Objective:To calculate the reference intervals of immune globulinG (IgG), IgA, IgM, complement 3 (C3) and C4 for adults using Hoffmann and refineR methods, and to compare them with the reference interval reported by WS/T 645 of the People′s Republic of China, exploring the clinical application value of the indirect methods.Methods:Cross-sectional study. The physical examination data were collected at Peking Union Medical College Hospital from 2013 to 2023. Box-Cox was used to normalize the data distribution, and the Tukey method was used to remove outliers. Mann-Whitney test and Kruskal-Wallis test were used to compare the differences between gender and age, respectively. Quantile regression analysis was used to examine the effects of age and gender. Hoffmann and refineR methods were employed to calculate RIs of the five parameters.Results:There were 82 251, 82 483, 49 236, 20 027 and 19 942 test results for IgG, IgA, IgM, C3 and C4, respectively. Gender was significantly correlated with IgG, IgA, IgM, C3, and C4 levels, and age was significantly correlated with IgA, IgM, C3, and C4 levels. Reference intervals were calculated using both Hoffmann and refineR methods, yielding comparable results: IgG (7.58-16.85 g/L; 7.54-16.88 g/L), IgA (0.97-4.26 g/L; 0.97-4.34 g/L), C3 (0.73-1.43 g/L; 0.73-1.44 g/L), and C4 (0.11-0.32 g/L). Gender-specific intervals were established for IgM: women (0.44-2.57 g/L; 0.44-2.62 g/L) and men (0.33-1.91 g/L; 0.31-1.87 g/L). Gender and/or age-specific reference intervals were further calculated according to the bias ratio values. The reference intervals calculated by Hoffmann and refineR are in good agreement. The upper and lower limits of reference intervals for IgA and C3, the lower limits of IgG, the upper limits of IgM and C3 calculated by the indirect methods have good comparability with those reported by standards.Conclusions:The total and gender/age-specific reference intervals of IgG, IgA, IgM, C3 and C4 in our hospital population were established by Hoffmann and refineR methods, and the reference intervals established by the two indirect methods were comparable. The reference intervals calculated using these indirect methods were also comparable with those established using the direct method reported in current health standards.

BACKGROUND:Implant restoration has become an important means to treat anterior tooth loss,and it is particularly important to select appropriate implant restoration materials.However,at present,there are some deficiencies in clinical implant materials,and researchers have been exploring suitable implant materials.OBJECTIVE:To compare the biomechanical characteristics of implants made of different materials in restoring single missing maxillary anterior teeth.METHODS:The cone beam CT data of a patient with single maxillary central incisor loss were imported into 3-matic software to establish a three-dimensional finite element analysis model of single maxillary anterior tooth loss.The model was then imported into Marc Mentat.Eight sets of implant restoration models were designed according to different implant materials(polyetheretherketone,titanium-zirconium alloy,titanium alloy,and zirconia,with the elastic modulus of the four materials increasing in sequence)and cancellous bone density(high density,low density)to simulate the stress conditions of the maxillary anterior teeth in centric occlusion.The total displacements and von Mises stresses of implants,cortical bone stresses and cancellous bone strains were compared and analyzed.RESULTS AND CONCLUSION:(1)The maximum displacement of the implant gradually decreased with the increase of the modulus of elasticity of the material,and the value of the maximum displacement of the implant in the polyetheretherketone group exceeded 10 μm;the implant stress was concentrated in the labial neck in the models.The maximum stress gradually increased with the increase of the modulus of elasticity of the implant material,among which,the zirconia-low density bone model had the highest stress,which was 21.31 MPa;the cortical bone stress was concentrated in the cortical bone at the junction of the implant with the labial side,and the polyetheretherketone-low density bone group had the highest value,which was 29.90 MPa.(2)From the biomechanical point of view,titanium-zirconium alloy,titanium alloy,and zirconia can be used as implant materials for restoration of a single missing anterior tooth,and implant displacement is one of the common problems during implant restorations,but pure polyetheretherketone material may cause excessive implant displacement in implant restorations of anterior areas,causing implant failure.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

