1.Intervertebral disc rehydration after posterior lumbar dynamic internal fixation
Peng WANG ; Zhijun LI ; Shaojie ZHANG ; Yimin WU
Chinese Journal of Tissue Engineering Research 2026;30(3):711-720
BACKGROUND:With the development of the concept of minimally invasive surgery,lumbar posterior dynamic internal fixation has become the mainstream operation for the treatment of diseases caused by intervertebral disc degeneration.OBJECTIVE:To review the latest progress of lumbar posterior dynamic internal fixation in the treatment of lumbar degenerative diseases and postoperative intervertebral disc rehydration.METHODS:The relevant literature published in CNKI,WanFang,and PubMed databases from 2010 to 2025 was searched with the Chinese and English search terms"lumbar spine,dynamic internal fixation,intervertebral disc degeneration,Coflex system,Dynesys system,In-space system,PercuDyn system,intervertebral disc rehydration,crushing stress."By reading the articles,we eliminated the literature with little relevance to the article topic,poor quality and outdated content,and finally 65 articles were included for summary.RESULTS AND CONCLUSION:(1)Although the main surgical method for the treatment of disc degeneration is still the traditional open surgical method of implantation,posterior lumbar dynamic internal fixation has made great progress.(2)Posterior lumbar dynamic fixation can be divided into open dynamic fixation system and percutaneous dynamic fixation system.Each system can be divided into interspinous dynamic internal fixation system and pedicle dynamic internal fixation system according to the different fixation positions.According to the design of specific instruments and the differences of operation methods in the surgery,different operation methods have been derived.At present,the focus of research at home and abroad is on open dynamic internal fixation system.(3)Under the premise that the clinical effect of posterior lumbar dynamic internal fixation is better than that of traditional interbody fusion surgery,it can cause the rehydration phenomenon of postoperative lumbar intervertebral disc,and further improve the long-term postoperative efficacy of patients.
2.Intervertebral disc rehydration after posterior lumbar dynamic internal fixation
Peng WANG ; Zhijun LI ; Shaojie ZHANG ; Yimin WU
Chinese Journal of Tissue Engineering Research 2026;30(3):711-720
BACKGROUND:With the development of the concept of minimally invasive surgery,lumbar posterior dynamic internal fixation has become the mainstream operation for the treatment of diseases caused by intervertebral disc degeneration.OBJECTIVE:To review the latest progress of lumbar posterior dynamic internal fixation in the treatment of lumbar degenerative diseases and postoperative intervertebral disc rehydration.METHODS:The relevant literature published in CNKI,WanFang,and PubMed databases from 2010 to 2025 was searched with the Chinese and English search terms"lumbar spine,dynamic internal fixation,intervertebral disc degeneration,Coflex system,Dynesys system,In-space system,PercuDyn system,intervertebral disc rehydration,crushing stress."By reading the articles,we eliminated the literature with little relevance to the article topic,poor quality and outdated content,and finally 65 articles were included for summary.RESULTS AND CONCLUSION:(1)Although the main surgical method for the treatment of disc degeneration is still the traditional open surgical method of implantation,posterior lumbar dynamic internal fixation has made great progress.(2)Posterior lumbar dynamic fixation can be divided into open dynamic fixation system and percutaneous dynamic fixation system.Each system can be divided into interspinous dynamic internal fixation system and pedicle dynamic internal fixation system according to the different fixation positions.According to the design of specific instruments and the differences of operation methods in the surgery,different operation methods have been derived.At present,the focus of research at home and abroad is on open dynamic internal fixation system.(3)Under the premise that the clinical effect of posterior lumbar dynamic internal fixation is better than that of traditional interbody fusion surgery,it can cause the rehydration phenomenon of postoperative lumbar intervertebral disc,and further improve the long-term postoperative efficacy of patients.
