Objective To investigate the effects of regenerating islet-derived protein 3β(Reg3β)on intestinal function and glycolysis in septic mice,as well as its role in promoting lactylation.Methods ① In vivo experiments:a total of 36 adult male C57BL/6 mice,including wild-type(WT)and Reg3β knockout(KO)mice,were randomly divided into six groups using a random number table:WT sham group,WT cecal ligation and puncture(CLP)-induced sepsis group(WT CLP group),WT sham+Reg3β intervention group(WT sham group),WT CLP+Reg3β intervention group(WT CLP+Reg3β group),KO sham group,and KO CLP group(n=6 per group).Blood glucose levels were measured at 24 hours and 48 hours after modeling;At 48 hours after modeling,ileum tissues were collected for hematoxylin-eosin(HE)staining to observe histopathological changes,immunofluorescence staining was performed to assess the positive expression levels of lactylated proteins,Western blotting was used to detect the expression levels of lactylated proteins in ileum tissues.② In vitro experiments:Cultured RAW264.7 cells were randomly divided into four groups using a random number table:blank control group,lipopolysaccharide(LPS)-induced sepsis model group(LPS group),Reg3β group,and LPS+Reg3β group.After 24 hours of drug induction,cells were collected,and Western blotting was performed to measure the levels of lactylated proteins,the culture medium was collected to determine lactylation levels.Results ① Histopathological observations showed that compared with the WT CLP group,the WT CLP+Reg3β group exhibited milder villus breakage and inflammatory cell infiltration.The KO CLP group showed more severe damage,with significantly shortened intestinal villi and separation of the epithelial layer from the lamina propria.Compared with the WT CLP group,blood glucose levels were significantly higher in the KO CLP group(mmol/L:6.83±1.15 vs.4.78±1.37,P<0.05).Both Western blotting and immunofluorescence staining results indicated that,compared with the WT CLP group,lactylation levels were significantly decreased in the KO CLP group[lactylated protein expression(lactylated protein/β-actin):0.48±0.20 vs.0.78±0.09;positive lactylated protein expression(mean fluorescence intensity):59.84±6.02 vs.100.00±5.26,both P<0.01].② Western blotting results of RAW264.7 cells cultured for 24 hours showed that compared with the LPS group,the LPS+Reg3β group exhibited significantly increased lactylated protein expression levels(lactylated protein expression/β-actin:3.67±0.48 vs.1.64±0.49,P<0.01).Compared with the blank control group,the lactate levels in the culture medium of the LPS group were significantly increased(mmol/L:4.95±0.20 vs.3.82±0.09,P<0.01).Compared with the LPS group,the lactate levels in the culture medium of the LPS+Reg3β group were also significantly increased(mmol/L:6.03±0.32 vs.4.95±0.20,P<0.01).Conclusion Reg3β promotes intestinal protein lactylation and exerts a protective effect on the intestine in sepsis,suggesting that Reg3β may serve as a novel therapeutic target for sepsis.

Objective To explore the impacts of remimazolam on intraoperative intracranial pressure(ICP)and cerebral oxygenation in patients undergoing laparoscopic lower abdominal and pelvic surgery under CO2 pneumoperitoneum combined with Trendelenburg position.Methods Eighty-eight patients scheduled to undergo laparoscopic lower abdominal and pelvic surgery were randomly assigned to the remimazolam group(n=44)and the sevoflurane group(n=44).In the remimazolam group,continuous infusion of remimazolam at a rate of 1 mg/(kg·h)was administered for anesthesia maintenance.In contrast,the sevoflurane group inhaled 2％sevoflurane.Heart rate(HR),mean arterial pressure(MAP),peak airway pressure(Peak),plateau airway pressure(Plat),end-tidal CO2(PETCO2),regional cerebral oxygen saturation(rSO2),and optic nerve sheath diameter(ONSD)of both eyes were measured and recorded at the following time points:prior to anesthesia induction(T0),5 minutes after induction(T1),10 minutes(T2),30 minutes(T3),and 60 minutes(T4)after the establishment of pneumo-peritoneum in Trendelenburg position,as well as 30 minutes after deflation in the supine position(T5).Results No significant intergroup differences were detected in HR,MAP,Peak,Plat,or PETCO2 at any time point(P>0.05).In both groups,Peak and Plat values were significantly higher at T2-T4 compared to T1(P<0.05).Regard-ing the ONSD)no intergroup differences were noted at T0 and T1(P>0.05).From T2 to T5,ONSD in both groups increased significantly relative to T0..It gradually rose with the prolongation of pneumoperitoneum and Trendelen-burg positioning and showed a slight decrease at T5(P<0.05).Specifically,at T3 and T4,the remimazolam group exhibited significantly smaller ONSD values than the sevoflurane group(P<0.05).Throughout the study,no inter-group differences in rSO2 were observed(P>0.05).Conclusion In laparoscopic lower abdominal and pelvic surgeries performed in the Trendelenburg position,intravenous anesthesia with remimazolam may be more effective in mitigating the elevation of intracranial pressure compared to sevoflurane inhalation.

