1.Research advances in neutrophil extracellular traps and liver diseases
Zhuoga RENZENG ; Kangjie YANG ; Yongliang LU ; Zhixin WANG ; Haijiu WANG
Journal of Clinical Hepatology 2024;40(3):639-643
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.
2.Expression of neutrophil extracellular traps and phagocytic functions among patients with hepatic alveolar echinococcosis
Zhuoga RENZENG ; Haining FAN ; Kangjie YANG ; Zhixin WANG ; Yaogang ZHANG ; Yongliang LU ; Haijiu WANG
Chinese Journal of Schistosomiasis Control 2024;36(1):25-33
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 (rs = −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 (rs = 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 (rs = 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.
3.Research progress on the formation mechanism of hepatocellular carcinoma with portal vein tumor thrombus
Wen WANG ; Wei LI ; Mengjian QI ; Xiaoxia SU ; Dalin SHI ; Mingquan PANG ; Haining FAN ; Li REN ; Qian LU ; Haijiu WANG ; Zhixin WANG
Chinese Journal of Hepatobiliary Surgery 2023;29(4):305-308
Hepatocellular carcinoma is a common malignant disease in clinical practice, and portal vein tumor thrombosis (PVTT) is one of the important factors affecting the prognosis of hepatocellular carcinoma. PVTT has strong oncologic characteristics and is highly susceptible to extrahepatic metastasis, complicating portal hypertension, leading to gastrointestinal bleeding or liver failure and causing death. In this paper, we review the formation mechanism of hepatocellular carcinoma combined with PVTT in terms of local anatomy, hemodynamics, molecular biology and tumor microenvironment to provide effective reference for clinical treatment.
4.Design, sensitivity and validity of wrist patient self-evaluation instrument
Lu LIU ; Qipei WEI ; Qiuya LI ; Fan BAI ; Zhixin WANG ; Chang LIU ; Shanlin CHEN
Chinese Journal of Orthopaedics 2023;43(5):300-307
Objective:To design a patient self-rating wrist scale suitable for Chinese patients, and evaluate its reliability and validity.Methods:The primary entry pool was established by referring to the existing foreign scales and the opinions of domestic experts. Opinions of 11 hand surgeons and 10 patients with wrist diseases were referred to select better items into the primary scale. During September 2015 to November 2016, 100 inpatients with wrist diseases in the hand surgery department of Beijing Jishuitan Hospital were selected by convenient sampling method, and the primary scale was conducted on them. Eight indices including item response rate, item differentiation, item-dimension attribution, variability, responsiveness, overall item attribution, internal consistency and factor loading were summarized. All the 8 indices were evaluated to establish the wrist patient self-evaluation instrument for Chinese. Test-retest reliability, Cronbach coefficient, expert score, KMO value, explanatory power, χ 2/df, root mean square error of approximation (RMSEA) and comparative fit index (CFI) were used to evaluate the reliability and validity of the scale. Results:A total of 40 subjective items in the primary entry pool were selected to form the primary scale, including 32 items (A1-D4), and 4 dimensions (physiology, safety, pain and emotion). There were 92 valid scale results in 100 cases. All cases' response rate were over 90%. In terms of item differentiation, only the high grouping score [3.20±0.577 points (range, 1-3 points)] and the low grouping score [2.68±0.627 points (range, 2-5 points)] of item B10 had no statistical significance ( t=5.11, P=0.340). There were 17 items: A1, A2, A5, A6, A7, A8, A9, A10, A11, A12, B4, B6, B7, C5, D1, D2, and D3 were considered to be deleted according to the result of item-dimension attribution. A total of 11 items had a variation less than 0.65: A4 (0.645), A7 (0.593), B1 (0.590), B5 (0.617), B8 (0.578), B9 (0.612), B10 (0.526), D1 (0.644), D2 (0.320), D3 (0.169), D4 (0.526). A2, A4, A6, A8, B4, B6, D1, D2, D3, C2, C3, C4, C5, C6 did not meet the reactivity requirements. Items with factor loads less than 0.4: D2 (-0.051), D3 (-0.127), and D4 (0.267). C4 (0.026), C5 (0.023), D1 (0.103), D2 (0.434), D3 (0.387), D4 (0.062) did not meet the internal consistency requirements. In multiple linear regression analysis, 19 items were not included in the final regression equation. Based on the above analysis, D1, D2, and D3 were finally deleted and the rest 29 valid items were remained to form the wrist patient self-evaluation instrument for Chinese. Reliability and validity of the scale: the test-retest reliability of physiology, safety, pain, emotion dimensions were 0.984, 0.976, 0.985 and 0.802 ( P<0.001), respectively. Except for there was only one item in emotion dimension, the Cronbach coefficients of total score, physiology, safety and pain dimensions were 0.943, 0.973, 0.944 and 0.881, respectively. KMO was 0.894 ( P<0.001). Except for there was only one item in emotion dimension, whose validity could not be evaluated. The χ 2/df, CFI, RMSEA results were as follows, physiology: 5.152, 0.817, 0.022, respectively; safety: 5.378, 0.795, respectively; pain: 7.439, 0.865, 0.028, respectively. Conclusion:The wrist patient self-evaluation instrument for Chinese is consisted of 4 dimensions and 29 items. As a subjective wrist self-rating scale suitable for modern Chinese patients, the scale has good reliability and validity, and can be one of the choices of the subjective evaluation for Chinese patients with wrist diseases.
