CLP in sepsis group (P < 0.05, F of RD-5 = 11. 76, F of TFF_3 = 16.86 and F of apoptosis = 122.52). In addition, the gut-origin bacterial DNA in plasma de-tected was positive in all sepsis animals. Conclusions It suggests that immunological function of intestinal mucosa is impaired in septic rats and further worsened following the course of sepsis.

Objective To observe the effect of injecting Xuebijing via different routes, as either treatment or pretreatment, on changes in intestinal mucosal morphology in a rat model of sepsis. Method Ninety-one healthy Sprague-Dawley rats were randomly divided into five groups: 1) control group ( n = 7) , 2) sepsis group ( n = 21) , 3) intragastric pretreatment group ( n = 21) , 4) intravenous pretreatment group (n = 21) , and 5) intravenous treatment group (n = 21) . Except for the control group, the other groups were further divided into three sub-groups for assessment at 3, 6 and 12 h post-operation ( n = 7 per group) . Sepsis was induced by cecal ligation and puncture (CLP) . For the intragastric pretreatment group, Xuebijing injection (5 mL/kg) was administered via intragastric injection 2 hours before CLP. For the intravenous pretreatment group, Xuebijing injection (5 mL/kg)was administered via the caudal vein 2 hours before CLP. For the intravenous treatment group, Xuebijing injection (5 mL/kg) was intravenously infused 2 hours after CLP. The control group received no treatment. The ileum was removed from all rats for measurement. The rats were sacrificed at 3, 6 or 12 h after operation to obtain the ileum.Intestinal mucosal damage index and morphological changes in the intestinal mucosa were detected by light microscopy and electron microscopy. Analysis of variance was used to compare the groups. P -values < 0.05 were considered to indicate statistically significant differences. Results Intestinal mucosal damage was significantly reduced in and the three treatment groups compared with the untreated sepsis group (3h, F =53.35; 6h, F =74.93; 12 h, F - 171.27; P =0.000). Intestinal damage was significantly reduced in the intravenous pretreatment group compared with the intragastric pretreatment group (3 h, F = 53.35,P =0.036; 6 h, F = 74.93,P =0.039; 12 h, F = 171.27, P =0.042). Conclusions Irrespective of the route, the administration of Xuebijing protected against intestinal mucosal damage and intravenous pretreatment exerted the most effective protection against intestinal mucosal damage in this rat model of sepsis.