1.Roles of THEM4 in the Akt pathway:a double-edged sword
XIE WEN ; LIU WEIDONG ; WANG LEI ; ZHU BIN ; ZHAO CONG ; LIAO ZILING ; LI YIHAN ; JIANG XINGJUN ; LIU JIE ; REN CAIPING
Journal of Zhejiang University. Science. B 2024;25(7):541-556
The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of diseases.Thioesterase superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding proteins.Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation.Initially,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous findings.Considering these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially cancer.This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.
2.Herpesvirus encephalomyelitis with the main symptom of myelitis:A case report
Xingjun LI ; Yue LANG ; Jing BAI
Journal of Apoplexy and Nervous Diseases 2024;41(10):941-944
Herpesvirus encephalomyelitis is an infectious disease of the central nervous system,and there are rare cases of herpesvirus encephalitis comorbid with myelitis.This article reports a case of herpesvirus encephalomyelitis with the main symptom of myelitis,as well as other symptoms of headache,immobility of both lower limbs,and dysurea.Related clinical data and diagnosis and treatment processes are analyzed,and a literature review was performed to improve the understanding of this disease among clinicians.
3.A case-control study on the risk factors of thyroid diseases in a coastal area, Dongtai City
Changgui ZHANG ; Yue ZHAO ; Xingjun ZHOU ; Li XU ; Peihua WANG
Chinese Journal of Endemiology 2024;43(11):874-878
Objective:To study the influencing factors of thyroid diseases among residents in a coastal area, Dongtai City, and provide scientific basis for further prevention and control of thyroid diseases.Methods:Thyroid disease patients of Dongtai City in the coastal area diagnosed by Dongtai People's Hospital from January to December 2019 were selected as the survey subjects, and diagnosis of various diseases and their gender and age distribution were analyzed. In the case-control study, confirmed new cases were selected as the case group, and healthy individuals matched 1∶1 by village group, gender, and age as the control group. A questionnaire survey and related examinations such as urinary iodine test and thyroid ultrasound examination were conducted. The survey results were summarized and analyzed (Wilcoxon rank sum test, conditional logistic regression multivariate analysis).Results:(1) A total of 3 508 patients with thyroid diseases were diagnosed, accounting for 319.46/100 000 of the total population, including 2 616 female patients, accounting for 74.57%; 2 824 cases aged 30 to 69 years old, accounting for 80.50%; 1 539 cases of hyperthyroidism, accounting for 43.87%; and 961 cases of hypothyroidism, accounting for 27.39%. (2) A total of 984 cases were surveyed in a 1∶1 paired manner. Multivariate analysis showed that the risk factors for thyroid diseases included monthly average income, family history, related surgeries, personality, working pressure, interpersonal relationships, and urinary iodine grading ( P < 0.05). The risk factors for hyperthyroidism included occupation, family history of hyperthyroidism, personality, family financial pressure, and interpersonal relationships ( P < 0.05), while the risk factor for goiter included urinary iodine grading ( P = 0.008). Conclusions:The occurrence of thyroid diseases in a coastal area, Dongtai City, may be related to family history, gender, age, personality, and working pressure. There is a correlation between goiter and low iodine nutrition level, which further confirms the correctness of the strategy of salt iodization in preventing and treating iodine deficiency disorders in coastal areas.
4.Correlation between red blood cell distribution width/platelet count and prognosis of newly diagnosed diffuse large B-cell lymphoma
Xiaobo LIU ; Yanliang BAI ; Ying LIU ; Weiya LI ; Yabin CUI ; Jinhui XU ; Xingjun XIAO ; Xiaona NIU ; Kai SUN
Blood Research 2023;58(4):187-193
Background:
Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL).Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma.
Methods:
We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis.
Results:
Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (<0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P < 0.05). A survival analysis showed that progression-free survival (PFS) (P =0.003) and overall survival (OS) (P <0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P <0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P <0.05).
Conclusion
A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.
