Objective:To evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on tourniquet-induced hypertension (TIH) in the patients undergoing anterior cruciate ligament reconstruction.Methods:Seventy-four patients of either sex, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification I or II, with body mass index of 18-30 kg/m 2, undergoing elective anterior cruciate ligament reconstruction under general anesthesia combined with preoperative femoral nerve block, were divided into 2 groups ( n=37 each) using a random number table method: sham stimulation group (group SS) and group taVNS. Group SS received stimulation on the ear lobe and the tail of the helix of the left ear. Group taVNS received stimulation on the cymba concha and the earlobe of the left ear. Both groups received stimulation from 1 h before induction of anesthesia until the end of the procedure (frequency of 30 Hz, pulse width of 300 μs, and amplitude of the strongest current that could be tolerated by the patient in the absence of pain). The tourniquet inflation pressure was 280 mmHg, with an inflation time of 60-90 min. Systolic blood pressure, diastolic blood pressure and heart rate were recorded before tourniquet inflation to assess the development of intraoperative TIH. The consumption of intraoperative propofol, remifentanil, nitroglycerin, esmolol, norepinephrine and atropine was recorded, and the occurrence of postoperative nausea and vomiting, skin itching and headache and dizziness was also recorded. Results:Compared with group SS, the incidence of TIH and the number of patients used nitroglycerin were significantly reduced ( P<0.05), and no significant changes were found in the other parameters in group taVNS ( P>0.05). Conclusions:taVNS can decrease the occurrence of TIH in the patients undergoing anterior cruciate ligament reconstruction.

Objective To explore the correlation of baseline CCL19+dendritic cell(CCL19+DC)infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+T cell infiltration.Methods We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January,2020 to December,2023,and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+DC and CD8+T cell infiltration using immunofluorescence assay.We evaluated the predictive value of baseline CCL19+DCs for patient responses to immunotherapy using receiver-operating characteristics(ROC)curves and analyzed the correlations of baseline CCL19+DC expression with immunotherapy efficacy and CD8+T cell and cytotoxic T lymphocyte(CTL)infiltrations.In co-culture systems of lung adenocarcinoma PC9 cells,CD8+T cells and DCs(overexpressing CCL19 with or without anti PD-1 antibody treatment),the expressions of granzyme B,perforin,IFN-γ,and Ki-67 in T cells were analyzed using flow cytometry.Results The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+DC infiltration level in lung adenocarcinoma tissues than those with poor responses.CCL19+DC infiltration had an area under ROC curve of 0.785,a sensitivity of 75.6%,and a specificity of 62.8%for predicting immunotherapy efficacy.The expression of CD8+T cell surface molecules Granzyme B(P<0.01),Perforin(P<0.01),IFN-γ(P<0.01)and Ki-67(P<0.001)in patients with high expression of CCL19+DC were higher than those in patients with low expression of CCL19+DC.The baseline CCL19+DC infiltration level was positively correlated with immunotherapy efficacy(P=0.003),CTL infiltration of(r=0.6657,P<0.001)and CD8+T cell infiltration(P=0.007).In the co-cultured cells,CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+T lymphocytes than either of the single treatments(P<0.01 or 0.001).Conclusion The baseline CCL19+DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

