Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

BACKGROUND:Currently,the mandibular joint prosthesis manufactured at home and abroad needs to rely on screws to fix the condylar part of the prosthesis during the replacement process,and the retention hole is reserved to facilitate the operation during the operation.However,due to the lack of personalized jaw design,the reattachment plate may not fit the jaw,resulting in screw loosening and dislocation.Therefore,personalized condylar prosthesis replacement is of great value in the repair of the temporomandibular joint.OBJECTIVE:To design a personalized condylar prosthesis with an internal GYROID for mandibular condylar repair and reconstruction.METHODS:The GYROID structure was selected in the Rhinoceros 7 software with the single cell size of 6 mm and the wall thickness of 0.2,0.3,0.4,0.5,0.6,0.7,0.8 mm.The mechanical properties of the GYROID structure were analyzed by finite element method.3D printing of GYROID structural test specimens with different wall thickness(0.2,0.3,0.4,0.5,0.6,0.7,and 0.8 mm)was performed to test the mechanical properties of the specimens through room temperature compression experiments.A wall thickness value conforming to the range of mandibular mechanical properties was selected through finite element analysis and room temperature compression test results.An adult male mandibular CT data were used for inverse modeling to design a condylar prosthesis with an internal GYROID.Finite element analysis was used to simulate the movement of the apical staggered position and the opposite-blade jaw position after condylar prosthesis replacement.RESULTS AND CONCLUSION:(1)The results of finite element analysis and room temperature compression experiment showed that the elastic modulus of the GYROID structure increased with the increase of wall thickness.The elastic modulus of the GYROID structure with wall thickness of 0.5-0.7 mm was within the range of the elastic modulus of the mandible(1.5-4.0 GPa).Therefore,the 6 mm monocellular GYROID structural model with a wall thickness of 0.6 mm was selected for the design of the condylar prosthesis.(2)The results of finite element analysis showed that the stress distribution of mandibular model was symmetrical.The stress distribution of the two types of occlusion was roughly the same,and the stress peak was not significantly different.The stress concentrated in the neck of the condylar prosthesis,and the stress on the replacement side was slightly larger than that on the healthy side.The maximum equivalent stress of the whole internal fixation model was 269.34 MPa,and the maximum equivalent stress of the screw was 20.14 MPa.The equivalent stress and equivalent strain values of the prosthesis were greater than that of the opposite edge jaw position when the tooth tip was interlaced.The equivalent stress and equivalent strain values of the screw were smaller than that of the opposite edge jaw position when the tooth tip was interlaced.(3)The results showed that the design and retention of the personalized GYROID condylar prosthesis were good,which was consistent with the mechanical conduction of the mandible.

Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of 3326 residents aged ≥60 years with complete data were selected as the survey participants. Multiple logistic regression models and restricted cubic splines (RCS) were used to assess the association between PA duration/volume and sarcopenia. Results In 10 provinces (autonomous regions) of China, the prevalence of sarcopenia in the elderly aged 60 years and above was 5.5% (95%CI: 4.7%, 6.2%). The logistic regression analysis showed that compared with the elderly reporting 0-7.0 h·week⁻¹ in LPA duration, the risk of sarcopenia in the elderly with LPA duration of >14.0-21.0 h·week⁻¹ was reduced by 51% (OR=0.49, 95%CI: 0.26, 0.96). Compared with the elderly with total physical activity ≥15.0 metabolic equivalent of task (MET)-h·week⁻¹, those with <7.5 MET-h·week⁻¹ had a 2.24-fold increased risk of sarcopenia (OR=2.24, 95%CI: 1.17, 4.29). The RCS results found that LPA duration and total physical activity volume each showed a nonlinear dose-response relationship with the risk of sarcopenia (P_overall<0.05, P_non-linear<0.05). Compared with the elderly with an LPA duration of 0 h· week⁻¹, the risk of sarcopenia in the elderly with an LPA duration of 12.6 h· week⁻¹ was the lowest (OR=0.42, 95%CI: 0.21, 0.83). Compared with the elderly with a total physical activity volume of 15.0 MET-h· week⁻¹, the elderly with a total physical activity volume of 46.0 MET-h· week⁻¹ had the lowest risk of sarcopenia (OR=0.57, 95%CI: 0.38, 0.84). There was no statistically significant association between weekly MVPA duration and the risk of sarcopenia (P>0.05). Conclusion Increasing weekly LPA duration and total physical activity volume would help to reduce the risk of sarcopenia.