In the era of intelligence and individualization, gastric cancer surgery is under-going multidimensional advancements. The authors focus on the cutting-edge progress and future challenges of artificial intelligence (AI) in the diagnosis and decision-making, treatment and drug development, as well as postoperative rehabilitation in gastric cancer surgery. In terms of diagnosis, AI integrates imaging, liquid biopsy, pathology, and multimodal technologies to enhance diagnostic comprehensiveness and accuracy. Regarding decision-making, AI assists in formulating personalized treatment plans, conducting risk assessments, and predicting prognoses. In the treatment domain, AI facilitates the advancement of individualized surgical approaches, supports postoperative follow-up, and aids in physician education and training. In drug development, the introduction of virtual cell models and AlphaFold has improved the efficiency and accuracy of mechanistic and clinical research. For postoperative rehabilitation guidance, AI provides personalized recommendations to optimize treatment outcomes.AI holds great promise in gastric cancer surgery across diagnosis and decision-making, treatment and drug development, and postoperative rehabilitation. However, current AI technologies face challenges such as data sharing and privacy protection, multicenter research and model generalization, human-machine collaboration, interpretability, ethical considerations, sustaina-bility, and widespread adoption. Addressing these challenges will require collective efforts to fully leverage AI′s advantages in gastric cancer diagnosis and treatment.

In the era of intelligence and individualization, gastric cancer surgery is under-going multidimensional advancements. The authors focus on the cutting-edge progress and future challenges of artificial intelligence (AI) in the diagnosis and decision-making, treatment and drug development, as well as postoperative rehabilitation in gastric cancer surgery. In terms of diagnosis, AI integrates imaging, liquid biopsy, pathology, and multimodal technologies to enhance diagnostic comprehensiveness and accuracy. Regarding decision-making, AI assists in formulating personalized treatment plans, conducting risk assessments, and predicting prognoses. In the treatment domain, AI facilitates the advancement of individualized surgical approaches, supports postoperative follow-up, and aids in physician education and training. In drug development, the introduction of virtual cell models and AlphaFold has improved the efficiency and accuracy of mechanistic and clinical research. For postoperative rehabilitation guidance, AI provides personalized recommendations to optimize treatment outcomes.AI holds great promise in gastric cancer surgery across diagnosis and decision-making, treatment and drug development, and postoperative rehabilitation. However, current AI technologies face challenges such as data sharing and privacy protection, multicenter research and model generalization, human-machine collaboration, interpretability, ethical considerations, sustaina-bility, and widespread adoption. Addressing these challenges will require collective efforts to fully leverage AI′s advantages in gastric cancer diagnosis and treatment.