5.Analysis of the initial symptoms and its diagnostic significance in children with neuroblastoma
Xindi WANG ; Chao DUAN ; Dawei ZHANG ; Mei JIN ; Wen ZHAO ; Xisi WANG ; Qian ZHAO ; Xingjun LI ; Cheng HUANG ; Sihui LI ; Ying CHEN ; Xiaolu NIE ; Xiaoxia PENG ; Xiaoli MA
Chinese Journal of Applied Clinical Pediatrics 2019;34(5):359-363
Objective To explore the significance of the initial clinical symptoms and clinical manifestations of neuroblastoma(NB)to achive early identification of NB. Methods A retrospective study was performed on patients diagnosed with NB,who attended the Hematology Oncology Center,Beijing Childrenˊs Hospital from March 31st ,2007 to March 31st,2015. The clinical characteristics were compared between the children 〈1_year_old and≥1_year_old. The result was analyzed to compare the difference in clinical symptoms and tumor biologic characteristics of patients with different initial clinical symptoms between 2 groups. Results A total of 330 patients were included in the study,43 of them were younger than 1 year old,and their most common symptoms were cough and fever( each 17 cases,and accounted for 39. 5%,respectively);while the most common symptoms in patients≥1_year_old(287 cases)was fe_ver(177 cases,61. 7%),followed by lymphadenopathy(107 cases,37. 3%),bone pain(97 cases,33. 8%)and anemia (48 cases,16. 7%). The frequency of symptoms differed significantly between 2 groups(all P〈0. 05),such as fever (39. 5% vs. 61. 7%,χ2 ﹦6. 68),anemia(4. 7% vs. 16. 7%,χ2 ﹦6. 00),bone pain(0 vs. 33. 8%,χ2 ﹦18. 99),abdo_minal pain(0 vs. 25. 3%,χ2 ﹦10. 19),diarrhea(16. 3% vs. 3. 0%,χ2 ﹦12. 73),lymphadenopathy(7. 0% vs. 37. 3%, χ2 ﹦14. 12)and anorexia(9. 3% vs. 33. 4%,χ2 ﹦9. 21). Datients had fever,anemia,lymphadenopathy,cutaneous hemorrhagic spot or periorbital ecchymosis,bone pain,abdominal pain,exophthalmos,and anorexia early in the initial course of the disease,whose serum lactate dehydrogenase values were significantly increased(P〈0. 05). Datients suf_fered from fever,anemia,lymphadenopathy,bone pain,limbs dysfunctions,abdominal pain at the beginning of the disease,whose urine vanillymandelic acid values were higher than normal(P〈0. 05). Conclusions The study of sympto_mology suggests the most common symptoms in patients with NB 〈1_year_old are cough and fever,while those ≥1_year_old are fever,lymphadenopathy,bone pain,and anemia. Por patients with symptoms mentioned,carrying out the necessary NB_diagnose_related laboratory and imaging studies was statistically relevant to patientsˊ ages(〈1_year_old and≥1_year_old),which may contribute to earlier identification and diagnosis of NB.
6.Establishment of a C57BL/6 J mouse model of metastatic melanoma in the lung
Xingjun MENG ; Xiaodong LI ; Jun LIU ; Kangxi ZHOU ; Qingya CUI ; Ren-Ping HU ; Rong YAN ; Kesheng DAI
Acta Laboratorium Animalis Scientia Sinica 2018;26(2):139-144
Objective To investigate the influencing factors involved in the establishment of a C57BL/6 J model of metastatic melanoma in the lung,including the way of tumor inoculation,the number of inoculated cells and the time of tumor formation. Methods Mouse melanoma B16F10 cells were cultured in vitro. 1)Eighteen healthy male C57BL/6 J mice were randomly divided into three groups. Mice in each group received 100 μL cell suspension(including 3 ×106 melanoma cells)via intravenous,intraperitoneal and subcutaneous injection,respectively. After two weeks,the mice were killed and dissected,and the tumor growth and metastasis were observed. 2)Eighteen male mice were randomly divided into three groups. Mice in each group were injected with 3 ×106cells,1 ×106cells, and 3 ×105cells through the tail vein,respectively. After two weeks,mice were killed and dissected,and the tumor growth and metastasis were observed. 3)Eighteen male mice were randomly divided into three groups. Mice in each group were injected with 1×106cells though the tail vein. Mice were killed and dissected after one week, two weeks and three weeks, respectively. The growth and metastasis of tumor were observed. Results 1)The success rate of lung metastasis was 100% in the mice with intravenous injection,but not in mice receiving intraperitoneal injection and subcutaneous injection. 2)The size of metastatic melanoma nodules were moderate in mice inoculated by 1 ×106cells. The number of melanoma metastatic foci was too high in the mice inoculated with 3 ×106cells,but too low in the mice inoculated with 3 ×105cells. 3)Significant metastatic melanoma foci were observed in the mice killed and dissected after two weeks with no death. The number of melanoma foci in the lung was too high in the mice killed after three weeks,while was too low in the mice killed at one week after tumor cell inoculation. Conclusions Intravenous injection of 1×106mouse melanoma cells into C57BL/6 J mice and killed after two weeks is an optimal method for establishment of a mouse model of metastatic melanoma in the lung, and is worth of recommendation.
