1.Construction of micropapillary lung adenocarcinoma organoids and screening of targeted drugs
Zhongmin JIANG ; Chunyan ZHANG ; Min LIU ; Jie ZHENG ; Yanxia LI ; Qingcuo REN ; Wei MENG ; Xiaozhi LIU
Tianjin Medical Journal 2024;52(1):22-27
Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.
2.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
3.Effect of Yishen Daluo Prescription on Rho/ROCK Signaling Pathway in EAE Mice Based on Silencing of β-arrestin1
Wenjing DING ; Zhongmin WANG ; Jiayan REN ; Xiang WANG ; Xiaoling SHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):110-116
ObjectiveTo investigate the effects of Yishen Daluo prescription (YSDL) on Ras homolog(Rho)/Rho-associated coiled-coil containing protein kinase(ROCK)signaling pathway in mice with experimental autoimmune encephalomyelitis (EAE) based on the silencing of β-arrestin1 gene. MethodSixty C57BL/6 female mice were randomly divided into a blank group, a model group, a virus group, a YSDL group, a virus + YSDL group, and a prednisone acetate group (hormone group). The EAE model was induced in mice except for those in the normal group. Adeno-associated virus(AAV)solution (150 μL, 1×1011 vg·mL-1) was injected into the tail vein of each mouse in the virus group and the virus + YSDL group on the 4th day of immunization. Drugs were administered on the 8th day of modeling. Specifically, normal saline was given to the mice in the normal group,the model group,and the virus group at 10 mL∙kg-1, prednisone acetate suspension to those in the hormone group at 3.9 g∙kg-1,and YSDL to those in other groups at 20 g∙kg-1 for 14 consecutive days. The mice were weighed and scored every day. The neurological function scores of mice in each group were recorded every day after immunization. Hematoxylin-eosin (HE) staining was used to determine the inflammatory response and lesion location in the brain tissues and spinal cord tissues of mice. The protein expression of β-arrestin1,Ras homolog gene family member A(RhoA), and Rho-associated coiled-coil forming protein kinase Ⅰ(ROCK Ⅰ) in spinal cord and brain tissues of EAE mice was determined by Western blot. ResultCompared with the model group, the virus group and the virus + YSDL group showed decreased neurological function scores (P<0.01),and the YSDL group also showed decreased neurological function scores(P<0.05). HE results showed that there was obvious inflammatory reaction in the central nervous system (CNS) of the model group, which was alleviated to varying degrees in other groups compared with the model group. Western blot results showed that compared with the blank group, the model group showed increased protein expression levels of β-arrestin1, RhoA, and ROCK Ⅰ in the spinal cord tissues (P<0.01). Compared with the model group, the virus group, the YSDL group, the virus + YSDL group, and the hormone group showed decreased protein expression levels of β-arrestin1, RhoA, and ROCKⅠ in the spinal cord tissues (P<0.01). Compared with the blank group, the model group showed increased protein expression levels of β-arrestin1, RhoA, and ROCK Ⅰ in the brain tissues (P<0.01). Compared with the model group, the virus group, the YSDL group, the virus + YSDL group, and the hormone group showed decreased protein expression level of β-arrestin1 in the brain tissues (P<0.01), and the virus group and the YSDL group showed decreased protein expression levels of RhoA, and ROCKⅠ in the brain tissues (P<0.05). Additionally, the virus + YSDL group and the hormone group showed decreased protein expression levels of RhoA and ROCKⅠ in the brain tissues (P<0.01). ConclusionYSDL can improve the clinical symptoms of EAE mice and improve the inflammatory response of CNS. The mechanism is presumably attributed to the fact that YSDL inhibits the expression of β-arrestin1 in CNS,thereby reducing the expression of Rho/ROCK signaling pathway. Furthermore, YSDL may have a synergistic effect with the inhibition of β-arrestin1 gene expression.
4.Circular RNA ame_circ_000115 regulates expression of genes in larval gusts of Apis mellifera ligustica stressed by Ascosphaera apis.
