Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective:To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis.Methods:A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusions:The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Objective:To investigate the effect and associated mechanism of tumor tissue-infiltrating NK cells after receiving radiotherapy for hepatocellular carcinoma (HCC).Methods:A HCC tumor-bearing mouse model was constructed using human hepatocellular carcinoma cell line (SK-Hep-1) and divided into four groups: control, radiotherapy, NK cell clearance, and NK clearance combined with radiotherapy. Tumor growth condition was simultaneously recorded. The NK cell ratio in peripheral blood and the NK cell intratumoral infiltration condition were detected by flow cytometry and immunohistochemistry. Lentiviral-constructed SK-Hep-1 cells was used to detect the effect of radiotherapy on the regulation of CXCL10 and NK cell chemotaxis following EZH2 overexpression. SK-Hep-1 cells were irradiated in vitro and in vivo. The expression levels of EZH2 and CXCL10 mRNA and protein in the two groups of cell lines and mouse tumor tissues were detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and immunohistochemistry. The chemotaxis and blocking experiments were used to validate the chemotaxis effect of CXCL10 on NK cells. The independent sample t-test was used to compare the groups. P<0.05 was considered statistically significant. Results:The HCC tumor-bearing mouse model experiment showed that HCC tumor growth was most remarkable in the NK clearance combined with the radiotherapy group compared to the radiotherapy group ( P<0.05). Compared with the control group, the number of NK cells in the peripheral blood of nude mice in the radiotherapy group was significantly reduced, while the NK cell intratumoral infiltration was significantly increased ( P<0.05). Flow cytometry and immunohistochemistry showed invitro and invivo expressional alterations. The average expression levels of EZH2 mRNA and protein in hepatocellular carcinoma cell lines and tumor tissues were decreased in the radiotherapy group than the control group and mouse tumor tissues ( P<0.05), while the mRNA and protein expression levels of CXCL10 increased ( P<0.05). The cell supernatant following radiotherapy enhanced NK cell chemotaxis but inhibited CXCL10 neutralization. EZH2 overexpression validated that radiotherapy up-regulated CXCL10 mRNA and down-regulated protein expression levels in in vitro and in vivo experiments ( P<0.05). The chemotactic effect on NK cells was significantly weakened with EZH2 overexpression following radiotherapy. Conclusion:NK cells, as immune effector cells, are directly involved in radiotherapy- activated anti-HCC immunity. Importantly, radiotherapy inhibits EZH2 expression in hepatocellular carcinoma, thereby upregulating CXCL10 expression and enhancing intratumoral NK cell invasion.

Animals ; Monkeypox/drug therapy* ; Antiviral Agents/therapeutic use* ; Phosphoric Monoester Hydrolases/therapeutic use* ; Macaca fascicularis

ObjectiveTo investigate the survival and adverse reactions of patients with unresectable cholangiocarcinoma after stereotactic body radiation therapy （SBRT）. MethodsA total of 27 patients with unresectable solitary cholangiocarcinoma without metastasis who underwent SBRT in The Fifth Medical Center of Chinese PLA General Hospital from February 2012 to July 2020 were enrolled. The prescribed dose to planning target volume was 42-60 Gy in 5-8 fractions， with 5-11 Gy/fraction. Among these patients， five patients were also treated with chemotherapy and transcatheter arterial chemoembolization. The 6-， 12-， 18-， and 24-month overall survival （OS） rates， progression-free survival （PFS） rates， and local control （LC） rates were used as the assessment indices for treatment outcome； Common Terminology Criteria for Adverse Events v.4.03 was used to evaluate adverse reactions； the Kaplan-Meier method was used to calculate OS， PFS， and LC rates. ResultsThe median follow-up time was 17 months. For all 27 patients， the 6-， 12-， 18-， and 24-month OS rates were 100%， 88%， 57.5%， and 47.9%， respectively； the 6-， 12-， 18-， and 24-month PFS rates were 74.1%， 58.6%， 47.9%， and 35.9%， respectively； the 6-， 12-， 18-， and 24-month LC rates were 96.3%， 91.9%， 84.8%， and 76.4%， respectively. No grade 3 or above toxic reactions were observed. Five patients were diagnosed with radiation-induced liver injury， but there was no death due to radiation-induced liver injury. ConclusionSBRT is safe and effective in the treatment of unresectable cholangiocarcinoma， with relatively high survival rate， PFS rate， and LC rate and low toxicity， and therefore， SBRT can be used as an alternative treatment method for patients with cholangiocarcinoma who are not candidates for surgery.