Objective To explore the correlation of baseline CCL19+dendritic cell(CCL19+DC)infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+T cell infiltration.Methods We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January,2020 to December,2023,and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+DC and CD8+T cell infiltration using immunofluorescence assay.We evaluated the predictive value of baseline CCL19+DCs for patient responses to immunotherapy using receiver-operating characteristics(ROC)curves and analyzed the correlations of baseline CCL19+DC expression with immunotherapy efficacy and CD8+T cell and cytotoxic T lymphocyte(CTL)infiltrations.In co-culture systems of lung adenocarcinoma PC9 cells,CD8+T cells and DCs(overexpressing CCL19 with or without anti PD-1 antibody treatment),the expressions of granzyme B,perforin,IFN-γ,and Ki-67 in T cells were analyzed using flow cytometry.Results The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+DC infiltration level in lung adenocarcinoma tissues than those with poor responses.CCL19+DC infiltration had an area under ROC curve of 0.785,a sensitivity of 75.6%,and a specificity of 62.8%for predicting immunotherapy efficacy.The expression of CD8+T cell surface molecules Granzyme B(P<0.01),Perforin(P<0.01),IFN-γ(P<0.01)and Ki-67(P<0.001)in patients with high expression of CCL19+DC were higher than those in patients with low expression of CCL19+DC.The baseline CCL19+DC infiltration level was positively correlated with immunotherapy efficacy(P=0.003),CTL infiltration of(r=0.6657,P<0.001)and CD8+T cell infiltration(P=0.007).In the co-cultured cells,CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+T lymphocytes than either of the single treatments(P<0.01 or 0.001).Conclusion The baseline CCL19+DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

Objective:To evaluate the effect of pre-infusion of hypertonic saline on the postoperative cognitive function in elderly patients.Methods:This was a prospective study. Seventy-six patients of both sexes, aged≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, who underwent elective shoulder arthroscopic surgery under brachial plexus block combined with general anesthesia from June 2022 to January 2023 in our hospital, were selected and divided into 2 groups ( n=38 each) by the random number table method: hypertonic saline group and normal saline group. At 30 min before anesthesia induction, 3% hypertonic saline of 4 ml/kg was intravenously infused in hypertonic saline group, and normal saline 4 ml/kg was intravenously infused in normal saline group. The occurrence of intraoperative cerebral desaturation events was recorded. Venous blood samples were collected at 24 h postoperatively, and the plasma concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha and S-100β were measured by enzyme-linked immunosorbent assay, and the expression of neutrophil CD11b was detected by flow cytometry. Rey auditory verbal learning test, trail making test, digit symbol substitution test, and stroop color-word test were performed at 1 day before surgery and 5 days after surgery, and the postoperative cognitive dysfunction was assessed using the Z-score method. Results:Compared with normal saline group, the concentrations of plasma IL-6, tumor necrosis factor-alpha and S-100β and expression of neutrophil CD11b were significantly decreased in hypertonic saline group, and the incidence of cognitive dysfunction and cerebral desaturation events was decreased in hypertonic saline group ( P<0.05). Conclusions:Pre-infusion of hypertonic saline can reduce inflammatory responses and improve postoperative cognitive function in elderly patients.

