BACKGROUND:Developmental dysplasia of the hip often leads to limb deformities in children,and the research related to its diagnosis and treatment has been gradually clarified.Recently,the finite element method has been paid attention to by scholars in the research related to developmental dysplasia of the hip because of its advantages. OBJECTIVE:Through literature search and review of the relevant research progress of finite element method in children's developmental dysplasia of the hip and treatment,analyze and summarize its advantages and disadvantages,and explore the direction of further research in the future. METHODS:PubMed,SCI,CBM,and CNKI were searched for relevant articles published from January 2014 to November 2023 with the key words of"developmental dysplasia(dislocation)of the hip,dysplasia of the hip,finite element analysis(method),pavlik harness,fixation in herringbone position,biomechanics,pelvic osteotomies,pemberton,salter,dega,periacetabular osteotomy,children"in Chinese and English.A small number of long-term articles were included,and 62 articles were finally included for analysis through screening. RESULTS AND CONCLUSION:(1)The mechanical environment of hip joint in children with developmental dysplasia of the hip was abnormal.The pressure in acetabulum was uneven.The stress increased and concentrated;the joint contact area decreased,and the local stress concentrated in femoral neck.(2)In the Pavlik sling and herringbone fixation,the mechanical environment of the hip was improved;the concentrated high stress area disappeared and the joint contact area increased,but the excessive abduction angle led to the increase of stress in the acetabulum and the lateral femoral head.(3)After pelvic osteotomy,the stress environment of hip joint and sacroiliac joint was improved.There was no single hinge in the three kinds of osteotomy,and the stress load position was different according to the age of the children.(4)After peri-acetabular osteotomy,the joint contact pressure was close to normal,but it was difficult to recover in patients with non-spherical femoral head.(5)The postoperative X-ray film findings could not show that the joint contact mechanics was the best.(6)It is indicated that the information that cannot be measured in the body can be obtained by using the finite element method,which can be operated in a virtual environment without the limitation of time and ethics.It can directly see the stress change area of normal and developmental dysplasia of the hip,explain the effectiveness of treatment from the point of view of mechanics,establish a specific finite element model and tailor-made operation plan for patients who need osteotomy.There is no standard or unified standard for the finite element modeling of developmental dysplasia of the hip and the material characteristic parameters of children's hip joint.Due to the inherent limitations of finite element method,it is impossible to analyze the model that contains bone,cartilage,ligament,muscle and other elements at the same time.The operation of finite element analysis is difficult,although it has advantages,it is not universal,and the current research sample size is small,which needs to be further expanded and verified.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Human parvovirus B19 (HPVB19) belongs to Parvoviridae, a genus of erythrovirus, and has been associated with various human diseases, and HPVB19 infection is one of the most important causes of refractory anemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study retrospectively analyzed 24 patients with HSCT combined with HPVB19 infection to collate and summarize the clinical presentation, treatment, and regression of patients with combined HPVB19 infection after allo-HSCT and provide experience in the management of HPVB19 infection after allo-HSCT. The median age of the patients with HPVB19 infection was 25 years, and the median time of infection occurrence was +107 days after transplantation, and 22 (91.7% ) had anemia with a median hemoglobin (HGB) level of 77.5 (46-149) g/L, and 13 (54.2% ) had new-onset anemia or persistent decline in HGB. The median length of hospital stay was 19 days. Among patients with new-onset anemia or persistent decline in HGB, the mean increase in HGB after treatment with intravenous immunoglobulin and/or antiviral therapy was 15.69 g/L, and treatment was effective in 10 (76.92% ) patients. HPVB19 infection should be alerted to the development of refractory anemia after HSCT; despite the lack of specific treatment, the overall prognosis of HPVB19-infected patients is good.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder involving digestive, renal, respiratory, and nervous systems caused by SLC7A7 gene mutation.It was first reported in Finland and now has been found worldwide.A total of 8 cases have been reported in China.The abnormal function of the y + amino acid transporter caused by SLC7A7 gene mutation can explain some clinical features, but the pathophysiological mechanism underlying the associated lung, kidney and blood system disorders is not clear.The varying clinical manifestations of LPI often lead to misdiagnosis or delayed diagnosis.This article reviews the pathogenesis, clinical characteristics, diagnosis and treatment of LPI, to enhance clinicians′ understanding of this disease.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective To explore the lateral lymph node metastasis in patients with rectal cancer below peritoneal reflection and construct predictive models.Methods A total of 102 patients with rectal cancer be-low peritoneal reflection admitted in the hospital from January 2020 to April 2023 were selected as the re-search objects.According to the existence of lateral lymph node metastasis(LLNM),the patients were divided into metastatic group(n=31)and non-metastatic group(n=71).The general clinical data,tumor pathologi-cal features,laboratory indexes[carcinoembryonic antigen(CEA).carbohydrate antigen 199(CA199),neutro-phil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR),transforming growth factor(TGF)-α and TGF-β1]between the two groups were compared.The risk factors of LLNM in patients with rectal cancer be-low peritoneal reflection were screened by Spearman correlation analysis and Logistic regression analysis,and the predictive model was constructed and the efficacy of the model was evaluated.Results The mean maxi-mum tumor diameter,the short diameter of lateral lymph nodes,the proportion of poorly differentiated pa-tients and the proportion of patients with T3-T4 stage in the metastasis group were significantly higher than those in the non-metastasis group(P＜0.05).The average levels of TGF-α,TGF-β1 and NLR in the metasta-sis group were significantly higher than those in the non-metastasis group(P＜0.05).Spearman correlation a-nalysis,univariate and multivariate Logistic regression analysis showed that poor differentiation,T3-T4 stage,maximum tumor diameter,longer short diameter of lateral lymph nodes,higher levels of TGF-α,TGF-β1 and NLR were independent risk factors for LLNM in patients with rectal cancer below peritoneal reflec-tion.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of the predictive model based on the above risk factors was 0.915(95％CI:0.847-0.984),which had high pre-dictive performance.Conclusion Patients with LLNM and rectal cancer below peritoneal reflection often have longer tumor diameter and lateral lymph node short diameter,and higher levels of TGF-α,TGF-β1 and NLR.Lateral lymph node dissection should be actively carried out for patients with above characteristics,and timely monitoring should be carried out to see if there is still lymph node metastasis after surgery,so as to provide certain clinical basis for improving the judgment of LLNM in rectal cancer below peritoneal reflection.

