Objective:To construct a prognostic model of hepatocellular carcinoma (HCC) with differential expression of autophagy genes.Method:Autophagy genes expression data of HCC and normal liver tissues were obtained from The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database respectively. The gene expression data from different platforms is normalized into log 2(FPKM value + 1). Differentially expressed autophagy-related genes of HCC were identified by using R program limma package from the TCGA-GTEx combined data set, the criteria of |logFC| > 1 and FDR < 0.05 was deemed to be of statistically significance. The Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using R program clusterProfiler package, as criteria of P<0.05. Univariate and multivariate Cox proportional hazards regression analyses were performed by using R program survival package to identify the HCC potential prognostic differentially expressed autophagy-related genes. Furthermore, the statistically significant ( P<0.05) autophagy genes in the univariate Cox regression analysis were included in the multivariate Cox regression analysis, and the expression of each differentially expressed autophagy gene and the corresponding regression coefficient coef value based on this, the autophagy gene prognosis model of HCC was constructed: expmRNA1×βmRNA1+ expmRNA2×βmRNA2+ …+ expmRNAn×βmRNAn (exp: gene expression level; β: regression coefficient coef of multivariate Cox regression analysis). Draw the receiver operating characteristic (ROC) curve of the predictive model and calculate the area under curve (AUC) to evaluate the predictive value of the model. Results:The genes expression data and clinical information of 374 HCC samples and 160 normal liver tissue samples were obtained from TCGA and GTEx databases. Total 205 autophagy genes expression data was obtained from the TCGA-GTEx combined sequence. Among them, SPNS1, DIRAS3, TMEM74, NRG2, NRG1, IRGM, IKBKE, NKX2-3, BIRC5, CDKN2A, TP73 are differentially expressed autophagy genes that meet the screening criteria. GO analysis mainly enriched in "regulation of protein serine/threonine kinase activity" , "ErbB 2 signaling pathway" , "protein kinase regulator activity" and "kinase regulator activity" ; KEGG analysis enriched frequently in "EGFR tyrosine kinase inhibitor resistance" , "Hippo signaling pathway" . After integrating and deleting samples with missing survival information, a total of 418 sample expressions were included in the Cox regression analysis. After univariate and multivariate Cox risk regression analysis, the two autophagy genes NRG1 ( HR=1.5565, 95% CI: 1.1793-2.0543) and IKBKE ( HR=1.7502, 95% CI: 1.2093-2.5330) were screened out and a prognostic prediction model was established: (0.44247 × NRG1 expression level) + (0.55977 × IKBKE expression level). The ROC of the prognosis model shows that the AUC of the overall seven-year survival is 0.711. Conclusion:The prognosis model of HCC based on NRG1 and IKBKE has high predictive value for the long-term survival rate of hepatocellular carcinoma patients.

Objective To evaluate the effect of dexmedetomidine on gastric mucosal injury induced by intestinal ischemia-reperfusion (I/R) in rats.Methods Thirty-six healthy male Sprague-Dawley rats,aged 4-5 months,weighing 200-250 g,were randomly divided into 4 groups (n =9 each) using a random number table:sham operation group (group S),intestinal I/R group (group I/R),low-dose dexmedetomidine group (group LD),and high-dose dexmedetomidine group (group HD).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 1 h followed by 2 h reperfusion in anesthetized rats.Dexmedetomidine 2.5 and 5.0 μg · kg-1 · h-1 were infused via the caudal vein for 1 h starting from 1 h before ischemia in LD and HD groups,respectively.The rats were sacrificed at 2 h of reperfusion,and the gastric mucosa was obtained for examination of the pathological changes (with light microscope) and for determination of the expression of serine/threonine kinase (Akt),phosphorylated Akt (p-Akt),activated caspase-3 and caspase-3 (by Western blot).The ratio of p-Akt to Akt (p-Akt/Akt)was calculated to reflect the phosphorylation of Akt.The ratio of activated caspase-3 to easpase-3 (activated caspase-3/caspase-3) was calculated to reflect the activation of caspase-3.Results Compared with group S,the expression of Akt was significantly up-regulated,the expression of p-Akt was significantly downregulated,the phosphorylation of Akt was significantly decreased,and the activation of caspase-3 was significantly increased in group I/R,and the expression of p-Akt was significantly up-regulated,and the phosphorylation of Akt and activation of caspase-3 were significantly increased in LD and HD groups (P＜0.05).Compared with group I/R,the expression of Akt was significantly down-regulated,the expression of p-Akt was significantly up-regulated,the phosphorylation of Akt was significantly increased,and the activation of caspase-3 was significantly decreased in LD and HD groups (P＜0.05).The degree of gastric mucosal injury was significantly lower in LD and HD groups than in group I/R,and there was no significant difference in the degree of gastric mucosal injury between group LD and group HD.Conclusion Dexmedetomidine can attenuate gastric mucosal injury induced by intestinal I/R,and the mechanism may be related to activation of PI3K/Akt signaling pathways and inhibition of cell apoptosis in rats.