7.Establishment of finite element model of ankle joint and its biomechanical study
Xingjun LI ; Chaoyu BAO ; Hua LI ; Weihao WANG ; Shuying LI ; Di WU
Chinese Journal of Trauma 2018;34(9):827-832
Objective The three-dimensional finite element model of the normal ankle joint was established to simulate the changes of stress and displacement under stress from different directions and of different magnitudes so as to provide a theoretical basis for the biomechanical mechanism of the ankle joint injury.Methods Spiral CT scan was performed on the left ankle of a 30 year old healthy male volunteer to obtain the original CT image data.The three-dimensional digital model of ankle joint generated by Mimics and Geomagic softwares was imported into the software Ansys.The three-dimensional finite element model of ankle joint with complete anatomical structure was obtained after the main steps of meshing,central node,element linking and module loading using finite element method.Stress from different directions and of different magnitudes were loaded unto the model.The stress changes were measured by foot stress distribution measurement system.The stress changes,displacement change distribution,the stress peak value of heel are,metatarsal stress,and plantar contact stress area as well as the maximum,minimum,and contact are of the tibial articular surface contact stress were compared between the finite element model and the volunteer himself to verify the consistency.Results For the finite element model of normal ankle joint,the plantar peak stress was [(0.33 ± 0.10) MPa],the metatarsal stress was [(0.13 ± 0.21)MPa],the foot contact stress area was [(78.60 ±0.32)mm2],the tibial articular surface maximum contact stress was [(2.72 ± 0.10) MPa],the minimum contact stress was [(1.35 ±0.12)MPa],and the contact stress area was [(79.1 ± 0.14)mm2].For the volunteer,double foot plantar peak stress was [(0.35 ± 0.12)MPa],the metatarsal stress [(0.13 ±0.16)MPa],the foot contact stress area was [(77.3 ± 0.42)mm2],the tibial articular surface maximum contact stress was [(2.79 ± 0.23) MPa],the minimum contact stress was [(1.37 ± 0.20) MPa],and the contact stress area was [(79.10 ±0.14)mm2] (P <0.05).Therefore,the three finite element model of ankle joint was basically consistent with the real human ankle joint because of the similiar distribution,trend,and values.Conclusion The three-dimensional finite element model of normal ankle joint can objectively reflect the anatomical structure and biomechanical characteristics of the joint,which is of great value to understand the changes of the internal mechanics and ankle joint injury.
8.Effect of miR-548j-5p expression on invasion of pancreatic cancer
Ruizhi HE ; Feng PENG ; Yechen FENG ; Xingjun GUO ; Xu LI ; Min WANG ; Rui TIAN ; Feng ZHU ; Renyi QIN
Chinese Journal of Hepatic Surgery(Electronic Edition) 2018;7(1):82-86
Objective To explore the expression of miR-548j-5p in pancreatic cancer and its effect on the invasion of pancreatic cancer. Methods Tissue samples of 16 patients with pancreatic cancer who received treatment in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science &Technology between January 2016 and January 2017 were collected. There were 8 males and 8 females, aged from 41 to 62, including 7 cases with an age of ≤50 and 9 cases with an age of >50. The informed consents of all patients were obtained and the local ethical committee approval was received. The expression of miR-548j-5p in pancreatic cancer and adjacent tissues was detected by RT-PCR. PANC-1 cells were transfected by mimic and inhibitor of miR-548j-5p to construct PANC-1 cells with over-expression and low-expression of miR-548j-5p. And in control group, PANC-1 cells were transfected with empty plasmid Ctrl. The effect of miR-548j-5p on PANC-1 invasion was detected by Transwell assay, and its effect on PANC-1 metastasis was evaluated by wound scratch assay. Comparison of three groups was conducted by one-way analysis of variance and LSD-t test. Results The median relative expression of miR-548j-5p in pancreatic cancer was 0.35(0.03-4.47), significantly lower than 4.30 (0.04-65.55) in adjacent tissues (Z=-2.689, P<0.05).Transwell assay results showed that the average number of cells penetrating membrane was(58±34) in miR-548j-5p over-expression group, significantly lower than (231±61) in control group (LSD-t=-2.852, P<0.05);and it was(491±149)in miR-548j-5p low-expression group,significantly higher than that in control group (LSD-t=4.313, P<0.05). The wound scratch assay results showed that the wound scratch healing rate was (20±8)% in miR-548j-5p over-expression group, significantly lower than (38±6)% in control group (LSD-t=-3.759, P<0.05); and it was (53±6)% in miR-548j-5p low-expression group, significantly higher than that in control group (LSD-t=2.946, P<0.05). Conclusions Low expression of miR-548j-5p is observed in pancreatic cancer. Over expression of miR-548j-5p can decrease the invasive and metastatic ability of pancreatic cancer.