3.Epidural fibrous scar formation in rabbits following autologous ligamentum flavum intervention
Debao ZHANG ; Peng WANG ; Kun LI ; Shaojie ZHANG ; Zhijun LI ; Shuwen LI ; Yimin WU
Chinese Journal of Tissue Engineering Research 2025;29(6):1168-1175
BACKGROUND:It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms,such as postoperative pain and numbness. OBJECTIVE:To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS:Forty-eight Japanese white rabbits(6-8 months old)were randomly divided into three groups:a ligamentum flavum preservation group,a ligamentum flavum non-preservation group,and an autologous fat reposition group.A lumbar laminectomy model was established in all the three groups of rabbits,and rabbit epidural tissues were collected at 3 and 6 weeks after modeling.Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts,VG staining was used to observe the percentage of collagen fiber area,and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged,while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged.The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P<0.05);however,there was no significant difference between the latter two groups.VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly,while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups.The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P<0.05),but there was no significant difference between the latter two groups.The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups.The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery(P<0.05),but there was no significant difference between the latter two groups.To conclude,there are different degrees of epidural fibrous scar formation after lumbar surgery.If the ligamentum flavum is preserved,it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers,thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root.The mechanism is not only a purely mechanical blockade,but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway.
4.Development and application of a three-dimensional digital visualization system for children's neck acupoints
Xiaojing AO ; Kun LI ; Yuhang LIU ; Xiaoxuan YANG ; Xing WANG ; Zhijun LI ; Xiaoyan REN ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1834-1840
BACKGROUND:Currently,there have been studies on three-dimensional digitalization and visualization systems for adult acupoints,but there are not many reports on the visualization of pediatric acupoints based on real pediatric digital sectional anatomical datasets. OBJECTIVE:To design and develop a digital three-dimensional visualization system for children's neck acupoints,to provide a basis for acupuncture and moxibustion,meridian and acupoint science teaching,clinical practice,acupuncture manipulation practice,and acupuncture safety research,and to provide a basis for the development of children's acupoint simulation system. METHODS:Based on a real cross-sectional anatomical dataset of pre-school boys,a three-dimensional digital virtual anatomical model of the neck region of children and internal multi-organ three-dimensional reconstruction were completed using PhotoShop 2021 and Digihuman Reconstruction System software.A database of 11 acupoints was compiled,including Fengfu and Fengchi,using the Unity database language.A three-dimensional model of children's neck anatomy,acupoint database,and writing acupuncture operation codes were integrated in Unity3D software.A three-dimensional digital visualization system for children's neck acupoints was successfully created,which integrated simulation acupoint positioning,three-dimensional acupoint anatomy,acupuncture training,clinical teaching,and acupuncture safety research. RESULTS AND CONCLUSION:(1)This study was based on real child specimens.Manual layer by layer segmentation of cross-sectional images was used to ensure the accuracy of the three-dimensional model to the greatest extent possible.The 3D software Digihuman Reconstruction System was utilized to extract and save independent segmentation data.PhotoShop 2021 software was collaborated with to complete dozens of three-dimensional reconstruction anatomical models of the outer skin of the neck and its internal bone structure,cervical spinal cord,blood vessels and nerves,muscles,and ligaments in children.The basic morphology and overall contour integrity verification of each independent structure were completed in MeshLab software.The 3-material research 13.0 software was applied for final fine tuning and anatomical position confirmation,successfully simulating and restoring the true anatomical morphology of the neck of preschool children.(2)Based on and referring to the national standards of the People's Republic of China,a database of commonly used acupoints in children's neck region was collected and organized,including their names,meridians,positioning,local anatomy,needle insertion levels,acupuncture methods,acupuncture accidents and prevention,acupoint indications,and two-dimensional anatomical sectional images.(3)Unity3D software was employed to integrate the three-dimensional model of children's neck,acupuncture simulation operation,and acupoint database,and a three-dimensional digital children's neck acupoint acupuncture visualization system was successfully constructed.The system displayed information on children's neck acupoints,two-dimensional and three-dimensional anatomical structures,and achieved two-dimensional and three-dimensional acupuncture simulation functions and acupuncture safety research functions for children's neck acupoints.Based on the ultra-thin sectional anatomical dataset of real child specimens,the first three-dimensional digital and visualization system for acupoints in the neck region of children had been constructed.Compared with previous acupoint acupuncture systems,it is more in line with the anatomical and morphological development characteristics of Asian children and has high application value in the fields of acupuncture safety research,clinical teaching,and acupuncture simulation training.
