Neutrophils play an immune defense role by releasing the proteases such as neutrophil elastase and myeloperoxidase to form neutrophil extracellular trap （NET） and participate in the inflammatory response of various liver diseases， but the excessive release of NET may worsen liver tissue damage and has thus become one of the risk factors for liver diseases. In recent years， studies have shown that the excessive release of NET can promote the progression of liver diseases （such as viral hepatitis， nonalcoholic steatohepatitis， and hepatic ischemia-reperfusion injury） to liver cancer， and clarifying the mechanism of action of NET is of great importance for the diagnosis and progression of liver diseases. Therefore， this article elaborates on the latest research advances in NET in liver diseases， so as to provide new insights into the diagnosis and treatment of liver diseases and the prevention of liver cancer.

Objective To investigate the expression of neutrophil extracellular traps (NETs) and phagocytic function in the peripheral blood of patients with hepatic alveolar echinococcosis (HAE), and to examine their correlations with clinical inflamma tory indicators and liver functions. Methods A total of 50 patients with HAE admitted to Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University from August 2022 to June 2023 were enrolled, while 50 age- and gender-matched healthy individuals from the Centre for Healthy Examinations of the hospital during the same period served as controls. The levels of NETs markers neutrophil myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using enzyme-linked immunosorbent assay (ELISA). Peripheral blood neutrophils were isolated using density gradient centrifugation, stimulated in vitro using phorbol 12-myristate 13 acetate (PMA), and the levels of MPO and citrullination histone H3 (CitH3) released by neutrophils were quantified using flow cytometry. The phagocytic functions of neutrophils were examined using flow cytometry. In addition, the correlations of MPO and NE levels with clinical inflammatory indicators and liver biochemical indicators were examined using Spearman correlation analysis among HAE patients. Results The peripheral blood plasma MPO［(417.15 ± 76.08) ng/mL vs. (255.70 ± 80.84) ng/mL; t = 10.28, P < 0.05］, NE［(23.16 ± 6.75) ng/mL vs. (11.92 ± 3.17) ng/mL; t = 10.65, P < 0.05］and CitH3 levels［(33.93 ± 18.93) ng/mL vs. (19.52 ± 13.89) ng/mL; t = 4.34, P < 0.05］were all significantly higher among HAE patients than among healthy controls, and a lower phagocytosis rate of neutrophils was detected among HAE patients than among healthy controls［(70.85 ± 7.32)% vs. (94.04 ± 3.90)%; t = 20.18, P < 0.05］, and the ability to produce NETs by neutrophils was higher among HAE patients than among healthy controls following in vitro PMA stimulation. Pearson correlation analysis showed that the phagocytosis rate of neutrophils correlated negatively with platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) level and C-reactive protein (CRP) level (r_s = −0.515 to −0.392, all P values < 0.05), and the MPO and NE levels positively correlated with inflammatory markers NLR, PLR, CRP and IL-6 (r_s = 0.333 to 0.445, all P values < 0.05) and clinical liver biochemical indicators aspartic transaminase, alanine aminotransferase, direct bilirubin and total bilirubin among HAE patients (r_s = 0.290 to 0.628, all P values < 0.001). Conclusions Excessive formation of NETs is found among HAE patients, which affects the phagocytic ability of neutrophils and results in elevated levels of inflammatory indicators. NETs markers may be promising novel biomarkers for early diagnosis, monitoring, and severity assessment of liver disease.

Objective:To explore the effects of a structured exercise intervention on the healthy physical fitness in patients with leukemia receiving umbilical cord blood transplantation.Methods:It was a randomized controlled trial, conducted from August 2022 to October 2023 at the Department of Hematology of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). Fifty leukemia patients undergoing umbilical cord blood transplantation were recruited and were randomly assigned to either the control group (24 cases) or the intervention group (26 cases) using a random number table method. The control group received routine nursing care, health education, and exercise guidance during hospitalization. The intervention group were given moderate-intensity structured exercise intervention, including aerobic, resistance exercises, and flexibility training, three times per week for 30 to 40 minutes per session, over a period of 6 to 8 weeks. During the study, 2 patients withdrew due to disease reasons, and finally, 22 patients in the control group and 26 patients in the intervention group were obtained. The paired t-test, Wilcoxon test, and covariance analysis were used to compare the indices of healthy physical fitness before and after the intervention between the two groups, aiming to explore the effects of a structured exercise intervention on the healthy physical fitness of leukemia patients undergoing umbilical cord blood transplantation. Results:Before the intervention, there was no significant differences in baseline characteristics, such as age, gender and disease status between the two groups (all P>0.05). During the hospitalization phase, the rate of exercise participation in the intervention group was 73.4%, the frequency of exercise was (2.20±0.41) sessions per week and the duration of each exercise session was (34.34±5.05) minutes, and the Borg′s rating of perceived exertion was (13.04±0.82) points. After intervention, the indicators including cardiovascular endurance, muscle fitness, and functional activity status in the two groups were all decreased, and the reduction degree of the indicators were all significantly lower in the intervention group when compared with those in the control group [6-minute walk distance (48.81±30.39) m vs (143.05±77.26) m, grip strength of left hand (2.57±1.30) kg vs (6.72±4.88) kg, grip strength of right hand (2.47±1.97) kg vs (6.34±5.70) kg, muscle strength of left upper limb (4.12±2.07) times vs (8.18±5.26) times, muscle strength of right upper limb (3.96±2.29) times vs (7.91±5.16) times, 30 second chair standing test (3.65±1.98) times vs (7.86±4.34) times, and timed-up-and-go test (0.65±0.53) s vs (2.35±1.79) s] (all P<0.05). The flexibility fitness was improved in the intervention group after the intervention [sit-and-reach 2.00(-4.75, 8.18) cm vs 0(-9.75, 6.43) cm] ( P=0.011), but no significant differences was found in the control group ( P>0.05). Conclusions:The structured exercise intervention has advantages in reducing the decline of healthy physical fitness in patients with leukemia receiving umbilical cord blood transplantation, and exerts a protective effect on healthy physical fitness.

