1.Establishment and evaluation of a rat model of heart failure with a preserved ejection fraction induced by combined factors
Yujiao SHI ; Chenguang YANG ; Wenbo QIAO ; Yongcheng LIU ; Siyu LIU ; Guoju DONG
Acta Laboratorium Animalis Scientia Sinica 2024;32(3):275-285
Objective To evaluate the characteristics of a rat model of heart failure with a preserved ejection fraction(HFpEF)induced by combined factors,and to investigate the correlation of myocardial strain parameters to myocardial hypertrophy and fibrosis.Methods Eight WKY rats and eight spontaneously hypertensive rats(SHR)served as control groups and were fed normal feed until the end of the experiment.Thirty-two SHR rats were equally divided into SHR+S,SHR+F,SHR+SF,and SHR+Combined groups,and fed high-salt,high-fat,high-salt-fat,or high-salt-fat-sugar feed,respectively,in combination with intraperitoneal injection of streptozotocin for 30 weeks.After modeling,the heart weight/body weight(HW/BW)ratio,systolic blood pressure(SBP),and diastolic blood pressure(DBP)were measured.Echocardiography was performed to measure the left ventricular(LV)end-diastolic internal diameter(LVIDd),LV anterior wall thickness(LVAWd),LV posterior wall thickness(LVPWd),LV ejection fraction(LVEF),isovolumetric diastolic time(IVRT),and peak early diastolic passive filling velocity(E)/early diastolic mitral annular velocity(e').Speckle tracking echocardiography was conducted to determine the global longitudinal strain(GLS)and strain rate(GLSr),global radial strain(GRS)and strain rate(GRSr),as well as the global circumferential strain(GCS)and strain rate(GCSr).Serum was collected and analyzed for triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),glucose(GLU),and glycated serum protein(GSP).ELISA were used to measure serum B-type brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ),and galectin-3(Gal-3).Myocardial tissue was subjected to HE and Masson staining for cardiomyocytes and myocardial fibrosis,and the cardiomyocyte cross-sectional area(CSA)and collagen volume fraction(CVF)were calculated.Additionally,the correlation of myocardial strain parameters to CSA and CVF was analyzed.Results Compared with the control group,in model groups,especially the SHR+combined group,HW/BW,SBP,DBP,serum indexes(TC,TG,LDL-C,GLU,GSP,BNP,AngⅡ,and Gal-3)and echocardiographic parameters(LVIDd,LVAWd,LVPWd,IVRT,and E/e')were significantly up-regulated.Absolute values of speckle-tracking echocardiographic parameters(GLS,GLSr,GRS,GRSr,GCS,and GCSr)were decreased considerably.HE and Masson staining of myocardial tissues suggested marked cardiomyocyte hypertrophy and fibrosis,and significant increases were observed in CSA and CVF(P<0.05).Correlation analysis showed that GLSr,GCS,and GCSr were strongly linked to CSA,and GLS,GLSr,and GCSr were strongly linked to CVF(P<0.01).Conclusions A rat model of HFpEF induced by hypertension and dysregulation of glucolipid metabolism replicated the basic characteristics of HFpEF in terms of etiology,clinical features,and myocardial pathological changes,and might be a reliable animal model of metabolic syndrome-related HFpEF.Moreover,myocardial strain indices were closely related to myocardial hypertrophy and fibrosis and might indirectly reflect subtle myocardial lesions and dysfunction.