Objective To explore the altered functional connectivity of the amygdala in adolescents with internet gaming disorder (IGD) using resting state functional connectivity (rsFC) and dynamic functional connectivity (dFC) analysis.Methods Thirty adolescents with IGD (IGD group) and 30 demographically matched healthy controls (HC group) were recruited.The right and left amygdala were selected as seed regions,the rsFC and dFC between 2 groups were calculated.The regions showing altered connectivity in IGD were adopted as ROIs for correlation analysis.Results Compared to HC group,IGD group had higher rsFC with the right amygdala over the right inferior temporal,middle temporal gyrus,middle frontal gyrus,lower rsFC with the right amygdala over the left inferior temporal,superior temporal and the right inferior occipital gyrus,superior occipital gyrus.The IGD group had lower rsFC with the left amygdala over the right rectal gyrus and thalamus.Compared to HC group,the IGD group showed higher dFC variance with the left amygdala over the right middle temporal and the left media frontal gyrus,and lower dFC variance over the right precuneus,inferior parietal lobe,posterior cingulate and the left postcentral gyrus.The IGD group showed higher dFC variance with the right amygdala over right middle frontal gyrus and lower dFC variance with the right amygdala over the right middle temporal,the left media frontal gyrus and paracingulate cortex,inferior parietal lobe.The rsFC between the left amygdala and right rectal gyrus was negatively correlated with Chinese Internet Addiction Scale (CIAS) scores.The dFC variance between the left amygdala over the left postcentral gyrus was positively correlated with CIAS scores.The dFC variance between the left amygdala and the right inferior parietal lobe were negatively correlated with CIAS scores.Conclusion The amygdala participates in the development of IGD.

Purpose To investigate the diagnosis,differential diagnosis and clinical manifestation of primary plasma cell leukemia (PPCL) and lymphoma with increased plasma cell.Methods Through clinical data and cell morphology,flow cytometry (FCM),immunofixation electrophoresis and immunohistochemistry of EliVision two-step examination were used to analyze 7 cases of PPCL and 3 cases of lymphoma with increased plasma cell.Results All patients with PPCL and lymphoma with increased plasma cell presented with anemia,thrombocytopenia,fever,liver and spleen and lymph node swelling.The proportion of plasma cells in peripheral blood morphology were larger than 20％,accompanied by morphological abnormality.FCM of peripheral blood showed all 7 cases of PPCL expressed CD38 and CD138,CD56 expression in the 2 cases and CD20 in the 2 cases.The light chain (Lamda,Kappa) showed a monoclonal restricted expression,which was consistent with the diagnosis of PPCL.CD19 and CD45 were weakly positive in 3 cases of lymphoma with increased plasma cell,CD38 and CD138 were positive,and no restricted expression was found in light chain IgL,wich belonging to the immunophenotypes of normal plasma cells.Of 3 cases of light chain (Ig) without restrictive expression,2 of them were angioimmunoblastic T-cell lymphoma (ATCL) and 1 case was CD30-positive sinusoidal large B-cell lymphoma (CD30 + SLBCL) that confirmed by lymph node biopsy and pathological examination.Conclusion The PPCL and lymphoma with increased plasma cell have the same clinical manifestations and similar morphological characteristics of blood cells.The diagnosis of PPCL should be combined with immunoelectrophoresis and FCM,and the diagnosis of lymphoma with increased plasma cell needs to be confirmed by histological examination of lymph nodes.