5.Value of platelet protein kinase C epsilon in risk stratification of acute chest pain in elderly with normal troponin levels
Cuijun HAO ; Rui WANG ; Yang HONG ; Xiaoying LI ; Shaojie HAN ; Fangjiang LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):159-163
Objective To investigate the role of additional platelet protein kinase C epsilon(PKCε)assay in risk stratification and additional diagnostic testing in elderly patients with acute chest pain and normal hypersensitive cardiac troponin I(hs-cTnI)level.Methods A prospective trial was conducted on 220 consecutive elderly patients with angina-like acute chest pain and normal hs-cTnI level in our hospital from April 2022 to April 2023.According to whether major adverse cardiovascular events(MACE)occurred during the 1-year follow-up period,they were assigned in-to MACE group(24 cases)and non-MACE group(196 cases).Their general clinical data and platelet PKCε expression were compared between the two groups.Kaplan-Meier survival curve was plotted to analyzed the event-free time between the platelet PKCε expression<2.05%group and the≥2.05%group.Multivariate Cox regression analysis was used to investigate the impact of baseline data on the occurrence of MACE during the 1-year follow-up period.Decision tree model was employed to analyze the influencing factors for MACE.Results During 1-year follow-up,24 patients(10.91%)developed MACE.The platelet PKCε expression was significantly higher in the MACE group than the non-MACE group[9.25%(6.60%,15.25%)vs 1.70%(0.80%,3.25%),Z=-7.596,P<0.01].Kaplan-Meier survival curve analysis showed that the patients in the PKCε<2.05%group had no events within 360 d,while those in the ≥2.05%group had an average event-free time of 297.13±12.77 d,with a statistical difference(log rank Chi-square=27.051,P=0.000).Multivariate Cox regression analysis showed that highly suspicious angina,hs-cTnI and platelet PKCε were independent risk factors for MACE within 1 year of follow-up(HR=3.011,95%CI:1.049-8.641,P=0.040;HR=1.216,95%CI:1.044-1.418,P=0.012;HR=1.160,95%CI:1.104-1.218,P=0.000).In the decision tree model,the 1-year incidence of MACE was notably higher in the platelet PKCε≥2.05%group than the<2.05%group(P=0.011).The probability of severe coronary artery stenosis or myocardial ischemia in the platelet PKCε≥2.05%group was remarkably higher than the<2.05%group(P=0.006).Conclusion In elderly patients suffering from acute chest pain with normal hs-cTnI level,additional platelet PKCε detection appears to have a good prognostic gain.