5.Learning curve analysis and influencing factors of operation time of laparoscopic sleeve gastrectomy
Zhixin SHANGGUAN ; Qing ZHONG ; Yiming JIANG ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jun LU ; Jianxian LIN ; Changming HUANG
Chinese Journal of Digestive Surgery 2023;22(8):996-1002
Objective:To investigate the influencing factors of operation time for laparos-copic sleeve gastrectomy (LSG) and analyze the learning curve of LSG in sarcopenic obesity (SO) and non-sarcopenic obesity (NSO).Methods:The retrospective cohort study was conducted. The clinical data of 240 obesity patients who underwent LSG in the Fujian Medical University Union Hospital from January 2018 to June 2022 were collected. There were 52 males and 188 females, aged (30±8)years. Patients underwent L3 vertebral body horizontal axial computer tomography (CT) scanning before and after receiving LSG to accurately segment muscles and fats. Observation indicators: (1) treatment and follow-up; (2) influencing factors of operation time for LSG; (3) cumulative sum (CUSUM) of learning curve; (4) comparison of clinical data between patients in the initial and profi-cient stages. Measurement data with normal distribution were represent as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(IQR), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. The CUSUM of learning curve was calculated and the fitting process was conducted on scatter plot of learning curves. Results:(1) Treatment and follow-up. Of the 240 patients, there were 97 cases of SO and 143 cases of NSO. All 240 patients underwent LSG successfully, without conversion to open surgery. The operation time of 240 patients was (108±23)minutes. None of patient died during the perioperative period and all patients underwent follow-up during the postoperative 6 months. (2) Influencing factors of operation time for LSG. Results of multivariate analysis showed that SO was an independent factor influencing operation time for LSG ( odds ratio=2.207, 95% confidence interval as 1.207-4.038, P<0.05). (3) CUSUM of learning curve. Results of CUSUM of operation time in patients of SO and NSO showed that the best fit equation of patients of SO was y=-4E-08x 6+1E-05x 5-0.001 1x 4+0.063 1x 3-1.89x 2+28.126x-48.671 (x means the number of surgical cases), with goodness-of-fit R 2 as 0.833, and the best fit equation of patients of NSO was y=3E-09x 6-1E-06x 5+0.000 2x 4-0.010 9x 3+0.063 8x 2+12.053x-65.025 (x means the number of surgical cases), with goodness-of-fit R 2 as 0.716. Based on the trend of CUSUM of learning curve of operation time, the peak value of number of surgical cases in patients of SO and NSO was 81 and 36, respec-tively, which was used to divide the learning curve as two stages of the initial stage and the proficient stage. (4) Comparison of clinical data between patients in the initial and proficient stages. ① Of the 97 patients of SO, there were 81 cases and 16 cases in the initial stage and the proficient stage of LSG, with the operation time, postoperative duration of hospital stay as (119±23)minutes, (5.9±2.3)days and (106±21)minutes, (4.7±0.5)days, showing significant differences between them ( t=2.074, 2.147, P<0.05). ②Of the 143 patients of NSO, there were 36 cases and 107 cases in the initial stage and the proficient stage of LSG, with gender (female), height, preoperative body mass, defatted body mass, operation time, postoperative duration of hospital stay, body mass at postoperative 6 month, body mass index (BMI) at postoperative 6 month, percentage of excess weight loss (EWL%) at postoperative 6 month, cases with EWL% >100% at postoperative 6 month, excess BMI at post-operative 6 month as 20, (170±10)cm, (110±25)kg, (57±12)kg, (108±22)minutes, (6.1±1.6)days, (80±16)kg, (27.63±4.22)kg/m2, 83%±35%, 9, 1.99(6.03)kg/m2 and 87, (164±8)cm, (99±20)kg, (52±12)kg, (100±19)minutes, (4.7±1.1)days, (71±16)kg, (25.89±4.48)kg/m2, 103%±42%, 48, 0.31(5.82)kg/m2, showing significant differences between them ( χ2=9.484, t=3.266, 2.424, 2.141, 2.137, 5.821, 2.740, 1.993, -2.524, χ2=4.432, Z=-2.300, P<0.05). Conclusions:SO is an independent factor influencing operation time for LSG. It is suggested that the surgeons need to finish 81 cases and 36 cases master LSG in patients of SO and NSO.