Objective To investigate the effects of different depths of anesthesia on incidence of postopera-tive cognitive dysfunction (POCD). Methods We systematically retrievedPubmed,OVID,CNKI,CBM and Wanfang database and VIP database for randomized controlled trials(RCTs)from inceptionto December 312016, comparing different depths of anesthesia for their impacts on incidence of early POCD. After data extraction and quality evaluation,Revman 5.3 software was used for statistical data analysis. Results A total of 714 patients in 8 eligible RCTs were identified. Results of meta-analysis were as follows.(1)Incidence of POCD of depth anesthesia (NTS=E0-E1)was lower than general anesthesia(NTS=D0-D1)1 d after surgery(OR=0.21,95%CI 0.13~0.35,P < 0.00001).(2)Incidence of POCD of depth anesthesia(NTS = E1)was lower than general anesthesia (NTS=D0)7 d after surgery(OR=0.45,95%CI 0.23~0.91,P=0.03).(3)Incidence of POCD of NTS=E1 was lower than NTS=D07d after surgery(OR=0.42,95%CI 0.24~0.71,P=0.001). Conclusion Comparedwith general anesthesia,depth anesthesia is associated with a lower incidence of early POCD.

Objective As a signaling molecule,NO regulates key physiological processes and is closely related to periodontitis.To investigate the effect of flavonoid NO donor composite nanoparticles(G10@HAP/MSN@ZnO@COS)on osteogenic differentiation of periodontal ligament stem cells(PDLSCs)by regulating macrophage polarization.Methods The novel NO donor drug G10 was loaded on hydroxyapatite/mesoporous silicanant particles(HAP/MSN),filled with zinc oxide(ZnO),and then coated with chitosan(COS)to prepare composite nanoparticles(G10@HAP/MSN@ZnO@COS).The best concentration of G10@HAP/MSN@ZnO@COS was screened to promote cell proliferation by CCK-8 cell experiment.After the mouse mononuclear macrophages were stimulated by lipopo-lysaccharide,the mice were divided into four groups:Control group,G10 group,HAP/MSN@ZnO@COS group and G10@HAP/MSN@ZnO@COS group.Each group was cultured with fresh medium,5 μg/mL G10,5 μg/mL HAP/MSN@ZnO@COS and 5 μg/mL G10@HAP/MSN@ZnO@COS for 72 h respectively.ELISA and RT-qPCR were used to detect the expression of cytokines(TNF-α,IL-6,IL-1β,iNOS,IL-10)and mRNA expression in each group,and the phenotypic changes of M1/M2 were evaluated.The supernatant of each culture medium was used as conditioned medium to culture PDLSCs,and the osteogenic ability and cell miner-alization were evaluated by alkaline phosphatase activity test and alizarin red staining.Results CCK-8 experiment showed that G10@HAP/MSN@ZnO@COS of 5 μg/mL could significantly promote the proliferation of PDLSCs.The results of ELISA showed that compared with Control group,the expression of M1 type marker IL-1β,IL-6,TNF-α and iNOS in G10@HAP/MSN@ZnO@COS group was significantly decreased(P＜0.000 1),while the expression of M2 type marker IL-10 was significantly increased(P＜0.000 1).The results of RT-qPCR were consistent with those of ELISA,which showed that the expression of M1-related genes in G10@HAP/MSN@ZnO@COS group decreased significantly(P＜0.01).The results of alizarin red staining and alkaline phosphatase activity test showed that the number of mineralized nodules and alkaline phosphatase activity in G10@HAP/MSN@ZnO@COS-CM group were significantly higher than those in other groups(P＜0.000 1).Conclusion Composite nanoparticles(G10@HAP/MSN@ZnO@COS)can effectively inhibit the polarization of macrophages to M1 phenotype and promote it to M2 phenotypic polarization.The anti-inflammatory microenvironment regulated by G10@HAP/MSN@ZnO@COS can en-hance the osteogenic differentiation of PDLSCs.

Objective To compare the effectiveness and feasibility of oral tracheal intubation with Clarus video stylet,HPHJ-A video laryngoscope and Airtraq laryngoscope and in snoring pa-tients.Methods Ninety patients undergoing elective snoring surgery with general anesthesia,3 9 males and 51 females,aged 22-55 years,BMI 25-29 kg/m2,ASA physical status Ⅰ-Ⅲ,were ran-domly divided into three equal-sized groups (n=30):Clarus Video Stylet group (group C),HPHJ-A video laryngoscope group (group H)and Airtraq laryngoscope group (group A).The time of success-ful endotracheal intubation and the success rate of initial intubation of all groups were observed.The mean arterial pressure (MAP),heart rate(HR)and Rate-pressure product(RPP)were also monitored before induction of anesthesia(T0),before tracheal intubation(T1),at 0 min(T2),1 min (T3),and 3 min (T4)after intubation,as well as the throat injury and hemorrhage were noted. Results Patients in group C were successful intubated.Two patients in group H and one patient in group A with failed intubation were successfully intubated by using Clarus video stylet.The time re-quired for successful intubation in group C was longer than groups H and A (P<0.05).Compared with T0,the increasing of hemodynamic parameters (MAP,HR,RPP)after induction of all groups were significant(P<0.05).Compared with T1,the HR,MAP and RPP were increased significantly at T2in all groups (P<0.05).Compared with T1,the MAP and RPP were increased significantly at T3in all groups,and the HR were increased significantly at T3in groups H and A (P<0.05).There was no significant difference in the HR between T1and T3in group C.The increase in the HR and RPP at T2 was lower in group C than that in both the groups H and A (P <0.05).The changes of hemodynamic parameters were no significant among the three groups at other time.The differences of sore throat score and hemorrhage were no significant.Conclusion Compared with HPHJ-A video laryngoscope and Airtraq laryngoscope,Clarus video stylet for guiding oral tracheal intubation in snoring patients have less influence on hemodynamic parameters,and have no limited mouth opening. But Clarus Video Stylet spends longer intubating times,and has no obvious advantages on preventing throat injury.