Rheumatoid arthritis(RA)is an autoimmune disease with the basic pathological manifestation of synovial inflammation.Symmetric poly-articular pain and swelling are the main symptoms in clinical practice,and even extra-articular manifestations and comorbidities such as interstitial fibrosis and coronary artery disease are triggered,which seriously affect the quality of life of patients.Traditional Chinese medicine(TCM)has achieved good clinical efficacy in the prevention and treatment of RA with the advantages of multi-pathway,multi-target,multi-component,and less toxic side effects,and plays an important role in the treatment of RA.Recently,many studies have demonstrated that Chinese medicine monomers and Chinese herbal compound can control inflammation,reduce angiogenesis,induce apoptosis of synovial fibroblasts,and inhibit their proliferation,invasion and migration by regulating the PI3K/Akt signaling pathway,so as to play a key role in the treatment of RA.For this reason,the article summarizes current knowledge regarding the PI3K/Akt signaling pathway and its role in RA,as well as summarizes the current research progress of TCM in the treatment of RA by regulating the PI3K/Akt signaling pathway.The aim of this review is to provide theoretical bases for the prevention and treatment of RA and the development of new drugs.

Objective To evaluate the measurement uncertainty of endocrine test items by"top-down"method.Methods The"top-down"method in the technical report of CNAS-CL01-G003:2021"Medical Laboratory-Evaluation and Expression of Measurement Uncertainty"was used,collecting the laboratory's internal quality control data and the external quality assurance results of Beijing Clinical Laboratory Center from 2019 to 2021.To evaluate the measurement uncertainty of 11 endocrine tests including free triiodothyronine(FT3),total triiodothyronine(TT3)and free thyroxine(FT4).Results The relative expanded uncertainties of 11 endocrine test items in laboratory were FT3:12.658％,TT3:13.372％,FT4:10.468％,total thyroxine(TT4):32.382％,thyroid stimulating hormone(TSH):8.594％,estradiol(E2):18.656％,follicle-stimulating hormone(FSH):14.650％,luteinizing hormone(LH):29.384％,progesterone(PRO):28.806％,prolactin(PRL):13.810％and testosterone(TESTO):31.610％.At the normal concentration level,the relative expanded uncertainties were FT3:12.424％,TT3:12.462％,FT4:8.606％,TT4:14.130％,TSH:12.536％,E2:19.586％,FSH:14.382％,LH:23.400％,PRO:38.346％,PRL:16.014％and TESTO:39.352％.The relative expanded uncertainties at high concentration levels are FT3:13.882％,TT3:14.096％,FT4:11.040％,TT4:8.614％,TSH:7.782％,E2:14.366％,FSH:13.436％,LH:14.804％,PRO:11.574％,PRL:17.742％,TESTO:39.322％.The relative extended measurement uncertainty of TT4,LH near low concentration levels,PRO near low and normal concentration levels,and TESTO near three concentration levels was higher than the target uncertainty(25％),and the remaining items are less than the target uncertainty.Conclusion The quality control data in the laboratory can reflect the measurement uncertainty of 11 endocrine detection items including FT3,TT3 and FT4 in Abbott i2000SR automatic chemiluminescence immunoassay analyzer,which has important clinical application value.

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)