Objective: To study the correlation between activated partial thromboplastin time (APTT) mixing test results and the inhibitor titers in hemophilia A inhibitor-positive patients. Methods: In this cross-sectional study, 41 patients with severe hemophilia A and inhibitors (and negative for lupus anticoagulant) were included from the hemophilia clinic of Shandong Blood Center from February 2022 to February 2024. All patients underwent APTT mixing test. The Rosner's index (RI, including the immediate RI and the RI after 2-hour water bath incubation [water bath 2h RI]), the time-dependent difference (Δ value), and the corrected percentage were calculated based on results of APTT mixing test. The median (interquartile range) of the corresponding indexes were calculated, and the ROC curves for identification of high inhibitor titers using the four indexes (the immediate RI, the water bath 2h RI, the Δ value, and the corrected percentage) were plotted, The correlations between APTT mixing test and inhibitor titers for coagulation factor Ⅷ (Factor Ⅷ, FⅧ) were investigated. Results: The median (lower quartile, upper quartile) of immediate RI, water bath 2h RI, Δ-value and corrected percentage for FⅧ inhibitor positive patients were 11.0 (5.4, 29.3)%, 45.0 (25.7, 75.0)%, 26.2 (7.6, 41.8) s, and 82.2 (58.5, 91.6)%, respectively. The median (lower quartile, upper quartile) of the immediate RI, water bath 2h RI, Δ-value and corrected percentage were 25.2 (13.0, 37.5)%, 64.1 (44.6, 72.6)%, 38.0 (14.3, 38.3) s, and 66.5 (50.1, 82.1)% for the high-titer inhibitor group, and 5.2 (4.2, 9.4)%, 17.9 (8.8, 28.0)%, 13.0 (7.6, 25.4) s, and 92.3 (88.0, 94.3)% for the low-titer inhibitor group. The AUCs of the ROC curves for discrimination between high and low titer inhibitor were: 0.9105 for immediate RI, 0.9118 for water bath 2h RI, 0.8873 for correcter percentage, and 0.6532 for Δ-value. Conclusion: High-titer inhibitors can be highly suspected in hemophiliac patients with an immediate RI >10% and a water bath 2h RI >45%, and the presence of low-titer inhibitors is suspected in patients with a 4-second < immediate RI <10% and a 13% < water bath 2h RI <45%.

OBJECTIVE To investigate the efficacy and safety of the interleukin-1 （IL-1） receptor antagonist anakinra in the treatment of refractory adult onset Still’s disease （AOSD）， and provide more real-world evidence and practical experience for the treatment of AOSD with this drug. METHODS A retrospective analysis was conducted on the diagnosis and treatment process of a patient with AOSD complicated with dermatomyositis who received anakinra； systematically searched for relevant literature on the treatment of AOSD with anakinra in Chinese and English databases such as CNKI， PubMed， Medline， etc.， and conduct literature review on its efficacy and safety. RESULTS The patient in this case had poor treatment with multiple traditional drugs and was considered to have AOSD combined with dermatomyositis. After being admitted to the hospital and treated with a combination therapy of anakinra and glucocorticoids for several days， the patient’s clinical symptoms and inflammatory indicators significantly improved， and no serious adverse drug reactions occurred. Pharmacists designed specialized pharmaceutical monitoring pathways and conduct regular follow-up after discharge. After discharge， the patient took medication regularly， and the condition was maintained and relieved； during this period， there was redness and swelling at the injection site which resolved on its own without any other obvious discomfort. Literature review showed that anakinra could increase the response rate and remission rate of AOSD patients， and significantly reduce the dosage of glucocorticoids； adverse events were mainly injection site reactions， with a low overall risk of infection and good safety； however， there was a significant difference in the treatment course， and there was currently no unified plan. CONCLUSIONS Anakinra is an efficient and safe biological agent for treating AOSD， which can rapidly induce and maintain disease remission. For AOSD patients， clinical consideration may be given to using IL-1 antagonists to reduce glucocorticoid dependence， while strengthening long-term medication monitoring.

