ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.

Objective:To explore the features of levels of lung cancer biomarkers in peripheral blood of adults in Beijing and surrounding areas, and establish personalized reference intervals for these biomarkers.Methods:A cross sectional study was conducted. The lung cancer biomarker data, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neuron specific enolase (NSE), progastrin-releasing peptide (ProGRP), and squamous cell carcinoma antigen (SCC-Ag), collected from adults who underwent cancer prevention examinations at the Cancer Hospital of the Chinese Academy of Medical Sciences from July 2021 to July 2022 were retrospectively analyzed. The interquartile range method was used to eliminate outliers, and the P95 value was calculated. Upper limit of 5 lung cancer biomarkers in different gender and age groups were obtained by referring to the reference intervals of quantitative analytes in the clinical laboratory (WS/T 402-2024). By analyzing the data of 208 adults who underwent cancer prevention physical examinations at the same center in June 2021 and 140 patients with benign lung masses confirmed by surgical resection pathology from January 2016 to June 2022, the established reference intervals for biomarkers were validated. Results:Two thousand six hundred and twenty-six cases of apparently healthy physical examiners were included for constructing reference intervals, including 1 456 males (55.4%) and 1 170 females (44.6%); the age range was 20-88 years old. The serum levels [ M ( Q1, Q3)] of CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 in 2 626 cases were 1.63 (1.07, 2.43) ng/ml, 13.08 (11.44, 14.77) ng/ml, 34.93 (29.02, 42.19) pg/ml, 0.80 (0.60, 1.00) ng/ml and 1.96 (1.48, 2.63) ng/ml, respectively. The serum levels of CEA [1.88 (1.22, 2.76) ng/ml vs. 1.41 (0.93, 2.02) ng/ml], NSE [13.31 (11.87, 15.00) ng/ml vs. 12.69 (10.96, 14.53) ng/ml], SCC-Ag [0.9 (0.7, 1.1) ng/ml vs. 0.7 (0.6, 0.9) ng/ml], and CYFRA21-1 [2.02 (1.53, 2.71) ng/ml vs. 1.87 (1.40, 2.51) ng/ml] in males were higher than those in females, and ProGRP [34.00 (28.25, 41.55) pg/ml vs. 36.12 (29.97, 42.98) pg/ml] was lower than that in females, and the differences were statistically significant (all P < 0.001). There were statistically significant differences in serum CEA levels between the groups of ≤ 40 years old (458 cases), >40-50 years old (827 cases), >50-60 years old (783 cases), >60-70 years old (412 cases), and >70 years old (146 cases) in pairwise comparison (all P < 0.05). Except for the age groups of ≤ 40 years old and >40-50 years old and the age groups of >60-70 years old and >70 years old, there were statistically significant differences in serum NSE levels among the other age groups in pairwise comparison (all P < 0.05). There were statistically significant differences in serum ProGRP levels between the 5 age groups (all P < 0.05). There were statistically significant differences when comparing the serum SCC-Ag level in the >40-50 age group, >50-60 age group and >60-70 age group with that in the ≤40 age group and >70 age group, respectively (all P < 0.05). However, there was no statistically significant difference between the