9.Negative immune regulatory molecule TIPE2 for treating SLE mice through regulating macrophage subtype
Xingjun LI ; Yufen ZHANG ; Feng LI ; Xiaohua ZHU ; Lan HUANG
Chongqing Medicine 2017;46(24):3318-3320,3323
Objective To investigate the role of tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) for regulating the macrophage polarization in systemic lupus erythematosus and its curative effects on experimental SLE mice.Methods The mice were treated with activated lymphocytes derived DNA (ALD-DNA) for inducing mice model,randomly divided into AAV-scr control group and AAV-TIPE2 experimental group,and injected with AAV-TIPE2 or AAV-scr virus solution from the tail vein of mice.The expression of TIPE2 mRNA and protein in polarized macrophages,serum dsDNA antibody titer,urine protein and renal pathological index were detected.Results (1) The TIPE2 expression level of TIPE2 mRNA and protein in AAV-TIPE2-transfected cells was 13.5±1.6 times and 10.8±1.6 times of AAV-scr control group respectively.(2) M2 macrophage specific molecule MGL+ was 59.6% in AAV-TIPE2 group and MGL + cells in the AAV-scr group was 8.4%.M2/M1 odds ratio of AAV-TIPE2 experimental group to AAV-scr control group was 16.(3) The recombinant TIPE2 adenovirus related vector could stably expressed in transfected HEK-293.In vitro and in vivo experiments confirmed that AAV-TIPE2 was able to induce M2 polarization of macrophages in ALD-DNA-induced lupus mice.(4) The serum anti-dsDNA antibody,urinary protein and renal pathology in the AAV-TIPE2 group were significantly lower than those in the AAV-scr group(P<0.01).Conclusion TIPE2 alleviates the disease condition of ALD-DNA induced SLE mice through induction of macrophage polarization to M2 phenotype,which may be used as a promising therapeutic method for ALD-DNA induced SLE mice.
10.Status and influencing factors of contracting and renewing on family doctor service in pilot areas in Guangzhou
Yujing NIU ; Miaowen YU ; Yue QIU ; Jin CAI ; Hongzheng HE ; Xingjun HUANG ; Zhaofei DING ; Jiaqing MIAO ; Yuanyi LIN ; Li LI
Chinese Journal of Hospital Administration 2017;33(12):939-943
Objective To learn the current status of family doctor service at pilot communities in Guangzhou, and discover existing problems and influencing factors by investigating the residents who have contracted such service , those have not and the family doctors . Methods This study chose typical community health centers of six communities in Guangzhou in January 2016 .In random sampling , residents who visited doctors during the survey and all the family doctors were surveyed .EpiData was used to doubly inputdata,withSPSS20.0forstatisticalanalysis.Results 66.0%ofthoseresidentswhohavenot contracted the service are willing to contract a family doctor .According to the binary logistic regression analysis after eliminating the interference factors , there are two factors affecting their willingness:gender and whether needing a family doctor for themselves and their family for health management .According to the binary logistic regression analysis after eliminating the interference factors , the influencing factors of renewing contract are overall satisfaction and necessity for signing family doctors .Conclusions The smooth development of the family doctor service is faced with many bottlenecks , while improving willingness to contract and renew contract to family doctors are the cornerstone for sustainability of the family doctor system.

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