BACKGROUND:The treatment of distal tibial comminuted fractures with soft tissue injury has always been challenging.The new retrograde tibial nailing and supercutaneous locking plate are important treatment methods,but their strain and stress shielding at the fracture end during different periods of fracture healing and different load conditions have not been reported. OBJECTIVE:To explore the biomechanical stability of retrograde tibial nailing and supercutaneous locking plate in different periods of fracture healing by finite element analysis to offer a scientific foundation for clinical application and rehabilitation exercise. METHODS:The finite element model of distal tibial comminuted fracture was established by utilizing the CT data of the tibia from a 40-year-old healthy male.Retrograde tibial nailing,supercutaneous locking plate,and callus models were assembled in accordance with the principle of fracture fixation.The finite element analysis was performed using ANSYS software to compare the displacement of the fracture end,the stress shielding of the tibia,the stress of the callus,and the stress distribution of the tibia and the fixation device during different periods of fracture healing. RESULTS AND CONCLUSION:(1)The relative displacement of the tibial fracture decreased gradually with the healing of the fracture,and the displacement decreased significantly after 3 months.At 0 and 1 months after operation,the vertical displacement and total displacement of the supercutaneous locking plate group were higher than those in the retrograde intramedullary nail group.The Z-axis displacement(horizontal medial and lateral displacement)of the two fixation methods was more obvious than the X-axis and Y-axis,and the Z-axis displacement of supercutaneous locking plate group was the most obvious.The maximum Z-axis displacement of the two fixation methods was located on the outside of the tibia,and the minimum displacement was located on the inside of the tibia.(2)The stress shielding rate at different periods of fracture healing gradually decreased with time.The stress shielding rate of the retrograde intramedullary nail was higher than that of the supercutaneous locking plate at different stages of fracture healing.After 3 months,the stress shielding rate of the supercutaneous locking plate was reduced to about 4%,and the stress shielding rate of the retrograde intramedullary nail was reduced to about 40%.(3)The stress of the stress concentration site of the callus in the two fixation methods increased with the increase of the load,and the stress of the callus in the supercutaneous locking plate group was always greater than that in the retrograde intramedullary nail group.The maximum stress distribution of the callus was approximately equally distributed among the two modes of fixation,both in the lateral portion of the tibia.(4)As the fracture healed,the maximum stress of the tibia in the two groups decreased gradually,and the stress in the supercutaneous locking plate group was always greater than that in the retrograde intramedullary nail group.The average stress of the maximum stress area of the tibia in the supercutaneous locking plate group under 1 500 N load was 285 MPa,while that in the retrograde intramedullary nail group was 26 MPa.(5)As the fracture healed,the stress of the fixation device in the two groups decreased gradually,and the stress in the supercutaneous locking plate group was significantly higher than that in the retrograde intramedullary nail group.After 3 months,the stress of the two fixation devices decreased significantly.(6)It is indicated that in the early stage of fracture healing,the strain on the fracture end in the retrograde intramedullary nail group is small,and the maximum stress of the tibia is moderate,allowing early loaded.The fractured ends in the supercutaneous locking plate group had too large strain and too large maximum stress of the tibia,which needed to be partially loaded under protection and could not be fully loaded.In the middle and late stages of fracture healing,the tibial retrograde intramedullary nail and the supercutaneous locking plate could be completely loaded,and the stress shielding rate of the supercutaneous locking plate was significantly lower than the tibial retrograde intramedullary nail.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To investigate the effects of liver-specific knockout of adenosine 5'-monophosphate-activated protein kinase α(AMPKα)on pancreatic function and glucose metabolism-related genes in mice.Methods AMPKα1/α2flox/flox mice were divided into blank group(common feed)and model group(60％high fat choline deficiency feet)with eight mice in each group,and another 8 AMPKα1/α2flox/flox/Alb-Cre+mice were divided into the knockout group(60％high fat choline deficiency feet).The kit detected the levels of blood lipids and liver function indexes.The differential genes in the mouse pancreas were detected by transcriptome sequencing.The expression of differential genes in mice was detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting.Results The levels of triglyceride in the blank group,model group and knockout group were(0.94±0.11),(0.71±0.14)and(1.05±0.17)mmol·L-1;the levels of triglyceride and high-density lipoprotein were(1.62±0.07),(0.44±0.08)and(0.90±0.06)mmol·L-1;the levels of glutamic oxaloacetic transaminase were(7.02±5.87),(15.60±3.15)and(22.70±2.14)U·L-1;the levels of glutamic pyruvic transaminase were(14.56±11.55),(48.64±15.84)and(75.40±11.96)U·L-1;the expression levels of phosphoenolpyruvate carboxykinase 1(PCK1)mRNA were 1.00±0,1.37±0.25 and 0.31±0.18;the relative expression levels of PCK1 protein were 0.77±0.27,1.23±0.43 and 0.51±0.40,respectively.Significant differences existed in the above indexes between the knockout group and the model group(all P＜0.05).Conclusion PCK1 gene may be an essential gene mediating the effect of liver AMPKα on islet function.