The Department of Thoracic Surgery of Shanghai Chest Hospital has performed esophageal function testing for over 30 years, being the only department of its kind in China with this capability. The pressure testing and 24-hour pH/impedance monitoring of the esophagus is of great help to assist in the diagnosis and treatment of benign and malignant esophageal diseases related to it. Thanks to the esophageal function test, in addition to the routine various endoscopic anti-reflux procedures, our hospital has taken the lead in China in recent years to carry out a series of clinical and research work for benign esophageal diseases, such as the development of magnetic ring, double nedoscopic combination and new anti-reflux endoscopic techniques. In recent years, we have carried out high-resolution esophageal manometry and 24-hour pH/impedance monitoring for patients with interstitial pneumonia and pulmonary fibrosis suspected to be caused by gastroesophageal acid reflux. We can better assess the correlation between gastroesophageal reflux and pulmonary fibrosis, and to provide the different clinical treatments and even surgical interventions. The Bravo capsule is used more often in the United States, and it has obvious advantages over traditional approach for acid measurement. We strongly call for the collaboration between industry and academic institutions in this field, and the development of our own related products with independent intellectual property rights.

OBJECTIVE: To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2). METHODS: From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116). RESULTS: The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c.3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+PM2_Supporting+PM3_Supporting+PP3_Moderate). CONCLUSION The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.
Humans ; Cholestasis, Intrahepatic/genetics* ; Female ; Infant ; ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics* ; Homozygote ; Mutation

Objective:To explore the effects of transcription factor adenovirus E4 promoter-binding protein(E4BP4)in regulating pathological myocardial fibrosis through the adenosine monophosphate-activated protein kinase(AMPK)-transforming growth factor(TGF)-β1/Smad homolog 3(SMAD3)pathway.Methods:A mouse model of myocardial fibrosis was established,and the expression of E4BP4 was determined in the model group and the sham-operation group.Primary cardiac fibroblasts were isolated,cultured,activated by angiotensin Ⅱ(Ang Ⅱ),and divided into the following groups:Ang Ⅱ+E4BP4 group(transfected with E4BP4 overexpression plasmids),Ang Ⅱ+siE4BP4 group(transfected with E4BP4 interfering plasmids),Ang Ⅱ group,and control group(without Ang Ⅱtreatment).The fluorescence intensity of ɑ-smooth muscle actin(α-SMA)was determined by the immunofluorescence assay,the cell viability by the cell counting kit,the expression of E4BP4,α-SMA,collagen type Ⅰ(collagen Ⅰ),and collagen type Ⅲ(collagen Ⅲ)by polymerase chain reaction,and the protein expression of TGF-β1,AMPK,and SMAD3 by Western blot.Results:Compared with the sham-operation group,the model group showed significantly in-creased myocardial fibrosis degree(38.46±1.21 vs.3.39±0.39,t=-78.564,P=0.000)and E4BP4 protein expression(0.96±0.03 vs.0.75±0.03,t=-11.480,P=0.000).In vitro experiments found that the mean fluorescence intensity(0.05±0.01 vs.0.42±0.03,F=677.591,P=0.000),cell viability(91.30±2.39 vs.123.74±2.60,F=132.696,P=0.000),and the levels of α-SMA(1.26±0.09 vs.3.59±0.86,F=52.274,P=0.000),collagen Ⅰ(1.16±0.11 vs.3.79±0.89,F=55.336,P=0.000),collagen Ⅲ(1.23±0.13 vs.2.92±0.36,F=119.929,P=0.000),TGF-β1(0.66±0.04 vs.0.96±0.02,F=142.954,P=0.000),and p-SMAD3/SMAD3(0.81±0.03 vs.1.37±0.02,F=739.609,P=0.000)in the Ang Ⅱ+siE4BP4 group were significantly lower than those in the Ang Ⅱ+E4BP4 group.The expression of p-AMPK/AMPK in the Ang Ⅱ+siE4BP4 group was significantly higher than that in the Ang Ⅱ+E4BP4 group(0.89±0.01 vs.0.58±0.02,F=284.541,P=0.000).Conclusion:E4BP4 plays a crucial role in the regulation of fibrosis.Inhibition of E4BP4 expression exerts an anti-fibrotic effect by activating AMPK and inhibiting TGF-β1/SMAD3 pathway.