Objective:To investigate the application value of laparoscopic duodenum-preserving pancreatic head resection (LDPPHR).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 25 patients undergoing LDPPHR in the Second Hospital of Hebei Medical University from November 2016 to November 2020 were collected. There were 7 males and 18 females, aged from 14 to 66 years, with a median age of 29 years. All the 25 patients underwent LDPPHR. Observation indicators: (1) surgical situations; (2) postoperative histopathological examination; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect the recovery of patients up to March 2021. Measurement data with skewed distribution were represented as M (range) and count data were descripted as absolute numbers. Results:(1) Surgical situations: all the 25 patients underwent LDPPHR successfully, including 23 cases undergoing total pancreatic head resection and 2 cases undergoing subtotal pancreatic head resection. The operation time and volume of intraoperative blood loss of 25 patients were 310 minutes (range, 207 to 540 minutes) and 200 mL (range, 50 to 800 mL), respectively. Of the 25 patients, 1 case was infused with 4 U of red blood cells and 400 mL of plasma, 1 case was infused with 500 mL of plasma, 1 case was infused with 600 mL of plasma and the remaining 22 cases were not infused with red blood cells or plasma. Of the 25 patients, 3 cases with pancreatic fistula of class B were discharged after drainage, 4 cases had biliary fistula including 2 cases undergoing symptoms disappeared after implantation of common bile duct stent by endoscopic retrograde cholangiopancreatography, 1 case recovering well with drainage, 1 case with postoperative perihepatic effusion undergoing symptoms disappeared after the treatment of drainage and common bile duct stent implantation, and the remaining 18 cases had no complications. The duration of postoperative hospital stay was 17 days (range, 9 to 27 days) of the 25 patients. (2) Postoperative histopathological examination: the tumor volume of the 25 patients was 6.0 cm×5.0 cm×2.0 cm (range, 1.0 cm×2.0 cm×1.5 cm to 10.0 cm×9.0 cm×8.0 cm). Results of the postoperative histopathological examination showed that there were 12 cases with pancreatic solid pseudopaillary neoplasm, 4 cases with intraductal papillary mucinous neoplasm, 3 cases with serous cystadenoma, 2 cases with mucinous cystadenoma, 1 case with neuroendocrine neoplasm, 1 case with pancreatic true cyst, 1 case with cholesterol crystals combined with calcification in the center of pancreatic nodules and 1 case with cavernous hemangioma of pancreas. (3) Follow-up: all the 25 patients were followed up for 4 months to 48 months, with a median follow-up time of 27 months. During the follow-up, 1 case of the 25 patients with postoperative diabetes controlled blood glucose in the normal range after regular injection of insulin, 1 case with fatty diarrhea had symptoms improved after oral supplement of pancreatic enzyme preparation, 1 case with preoperative intermittent dizziness, weakness of both lower limbs and hypoglycemia had the level of blood glucose returned to normal without any special treatment after operation, and the remaining 23 cases had no metabolic complications. None of the 25 patients had tumor malignant transformation, recurrence or death. No long-term complications such as delayed gastric emptying, bile duct stones or stricture occurred to the 25 patients.Conclusion:LDPPHR is safe and feasible for the treatment of benign or low-grade malignant tumors of the pancreatic head, with the advantage of preserving the integrity of digestive tract.

Objective:To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium.Methods:Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores.Results:A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. ① No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). ② fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium ( r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. ③ DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. Conclusions:Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.

Objective To evaluate treatment outcomes in patients with Cockett syndrome complicating acute lower extremity deep vein thrombosis (DVT) either by direct stenting after taking angioplasty followed by catheter-directed thrombolysis or staged stenting after taking angioplasty and catheterdirected thrombolysis with urokinase.Methods From Jun 2015 to Jun 2017,35 Cockett syndrome patients with DVT were divided into group A (direct stenting after taking angioplasty followed by catheterdirected thrombolysis,n =15) and group B (staged stenting after taking angioplasty and catheter-directed thrombolysis with urokinase,n =20).The total urokinase dosage,the time of thrombolysis,and the score of thrombolysis rate were evaluated.After six months of follow-up,the difference between two groups of limb circumference,patency rate and PTS rate were compared.Results The technical success rate in both group was 100％.There was no fatal pulmonary embolism and massive bleeding during the perioperative period.During treatment,both groups showed significant improvement in limb swelling compared with that before operation.The differences in the total used dosages of urokinase and thrombolysis time were not statistically significant (P =0.47,P =0.51 respectively).Thrombolysis rates above grade Ⅱ in group A and group B were 93.33％ and 90％ (P =0.64),but stent placement was not satisfactory in 2 cases in group A.After six months of follow-up,there was no significant difference between two groups of limb circumference and PTS rate,but patency rate of the two groups was 85.2％ ± 2.4％ and 87.6％ ± 1.8％ respectively (P =0.02).Conclusions For the treatment of Cockett syndrome with DVT,the timing of stent implantation does not affect thrombolytic treatment process.However,the complete removal of the iliac vein thrombosis is beneficial to precise release of the stent and the stent implantation can better maintain iliac vein lumen patency.

