1.Effect of finite element method in treatment of developmental dysplasia of the hip in children
Xiaojun SUN ; Huaming WANG ; Dehong ZHANG ; Xuewen SONG ; Jin HUANG ; Chen ZHANG ; Shengtai PEI
Chinese Journal of Tissue Engineering Research 2025;29(9):1897-1904
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.
2.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
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.
3.Association between quantitative CT-measured body composition and metabolic syndrome components in obese patients before bariatric surgery
Wei HONG ; Xiaojun HAO ; Chao TAO ; Pengzhan YIN ; Yabin XIA ; Yan JIN ; Yunfeng ZHOU
Chinese Journal of Health Management 2024;18(2):127-134
Objective:To investigate the association between quantified CT (QCT)-measured body composition and metabolic syndrome (MS) components in obese populations before bariatric surgery.Methods:A cross-sectional study. A retrospective analysis was conducted on a cohort of 97 obese patients scheduled for weight-loss surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to March 2023. The patients′ body mass index (BMI), biochemical parameters and body composition measurements obtained by QCT were recorded. The patients were stratified into groups based on gender, obesity severity and the number of MS components. Differences in body composition among the groups were compared. Additionally, the correlations between each body composition parameter and metabolic indicators were analyzed. The diagnostic efficacy of each body composition parameter for identifying obese individuals with different MS components was assessed using receiver operating characteristic (ROC) curve analysis.Results:There were 75 females (77.3%). Male obese patients had higher total abdominal fat area [(693.23±148.90) vs (574.99±114.89) cm 2, t=-3.958, P<0.001], visceral fat area [(289.65±57.67) vs (195.60±57.37) cm 2, t=-6.753, P<0.001], fat content of pancreatic head [27.45%(21.65%, 45.48%) vs 21.60%(17.6%, 26.9%), Z=-2.675, P=0.007], and skeletal muscle index [73.36(68.74, 81.26) vs 61.52(55.74, 66.41) cm 2/m 2, Z=-5.246, P<0.001]. With the increase of obesity, abdominal fat mainly increases in subcutaneous fat. With the increase of MS components (MS2 group, MS3 group, MS4 group, MS5 group), the abdominal fat area, abdominal fat/subcutaneous fat, liver fat content, pancreatic head fat content, and skeletal muscle index of patients all increased accordingly. In diagnosing the presence of two components of MS, area under the curve of visceral fat area was the largest (AUC=0.706, 95% CI=0.577-0.834). For diagnosing the presence of three, four and five components of MS, area under curve of liver fat content were all the largest (MS3=0.712, 95% CI=0.605-0.818; MS4=0.652, 95% CI=0.537-0.766; MS5=0.706, 95% CI=0.576-0.836). Conclusion:There are differences in QCT body composition among obese patients with different MS components, and there is a correlation between each body composition and MS component. Among them, intra-abdominal fat area and liver fat content are of great value in evaluating obese patients with different MS components.
4.Quantitative CT for assessing complications of type 2 diabetes mellitus
Xiaojun CHEN ; Jin LIU ; Xiaoling LIANG ; Jun GONG ; Shaolin LI
Chinese Journal of Interventional Imaging and Therapy 2024;21(11):702-707
Objective To explore the value of quantitative CT(QCT)for assessing complications of type 2 diabetes mellitus(T2DM).Methods Totally 220 T2DM patients were included and divided into uncomplicated group(n=40),mono-complicated group(n=84)and multi-complicated group(n=96).Bone mineral density(BMD)of L2—L4,as well as visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT)area were collected using QCT and compared among groups.The operator characteristic curves were drawn,and the area under the curves(AUC)were calculated to observe the value of QCT indicators and comprehensive model based on clinical indicators and QCT indicators for evaluating complications of T2DM.Decision curve analysis(DCA)and clinical impact curve(CIC)analysis were used to analyze the clinical application value of the comprehensive model.Results Significant differences of patients’age,lumbar BMDs and areas of VAT were found among 3 groups(all P<0.05).The AUC of comprehensive model for differentiating uncomplicated group from mono-complicated group,uncomplicated group from multi-complicated group and mono-complicated group from multi-complicated group was 0.753,0.865,and 0.761,respectively,higher than that of BMD,VAT and SAT area(all P<0.05).DCA and CIC analyses showed that comprehensive model yielded clinical benefits and had good clinical applicability for assessing complications of T2DM.Conclusion QCT was valuable for assessing complications of T2DM.