Objective:To compare the clinical effects of endoscopic thyroidectomy using the modified gasless transaxillary approach (TA group) and transsubclavian approach (TS group) in the treatment of cN0 papillary thyroid carcinoma (PTC) .Methods:A total of 190 PTC patients (mean age 39.88±9.35 years,38 males, 152 females), who underwent unilateral thyroidectomy in the Department of Thyroid Surgery, the First Hospital of Jilin University from Oct. 2020 to Oct. 2022 were retrospectively analyzed, including 65 cases in TA group, 43 cases in TS group and 82 cases through traditional neck approach (TN group). The endoscopic group (TA+TS) consists of the TA group and the TS group. Comparative analyses were performed on operation time, full exposure rate of central compartment, postoperative hospitalization time, postoperative drainage, hospitalization costs, the number of dissected lymph nodes and postoperative complications. The t-test or Wilcoxon rank sum test, the χ2 test or the exact probability method were used for statistical analysis. Results:All endoscopic operations were successfully completed without conversion to traditional neck approach. ① Compared with the TN group, the endoscopic group (TA+TS) had longer operation time[TN group =74.5 (65-87) min, (TA+TS) group =102 (89-121) min, P<0.001], lower full exposure rate of central compartment (TN group=100%, (TA+TS) group=89.8%, P=0.008), more postoperative drainage[TN group=60 (45-76) ml, (TA+TS) group =100 (80-130) ml, P<0.001], higher hospitalization costs[TN group=￥23638 (22158-25901), (TA+TS) group =￥26967 (25572-28284), P<0.001], and higher parathyroid autotransplantation rate (TN group=4.9%, (TA+TS) group =50.9%, P<0.001). There were no significant differences in the number of dissected lymph nodes, the number of metastatic lymph nodes, preoperative and postoperative parathyroid hormone (PTH) ( P>0.05). ② Compared with the TS group, the TA group had longer operation time[TA group=110 (97-127) min, TS group=89 (80-111) min, P<0.001], lower full exposure rate of central compartment (TA group=83.1%, TS group=100%, P=0.012), longer postoperative hospitalization time[TA group=3 (3-4) d, TS group=3 (3-3) d, P=0.002], more postoperative drainage[TA group=110 (82-140) ml,TS group=95 (65~120) ml, P=0.046] and higher hospitalization costs (TA group=￥27510±2578,TS group=￥26609±1878, P=0.038). There were no significant differences in the number of dissected lymph nodes, the number of metastatic lymph nodes, preoperative and postoperative PTH, and parathyroid autotransplantation between the two groups ( P>0.05) . Conclusions:Endoscopic thyroidectomy through axillary/subclavian approach is safe and feasible for the treatment of cN0 PTC. There was no significant difference in the number of dissected central lymph nodes compared with conventional surgery, and the incision was well concealed. In comparison, transsubclavian endoscopic surgery has better clinical application value, with shorter operation time, higher full exposure rate of central compartment and faster postoperative recovery.

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

Objective To evaluate the value of dual-source CT angiography for evaluating the degree of coronary stenosis. Methods A total of 110 patients with a high likelihood of coronary stenosis identified by dual-source CT angiography or conventional coronary angiography were enrolled. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of dual-source CT angiography for diagnosis of coronary stenosis were evaluated with conventional coronary angiography as a gold standard. The agreement between dual-source CT angiography and conventional coronary angiography for evaluation of coronary stenosis was evaluated using Kappa statistic. Results A total of 1 401 coronary artery segments from 110 patients were displayed on conventional coronary angiography, while 1 382 segments were successfully visualized in dual-source CT angiography (98.64%). The sensitivity, specificity, positive predictive value and negative predictive value of dual-source CT angiography were 97.9%, 97.3%, 90.4% and 99.4% for diagnosis of coronary stenosis, and there was high consistence between dual-source CT angiography and conventional coronary angiography for grading coronary stenosis (Kappa statistic = 0.87, U = 58.36, P < 0.01). In addition, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of dual-source CT angiography were 94.7%, 96.8%, 83.7%, 99.0% and 96.5% for grading stenosis of coronary artery segments. Conclusion Dual-source CT angiography is accurate and reliable for diagnosis of coronary stenosis, which may be a non-invasive tool for assessment of coronary stenosis.