6.Relationship between CSF2RB mRNA and GZMA mRNA Expression Levels in PBMC of Patients with Acute Myocardial Infarction and Ventricular Remodeling after PCI
Cuijun HAO ; Rui WANG ; Yang HONG ; Xiaoying LI ; Shaojie HAN ; Fangjiang LI
Journal of Modern Laboratory Medicine 2025;40(2):77-82
Objective To investigate the relationship between the mRNA expression levels of colony stimulating factor 2 receptor subunit beta CSF2RB and granase A(GZMA)in peripheral blood mononuclear cells(PBMC)of patients with acute myocardial infarction(AMI)and ventricular remodeling after percutaneous coronary intervention(PCI).Methods A total of 161 AMI patients admitted to the First Affiliated Hospital of Hebei North University from February 2022 to August 2023 were selected as the study objects,and were further divided into non-remodeling group(n=105)and remodeling group(n=56)according to whether ventricular remodeling was possible.A total of 85 patients with coronary heart disease who did not have myocardial infarction were taken as control group.The clinical data of patients were collected,and the expression levels of CSF2RB and GZMA mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR.Cardiac structural parameters were detected by echocardiography,and the relationship between CSF2RB and GZMA mRNA levels and cardiac structural parameters was analyzed by Pearson correlation.The influencing factors of ventricular remodeling in AMI patients were analyzed by univariate and Logistic regression,and P<0.05 was considered statistically significant.Results The mRNA expression of CSF2RB(1.15±0.28 vs 1.80±0.37),GZMA(0.85±0.16 vs 1.15±0.26),Cys C and Hcy levels were compared between the two groups,and the differences were statistically significant(t=-39.002~-4.854,all P<0.05).The follow-up was up to August 2024.Among 161 AMI patients who underwent PCI,56 cases had ventricular remodeling.The expression level of CSF2RB mRNA(1.85±0.31),GZMA mRNA(1.27±0.29)in the reconstructed group were significantly higher than that in the non-reconstructed group(1.71±0.34,1.12±0.30),and the differences were statistically significant(t=2.564,3.057,all P<0.001).LAD,LVEDD,LVPWTd and IVST in the postoperative reconstruction group were higher than those in the non-reconstruction group(t=11.247~26.008),and LVEF was lower than that in the reconstruction group(t=-15.271),with statistical significance(all P<0.001).The level of CSF2RB and GZMA in AMI patients was positively correlated with LAD,LVEDD,LVPWTd and IVST(rCSF2RB mRNA=0.657~0.754,rGZMA mRNA=0.512~0.745),and negatively correlated with LVEF(r=-0.684,-0.754),with statistical significance(all P<0.05).There was a statistically significant differences in the levels of Cys C and Hcy between the reconstructed group and non-reconstructed group after the use of aldehyed steroid receptor antagonsts(t=5.495,20.710,30.906,all P<0.05).Logistic regression analysis showed that CSF2RBmRNA>1.79,GZMAmRNA>1.18,Hcy>20.15μmol/L and no use of aldosterol receptorantagonists were independent risk factors for ventricular remodeling in AMI patients.LVEF>58.11%was an independent protective factor for ventricular remodeling in AMI patients(Wald χ2=1.137~3.206,P<0.05).Conclusion The expression levels of CSF2RB and GZMA in PBMC of AMI patients were significantly increased.CSF2RB and GZMA are independent risk factors for postoperative ventricular remodeling in patients with AMI,and can be used as potential diagnostic markers for ventricular remodeling after acute myocardial infarction.
7.Digital three-dimensional morphological analysis of developmental characteristics of cervical facet joints in adolescents aged 13-18 years
Guihua LI ; Yujie HE ; Jun SHI ; Kun LI ; Shaojie ZHANG ; Lu LIU ; Zhijun LI ; Xing WANG
Chinese Journal of Tissue Engineering Research 2025;29(21):4486-4491
BACKGROUND:The cervical facet joint,as an important anatomical structure of the posterior column of the cervical spine,plays an important role in neck activity,stress transmission,and maintaining cervical stability. In recent years,anatomical and biomechanical studies have shown that asymmetry of cervical facet joints can cause degeneration of facet joints,which may be the main cause of cervical spine degeneration in young people. Existing research is mostly focused on adults,and there are also reports on preschool and school-age children in China,while there are few reports on the morphological parameters of cervical facet joints in adolescents.OBJECTIVE:Through three-dimensional reconstruction of the cervical facet joints in adolescents,measuring their relevant morphological parameters,and comparing them with those in children and adults,we explored the age-related changes in the