Yaping YE ; Jie WANG ; Jiaxin ZHANG ; Kaiyao ZHANG ; Xiaoyu GU ; Yutong YAO ; Zhongmin REN ; Yang ZHANG ; Dafu CHEN ; Rui GUO
Chinese Journal of Biotechnology 2023;39(1):217-230
Circular RNAs (circRNAs) are a new class of non-coding RNAs, which have been confirmed to regulate insect gene expression and immune response through multiple manners such as competing endogenous RNA (ceRNA) regulatory network. Currently, function of circRNA in honey bee immune response remains unclear. In this study, PCR and Sanger sequencing were performed to validate the back splicing (BS) site of ame_circ_000115 (in short ac115). RT-qPCR was used to detect the expression profile of ac115 in larval guts of Apis mellifera ligustica stressed by Ascosphaera apis. Dual-luciferase reporter gene assay was conducted to verify the binding relationship between ac115 and ame-miR-13b. Interference of ac115 in larval guts was carried out by feeding specific siRNA, followed by determination of the effect of ac115 interference on expression of six genes relevant to host immune response. The results confirmed the existence of BS site within ac115. Compared with the un-inoculated group, the expression of ac115 in 4-day-old larval gut of the A. apis-inoculated group was up-regulated with extreme significance (P < 0.000 1), while that in 5- and 6-day-old larval guts were significantly up-regulated (P < 0.05). The brightness of specific band for ac115 in 4-, 5- and 6-day-old larval guts of the siRNA-circ_000115-fed group gradually became weak, whereas that of the siRNA-scrambl-fed group was pretty high without obvious variation. Compared with that of the siRNA-scramble-fed group, the expression of ac115 in 4-day-old larval gut of the siRNA-circ_000115-fed group was significantly down-regulated (P < 0.05), whereas that of the 5- and 6-day-old larval guts were down-regulated with extreme significance (P < 0.001). Ame-miR-13b was truly existed and expressed in A. m. ligustica larval guts, and there was true binding relationship between ac115 and ame-miR-13b. Compared with that of the siRNA-scramble-fed group, the expression of antimicrobial peptide genes hymenoptaecin and abaecin in 6-day-old larval gut of the siRNA-circ_000115-fed group was significantly up-regulated (P < 0.05), while that of ecdysone receptor (Ecr) was down-regulated with extreme significance (P < 0.01). These results indicate that ac115 is truly expressed in A. m. ligustica larval guts, BS site truly exists within ac115, and effective interference of ac115 in A. m. ligustica larval guts can be achieved via feeding siRNA. Moreover, ac115 potentially regulates Ecr expression through adsorption of ame-miR-13b and expression of hymenoptaecin and abaecin using a non-ceRNA manner, further participating in host stress-response.
Bees/genetics*
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Animals
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Larva/metabolism*
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RNA, Circular/genetics*
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RNA, Small Interfering/genetics*
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MicroRNAs/genetics*
5.Musculoskeletal multibody dynamics investigation for the different medial-lateral installation position of the femoral component in unicompartmental knee arthroplasty.
Jiaxuan REN ; Zhenxian CHEN ; Jing ZHANG ; Yongchang GAO ; Feng QIAO ; Zhongmin JIN
Journal of Biomedical Engineering 2023;40(3):508-514
The surgical installation accuracy of the components in unicompartmental knee arthroplasty (UKA) is an important factor affecting the joint function and the implant life. Taking the ratio of the medial-lateral position of the femoral component relative to the tibial insert (a/A) as a parameter, and considering nine installation conditions of the femoral component, this study established the musculoskeletal multibody dynamics models of UKA to simulate the patients' walking gait, and investigated the influences of the medial-lateral installation positions of the femoral component in UKA on the contact force, joint motion and ligament force of the knee joint. The results showed that, with the increase of a/A ratio, the medial contact force of the UKA implant was decreased and the lateral contact force of the cartilage was increased; the varus rotation, external rotation and posterior translation of the knee joint were increased; and the anterior cruciate ligament force, posterior cruciate ligament force and medial collateral ligament force were decreased. The medial-lateral installation positions of the femoral component in UKA had little effect on knee flexion-extension movement and lateral collateral ligament force. When the a/A ratio was less than or equalled to 0.375, the femoral component collided with the tibia. In order to prevent the overload on the medial implant and lateral cartilage, the excessive ligament force, and the collision between the femoral component and the tibia, it is suggested that the a/A ratio should be controlled within the range of 0.427-0.688 when the femoral component is installed in UKA. This study provides a reference for the accurate installation of the femoral component in UKA.