2.Correlation between subjective hearing impairment and cognitive function in the elderly in the community of Changzhou City
Xuelian CUI ; Yi ZHANG ; Dan ZHANG ; Fan XIE ; Yu LIU ; Yongcheng LIU
Chinese Journal of Health Management 2024;18(9):674-679
Objective:To investigate the correlation between subjective hearing impairment and cognitive function in the elderly in the community of Changzhou City.Methods:This study was a retrospective cohort study. A total of 1 132 elderly people recruited from 4 communities in Changzhou City from August to October in 2023 were selected as the research objects. The social demographic and cognitive function were collected, cognitive function was assessed using the mini-mental state examination (MMSE), while the connected test, replica cube, and clock draw in the Montreal cognitive assessment (MoCA) were selected to assess visuospatial and executive function. The subjects were divided into the no-hearing impairment group (726 subjects) and hearing impairment group (406 subjects) according to the self-reported hearing impairment of the elderly. The basic data of the two groups and the differences in different cognitive domains were analyzed, and the correlation between subjective hearing impairment and cognitive function of the elderly in the community was analyzed by univariate and multivariate logistic regression analysis.Results:The incidence of cognitive impairment in the hearing impairment group was significantly higher than that in the no-hearing impairment group (20.2% vs 6.6%), the scores of location orientation, memory, attention and calculation, recall, language ability, clock draw, and the total score of MMSE, visuospatial and executive function in the hearing impairment group were all significantly lower than those in the normal hearing group [(4.76±0.78) vs (4.91±0.45) points, (2.79±0.59) vs (2.90±0.36) points, 4 (3, 5) vs 5 (4, 5) points, 2 (1, 3) vs 2 (2, 3) points, 8 (7, 9) vs 9 (8, 9) points, 2 (2, 3) vs 3 (2, 3) points, 27 (24, 29) vs 27 (26, 29) points, 3 (2, 3) vs 3 (2, 4) points] (all P<0.05). There was a positive correlation between subjective hearing impairment and cognitive function impairment in community-dwelling elderly ( OR=3.544, 95% CI: 2.410-5.213) ( P<0.001). Conclusion:The incidence of cognitive impairment is higher in the community-dwelling elderly with subjective hearing impairment, and hearing impairment is a positive correlation factor of cognitive impairment.
3.Combined liver-kidney transplantation for giant polycystic liver and polycystic kidney involving iliac fossa: one case report
Longshan LIU ; Wenbin ZHANG ; Weiqiang JU ; Maogen CHEN ; Yongcheng WEI ; Yingzhen HE ; Jun LI ; Changxi WANG ; Xiaoshun HE
Chinese Journal of Organ Transplantation 2024;45(10):728-729
This report described one patient of giant polycystic liver and polycystic kidney involving iliac fossa. Preoperative computed tomography (CT) revealed a large polycystic kidney occupying partially iliac fossa space. A decompression of lower pole of original kidney was planned for placing transplanted kidney. During total liver resection plus orthotopic liver transplantation, right polycystic kidney could move up on its own and iliac fossa space was released for placing transplanted kidney smoothly. Polycystic kidney shrunk markedly post-operation. It provided references for surgical planning of combined liver-kidney transplantation for this type of disease.
4.Targeting the chromatin structural changes of antitumor immunity
Li NIAN-NIAN ; Lun DENG-XING ; Gong NINGNING ; Meng GANG ; Du XIN-YING ; Wang HE ; Bao XIANGXIANG ; Li XIN-YANG ; Song JI-WU ; Hu KEWEI ; Li LALA ; Li SI-YING ; Liu WENBO ; Zhu WANPING ; Zhang YUNLONG ; Li JIKAI ; Yao TING ; Mou LEMING ; Han XIAOQING ; Hao FURONG ; Hu YONGCHENG ; Liu LIN ; Zhu HONGGUANG ; Wu YUYUN ; Liu BIN
Journal of Pharmaceutical Analysis 2024;14(4):460-482
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.
5.Analysis of risk factors for 1-year survival rate in patients with spinal metastasis secondary to lung cancer
Bingshan YAN ; Jingyu ZHANG ; Yancheng LIU ; Xiuchun YU ; Guochuan ZHANG ; Zhaoming YE ; Guowen WANG ; Yu ZHANG ; Yongcheng HU
Chinese Journal of Orthopaedics 2024;44(6):409-418
Objective:To investigate the risk factors for 1-year survival rate in patients with spinal metastasis secondary to lung cancer.Methods:The data of 343 patients with spinal metastases secondary to lung cancer from January 2011 to December 2018 were retrospectively studied. There were 188 males (54.8%) and 155 females (45.2%) with an average age of 59.47±10.21 years old (range 23-91 years). The patients were divided into operation group (150 cases, 43.7%) and non operation group (193 cases, 56.3%). The demographics, types of primary tumor, non spinal metastasis, visceral metastasis, spinal metastasis and segments, pathological fractures of vertebra, Frankel classification, physical function status (Karnofsky performance scale, KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS) were recorded and analyzed. The impact of different treatments on the survival prognosis of patients with spinal metastasis was evaluated. The independent factors affecting survival in those patients were analyzed by Cox proportional hazards regression model.Results:The peak incidence of spinal metastases was found in the age group of 46-60 years (43.7%, 150/343). 