morphological development of cervical facet joints,providing a theoretical basis for the diagnosis,treatment,and prevention of cervical spondylosis arising from cervical facet joints.METHODS:A total of 62 adolescents aged 13-18 years were selected to undergo spiral CT scan of cervical vertebrae and 3D reconstruction,requiring no bone destruction,tumor,deformity,or fracture,no changes in vertebrae morphology and structure,no previous spinal operations. The guardian's informed consent to the experimental protocol was obtained. By age group,group A was 13-14 years old;group B was 15-16 years old;group C was 17-18 years old. Thecorrelation morphometry and statistical analysis of C2-C7 facet joints were performed in adolescents of each group.RESULTS AND CONCLUSION:(1) In three groups of subjects,the facet joint surface heights and widths displayed decreasing and increasing trends in relation to the change of vertebra order. The facet joint surfaces on the inferior surface showed larger height and width compared to the corresponding indicators on the superior surface. (2) The intra-articular height of the articular process was lowest in C5 among the three groups of ages,and it showed a positive correlation with age. (3) Among the three groups,the gaps between the articular surfaces of the joints in C4-5 of group A,C3-4 of group B,and C4-5 of group C weresignificantly larger than the rest of the gaps in each group. Except for C4-5,there were no significant differences between the two groups. Except for C2-3,the remaining gaps between the vertebrae in group C were significantly larger than those in the two groups. (4) It is indicated that the morphology of the cervical facet joint surface gradually transitions from circular to elliptical as the vertebral order increases. In inter-group comparison,facet joint surface height is significantly affected by age compared to facet joint surface width. The area of the lower facet joint surface of each segment is greater than that of the upper facet joint surface,with only significant differences in the shape and area of C4-5 and C5-6. In addition,the minimum height of the facet joint is located at C5,and the significantly widened gap between the facet joint surfaces is mainly located at C3-4 and C4-5. Therefore,cervical instability often occurs at the mid-level.
8.Analyses on sanitary status of tableware cleaning and disinfection in 41 catering facilities of Shanghai
Yiqi LI ; Shenghao YU ; Ye YAO ; Shaojie PENG
Shanghai Journal of Preventive Medicine 2025;37(10):852-857
ObjectiveTo analyze the hygienic status of tableware cleaning and disinfection in 41 catering facilities of Shanghai in 2020, to identify its influencing factors, so as to propose evidence-based improvements for future scientific supervision. MethodsA field survey was conducted on the cleaning and disinfection methods of tableware in 41 catering establishments in Shanghai. A total of 180 tableware samples were collected and tested for four indicators, including free residual chlorine, anionic synthetic detergent residues, coliforms, and total number of bacterial colonies. The results were classified and statistically analyzed based on the type of catering establishment, tableware material, tableware function, and cleaning and disinfection methods. ResultsThe tableware passed the tests for coliforms and free residual chlorine. The qualification rate for anionic synthetic detergent residues was 48.89% (88/180), with an average of 0.02 mg per 100 cm² and a maximum of0.25 mg per 100 cm² (This unit complied with the requirements of national standardard: GB 14934—2016). Based on the type of catering enterprises, large restaurants had the lowest qualification rate for anionic synthetic detergent residues in tableware at 46.15%. In terms of the function of tableware, chopsticks had the lowest qualification rate for anionic synthetic detergent residues at 26.32%. The detection rate of total number of bacterial colonies in tableware was 42.22% (76/180), with an average of 0.5 log10 (CFU·mL⁻¹) and a maximum of 3.4 log10 (CFU·mL⁻¹). Among them, medium-sized restaurants had the highest detection rate of total number of bacterial colonies in tableware at 47.73% (21/44). ConclusionThe qualification rate of anionic synthetic detergent residues in tableware is relatively low.It is recommended to strengthen research on the occurrence patterns of unqualified tableware and establish early warning values for the qualification rate of anionic synthetic detergent residues, enhance law enforcement inspections on relevant catering establishments, guide enterprises to fulfill their main responsibilities, and improve the quality and safety of tableware.