Humans
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Arthroplasty, Replacement, Knee
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Knee Joint/surgery*
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Knee Prosthesis
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Gait
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Rotation
6.The influence of UKA Installation Error of Joint Line on Contact Mechanics and Kinematics of Knee Joint
Jiaxuan REN ; Zhenxian CHEN ; Jing ZHANG ; Xuan ZHANG ; Zhangwe MA ; Zhongmin JIN
Journal of Medical Biomechanics 2023;38(2):E290-E296
Objective Aiming at the medial prosthetic loosening failure and lateral cartilage degeneration after unicompartmental knee arthroplasty ( UKA), the effects of prosthetic installation errors of joint line in UKA on knee contact mechanics and kinematics during different physiologic activities were studied using musculoskeletal multi-body dynamic method. Methods Taking the medial natural joint line as 0 mm error, six installation errors ofjoint line including ±2 mm, ±4 mm and ±6 mm were considered respectively, and seven musculoskeletal multi body dynamic models of medial UKA were established, to comparatively study the variations in knee contact mechanics and kinematics during walking and squatting. Results At 70% of walking gait cycle, compared with 0 mm error, the medial prosthetic contact force was increased by 127. 3% and the contact force of the lateral cartilage was decreased by 12. 0% under 2 mm elevation in joint line, the medial prosthetic contact force was close to 0 N, but the lateral cartilage contact forces were increased by 10. 1% under 4 mm reduction in joint line. The tibiofemoral total contact forces were increased by 19. 7% and decreased by 14. 2% under 2 mm elevation and 2 mm reduction in joint line, respectively. At the 100°knee flexion during squatting, compared with 0 mm error, the medial prosthetic contact force and the tibiofemoral total contact force increased by 31. 6% and 11. 1% under 2 mm elevation in joint line, and decreased by 24. 5% and 8. 5% under 2 mm reduction in joint line, respectively. The change in the lateral cartilage contact force was not marked. Moreover, at 70% of walking gait cycle, the varus angle decreased, the internal rotation and the anterior translation increased along with the elevation of joint line in UKA, while it was just the opposite along with the reduction of joint line in UKA. The trends of the varus valgus movement and anterior-posterior translation during squatting were consistent with those during swing phase of walking, but the trend of the internal-external rotation was opposite. Conclusions In order to reduce the risk of medial prosthetic loosening failure and lateral cartilage degeneration, it is recommended that the installation error of joint line in UKA should be controlled in the range of -2 mm to +2 mm. This study provides theoretical basis for UKA clinical failure caused by changes in joint line
7.Research on protective function of aspirin-triggered lipoxins on acute kidney injury in mice
Pei ZHANG ; Hongjun PENG ; Yuanfu GAO ; Zhongmin FAN ; Xianguo REN ; Chunlin GAO ; Suling WEI ; Zhengkun XIA
Chinese Journal of Applied Clinical Pediatrics 2018;33(5):338-341
Objective To investigate the renoprotective effect of aspirin-triggered lipoxins(ATL)on kidney of mice with acute kidney injury(AKI).Methods Eighty-eight male specific pathogen-free(SPF)C57BL/6J mice were randomly divided into lipopolysaccharide(LPS)groups(including 2 h group,4 h group,8 h group,12 h group, 24 h group),ATL+LPS(including 2 h group,4 h group,8 h group,12 h group,24 h group)and normal control group according to random numble table,and each group had 8 mice.The mice in LPS groups were given LPS intraperitoneal injection to establish AKI animal models,while the mice in ATL+LPS groups were given ATL intraperitoneal injection 30 minutes before LPS intraperitoneal injection.The enzyme linked immunosorbent assay was used to test the serum creatinine(Scr),serum urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),cysteine-rich protein-61 (Cyr61)and netrin-1 levels of mice.Results The kidney tissue injury scores of mice of ATL+LPS group[4 h:(22.32 ± 1.04)scores,8 h:(31.11 ± 1.86)scores,12 h:(18.22 ± 0.92)scores,24 h:(20.87 ± 3.18)scores] were lower than those of LPS group at the corresponding time points[4 h:(35.47 ± 2.27)scores,8 h:(52.28 ± 2.82) scores,12 h:(54.99 ± 4.56)scores,24 h:(53.41 ± 4.76)scores],and the differences were statistically significant(all P<0.01).The values of Scr,BUN,TNF-α and IL-1β in ATL+LPS group[Scr 8 h:(143.07 ± 5.02)μmol/L, BUN 12 h:(33.07 ± 3.52)mmol/L,TNF-α 4 h:(196.33 ± 14.181)ng/L and 8 h:(221.77 ± 10.11)ng/L,IL-1β 4 h:(50.25 ± 2.67 ng/L)]were lower than those in LPS group at the corresponding time points[Scr 8 h:(227.43 ± 11.17)μmol/L,BUN 12 h:(59.68 ± 3.84)mmol/L,TNF-α 4 h:(267.87 ± 26.48)ng/L and 8 h:(334.78 ± 21.08)ng/L,IL-1β 4 h:(89.45 ± 5.87)ng/L],and the differences were statistically significant(all P<0.01). The urine NGAL[4 h:(56.76 ± 4.01)μg/L,8 h:(65.44 ± 7.81)μg/L],KIM-1[8 h:(78.19 ± 9.48)μg/L] and netrin-1[8 h:(40.12 ± 2.01)ng/L,12 h:(36.87 ± 2.87)ng/L]of mice in ATL+LPS group were lower than those in LPS group at the corresponding time points[NGAL 4 h:(168.77 ± 10.77)μg/L,8 h:(155.33 ± 8.26) μg/L;KIM-1 8 h:(124.73 ± 13.47)μg/L;netrin-1 8 h:(89.17 ± 2.74)ng/L,12 h:(81.11 ± 3.88)ng/L],and the differences were statistically significant(all P<0.01).Conclusions ATL can treat LPS-induced AKI and play a renoprotective role in the kidney.