Objective:To evaluate the effects of remazolam and propofol on the hemodynamics during induction of anaesthesia in elderly patients using the area under curve (AUC) method.Methods:Eighty elderly patients of either sex, aged 65-75 yr, with body mass index of 20-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective non-cardiac surgery, were divided into 2 groups ( n=40 each) by using a random number table method: remazolam group (R group) and propofol group (P group). Remazolam 1 mg/ml or propofol 10 mg/ml was slowly and intravenously injected through titration to achieve loss of responsiveness to verbal command. The accumulative areas under the curve below (AUC MAP-) or above (AUC MAP+ ) baseline mean arterial pressure and under the curve below or above 10% of baseline heart rate at the same time (AUC HR-, AUC HR+ ) were calculated within the first 10 min after administration of propofol or remazolam. The use of vasoactive drugs and injection pain were recorded during this period. The intraoperative awareness during the 24-h follow-up after surgery and development of cardiovascular complications, cerebral infarction and oliguria or anuria within 30 days after surgery were recorded. Results:Compared with R group, AUC MAP- was significantly enlarged (the mean difference 59.375 mmHg·min, 95% confidence interval 26.763-91.987 mmHg·min), AUC HR- was enlarged ( P<0.05), and no significant change was found in AUC MAP+, AUC HR+, requirement for vasoactive drugs, frequency of vasoactive drugs, and postoperative complications in P group ( P>0.05). No injection pain or intraoperative awareness was found in two groups. Conclusions:Remazolam is superior to propofol in maintaining hemodynamic stability during anesthesia induction in elderly patients.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Objective:This study was performed to assess the effect of glycemic control on atrial fibrillation recurrence rates after heart surgery concomitant with Cox-Maze Ⅳ ablation.Methods:A retrospective analysis was performed on 317 diabetic patients with atrial fibrillation who underwent cardiac surgery combined with Cox-Maze Ⅳ ablation in our hospital from May 2016 to February 2020. The patients were followed up for(37.7±27.7) months, and the data of atrial fibrillation recurrence and clinical outcome were collected and compared. The limited cubic spline model was used to analyze the dose-relationship between HbA1c level and the recurrence of atrial fibrillation. The univariate and multivariate Cox proportional regression analysis was used to explore the risk factors of recurrent atrial fibrillation after Cox-Maze Ⅳ ablation. Results:Higher glycated hemoglobin(HbA1c) at the time of ablation was associated with higher post-ablation recurrence rates. The cumulative survival freedom from atrial fibrillation recurrence for patients with HbA1c ≥7.4% at time of operation at 12, 24, 36 and 48 months were 96.3%、75.8%、52.7% and 35.7%, respectively( P<0.001). Besides, the rates of all-cause mortality, cardiac mortality and rehospitalization were significantly lower in patients with HbA1c<7.4%(1.7% vs. 6.3%, P=0.03; 1.1% vs. 5.6%, P=0.02 and 5.7% vs. 20.4%, P=0.01). The multivariate Cox regression model showed that HbA1c was an independent risk factor for atrial fibrillation recurrence( P<0.05). Conclusion:Higher preoperative HbA1c levels were associated with increased recurrence of atrial fibrillation and adverse clinical outcomes in patients undergoing cardiac surgery combined with Cox-Maze Ⅳ ablation.

Objective:To evaluate the role of 1, 4, 5-inositol triphosphate receptor (IP3R) in necroptosis of hippocampal neurons induced by sevoflurane anesthesia in aged rats.Methods:Sixty healthy male Sprague-Dawley rats, aged 18 months, weighing 500-600 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S) and sevoflurane anesthesia + IP3R antagonist group (group S+ I). S and S+ I groups inhaled 2% sevoflurane for 5 h. In group S+ I, IP3 receptor antagonist 2-APB 3 mg/kg was intraperitoneally injected at 10 min before sevoflurane inhalation, and the equal volume of dimethyl sulfoxide was intraperitoneally injected in group C and group S. Morris water maze test was used to test the cognitive function on the day after the end of sevoflurane anesthesia.Then the animals were sacrificed and the brain tissues were obtained for microscopic examination of the pathological changes after HE staining and Nissl staining (with a light microscope) and for determination of the free calcium concentration ([Ca 2+ ] i) and rate of necroptosis of hippocampal neurons (by flow cytometry) and expression of IP3R, receptor-interacting protein kinase-1 (RIPK1), receptor-interacting protein kinase-3 (RIPK3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) (by Western blot). Results:Compared with group C, the escape latency was significantly prolonged, the times of crossing the platform were reduced, the time of staying at the target quadrant was shortened, the [Ca 2+ ] i and necroptosis rate of hippocampal neurons were increased, and the expression of IP3R, RIPK1, RIPK3 and p-MLKL in hippocampal neurons was up-regulated in group S and group S+ I ( P<0.05). Compared with group S, the escape latency was significantly shortened, the times of crossing the platform were increased, the time of staying at the target quadrant was prolonged, the [Ca 2+ ] i and necroptosis rate of hippocampal neurons were decreased, and the expression of IP3R, RIPK1, RIPK3 and p-MLKL in hippocampal neurons was down-regulated in group S+ I ( P<0.05). Conclusions:The mechanism by which sevoflurane induces cognitive dysfunction may be related to the imbalance of calcium homeostasis caused by activation of IP3R and thus inducing programmed necrosis in aged rats.