9.The trend and prediction of health literacy level of Chinese residents from 2012 to 2023
Shaojie LI ; Yang HU ; Longbing REN ; Yuling JIANG ; Yifei WU ; Yao YAO
Chinese Journal of Preventive Medicine 2025;59(1):8-15
Objective:To analyze the trend of the health literacy level of Chinese residents from 2012 to 2023 and predict the health literacy level from 2024 to 2027.Methods:The study collected data on the health literacy surveillance of Chinese residents from 2012 to 2023. The Joinpoint regression model was used to calculate the average annual percent change (AAPC) and analyze the trend. The interrupted time series analysis with Prais-Winsten transformed generalized least squares estimation was employed to investigate the impact of the"Healthy China 2030" policy on residents′ health literacy levels. Joinpoint regression, autoregressive integrated moving average model and grey forecasting models were established to select the optimal model for forecasting health literacy levels from 2024 to 2027.Results:The results showed that the health literacy level of Chinese residents increased from 8.80% in 2012 to 29.70% in 2023 (AAPC=11.65%, P<0.05). The health literacy level of urban and rural residents increased from 11.79% and 7.13% in 2012 to 33.25% and 26.23% in 2023, respectively (AAPC=9.57% and 12.60%, both P<0.05). Rural (1.59% per year) saw a lower average annual increase than urban (1.79% per year), widening the urban-rural health literacy gap. All aspects of health literacy, including basic knowledge and concepts, healthy lifestyles and behaviors, and health skills, showed an upward trend. The literacy level of six health issues—safety and first aid, scientific health views, health information, infectious disease prevention, chronic disease prevention, and basic medical care—also exhibited rising trends. Interrupted time series analysis indicated a significant further increase in the health literacy level of Chinese residents after the implementation of the "Healthy China 2030" policy, with the growth rate increasing from 0.615% per year before implementation to 2.655% per year afterwards. The Joinpoint regression model showed superior predictive performance compared to autoregressive integrated moving average model and grey forecasting models. The prediction results suggested a continued upward trend in the health literacy level from 2024 to 2027, reaching 32.68%, 35.62%, 38.84%, and 42.34%, respectively. Conclusion:From 2012 to 2023, the overall and various aspects of health literacy among Chinese residents show a continuous upward trend. This study predicts that the level of residents′ health literacy will continue to rise by 2027.
10.Effects of ascites grading and the application of non-selective beta-blockers on the 1-year prognosis of acute-on-chronic liver failure
Wanshu LIU ; Lijun SHEN ; Xi HE ; Hua TIAN ; Qinghui ZHAI ; Dongze LI ; Shaojie XIN ; Shaoli YOU
Chinese Journal of Hepatology 2025;33(1):57-62
Objective:To investigate the effects of ascites grading and the application of non-selective beta-blockers (NSBBs) on the 1-year prognosis of acute-on-chronic liver failure (ACLF).Methods:1 386 ascitic cases with ACLF were graded and followed up for one year. The 1-year prognostic effect of ascites grade and NSBBs was analyzed on ACLF by the Kaplan Meier Log-rank test, Cox stepwise regression, and multivariate regression.The t-test, Mann-Whitney U, or Kruskal-Wallis test were used for intergroup comparison of measurement data. The χ2 test was used for intergroup comparison of numerical data. Results:The incidence rate of ascites at admission was 77.56% in 1 386 ACLF cases. The Log-rank (Mantel-Cox) of the 1-year survival curve test for 1 386 ACLF patients with ascites grade was 21.384, P<0.01. Multivariate regression and Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin activity (PTA), urea, MELD-Na score, and the use of NSBBs were closely related to the 1-year prognosis of ACLF. The log rank (Mantel-Cox) of NSBBs treatment in the grade 2/3 ascites group was 6.113, P=0.013, and the difference was statistically significant, suggesting that NSBBs treatment can help improve the 1-year survival rate in ACLF patients with grade 2 and 3 ascites. Conclusions:Ascites grading and the use of NSBBs affect the prognostic factor of ACLF at one year. NSBBs may be beneficial for the long-term prognosis of ACLF, and treatment can be continued in patients who have already received NSBBs prior to the onset of ACLF.

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