8.Design and Application of Dual-active Data Centers of Hospitals
Bin LI ; Yuehong SU ; Ziming MAI ; Zhongmin REN ; Caisheng HE
Journal of Medical Informatics 2017;38(2):33-37
In order to achieve the real-time online disaster recovery objectives of the main data center and disaster recovery center,the paper takes Cancer Hospital Affiliated to Sun Yat-Sen University as an example to analyze the status of Hospital Information System (HIS),puts forward the construction of dual-active storage data center based on EMC VPLEX,introduces the disaster recovery schemes of the data center,conducts system test,and provides reference for information construction of the hospital.
9.Construction and Management of Official Websites of Medical Institutions
Ziming MAI ; Bin LI ; Yuehong SU ; Zhongmin REN ; Caisheng HE
Journal of Medical Informatics 2017;38(7):68-71
The paper summarizes the significance of the construction of official websites of medical institutions,introduces the requirements of Guangdong Health and Family Planning Commission for the construction of official websites of medical institutions,and describes the construction thought,safety protection and deployment,website management,etc.of the Cancer Hospital Affiliated to Sun Yat -Sen University,in order to provide reference for website construction and management in the industry.
10.Surgical Treatment and Prognosis for Patients with Synchronous Multiple Primary Lung Adenocarcinomas
PENG YUE ; WANG HUI ; XIE HOUNAI ; REN WANGANG ; FENG ZHEN ; LI MENG ; PENG ZHONGMIN
Chinese Journal of Lung Cancer 2017;20(2):107-113
Background and objective With the popularization of high-resolution computed tomography (HRCT), there is a rising trend of the detection of multiple primary lung cancers (MPLC). Adenocarcinomas is the major pathological type of MPLC. At present, reports on MPLC are relatively common, but few study focused on synchronous multiple primary lung adenocarcinomas (SMPLA). We carried out this study in an attempt to enhance our understanding about SMPLA.Meth-ods Data from 38 patients undergoing surgery for SMPLA in our institution frrom December 2012 and July 2016 were retro-spectively collected.Results Among the 38 patients, 12 patients were male, 26 patients were female, with a median age of 58 (ranging from 39 to 73). Surgical outcomes verified 29 patients with 2 tumors and 9 patients with more than 2 tumors. There were 26 patients with tumors in ipsilateral lung while 12 patients in contralateral lung. Eight patients underwent one-stage surgical treatment for contralateral tumors with mean postoperative hospitalization of 10 days. The gene detection results of 5 patients showed different epidermal growth factor receptor (EGFR) mutations can be found in one patient's different tumors. The 1-year and 3-year overall survival (OS) rate were 96.6% and 74.2%. Larger maximal tumor dimension (P<0.001), advanced pT stage (P=0.003), lymph nodes metastases positive (P=0.001), advanced TNM stage (P=0.022) and postoperative adjuvant chemoradiotherapy (P=0.009) were correlated with poor OS.Conclusion Multiple lung malignant lesions should not be taken as metastasis for granted and the possibility of MPLC also should be considered. Mutational status ofEGFR could be used as a clinical reference to diagnose patients with SMPLA.

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