PD-1 and PD-L1 together constitute the stimulus signaling pathway of adaptive immune response, which has been widely used in the research on the mechanism of tumor immune escape and tumor therapy. At the same time, its signaling pathway has been proved to be closely associated with the immune escape of hepatic echinococcosis. This article reviews the chemical structures of PD-1 and PD-L1, the mechanism of the PD-1/PD-L1 signaling pathway, and the role of the PD-1/PD-L1 signaling pathway in immune escape of hepatic echinococcosis, i.e., the PD-1/PD-L1 signaling pathway is involved in immune escape of hepatic echinococcosis under three theories, so as to explore the immune escape of hepatic echinococcosis from a new perspective and provide a basis and ideas for the diagnosis and treatment of hepatic echinococcosis.

The MAPK signaling pathway can mediate a variety of cytokines to participate in the processes of inflammation, cancer, immune disorder, and neurodegenerative diseases, and it also plays an important role in the development and progression of hepatic echinococcosis. This article reviews the structure and regulation of the MAPK signaling pathway and elaborates on the role of the MAPK signaling pathway in hepatic echinococcosis. It is pointed out that the MAPK signaling pathway can activate both the cyst and the host in hepatic echinococcosis, participate in the development and progression of the disease, and exert an impact on its treatment. Drug therapy targeting the MAPK signaling pathway is expected to become a new strategy for the treatment of hepatic echinococcosis.

Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

Objective To investigate the association between serum macrophage polarization-related factors and liver fibrosis in patients with alveolar echinococcosis (AE). Methods A total of 120 patients with AE who attended Department of Hepatobiliary and Pancreatic Surgery in The Affiliated Hospital of Qinghai University from September 2018 to October 2020 were enrolled as AE group, and 33 healthy controls were enrolled as normal control group. The two groups and the patients with varying degrees of liver fibrosis were compared in terms of the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Comparison of normally distributed continuous data between two groups was made by the independent samples t -test, while comparison of non-normally distributed continuous data was made by the Mann-Whitney U test or Kruskal-Wallis H test. Comparison of categorical data between groups was made by the chi-square test. Univariate and multivariate logistic regression analyses were used to investigate the association between serum macrophage polarization-related factors and liver fibrosis in patients with AE, and the receiver operating characteristic (ROC) curve was used to analyze the value of serological examination in the diagnosis of liver fibrosis in patients with AE. A Spearman correlation analysis was used to analyze the correlation of each index with HAI score and Metavir score. Results Compared with the normal control group, the AE group had significant increases in the serum levels of IL-6 [13.97 (9.64-23.62) pg/mL vs 1.30 (0.35-2.71) pg/mL, Z =-5.980, P < 0.001], TNF-α [2.26 (1.65-4.13) pg/mL vs 1.40 (1.04-2.10) pg/mL, Z =-3.114, P < 0.01], and TGF-β1 [3.64(2.71-5.72) pg/mL vs 2.91(2.20-3.35) pg/mL, Z =-2.594, P < 0.05], and increases in the serum levels of IL-6 (hazard ratio [ HR ]=2.721, 95% confidence interval [ CI ]: 1.730-4.280, P < 0.05) and TNF-α( HR =3.527, 95% CI : 1.158-10.747, P < 0.05) were independent risk factors for the onset of liver fibrosis in AE patients. The ROC curve analysis showed that hydatid IgG combined with the serum levels of IL-6 and TNF-α had a sensitivity of 88.4%, a specificity of 95.8%, and an area under the ROC curve of 0.951(95% CI : 0.937-0.964) in the diagnosis of liver fibrosis, which were significantly higher than those of IL-6, TNF-α, or hydatid IgG alone ( Z =-3.458, -4.011, and 2.379, all P < 0.05). The Spearman analysis showed that the serum levels of IL-6, TNF-α, and TGF-β1 were positively correlated with HAI score ( r =0.560, 0.644, and 0.465, all P < 0.001) and Metavir fibrosis score ( r =0.530, 0.758, and 0.567, all P < 0.001), and the serum level of IL-10 was negatively correlated with HAI score ( r =-0.232, P =0.011) and Metavir fibrosis score ( r =-0.288, P =0.001). Conclusion Macrophage polarization is often observed in patients with hepatic AE, and the levels of the macrophage polarization-related factors IL-6, TNF-α, and TGF-β1 are associated with the development and progression of liver fibrosis, which can provide certain reference information for predicting the onset of liver fibrosis.