6.Value of three-dimensional visualization technique in precise stent drainage for hilar cholangiocarcinoma
Jican YAN ; Wenhao YU ; Zhixin WANG ; Fanyu KONG ; Zhi XIE ; Haining FAN ; Haijiu WANG ; Qian LU ; Li REN
Chinese Journal of Digestive Endoscopy 2023;40(9):713-718
Objective:To investigate the clinical value of three-dimensional (3D) visualization technology in the precise drainage through endoscopic retrograde biliary drainage (ERBD) for hilar cholangiocarcinoma.Methods:Clinical data of 42 patients with highly suspected hilar cholangiocarcinoma who underwent ERBD in Qinghai University Affiliated Hospital from September 2019 to August 2022 were retrospectively collected. Twenty patients underwent 3D biliary tract reconstruction before surgery (the reconstruction group) and 22 others did not undergo 3D biliary tract reconstruction before surgery (the non-reconstruction group). The surgery time, X-ray exposure time, the technical success rate, the clinical success rate, incidence of postoperative complications, recent and short-term endoscopic retrograde cholangiopancreatography (ERCP) reintervention rate of the two groups were compared.Results:There was no significant difference in preoperative baseline data between the two groups ( P>0.05). ERBD was conducted successfully in all 42 patients. The operation time in the reconstruction group [35.00 (25.00, 57.50) min] was significantly shorter than that in the non-reconstruction group [60.00 (33.75, 60.00) min] with significant difference ( Z=-2.251, P=0.024). There was no significant difference in the X-ray exposure time between the two groups [10.00 (5.00, 12.00) min VS 10.55 (9.50, 17.50) min, Z=-1.552, P=0.121]. The technical success rates of both groups were 100.0%, and the clinical success rate of the reconstruction group was higher than that of the non-reconstruction group [70.0% (14/20) VS 31.8% (7/22)] with significant difference ( χ 2=6.109, P=0.013). There was no significant difference in the incidence of postoperative complications between the two groups [20.0% (4/20) VS 22.7% (5/22), χ 2=0.141, P=0.708]. All patients were followed up for 6 months after the procedure. The median survival time was 3.91 months in the reconstruction group and 2.78 months in the non-reconstruction group. There was no ERCP intervention in the reconstruction group within 2 weeks after the procedure, while 4 cases (18.2%) in the non-reconstruction group received 6 ERCP interventions due to cholangitis and postoperative pancreatitis. Within 2 weeks to 3 months, 2 patients (10.0%) in the reconstruction group received 4 ERCP interventions for cholangitis, and 2 patients (9.1%) in the non-reconstruction group received 3 ERCP interventions for cholangitis. There was no significant difference in recent ( χ 2=2.183, P=0.140) or short-term ( χ 2=0.000, P=1.000) ERCP reintervention rate between the reconstruction group and the non-reconstruction group. Conclusion:3D visualization biliary duct reconstruction technology can measure the volume of liver drainage for hilar cholangiocarcinoma, shorten the operation time and improve the clinical success rate through precise preoperative planning, which is worth of promotion.