BACKGROUND:Implant restoration has become an important means to treat anterior tooth loss,and it is particularly important to select appropriate implant restoration materials.However,at present,there are some deficiencies in clinical implant materials,and researchers have been exploring suitable implant materials.OBJECTIVE:To compare the biomechanical characteristics of implants made of different materials in restoring single missing maxillary anterior teeth.METHODS:The cone beam CT data of a patient with single maxillary central incisor loss were imported into 3-matic software to establish a three-dimensional finite element analysis model of single maxillary anterior tooth loss.The model was then imported into Marc Mentat.Eight sets of implant restoration models were designed according to different implant materials(polyetheretherketone,titanium-zirconium alloy,titanium alloy,and zirconia,with the elastic modulus of the four materials increasing in sequence)and cancellous bone density(high density,low density)to simulate the stress conditions of the maxillary anterior teeth in centric occlusion.The total displacements and von Mises stresses of implants,cortical bone stresses and cancellous bone strains were compared and analyzed.RESULTS AND CONCLUSION:(1)The maximum displacement of the implant gradually decreased with the increase of the modulus of elasticity of the material,and the value of the maximum displacement of the implant in the polyetheretherketone group exceeded 10 μm;the implant stress was concentrated in the labial neck in the models.The maximum stress gradually increased with the increase of the modulus of elasticity of the implant material,among which,the zirconia-low density bone model had the highest stress,which was 21.31 MPa;the cortical bone stress was concentrated in the cortical bone at the junction of the implant with the labial side,and the polyetheretherketone-low density bone group had the highest value,which was 29.90 MPa.(2)From the biomechanical point of view,titanium-zirconium alloy,titanium alloy,and zirconia can be used as implant materials for restoration of a single missing anterior tooth,and implant displacement is one of the common problems during implant restorations,but pure polyetheretherketone material may cause excessive implant displacement in implant restorations of anterior areas,causing implant failure.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective:To calculate the reference intervals of immune globulinG (IgG), IgA, IgM, complement 3 (C3) and C4 for adults using Hoffmann and refineR methods, and to compare them with the reference interval reported by WS/T 645 of the People′s Republic of China, exploring the clinical application value of the indirect methods.Methods:Cross-sectional study. The physical examination data were collected at Peking Union Medical College Hospital from 2013 to 2023. Box-Cox was used to normalize the data distribution, and the Tukey method was used to remove outliers. Mann-Whitney test and Kruskal-Wallis test were used to compare the differences between gender and age, respectively. Quantile regression analysis was used to examine the effects of age and gender. Hoffmann and refineR methods were employed to calculate RIs of the five parameters.Results:There were 82 251, 82 483, 49 236, 20 027 and 19 942 test results for IgG, IgA, IgM, C3 and C4, respectively. Gender was significantly correlated with IgG, IgA, IgM, C3, and C4 levels, and age was significantly correlated with IgA, IgM, C3, and C4 levels. Reference intervals were calculated using both Hoffmann and refineR methods, yielding comparable results: IgG (7.58-16.85 g/L; 7.54-16.88 g/L), IgA (0.97-4.26 g/L; 0.97-4.34 g/L), C3 (0.73-1.43 g/L; 0.73-1.44 g/L), and C4 (0.11-0.32 g/L). Gender-specific intervals were established for IgM: women (0.44-2.57 g/L; 0.44-2.62 g/L) and men (0.33-1.91 g/L; 0.31-1.87 g/L). Gender and/or age-specific reference intervals were further calculated according to the bias ratio values. The reference intervals calculated by Hoffmann and refineR are in good agreement. The upper and lower limits of reference intervals for IgA and C3, the lower limits of IgG, the upper limits of IgM and C3 calculated by the indirect methods have good comparability with those reported by standards.Conclusions:The total and gender/age-specific reference intervals of IgG, IgA, IgM, C3 and C4 in our hospital population were established by Hoffmann and refineR methods, and the reference intervals established by the two indirect methods were comparable. The reference intervals calculated using these indirect methods were also comparable with those established using the direct method reported in current health standards.

ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function. MethodsUsing panel group study design， 223 students in five classes of grade 4 from two primary schools （a， b） in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide （FeNO）. The first three tests were carried out from May to June in 2020， and the fourth test was carried out from September to December in 2021. At the same time， the daily and hourly mean values of PM_2.5， PM₁₀， SO₂， NO₂， O₃ and CO was collected from the nearby air quality monitoring points of the two schools during the same period ， as well as meteorological monitoring data （temperature， humidity， wind speed and atmospheric pressure）. The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer. ResultsThe results of single pollutant model showed that PM_2.5， PM_10， SO₂ and NO₂ were positively correlated with FeNO， and the effect was reflected in lag0， lag1 and lag3 （P<0.05）. PM_2.5， PM₁₀ and NO₂ were negatively correlated with the changes of lung function FEF_25%， FEF_50%， FEF_75%， FeF_25%-75%， PEF， FVC， FEV1 and FEV1/FVC， and the effect was reflected in lag0 to lag3 days （P<0.05）. The results of the dual pollutant model showed that the concentration changes of SO₂ and NO₂ were significantly correlated with the decrease of FEV1 when combined with O₃ or PM_2.5 （P<0.01）， and the concentration changes of PM_2.5 was significantly correlated with the increase of FeNO when O₃， SO₂ and NO₂ were combined respectively （P<0.01）. The effects of the dual pollutant model were greater than the effect of PM_2.5 single pollutant model. ConclusionThe health effects of different air pollutants on children’s respiratory tract function indexes in summer are different. The combined effects of two pollutants on the lung function of children increased to different degrees. Although air pollution is light in summer， it still has an impact on children’s respiratory tract function index and inflammation index， and the combined effect of dual pollutants is more significant than that of single pollutant.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.