Objective To investigate the differential effect of neutrophil to lymphocyte ratio (NLR) at admission on large artery atherosclerosis (LAA) and small vessel occlusion (SVO) in patients with minor stroke.Methods Patients with first-ever acute ischemic stroke registered in Nanjing Stroke Registration System were enrolled retrospectively.Minor stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤3.Binary logistic regression was used to evaluate the independent relationship between NLR and LAA.Results A total of 417 patients with minor stroke were included,of which 242 were in a LAA group and 175 were in a SVO group.Univariate analysis showed that there were significant differences in leukocyte count,neutrophil count,lymphocyte count,NLR,glycosylated hemoglobin,highdensity lipoprotein cholesterol,onset to treatment time,and onset to NLR detection time between the patients of the LAA group and the SVO group (all P ＞0.05).Binary logistic regression analysis suggested that after adjusting for sex and high-density lipoprotein cholesterol,NLR (with the highest quartile as a reference,the first quartile:odds ratio [OR] 0.207,95％ confidence interval [CI]0.089-0.482;P ＞ 0.001;the second quartile:OR 0.277,95％ CI 0.122-0.625,P=0.002;the third quartile:OR 0.456,95％ CI 0.197-1.057;P =0.067),onset to NLR detection time (OR 1.216,95％ CI 1.038-1.424;P =0.015),and glycosylated hemoglobin (OR 1.414,95％ CI 1.142-0.751;P=0.002) were independently associated with LAA.The area under the ROC curve of NLR predicting the LAA was 0.611 in patients admitted within 7 d after onset,and was 0.673 in patients admitted within 24 h after onset.Conclusions The increased NLR was independently associated with the LAA in patients with minor stroke.Early NLR value may have higher predictive value for LAA.

Objective To investigate the capillary index score (CIS) and clinical outcome after endovascular treatment in patients with anterior circulation acute ischemic stroke (AIS). Methods From March 2014 to March 2017,patients with anterior circulation AIS received endovascular treatment in Jinling Hospital and Wuhu Yijishan Hospital were enrolled retrospectively. The data of intraoperative digital subtraction angiography were collected and CIS was calculated. They were divided into either a poor CIS group (score 0-1) or a good CIS group (scores 2-3). Univariate analysis was used to compare the baseline data, clinical data, and outcomes between the 2 groups. Multivariate logistic regression analysis was used to determine the correlation between CIS and symptomatic intracerebral hemorrhage (sICH), death, and functional outcome at 90 d after endovascular treatment(modified Rankin Scale score 0 to 2 was defined as good outcome). Results A total of 157 patients were enrolled, including 91 (58.0％) had poor CIS and 66 (42.0％) had good CIS.Age(P=0.020),baseline systolic pressure(P=0.014),baseline National Institutes of Health Stroke Scale score (P=0.011), early infarct size (P<0.001), as well as the proportions of internal carotid artery occlusion(P<0.001)and embolectomy >3 times(P=0.042)of the poor CIS group were significantly higher than those of the good CIS group.The vascular successful recanalization rate(P<0.001) and good outcome rate (P<0.001) at 90 d in the good CIS group were significantly higher than those in the poor CIS group, while the incidence of sICH (P=0.002) and mortality (P<0.001) were significantly lower than those of the poor CIS group. Multivariate logistic regression analysis showed that CIS were significantly correlated with the functional outcome at 90 d (odd ratio [OR] 0.581, 95％ confidence interval[CI]0.419-0.805;P=0.001)and the risk of sICH at 72 h(OR 0.611,95％ CI 0.407-0.919; P=0.018) after endovascular treatment in patients with anterior circulation AIS,but it did not have a significant correlation with the risk of death (OR 0.783, 95％ CI 0.492-1.246; P=0.301). Conclusions CIS was significantly correlated with the clinical outcome in patients with anterior circulation AIS after endovascular treatment. It can be used as a tool to select patients for endovascular treatment.