Objective:To analyzed effect of stratified positive psychological intervention based on Self-reporting Inventory (SCL-90) in patients with digestive tract tumors.Methods:Totally 78 patients with digestive tract cancer from January 2019 to February 2020 were divided into observation group (78 cases) and control group (76 cases), the control group given disease knowledge education, psychological intervention, diet and exercise management, and complication prevention etc routine nursing intervention, the observation group combined with stratified positive psychological intervention based on SCL-90 assessment strategy. Cancer-related fatigue, hope level and nurse satisfaction were compared between two groups.Results:6 months after intervention, the observation group cognitive fatigue, mental fatigue, physical fatigue, the influence of fatigue on life, cancer-related fatigue score were respectively (7.24±1.21), (7.58±1.16), (5.16±1.24), (7.65±1.42), (27.63±4.32) points. The control group were respectively (8.35±1.32), (8.02±1.12), (5.87±1.16), (8.72±1.56), (30.96±4.56) points. There were statistically significant of difference between the two groups ( t values were 2.265-5.442, P<0.05 or 0.01). Observation group Grade Ⅲ cancer-related fatigue total score were respectively (27.34±4.32), (27.65±4.25), (27.63±4.41) points, and the control group were respectively (29.56±5.12), (30.23±4.35), (40.77±5.45) points. There were statistically significant of difference between the two groups ( t values were 8.528, 2.163, 5.812, P<0.05 or 0.01). Observation group attitudes towards reality and the future, maintain close relationships with others, adopt positive action, hope level total score were respectively (10.35±2.01), (9.87±1.43), (10.16±1.42), (30.28±5.20) points, and control group were respectively (9.12±1.45), (9.15±1.32), (9.24±1.36), (27.51±4.36) points. There were statistically significant of difference between the two groups ( t values were 3.245-4.104, P<0.05 or 0.01). Observation group second and third grade hope level total score were respectively (30.24±5.20), (31.87±5.45) points, control group were respectively (27.24±4.23), (19.41±3.52) points. There were statistically significant of difference between the two groups ( t values were 2.271, 5.644, P<0.05 or 0.01). 6 months after intervention, The observation group nurse satisfaction 94.87% (74/78) higher than that control group 82.89% (63/76) ( χ2 value was 5.623, P=0.021) . Conclusion:Stratified positive psychological intervention based on SCL-90 assessment strategy help to ensure the balance of the intervention effect, alleviate cancer-related fatigue, Promote development of hope levels, and improve nurse satisfaction.

Benign anastomotic stenosis remains a common complication after bilojejunal anastomosis. Its pathogenesis includes the histology of bile duct, bile erosion, and inappropriate choice of surgical anastomosis or suture materials. Biliojejunal anastomotic stenosis can be determined preoperatively by MRCP, CT, and three-dimensional image reconstruction. Surgery remains treatment of choice for most cases, including surgical reconstruction and minimally invasive treatment, while the incidence of restenosis, residual stone, and reoperation is still high. Surgeons are still in search of optimal treatment modality to avoid anastomotic stenosis. In this article, we review the literature and summarize the latest clinical progress in the diagnosis and treatment of biliojejunal anastomotic stenosis combined with hepatic ductal stones.

Objective To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [ CI ]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95% CI : 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P =0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95% CI : 5.6-17.6) vs 2.8 months (95% CI : 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95% CI: 7.9-11.3) vs 21.9 months (95% CI : 0-44.9), P =0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95% CI : 9.0-24.2) vs 6.9 months (95% CI : 3.6-10.2), P =0.011]. Conclusion Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.