AIM To identify the endophytic fungus G-(JK)-2 from Orixa japonica Thunb.and to study its secondary metabolites and their α-glucosidase inhibitory activities.METHODS Through the ITS sequence,the evolutionary tree that identifies the endophytic fungus G-(JK)-2 was established.Then 45 days rice solid medium of endophytic fungus G-(JK)-2 was extracted by methanol,and then by ethyl acetate.The ethyl acetate extract was separated and purified by silica gel chromatography,Sephadex LH-20,and semi-preparative HPLC.The structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG method.RESULTS The endophytic fungus G-(JK)-2 from O.japonica was identified as Fusarium nematophilum.Thirteen compounds were isolated and identified as p-hydroxybenzaldehyde(G1),4-hydroxyacetophenone(G2),anhydromevalonolactone(G3),flazine(G4),salicylic acid(G5),p-hydroxybenzoic acid(G6),di-(2-ethylhexyl)-phthalate(G7),terephthalic acid bis(2-ethyl-hexyl)ester(G8),thymine(G9),uridine(G10),adenosine(G11),2′-deoxyuridine(G12),nicotinic acid(G13).The inhibitory effect of each compound on α-glucosidase was in sequence of G4>G11>G10>G13>G12.CONCLUSION All compounds are first isolated from the endophytic fungi of the O.japonica,and G10,G11,G13 are first isolated from the endophytic fungi of Fusarium.G4 and G11 have mild inhibition to α-glucosidase.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective To develop a biological safety protection third-level(BSL-3)laboratory based on folding-modular shelters to solve the problems of the existing laboratories in space and function expansion,large-scale deployment and low-cost transportation.Methods The BSL-3 laboratory was composed of a folding combined shelter module,a ventilation and purification module,a power supply and distribution module,a monitoring and communication module,a control system module and an equipment module.The folding combined shelter module used a leveling base frame as the foundation and a lightweight panel as the enclosure mechanism,and was divided into an auxiliary area and a protection protected area;the ventilation and purification module was made up of an air supply unit and an air exhaust unit,the air supply unit was integrated with a fresh-air air conditioner and the exhaust unit was equipped with a main fan,a standby fan and a bag in/bag out filter;the control system module adopted a supervision mode of decentralized control and centralized management,which executed communication with the data server as the center and Profinet protocol and MODBUS-TCP.Results The BSL-3 laboratory proved to meet the requirements of relevant standards in internal microenvironment,airflow direction,airtightness,working condition and disinfection effect.Conclusion The BSL-3 laboratory is compatible with large-scale transport and deployment and facilitates reliable and safe experiments for epidemic prevention and control and cross-regional support.[Chinese Medical Equipment Journal,2024,45(3):41-46]

Objective:Non-alcoholic fatty liver disease(NAFLD)has significant genetic susceptibility.Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis.However,the association between adipocytokine pathway genes and NAFLD remains unclear.This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. Methods:A case-control study was conducted,dividing obese children into NAFLD and control groups.Peripheral venous blood(2 mL)was collected from each participant for DNA extraction.A total of 14 single nucleotide polymorphisms(SNP)in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing.Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children.Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression.Generalized multifactor dimensionality reduction(GMDR)was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. Results:A total of 1 022 children were included,with 511 in the NAFLD group and 511 in the control group.After adjusting for age,gender,and BMI,multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models:heterozygote model(CG vs CC,OR=0.58,95%CI 0.36 to 0.95,P=0.029),dominant model(GG+CG vs CC,OR=0.62,95%CI 0.38 to 1.00,P=0.049),and overdominant model(CC+GG vs CG,OR=1.72,95%CI 1.06 to 2.80,P=0.028).PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models:heterozygous model(CT vs CC,OR=1.51,95%CI 1.10 to 2.07,P=0.011),dominant model(CT+TT vs CC,OR=1.50,95%CI 1.10 to 2.03,P=0.010),overdominant model(CC+TT vs CT,OR=0.67,95%CI 0.49 to 0.92,P=0.012),and additive model(CC vs CT vs TT,OR=1.40,95%CI 1.07 to 1.83,P=0.015).No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD.GMDR analysis,adjusted for age,gender,and BMI,revealed no statistically significant interactions among the 14 SNPs(all P>0.05). Conclusion:Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children.However,no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.