Objective:To explore the efficacy of dialectical behavior therapy (DBT) in treating self-injury among adolescents with depressive disorders, and to examine the influencing factors of the efficacy.Methods:Fifty-five depressive adolescent in-patients with self-injury behaviors, admitted to the Qingdao Mental Health Center between December 2022 and June 2024 were enrolled and received dialectical behaviour therapy (DBT). Pre- and post-treatment assessments were conducted with a self-compiled questionnaire, Hamilton depression scale-17(HAMD-17), family adaptability and cohesion scale (FACES Ⅱ-CV), simplified coping style questionnaire (SCSQ), and self-injurious thoughts and behaviours interview (SITBI) in all patients.Based on the magnitude of reduction in self-injury after treatment, participants were classified into high-reduction group ( n=17), moderate-reduction group ( n=28), and low-reduction group ( n=10). SPSS 27.0 software was used to perform one-way ANOVA, Spearman correlation analysis and Logistic regression analysis to examine the effects of sex, only-child status, parental divorce, family cohesion and adaptability, and coping style on DBT efficacy. Results:The HAMD-17 score before treatment was 20.0(18.0, 22.0), and the score dropped to 7.0(5.0, 11.0) after treatment, and the difference was statistically significant ( Z=-6.460, P<0.01), yielding the reduction rate of (44.8±0.2)%.Self-injury frequency fell from a median of 5.0(2.0, 9.5) episodes per week before treatment to 0(0, 1.8) after treatment, and this decrease was also significant ( Z=-4.945, P<0.01), representing the reduction rate of (81.6±0.2)%. High positive coping styles ( OR=0.690, P=0.008) and strong family cohesion ( OR=0.491, P=0.007) were associated with better treatment efficacy. Conclusion:DBT can reduce the self-injury behaviors in adolescents with depressive disorders. High family cohesion and the use of positive coping strategies are important factors influencing the therapeutic effect.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

BACKGROUND:Condylar prosthesis replacement,as one of the surgical methods for the treatment of temporomandibular joint diseases,not only needs to restore the morphology and function,but also needs to ensure long-term stable application.OBJECTIVE:To design finite element analysis of a customized Gyroid condylar prosthesis.METHODS:Gyroid structure specimens with different wall thicknesses(250,350,450,550,650,and 750 μm)were designed by software.Finite element simulation compression experiments were carried out to test the elastic modulus of the specimens.The Gyroid structure wall thickness range that matches the elastic modulus of mandibular cancellous bone and whose pore size meets the osteogenesis conditions was screened out.This range was subdivided and Gyroid structure specimens were made using 3D printing technology.Mechanical compression experiments were carried out on a universal testing machine.The Gyroid structure wall thickness that meets the mechanical properties of mandibular bone,has an easier osteogenesis and a smaller strength was screened out by elastic modulus and compressive strength,and subsequent experiments were carried out.A three-dimensional model of a customized Gyroid condylar prosthesis was designed,and the finite element analysis of the blade jaw position and cusp interdigitation position of the model under natural occlusion was simulated.RESULTS AND CONCLUSION:(1)Finite element analysis results showed that with the increase of wall thickness,the elastic modulus of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 350,450,550,650,and 750 μm matched the elastic modulus of mandibular cancellous bone.Since the subsequent experiments needed to be subdivided into groups and the pore size of the 550,650,and 750 μm wall thickness group(pore size 800-1 000 μm)was within the osteogenesis range.Gyroid structure specimens with wall thickness of 550,600,650,700,and 750μm were selected for mechanical compression experiments on a universal testing machine.(2)The results of mechanical compression experiments showed that with the increase of wall thickness,the elastic modulus and compressive strength of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 550,600,and 650 μm was within the elastic modulus of the mandibular cancellous bone.Finally,the wall thickness of 650 μm and the pore size of 900 μm were selected to construct the three-dimensional model of the mandibular customized Gyroid condylar prosthesis.(3)The results of finite element analysis of three-dimensional model of the mandibular customized Gyroid condylar prosthesis showed that the stress of the articular disc in the edge-to-edge occlusion was mainly concentrated on the lower surface of the anterior middle band,and the stress of the articular disc in the interposition of tooth tips was mainly concentrated on the lateral surface of the lower surface.The maximum displacement and the maximum equivalent stress of the left and right articular discs in the edge-to-edge occlusion and the interposition of tooth tips were similar.The maximum displacement was 0.031,0.030,0.028,and 0.018 mm,and the maximum equivalent stress was 2.87,2.30,2.73,and 1.71 MPa,respectively.(4)The results showed that the Gyroid structure with a wall thickness of 650 μm was consistent with the mechanical properties of the mandible,which reduced the strength of the titanium alloy and reduced the damage of the articular disc caused by the customized Gyroid condylar prosthesis.