Objective To explore the impacts of remimazolam on intraoperative intracranial pressure(ICP)and cerebral oxygenation in patients undergoing laparoscopic lower abdominal and pelvic surgery under CO2 pneumoperitoneum combined with Trendelenburg position.Methods Eighty-eight patients scheduled to undergo laparoscopic lower abdominal and pelvic surgery were randomly assigned to the remimazolam group(n=44)and the sevoflurane group(n=44).In the remimazolam group,continuous infusion of remimazolam at a rate of 1 mg/(kg·h)was administered for anesthesia maintenance.In contrast,the sevoflurane group inhaled 2％sevoflurane.Heart rate(HR),mean arterial pressure(MAP),peak airway pressure(Peak),plateau airway pressure(Plat),end-tidal CO2(PETCO2),regional cerebral oxygen saturation(rSO2),and optic nerve sheath diameter(ONSD)of both eyes were measured and recorded at the following time points:prior to anesthesia induction(T0),5 minutes after induction(T1),10 minutes(T2),30 minutes(T3),and 60 minutes(T4)after the establishment of pneumo-peritoneum in Trendelenburg position,as well as 30 minutes after deflation in the supine position(T5).Results No significant intergroup differences were detected in HR,MAP,Peak,Plat,or PETCO2 at any time point(P>0.05).In both groups,Peak and Plat values were significantly higher at T2-T4 compared to T1(P<0.05).Regard-ing the ONSD)no intergroup differences were noted at T0 and T1(P>0.05).From T2 to T5,ONSD in both groups increased significantly relative to T0..It gradually rose with the prolongation of pneumoperitoneum and Trendelen-burg positioning and showed a slight decrease at T5(P<0.05).Specifically,at T3 and T4,the remimazolam group exhibited significantly smaller ONSD values than the sevoflurane group(P<0.05).Throughout the study,no inter-group differences in rSO2 were observed(P>0.05).Conclusion In laparoscopic lower abdominal and pelvic surgeries performed in the Trendelenburg position,intravenous anesthesia with remimazolam may be more effective in mitigating the elevation of intracranial pressure compared to sevoflurane inhalation.

Objective To investigate the effects of regenerating islet-derived protein 3β(Reg3β)on intestinal function and glycolysis in septic mice,as well as its role in promoting lactylation.Methods ① In vivo experiments:a total of 36 adult male C57BL/6 mice,including wild-type(WT)and Reg3β knockout(KO)mice,were randomly divided into six groups using a random number table:WT sham group,WT cecal ligation and puncture(CLP)-induced sepsis group(WT CLP group),WT sham+Reg3β intervention group(WT sham group),WT CLP+Reg3β intervention group(WT CLP+Reg3β group),KO sham group,and KO CLP group(n=6 per group).Blood glucose levels were measured at 24 hours and 48 hours after modeling;At 48 hours after modeling,ileum tissues were collected for hematoxylin-eosin(HE)staining to observe histopathological changes,immunofluorescence staining was performed to assess the positive expression levels of lactylated proteins,Western blotting was used to detect the expression levels of lactylated proteins in ileum tissues.② In vitro experiments:Cultured RAW264.7 cells were randomly divided into four groups using a random number table:blank control group,lipopolysaccharide(LPS)-induced sepsis model group(LPS group),Reg3β group,and LPS+Reg3β group.After 24 hours of drug induction,cells were collected,and Western blotting was performed to measure the levels of lactylated proteins,the culture medium was collected to determine lactylation levels.Results ① Histopathological observations showed that compared with the WT CLP group,the WT CLP+Reg3β group exhibited milder villus breakage and inflammatory cell infiltration.The KO CLP group showed more severe damage,with significantly shortened intestinal villi and separation of the epithelial layer from the lamina propria.Compared with the WT CLP group,blood glucose levels were significantly higher in the KO CLP group(mmol/L:6.83±1.15 vs.4.78±1.37,P<0.05).Both Western blotting and immunofluorescence staining results indicated that,compared with the WT CLP group,lactylation levels were significantly decreased in the KO CLP group[lactylated protein expression(lactylated protein/β-actin):0.48±0.20 vs.0.78±0.09;positive lactylated protein expression(mean fluorescence intensity):59.84±6.02 vs.100.00±5.26,both P<0.01].② Western blotting results of RAW264.7 cells cultured for 24 hours showed that compared with the LPS group,the LPS+Reg3β group exhibited significantly increased lactylated protein expression levels(lactylated protein expression/β-actin:3.67±0.48 vs.1.64±0.49,P<0.01).Compared with the blank control group,the lactate levels in the culture medium of the LPS group were significantly increased(mmol/L:4.95±0.20 vs.3.82±0.09,P<0.01).Compared with the LPS group,the lactate levels in the culture medium of the LPS+Reg3β group were also significantly increased(mmol/L:6.03±0.32 vs.4.95±0.20,P<0.01).Conclusion Reg3β promotes intestinal protein lactylation and exerts a protective effect on the intestine in sepsis,suggesting that Reg3β may serve as a novel therapeutic target for sepsis.