5.Inhibition of inflammation and bone destruction in mice with colla-gen-induced arthritis by Zushima Plaster
Juanjuan YANG ; Haolin LI ; Tianning YANG ; Weigang CHENG ; Zhendong WANG ; Fangmei JIN ; Fanghong NIAN ; Xiaojun SU ; Jiaqiang WANG ; Haiping WANG ; Haidong WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(9):979-987
AIM:To investigate the inhibitory ef-fect of Zushima ointment on inflammation and bone destruction in CIA mice.METHODS:SPF grade male DBA/1 mice were used,6 were random-ly selected as the normal group,and 18 CIA mice that were successfully modelled were randomly di-vided into the model group,the plaster group(1.0 g/kg),and the fuselage group(0.12 g per time)ac-cording to the random number table method,6 mice in each group,and each administered group was given medication according to the body mass,and saline was given to both the normal and model groups.The normal group and the model group were given saline,and breathable adhesive paper was applied once a day for 4 h/session for 4 consec-utive weeks.The arthritis scoring index was used to observe the changes of arthritis symptoms and ar-thritis index scores of mice in each group.Micro-CT was used to observe the damage of hind paw of mice,real-time fluorescence PCR was used to de-tect the mRNA expression of IL-17,IL-1β and TNF-αin ankle joint tissues,and immunohistochemistry was used to detect the expression of OPG and RANKL proteins in ankle joint tissues,and hematox-ylin-eosin(HE)staining was used to observe the pathological changes of synovial tissues after the treatment.The pathological changes of synovial tis-sue were observed after hematoxylin-eosin(HE)staining,and the changes of osteoclasts in ankle joint tissue were observed by anti-tartaric acid phosphatase(TRAP)method.RESULTS:Compared with the normal group,the arthritis index score of the model mice was significantly higher(P<0.05).Micro-CT showed severe bone erosion in the hind paws of the mice,destruction of the bone surface and reduction of bone volume.The expression of IL-17,IL-1β and TNF-α mRNA(PCR)in the ankle joint tissues was significantly higher(P<0.05).Im-munohistochemistry showed that the relative ex-pression of OPG protein in the ankle joint tissues was reduced(P<0.05).Immunohistochemistry showed a decrease in the relative expression of OPG protein(P<0.01)and an increase in the rela-tive expression of RANKL protein(P<0.01).HE re-sults showed moderate inflammatory cell infiltra-tion,swelling of synovial cells,massive formation of vascular opacities and synovial hyperplasia;an increase in the number of osteoclasts,roughness of the surface of articular cartilage tissue,severe bone destruction and thinning of the cartilage lay-er.Compared with the model group,the arthritic symptoms of mice in the cream group and the futa-lin group were relieved and the arthritis index score was reduced;the bone density of the mice's hind paws improved,effectively relieving osteopo-rosis;the expression of IL-17,IL-1β and TNF-αmRNA(PCR)in the ankle joint tissue was signifi-cantly reduced(P<0.05);the immunohistochemical results showed that the relative expression of OPG protein was increased(P<0.05),the relative expres-sion of RANKL protein decreased(P<0.01).HE re-sults showed that synovial cell enlargement was significantly improved,mild inflammatory cell infil-tration,synovial hyperplasia was not obvious;the number of broken bone was reduced,articular car-tilage destruction was significantly improved and relieved,and the thickness of cartilage layer was significantly increased.CONCLUSION:Ancestral hemp poultice relieves local symptoms of RA,re-duces the expression of inflammatory factors and attenuates the inflammatory response,possibly by inhibiting osteoclast differentiation and activation through modulation of the OPG/RANKL signalling axis,which further ameliorates the biological ef-fects of articular bone and cartilage destruction.
6.Clinical characteristics of human parvovirus B19 infection after allogeneic stem cell transplantation
Jin ZHANG ; Rui MA ; Xueyi LUO ; Xiaohui ZHANG ; Lanping XU ; Yu WANG ; Xiaodong MO ; Meng LYU ; Kaiyan LIU ; Xiaojun HUANG ; Yuqian SUN
Chinese Journal of Hematology 2024;45(6):591-593
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.
7.Advances in the lysinuric protein intolerance
Jiyan ZHANG ; Xiaojun DUAN ; Jin ZHANG ; Yanping CHEN
Chinese Journal of Applied Clinical Pediatrics 2024;39(7):547-551
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.
8.A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children
Li SONG ; Ling JIN ; Yonghong ZHANG ; Xiaomei YANG ; Yanlong DUAN ; Mincui ZHENG ; Xiaowen ZHAI ; Ying LIU ; Wei LIU ; Ansheng LIU ; Xiaojun YUAN ; Yunpeng DAI ; Leping ZHANG ; Jian WANG ; Lirong SUN ; Rong LIU ; Baoxi ZHANG ; Lian JIANG ; Huixia WEI ; Kailan CHEN ; Runming JIN ; Xige WANG ; Haixia ZHOU ; Hongmei WANG ; Shushuan ZHUANG ; Chunju ZHOU ; Zifen GAO ; Xiao MU ; Kaihui ZHANG ; Fu LI
Chinese Journal of Pediatrics 2024;62(10):941-948
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.
9.Progress of Traditional Chinese Medicine in Regulating PI3K/Akt Signaling Pathway for the Treatment of Rheumatoid Arthritis
Weigang CHENG ; Haolin LI ; Juanjuan YANG ; Fangmei JIN ; Lili KAN ; Pengfei TAO ; Zhendong WANG ; Qian BAI ; Xiaojun SU ; Haidong WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):756-764
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.
10.Construction of a predictive model for lateral lymph node metastasis in patients with rectal cancer below peritoneal reflection
Jin LYU ; Chengyu LYU ; Mu XU ; Xiaojun XU ; Zhi WANG ; Heming WANG
International Journal of Laboratory Medicine 2024;45(22):2732-2736,2742
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.

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