Objective     To summarize the clinical characteristics and surgical treatment experience of 1 106 patients with cardiac myxoma. Methods     Clinical data of 1 106 patients with cardiac myxoma who underwent surgical treatment in Beijing Anzhen Hospital from 2002 to 2018 were retrospectively analyzed. There were 749 (67.7%) females and 357 (32.3%) males. Results     The highest incidence rate was at the age of 51-70 years. The location of the disease was: left atrium in 987 (89.2%) patients, right atrium in 99 (9.0%) patients, left ventricle in 10 (0.9%) patients, right ventricle in 8 (0.7%) patients. There were 1 013 patients of heart classification (NYHA) Ⅰ-Ⅱ and 93 patients of Ⅲ-Ⅳ. There were 301 patients with cerebral infarction and 57 patients with peripheral arterial embolism. Tumor size was closely related to hemodynamic symptoms (P≤0.05), but not to peripheral vascular embolism (P>0.05). Two (0.2%) patients died in hospital and 306 patients were followed up, with a follow-up rate of 27.7%. The median follow-up time was 7 years (range, 1-18 years). One patient died of all causes, and 23 patients recurred, with a recurrence rate of 2.1%. Among 23 recurrent patients, 15 (65.2%) patients were atypical myxoma and 8 (34.8%) patients were typical myxoma. There was no statistical difference in aortic clamping time, ICU stay time, ventilator-assisted breathing time, postoperative hospital stay time, postoperative mortality, or cardiac ejection fraction at discharge between the reoperation in 23 recurrent patients and the first operation in 1 083 non-recurrentpatients. Conclusion     Cardiac myxoma is more common in middle-aged and elderly women, and it often occurs in the left atrium. The size of cardiac myxoma can affect the hemodynamic changes. Surgical treatment is effective. Atypical myxoma is more common in recurrent patients, and the effect is still satisfactory through surgical treatment.

Objective:To summarize the experience of reoperation for 23 cases of cardiac myxoma recurrence.Methods:From January 2002 to December 2018, 1106 patients with cardiac myxoma underwent surgical treatment. Among them, 23 patients underwent reoperation after recurrence. 10 males and 13 females with an average age of (50.5±10.8) years old. There were 22 patients with secondary operation and 1 patient with four operations. 3 cases with mitral insufficiency and 1 case with tricuspid insufficiency. There were 20 patients with NYHA Ⅰ-Ⅱ and 3 patients with Ⅲ-Ⅳ. A total of 1 083 patients with cardiac myxoma undergoing primary operation were selected as the control group. The operation time, cardiopulmonary bypass time, aortic clamping time, ICU monitoring time, ventilator assisted breathing time, postoperative hospital stay, in-hospital mortality and cardiac ejection fraction at discharge were compared between the two groups.Results:8 cases (34.8%) had the first onset in the left atrial septum, and 15 cases (65.2%) in other parts. Recurrence site: left atrium in 17 cases(73.9%), left ventricle in 2 cases (8.7%), right atrium in 3 cases (13.0%), right ventricle in 1 case (4.3%). Reoperation accounted for 2.1% of cardiac myxoma surgery in the same period. The median recurrence time of 13 patients was 24 months. During the same period, mitral valve replacement was performed in 2 cases, mitral valvuloplasty in 1 case and tricuspid valve plasty in 1 case. The average operation time was (3.9±2.8) h, cardiopulmonary bypass time was (107.6±33.8) min, aortic clamping time was (64.9±23.8) min, ICU monitoring time was (20.1±16.0) h, ventilator assisted breathing time was (16.9±8.5) h, cardiac ejection fraction at discharge was 0.51±0.10, postoperative hospital stay was (8.3±1.5) days. The median follow-up time was 5 (1-18) years. One case (4.3%) died of all causes. There was no significant difference in ICU monitoring time, ventilator assisted breathing time, discharge cardiac ejection fraction, postoperative hospital stay and hospital mortality between reoperation patients and one operation ( P>0.05). Conclusion:Atypical cardiac myxoma has a high recurrence tendency after operation. Regular follow-up after the first operation of cardiac myxoma is a necessary means to early detect recurrence and avoid complications. Reoperation after recurrence can still achieve satisfactory results.