Objective:To evaluate the effect of obesity on the displacement of a left-sided double-lumen tube (DLT) during positional changes.Methods:This was a prospective cohort study. Six hundred and two patients who underwent elective chest surgery and required insertion of a left-sided DLT from February 2020 to November 2023 in our hospital were selected and divided into 2 groups based on the body mass index (BMI): obesity group (BMI≥28 kg/m 2,n=208) and non-obesity group (18.5 kg/m 2≤BMI<28 kg/m 2,n=394). General characteristics of patients, history of chest surgery, DLT model, depth of DLT placement in supine position, height/depth of placement (H/D) ratio, and distance of DLT displacement were recorded. DLT displacement was defined as a displacement distance of ≥15 mm. The logistic regression was used for analysis of the relationship between BMI and left DLT shift during positional changes. The receiver operating characteristic curve was used to evaluate the accuracy of BMI in predicting the left-sided DLT displacement during positional changes. Results:Compared with non-obese group, the depth of DLT placement was significantly reduced, the H/D ratio was increased, the distance of DLT displacement was increased, and the incidence of DLT displacement was increased in obese group ( P<0.05). The results of binary logistic regression analysis showed that a BMI≥28 kg/m 2 was an independent risk factor for DLT displacement ( OR value [95% confidence interval]=4.18 (2.36-7.38), P<0.001). The sensitivity of BMI in predicting the left-sided DLT displacement during positional changes was 77.4%, and the specificity was 69.6%, with an optimal cutoff value of 27.48 kg/m 2 and an area under the receiver operating characteristic curve of 0.757. Conclusions:Obesity can increase the probability of the left-sided DLT displacement during positional changes.

Objective:To compare the effects of left paratracheal pressure (LPP) and cricoid pressure (CP) during mask ventilation in obese patients.Methods:Sixty patients of either sex, aged 18-60 yr, with 28 kg/m 2≤body mass index<35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: LPP group and CP group. In LPP group, pressure was applied beside the trachea, above the clavicle towards the vertebral direction, while in CP group, pressure was applied downwards to the cricoid cartilage, with a force of pressure between 25-35 N. The spatial relationship between the esophagus, trachea, and cricoid cartilage, the presence of air shadows in the gastric antrum during mask ventilation, and the cross-sectional area (CSA) of the gastric antrum before and after mask ventilation as well as the airway pressure during mask ventilation were observed. Results:In both groups, the esophagus was located in the left of the trachea in the supraclavicular region. There were no statistically significant differences in the airway pressure during mask ventilation and the CSA of the gastric antrum prior to mask ventilation between the two groups ( P>0.05). Compared to LPP group, the proportion of patients with air shadows in the gastric antrum during mask ventilation was significantly increased, and the CSA of the gastric antrum was increased after mask ventilation in CP group ( P<0.05). Conclusions:Compared to CP, LPP can decrease the development of air entering the stomach during mask ventilation and reduce the CSA of the gastric antrum after mask ventilation in obese patients.