other age groups in pairwise comparison (all P > 0.05). There were statistically significant differences in serum CYFRA21-1 levels between the 5 age groups (all P < 0.05). When gender and age were not distinguished, the P95 values of serum CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 levels were 4.44 ng/ml, 16.61 ng/ml, 57.65 pg/ml, 1.50 ng/ml, and 4.21 ng/ml, respectively. Considering gender and age, except for the >70 age group with no statistically significant difference in the P95 value of serum CEA level between males and females ( P > 0.05), the P95 value of serum CEA level in males was higher than that in females in all other age groups (all P < 0.001); the P95 values of serum CEA level in both males and females increased with age, but showed a decreasing trend in males over the age of 70. The P95 value of serum NSE level in males was higher than that in females in the age groups of ≤ 40 years and >40-50 years (both P < 0.05), while there was no statistically significant difference in the P95 value of serum NSE level between males and females in other age groups (all P > 0.05). The P95 values of serum NSE level in both males and females decreased firstly and increased later with age, reaching their highest levels at the age of >70. The P95 values of serum ProGRP level in females aged ≤ 40 and >50-60 were higher than those in males (both P < 0.05), while there was no statistically significant difference in the P95 value of serum ProGRP level between genders in other age groups (all P > 0.05); the P95 values of serum ProGRP level in both males and females increased with age. There was no statistically significant difference in the P95 value of serum SCC-Ag level between males and females in the ≤ 40 age group ( P > 0.05), while the P95 value of serum SCC-Ag level in males was higher than that in females in all other age groups (all P < 0.05). The P95 values of serum SCC-Ag level in males increased with age, while they were stable in females. There was no statistically significant difference in the P95 value of serum CYFRA21-1 level between males and females in the >60-70 age group ( P > 0.05), while the P95 value of serum CYFRA21-1 level in males was higher than those in females in all other age groups (all P < 0.05); the P95 values of serum CYFRA21-1 level in both males and females increased with age. Based on data from 2 626 apparently healthy physical examiners, reference intervals for the levels of 5 lung cancer biomarkers were constructed in different age groups of different genders. Validation was conducted on 208 physical examiners and 140 patients with benign lung lesions, and it was found that the compliance rate of using newly created reference intervals for different gender and age groups to interpret detection results was >90%, and the validation was passed. Conclusions:There are gender and age differences in the reference intervals of CEA, CYFRA21-1, NSE, ProGRP, and SCC-Ag in peripheral blood of adults in Beijing and surrounding areas. The constructed reference intervals of gender and age for biomarkers have been validated and shown good results, providing reference for optimizing the clinical application of lung cancer-related biomarkers.

Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.

Objective:To explore the features of levels of lung cancer biomarkers in peripheral blood of adults in Beijing and surrounding areas, and establish personalized reference intervals for these biomarkers.Methods:A cross sectional study was conducted. The lung cancer biomarker data, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neuron specific enolase (NSE), progastrin-releasing peptide (ProGRP), and squamous cell carcinoma antigen (SCC-Ag), collected from adults who underwent cancer prevention examinations at the Cancer Hospital of the Chinese Academy of Medical Sciences from July 2021 to July 2022 were retrospectively analyzed. The interquartile range method was used to eliminate outliers, and the P95 value was calculated. Upper limit of 5 lung cancer biomarkers in different gender and age groups were obtained by referring to the reference intervals of quantitative analytes in the clinical laboratory (WS/T 402-2024). By analyzing the data of 208 adults who underwent cancer prevention physical examinations at the same center in June 2021 and 140 patients with benign lung masses confirmed by surgical resection pathology from January 2016 to June 2022, the established reference intervals for biomarkers were validated. Results:Two thousand six hundred and twenty-six cases of apparently healthy physical examiners were included for constructing reference intervals, including 1 456 males (55.4%) and 1 170 females (44.6%); the age range was 20-88 years old. The serum levels [ M ( Q1, Q3)] of CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 in 2 626 cases were 1.63 (1.07, 2.43) ng/ml, 13.08 (11.44, 14.77) ng/ml, 34.93 (29.02, 42.19) pg/ml, 0.80 (0.60, 1.00) ng/ml and 1.96 (1.48, 2.63) ng/ml, respectively. The serum levels of CEA [1.88 (1.22, 2.76) ng/ml vs. 1.41 (0.93, 2.02) ng/ml], NSE [13.31 (11.87, 15.00) ng/ml vs. 12.69 (10.96, 14.53) ng/ml], SCC-Ag [0.9 (0.7, 1.1) ng/ml vs. 0.7 (0.6, 0.9) ng/ml], and CYFRA21-1 [2.02 (1.53, 2.71) ng/ml vs. 1.87 (1.40, 2.51) ng/ml] in males were higher than those in females, and ProGRP [34.00 (28.25, 41.55) pg/ml vs. 36.12 (29.97, 42.98) pg/ml] was lower than that in females, and the differences were statistically significant (all P < 0.001). There were statistically significant differences in serum CEA levels between the groups of ≤ 40 years old (458 cases), >40-50 years old (827 cases), >50-60 years old (783 cases), >60-70 years old (412 cases), and >70 years old (146 cases) in pairwise comparison (all P < 0.05). Except for the age groups of ≤ 40 years old and >40-50 years old and the age groups of >60-70 years old and >70 years old, there were statistically significant differences in serum NSE levels among the other age groups in pairwise comparison (all P < 0.05). There were statistically significant differences in serum ProGRP levels between the 5 age groups (all P < 0.05). There were statistically significant differences when comparing the serum SCC-Ag level in the >40-50 age group, >50-60 age group and >60-70 age group with that in the ≤40 age group and >70 age group, respectively (all P < 0.05). However, there was no statistically significant difference between the other age groups in pairwise comparison (all P > 0.05). There were statistically significant differences in serum CYFRA21-1 levels between the 5 age groups (all P < 0.05). When gender and age were not distinguished, the P95 values of serum CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 levels were 4.44 ng/ml, 16.61 ng/ml, 57.65 pg/ml, 1.50 ng/ml, and 4.21 ng/ml, respectively. Considering gender and age, except for the >70 age group with no statistically significant difference in the P95 value of serum CEA level between males and females ( P > 0.05), the P95 value of serum CEA level in males was higher than that in females in all other age groups (all P < 0.001); the P95 values of serum CEA level in both males and females increased with age, but showed a decreasing trend in males over the age of 70. The P95 value of serum NSE level in males was higher than that in females in the age groups of ≤ 40 years and >40-50 years (both P < 0.05), while there was no statistically significant difference in the P95 value of serum NSE level between males and females in other age groups (all P > 0.05). The P95 values of serum NSE level in both males and females decreased firstly and increased later with age, reaching their highest levels at the age of >70. The P95 values of serum ProGRP level in females aged ≤ 40 and >50-60 were higher than those in males (both P < 0.05), while there was no statistically significant difference in the P95 value of serum ProGRP level between genders in other age groups (all P > 0.05); the P95 values of serum ProGRP level in both males and females increased with age. There was no statistically significant difference in the P95 value of serum SCC-Ag level between males and females in the ≤ 40 age group ( P > 0.05), while the P95 value of serum SCC-Ag level in males was higher than that in females in all other age groups (all P < 0.05). The P95 values of serum SCC-Ag level in males increased with age, while they were stable in females. There was no statistically significant difference in the P95 value of serum CYFRA21-1 level between males and females in the >60-70 age group ( P > 0.05), while the P95 value of serum CYFRA21-1 level in males was higher than those in females in all other age groups (all P < 0.05); the P95 values of serum CYFRA21-1 level in both males and females increased with age. Based on data from 2 626 apparently healthy physical examiners, reference intervals for the levels of 5 lung cancer biomarkers were constructed in different age groups of different genders. Validation was conducted on 208 physical examiners and 140 patients with benign lung lesions, and it was found that the compliance rate of using newly created reference intervals for different gender and age groups to interpret detection results was >90%, and the validation was passed. Conclusions:There are gender and age differences in the reference intervals of CEA, CYFRA21-1, NSE, ProGRP, and SCC-Ag in peripheral blood of adults in Beijing and surrounding areas. The constructed reference intervals of gender and age for biomarkers have been validated and shown good results, providing reference for optimizing the clinical application of lung cancer-related biomarkers.

