Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.

BACKGROUND:Total knee arthroplasty serves as an effective intervention for the treatment of late-stage knee joint disorders.However,prosthetic liners are prone to wear and failure due to internal stress variations,resulting in limited lifespan and decreased postoperative patient activity.Addressing how to enhance prosthetic design to meet a broader range of patient needs constitutes a significant focus in prosthesis research. OBJECTIVE:Based on the morphological design of the meniscus,we propose an asymmetric design prosthesis and compare it with a symmetric posterior stabilized prosthesis.The stress distribution patterns and variations in the contact area of the liners for both prostheses were analyzed to explore whether the asymmetric prosthesis design offers advantages over the symmetric design. METHODS:Using the finite element method,we simulated the osteotomy and prosthesis assembly in a knee osteoarthritis patient.Two different prostheses(asymmetric design and posterior stabilized)were employed to establish post-total knee arthroplasty knee joint models.Under flexion conditions at 0°,10°,20°,and 30°,we investigated the Mises stress on the femoral and tibial components as well as the liner.Additionally,by comparing the contact area on the inner and outer sides of the liner,we aimed to explore the changes in biomechanics and alterations in motion behavior in the post-total knee arthroplasty knee joint. RESULTS AND CONCLUSION:(1)Throughout the flexion range from 0 to 30 degrees,the Mises stress peak on the liner exhibited a trend of initial decrease followed by an increase,with the stress on the medial side consistently surpassing that on the lateral side.(2)In comparison to the posterior stabilized prosthesis,the asymmetrically designed prosthesis demonstrated smaller stress peaks.At a flexion angle of 30 degrees,the Mises stress peak values of the medial and lateral parts of the asymmetric prosthesis were 15.81 MPa and 11.95 MPa,and those of the posterior stabilization prosthesis were 16.70 MPa and 13.76 MPa.The difference of Mises stress on the medial part was 5.33%,and the difference of Mises stress on the lateral part was 13.15%.Comparing the peak Mises stress on the femoral and tibial components,the asymmetric component was always lower than the posterior stable component during knee flexion.(3)In the upright position at 0 degrees,the medial contact area of the posterior stabilization prosthesis was 17.96 mm2,and the lateral contact area was 34.10 mm2.The contact area on the inner and outer sides of the asymmetric design prosthesis liner was 105.47 mm2 and 107.80 mm2,respectively,indicating a larger contact area with a smaller difference between the inner and outer sides.(4)These results suggest that the biomechanical performance of the asymmetric prosthesis is superior,contributing to the maintenance of knee joint stability and improved joint mobility.This design,to a certain extent,mimics the rotational motion mechanism of the knee joint about the medial condyle as an axis,making it a more effective choice for knee joint prosthesis selection.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To construct the demand model of four types of medical resources including beds in hospi-tal,beds in intensive care unit(ICU),ventilators and medical human resources during the major infectious disease epidemic events,simulate and analyze the treatment of infectious diseases when different medical resources are in short supply.Methods Based on the susceptible-exposed-infectious-recovered(SEIR)model,considering the infec-tivity of infected persons,the susceptibility of the population and the immunity of convalescents,the characteristics of asymptomatic COVID-19 patients and different clinical types,the"COVID-19 infection-hospitalization model"was constructed.By collecting and setting the parameters of disease transmission,clinical course and medical re-source shortage scenarios,an analysis model of allocation and supply of urban medical resources during infectious di-sease epidemic events was initially formed based on Anylogic platform,the supply and demand of medical resources during infectious disease events in different scenarios were analyzed.Results In the non-intervention scenario,the peak time of bed demand was on the 107th day,and the peak value was 160.92 beds per thousand people;the peak time of ventilator demand was on the 122nd day,and the peak value was 5.61 units per thousand people;the peak time of ICU bed demand was on the 117th day,and the peak value was 12.78 beds per thousand people;the peak time of the demand for medical human resources was on the 109th day,and the peak value was 151.12 persons per thousand persons.The simulation results suggested that there were some differences in the impact of different medi-cal resources on the outcome of medical treatment.Conclusion This study constructs an analytical tool for the allo-cation and supply of urban medical resources under the epidemic events of infectious diseases,and the results of mul-tiple simulation experiments suggest that bed resources and medical human resources play more important roles in the outcome of medical treatment.

BACKGROUND:With social progress,the incidence rate of knee osteoarthritis is getting higher and higher in the face of the rapidly developing aging problem in the social population,and the number of total knee replacement operations is gradually increasing. OBJECTIVE:To study the relationship between prosthesis size and stress shielding by improving the tibial prosthesis base. METHODS:A female patient with severe knee osteoarthritis was selected.Based on Mimics,through extracting the bone structure of the knee joint and simulating the total knee replacement surgery,osteotomy,positioning,and implantation operations were carried out to establish the geometric modeling of the total knee replacement prosthesis(including the femoral prosthesis,tibial bracket,and tibial pad),and improve the design of the tibial prosthesis base,analyze the effect of different tibial prosthesis bases on stress shielding of surrounding bone tissue. RESULTS AND CONCLUSION:(1)Compared with single-stem tibial intramedullary stem prosthesis,the design of four-post tibial intramedullary stem prosthesis created a certain degree of stress shielding around the short stem.However,compared with a thicker single long stem,this stress shielding effect was significantly reduced,and the load was evenly distributed among the four short stems,so there was no stress concentration at the bottom of the pile.(2)The design with a rectangular hole in the middle not only provided relatively good stability,but also helped to reduce stress shielding of cancellous bone to a certain extent,with a reduction rate of 77.5%.(3)Compared with a single-stem tibial intramedullary stem prosthesis,both the four-post tibial intramedullary stem prosthesis and the four-post tibial intramedullary stem prosthesis with a hole in the middle have good stability,which can reduce stress shielding to a certain extent without causing stress concentration,providing theoretical guidance for the design of the tibial intramedullary stem.