Objective:To evaluate the efficacy of esketamine for patient-controlled intravenous analgesia (PCIA) in elderly patients undergoing modified radical mastectomy for breast cancer.Methods:Ninety elderly female patients, aged 65-78 yr, weighing 46-75 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective modified radical surgery for breast cancer under general anesthesia, were divided into 2 groups ( n=45 each) using a random number table method: esketamine PCIA group (group E) and sufentanil PCIA group (group S). Anesthesia was induced with target-controlled infusion of propofol, intravenous atracurium besylate and sufentanil and maintained with target-controlled infusion of propofol and remifentanil and intermittent intravenous boluses of cis-benzenesulfonic acid atracurium.The patients were connected to an analgesic pump for PCIA at 10 min before completion of operation.The PCIA solution in group E contained esketamine 2 mg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCIA solution in group S contained sufentanil 1 μg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCA pump was set up with a 1.5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 1.5 ml/h, and the analgesia was performed until 48 h after operation.When numeric rating scale score ≥ 4 points and the efficacy of patient-controlled analgesia was not good, tramadol 100 mg was intravenously injected for rescue analgesia.Steward recovery scores were recorded at 4, 8, 24 and 48 h after operation.The requirement for rescue analgesia, effective pressing times of analgesic pump and time to first flatus were recorded within 48 h after operation.The nausea and vomiting, respiratory depression, dizziness and pruritus within 48 h after operation and delirium within 7 days after operation were recorded.The 40-item Quality of-Recovery scale was used to evaluate the early postoperative recovery of patients at 24 and 48 h after operation. Results:Compared with group S, the 40-item Quality of Recovery scale score was significantly increased at each time point, postoperative time to first flatus was shortened, the incidence of postoperative nausea and vomiting and pruritus was decreased ( P<0.05), and no significant change was found in the Steward recovery score at each time point after operation, effective pressing times of PCA and requirement for rescue analgesia in group E ( P>0.05). Conclusions:Esketamine provides better efficacy than sufentanil when used for PCIA in elderly patients undergoing modified radical mastectomy for breast cancer.

Objective:To evaluate the effect of remimazolam pretreatment on brain injury following thalamic hemorrhage in mice.Methods:Sixty clean-grade healthy adult CD1 male mice, weighing 25-30 g, aged 7-8 weeks, were divided into 3 groups ( n=20 each) by using a random number table method: sham operation group (Sham group), brain injury group (BI group) and remimazolam pretreatment group (Rem group). Remimazolam 25 mg/kg was intravenously injected via the tail vein in group Rem.and the equal volume of normal saline was given instead in Sham group and BI group.Ten min later, type Ⅳ collagenase 0.01 U/10 nl was microinjected into unilateral ventroposterolateral nucleus and ventromedial nucleus to develop a mouse model of brain jury induced by thalamic hemorrhage.The rats were sacrificed at 6 h after developing the model, brain tissues were taken for measurement of the wet/dry weight (W/D) ratio, and hippocampal tissues were taken and stained with haematoxylin and eosin for determination of the count of the viable neurons in the hippocampal dentategyrus area, count of apoptotic neurons in the hippocampal CA1 region (by TUNEL), expression of CCAAT/enhancer-binding protein homologous protein (CHOP), activating transcription factor 4 (ATF4) and X-box binding protein-1 (XBP1) mRNA (by real-time polymerase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot) and for microscopic examination of ultrastructure of hippocampal tissues (with a transmission electron microscope). Results:Compared with group Sham, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly increased, the count of viable neurons in the hippocampal dentate gyrus was decreased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was up-regulated, the expression of CHOP, caspase-3 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in BI and Rem groups ( P<0.05). Compared with group BI, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly decreased, the number of viable neurons in the hippocampal dentate gyrus was increased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was down-regulated, the expression of CHOP, caspase-3 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group Rem ( P<0.05). Conclusion:Remimazolam pretreatment can reduce the brain injury following thalamic hemorrhage in mice, and the mechanism may be related to inhibition of cell apoptosis induced by endoplasmic reticulum stress in hippocampus.