Objective:To investigate the application value of laparoscopic-assisted total liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinical data of 9 pairs of donors and recipients who underwent laparoscopic-assisted total liver transplanta-tion in People′s Hospital of Guangxi Zhuang Autonomous Region from January to April 2024 were collected. Of the donors, there were 8 males and 1 female, aged (39±18)years and with body mass index (BMI) of (20±4)kg/m 2. Of the recipients, there were 7 males and 2 females, aged (41±13)years and with BMI of (24±4)kg/m 2. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. Of the 9 recipients, 7 recipients underwent laparoscopic-assisted total liver transplantation successfully, 1 recipient with severe portal hypertension converted to open surgery with reverse L-shaped incision due to the hemorrhage during the dissection of the first hepatic portal after completing liver mobilization under laparoscopy, and 1 recipient underwent trans-umbilical extension incision through the middle of the epigastric region due to the limited space for operation in the implantation of the donor liver. The total operation time for 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (648±31)minutes, with a time of anhepatic phase of (57±5)minutes, the volume of intraoperative blood loss of (1 322±627)mL, the donor liver mass of (1 195±232)g, and the ratio of donor liver mass to recipient body mass of 1.86%±0.42%. The operation time for laparoscopic liver dissection and porta hepatis dissection in 8 recipients during surgery was (212±35)minutes. (2) Postoperative conditions. All 9 recipients recovered smoothly after surgery, without any vascular or biliary related complications, and the surgical incision recovered well. The duration of postoperative hospital stay of 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (14.2±2.0)days. (3) Follow-up. All 9 recipients were followed up for 3 months after surgery. During the follow-up period, there was no vascular or bile duct related complication.Conclusion:Laparoscopic-assisted total liver transplantation can be applied to recipients who meet surgical conditions and achieve good short-term clinical efficacy.

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

Objective:To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD).Methods:A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c. 11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+ PM2_Supporting+ PP3). Conclusion:The c. 11098C>T (p.R3700C) and c. 11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

Objective To evaluate the nutritional status of elderly inpatients by using the nutritional risk screening table 2002(NRS2002)and the short-form mini-nutritional assessment(MNA-SF),and to eval-uate the applicability of the two tools.Methods The general data were collected from the inpatients aged ≥80 years old by the random sampling method.They were divided into the two age groups:≥90 years old and＜90 years old,and their nutritional status was assessed by using the two nutritional screening tools.Meanwhile,the fasting venous blood nutritional related indicators including albumin(Alb),hemoglobin(Hb),C-reactive protein(CRP),transferrin(TRF),prealbumin(PA)and retinol-binding protein(RBP)levels were detected.Furthermore the results conducted the correlation analysis.Results There were 404 cases(48.56％)of nutri-tional risk in the NRS2002 evaluation.The occurrence rate of nutritional risk in the ≥90 years old group was higher than that in the＜90 years old group(P＜0.01).There were 616 cases(74.04％)of malnutrition/risk of malnutrition in the MNA-SF evaluation.The incidence rate of malnutrition risk in the≥90 years old group was higher than that in the＜90 years old group(P＜0.01).With the serum ALB＜30 g/L as the ref-erence standard,the applicabilities were compared between the two kinds of nutritional screening tools,the re-sults found that the two kinds of nutritional screening tools all were suitable for the nutritional status screen-ing of elderly inpatients.The area under the receiver operating characteristic(ROC)curve(AUC)of the MNA-SF for evaluating the nutritional status in the elderly inpatients was 0.814,the sensitivity and specificity were 75.7％and 87.7％respectively.AUC of ROC in NRS2002 for evaluating the nutritional status in the elderly inpatients was 0.805,the sensitivity and specificity were 88.6％and 62.2％respectively.The correla-tion analysis results of Hb,CRP,PA,RBP and TRF biochemical indexes with MNA-SF score and NRS2002 score showed that NRS2002 score and MNA-SF score were correlated with PA,RBP and TRF.Conclusion The incidence rate of nutritional risk in elderly inpatients is high.Both NRS2002 and MNF-SF nutritional screening tools are suitable for elderly inpatients and have high accuracy.Meanwhile,combining nutrition-related indicators to evaluate the nutritional status of elderly patients can improve the accuracy of nutritional assessment.