7.Correlation between the Expression of Ang-2,LYVE-1 and the Biological Characteristics of Cutaneous Squamous Cell Carcinoma
Journal of Medical Research 2023;52(12):49-53
Objective To investigate the correlation between the expression of angiopoietin-2(Ang-2),lymphatic vessel endo-thelial hyaluronan receptor-1(LYVE-1)and the biological characteristics of cutaneous squamous cell carcinoma.Methods A total of 44 patients with primary cSCC admitted to the Affiliated Hospital of Jiangsu University from September 2013 and February 2021 were in-cluded.The expression levels of Ang-2 and LYVE-1 in their cSCC specimens was detected by immunohistochemistry(IHC).The ex-pression level of LYVE-1 was expressed by the microlymphatic vessel density(MLVD).Results The high expression rate of Ang-2 in cSCC group without lymph node metastasis was 44%(15/34),which was significantly lower than that in CSCC group(90%,9/10),and the difference was statistically significant(P<0.05).The high expression rate of Ang-2 in the highly differentiated cSCC group was 35%(9/26),which was significantly lower than that in the medium and poorly differentiated CSCC group(83%,15/18),and the differ-ence was statistically significant(P<0.05).The expression of LYVE-1 in cSCC group without lymph node metastasis was 8.49±4.26,which was significantly lower than that in cSCC group(13.48±5.91),and the difference was statistically significant(P<0.05).The expression of LYVE-1 in highly differentiated cSCC group was 6.39±2.09,which was significantly lower than that in medium and poor-ly differentiated cSCC group(14.28±4.42),and the difference was statistically significant(P<0.05).The expression of Ang-2 and LYVE-1 was not related to gender,age and tumor size(P>0.05).The expression level of Ang-2 was positively correlated with LYVE-1(r=0.598,P<0.01).Conclusion Ang-2 and LYVE-1 are involved in promoting the occurrence,development and lymph node metastasis of cSCC.
8.Association between serum macrophage polarization-related factors and liver fibrosis in echinococcosis multilocularis
Weijian E ; Yongliang LU ; Bingmin QI ; Mingquan PANG ; Zhixin WANG ; Lingqiang ZHANG ; Haining FAN
Journal of Clinical Hepatology 2021;37(12):2813-2818
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.
9.Diagnosis and treatment of hepatic alveolar echinococcosis with intraperitoneal implantable metastasis
Jican YAN ; Zhiyu CHEN ; Wenhao YU ; Xinjian GUO ; Haijiu WANG ; Qian LU ; Liuxin ZHOU ; Haining FAN ; Zhixin WANG
Chinese Journal of Digestive Surgery 2021;20(9):1007-1010
Hepatic alveolar echinococcosis is a zoonotic parasitic disease caused by echinococcus multilocularis infection. The growth pattern of the lesions of hepatic alveolar echinococcosis is similar to that of liver malignant tumor showing invasive growth. Hepatic alveolar echinococcosis can not only directly invade the adjacent tissue structure, but also metastasize through the lymphatic tracts and blood vessels. Hepatic alveolar echinococcosis with intraperitoneal implantable metastasis is extremely rare. The authors introduce the diagnosis and treatment of 1 patient who had hepatic alveolar echinococcosis with intraperitoneal implantable metastasis.
10.Diagnostic value of high-resolution 3T MRI for triangular fibrocartilage complex injuries
Zhixin WANG ; Shanlin CHEN ; Bo LIU ; Huili ZHAN ; Jin ZHU ; Lu LIU
Chinese Journal of Trauma 2020;36(2):143-147
Objective:To investigate the value of high-resolution 3T MRI in the detection of triangular fibrocartilage complex (TFCC) injuries through a diagnostic test.Methods:A retrospective case series analysis was performed in 133 patients with ulnar wrist pain admitted in Beijing Jishuitan Hospital from January 2013 to April 2018. There were 68 males and 65 females, aged 14-69 years (mean 32.6 years). The patients was examined with the wrist MRI with consistent parameters and then received wrist arthroscopic detection or treatment. The TFCC injuries were classified as central injury, namely triangular fibrocartilage disc injury and peripheral injury, namely the tear of ulnar attachment, radial attachment, distal radioulnar ligaments and ulnocarpal ligaments. Take the results of wrist arthroscopy as the gold standard, the MRI and arthroscopic findings were compared and the sensitivity, specificity, positive/negative predictive value and positive/negative likelihood ratio were determined.Results:Wrist arthroscopy confirmed TFCC injuries in 122 patients, among which 72 patients were with central injury and 102 with peripheral injury. Meanwhile, TFCC injuries were diagnosed with MRI in 124 patients, among which 75 patients were central injury and 111 cases were peripheral injury. As for central injury, the sensitivity/specificity, positive/negative predictive value and positive/negative likelihood ratio of MRI were 0.972/0.918, 0.933/0.966 and 11.85/0.03, respectively; when the target pathology was peripheral injury, the sensitivity/specificity, positive/negative predictive value and positive/negative likelihood ratio of MRI were 0.882/0.323, 0.811/0.45 and 1.30/0.37, respectively.Conclusions:High-resolution 3T MRI is accurate in detection of central injury of TFCC, no matter the injury is traumatic or degenerated. In the diagnosis of peripheral injury of the TFCC, MRI can provide some help for its high sensitivity. However, the positive findings of MRI on peripheral structures should be cautious because of the poor specificity, and hence the results of history, physical examination and MRI should be considered together to attain an accurate diagnosis.

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