Objective:To evaluate the optimized efficacy of thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia for elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes, aged 66-78 yr, weighing 46-80 kg, undergoing elective thoracoscopic combined with laparoscopic radical resection of esophageal cancer, were divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group G) and thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia group (TSG group). Both groups received target-controlled infusion of propofol and remifentanil and intravenous injection of cisatracurium besilate for anesthesia induction and maintenance, with BIS value maintained at 45-60 during operation.Thoracic paravertebral nerve block on the affected side was performed under ultrasound guidance after the end of anesthesia induction, and 0.5% ropivacaine 15 ml was injected in TSG group.The patients were turned to the supine position after the thoracic operation was completed, and the bilateral subcostal approach to the transversus abdominis plane block was performed under ultrasound guidance, and 0.3% ropivacaine 20 ml was injected into each side.Sufentanil was used for patient-controlled intravenous anesthesia (PCIA) after operation.The background infusion rate was 0.05 μg·kg -1·h -1, PCA was 0.04 μg/kg, and the lockout interval was 10 min in group G. The background infusion rate was 0.03 μg·kg -1·h -1, PCA was 0.025 μg/kg, the lockout interval was 10 min in group TSG.Both groups received analgesia until 48 h after operation, and VAS score was maintained ≤3.When VAS score ≥ 4, tramadol 100 mg was intravenously injected for rescue analgesia.At 1 day before operation (T 0), immediately before anesthesia induction (T 1), at 1 h after emergence from anesthesia (T 2), and 4, 8, 12, 24 and 48 h after operation (T 3-7), venous blood samples were collected for determination of serum norepinephrine, epinephrine and cortisol concentrations (by enzyme-linked immunosorbent assay). The intraoperative consumption of remifentanil and occurrence of cardiovascular events were recorded.The pressing times of PCA, consumption of sufentanil and requirement for rescue analgesia within 48 h after operation were recorded.The occurrence of nerve block-related complications (hematoma at the puncture site, infection, local anesthetic poisoning, etc.) and adverse reactions such as nausea and vomiting, respiratory depression and pruritus were recorded within 48 h after the operation. Results:Compared with group G, the concentrations of serum epinephrine, norepinephrine and cortisol were significantly decreased, the consumption of intraoperative remifentanil and postoperative sufentanil and pressing times of PCA were reduced, the rate of rescue analgesia was decreased, scores of satisfaction with analgesia were increased, and the incidence of intraoperative cardiovascular events and postoperative adverse reactions such as nausea and vomiting, pruritus and respiratory depression were decreased in group TSG ( P<0.05). Conclusion:Thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia can reduce the perioperative consumption of opioids and inhibit perioperative stress responses and postoperative hyperalgesia with fewer adverse reactions when used for the elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.

Objective To investigate the effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats. Methods A total of 60 pathogen-free male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-300 g, were divided into 3 groups (n= 20 each) by using a random number table: control group (C group), as-phyxial cardiac arrest-resuscitation group ( CA group) and dexmedetomidine pretreatment group ( Dex group). The anaesthetized rats were intubated with a 16G tracheal catheter which was connected to a rodent ventilator for mechanical ventilation. Cardiac arrest was induced by clamping the tracheal tube at the end of the exhalation until systolic blood pressure decreased to 25 mmHg lasting for 5 min, and then resuscitation was started. At 5 min before cardiac arrest, dexmedetomidine 4. 0 μg∕kg was intravenously injected in group Dex, and the equal volume of normal saline was given instead in C and CA groups. Rats were sacri-ficed at 6 h after successful resuscitation, brain tissues were removed for determination of wet to dry weight ratio ( W∕D ratio), and hippocampal tissues were obtained for examination of the pathological changes (with a light microscope) and ultrastructure (with an electron microscope) and for determination of cell ap-optosis (by TUNEL), expression of CCAAT∕enhancer-binding protein homologous protein (CHOP) and ac-tivated transcription factors (ATF4) and X-4 box binding protein 1 (XBP1) mRNA (by real-time polymer-ase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot). The apoptosis rate was calculated. Results Compared with group C, W∕D ratio of brain tissues was significantly in-creased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was up-regulated, the expression of CHOP, Bax and caspase-3 was up-regulated, and the expression of Bcl-2 was down-regulated in CA and Dex groups (P<0. 05). Compared with group CA, W∕D ratio of brain tissues was significantly decreased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was down-regulated, the expression of CHOP, Bax and caspase-3 was down-regulated, the expression of Bcl-2 was up-regulated (P<0. 05), and the pathological changes were significantly attenuated in group Dex. Conclusion The mechanism by which dexmedetomi-dine pretreatment mitigates brain injury after asphyxial cardiac arrest-resuscitation may be related to inhibi-ting cell apoptosis induced by endoplasmic reticulum stress in rats.