38.5% (132/343) of the patients had pathological fractures of the involved vertebral body. 58.3% (200/343) of the patients had extraspinal bone metastasis. 36.2% (124/343) of the patients had visceral metastasis. Among the primary tumors, adenocarcinoma was the most common tpye (61.5%, 211/343), followed by large cell lung cancer (12.5%, 43/343), small cell lung cancer (6.4%, 22/343), squamous cell cancer (6.1%, 21/343) and mixed cell lung cancer (5.3%, 18/343). The type of lung cancer cells in about 8.2 (28/343) patients was unknown. Among the surgical patients, 21 patients underwent minimally invasive surgery (14.0%), 28 patients underwent simple decompression surgery (18.7%), 76 patients underwent separation surgery (50.7%), and 25 patients underwent radical surgery (16.6%). 59.3% (89/150) of the patients had a better neurological function than before surgery. The average survival time of all patients was 9.88 months with the median survival time of 8 (5,14) months. The survival rates were 62.1% (213/343), 30.0% (103/343), and 3.8% (13/343) at 6, 12, and 24 months, respectively. The average survival time of patients in the operation group was 10.24 months with the median survival time of 9 (5, 15) months, and the average survival time of patients in the non operation group was 9.41 months with the median survival time of 7 (5, 13) months with no significant difference between the groups (χ 2=0.300, P=0.584). Multivariate Cox proportional hazard regression model analysis showed that radiotherapy [ HR=1.913, 95% CI(1.471, 2.488), P<0.001], chemotherapy [ HR=1.313, 95% CI(1.040, 1.658), P=0.022], targeted drug therapy [ HR=1.683, 95% CI(1.221, 2.319), P=0.001], KPS [ HR=1.593, 95% CI(1.140, 2.225), P=0.006] and pathological type (non-small cell lung cancer) were independent factors affecting the 1-year survival rate of patients with spinal metastasis secondary to lung cancer [ HR=0.322, 95% CI(0.225, 0.460), P<0.001] with significant difference. Conclusion:Surgical treatment can improve both the neurological function and general status of patients with spinal metastasis. Treatments of radiotherapy, chemotherapy, and targeted drug therapy can significantly improve 1-year survival rate, while a KPS less than 50 points and a primary lung cancer other than adenocarcinoma were independent risk factors reducing 1-year survival rate.
6.Exploration on the pharmacological basis of Lycopi Herba as alternative of Alismatis Rhizoma for the treatment of heart failure based on network pharmacology and molecular docking techniques
Siyu LIU ; Yujiao SHI ; Yongcheng LIU ; Xiaoyu LIANG ; Chenguang YANG ; Wenbo QIAO ; Guoju DONG
International Journal of Traditional Chinese Medicine 2024;46(8):1045-1052
Objective:To investigate whether Lycopi Herba can serve as a viable alternative to Alismatis Rhizoma in the treatment of heart failure (HF) through network pharmacology and molecular docking techniques.Methods:TCMSP database was used to filter active components of Lycopi Herba and Alismatis Rhizoma. SwissTargetPrediction database was used to predict potential targets. HF-related targets were collected from databases such as GeneCards, OMIM, and DisGeNET. Venny 2.1.0 was used to draw a Venn diagram illustrating the intersection of targets between Lycopi Herba and Alismatis Rhizoma and HF. A protein-protein interaction (PPI) network was established using the String database, and key targets for the treatment of HF with Lycopi Herba and Alismatis Rhizoma were selected using Cytoscape 3.9.1 software to construct a component-intersection target network. The intersection targets were then analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. Molecular docking techniques were used to evaluate the affinity between active components and key targets.Results:Lycopi Herba primarily targeted pivotal proteins such as HMGCR and CYP27B1, while Alismatis Rhizoma had a broader target spectrum, including PPARA, JAK2, among others. Shared key targets between the two included HMGCR and ESR1, which were primarily involved in cholesterol synthesis and steroid hormone biosynthesis. Enrichment pathway analysis showed similarities in steroid metabolism between the two; Alismatis Rhizoma, however, was more likely to act through protein phosphorylation regulation and modulating the PI3K-Akt signaling pathway for HF treatment. A unique target for Lycopi Herba in treating HF was CHRM4, indicating its potential for blood pressure regulation and myocardial protection.Conclusions:Both Lycopi Herba and Alismatis Rhizoma exhibit certain commonalities in the treatment of HF, but Alismatis Rhizoma has a wider range of targets and signaling pathways, implying more extensive therapeutic potential. However, considering the nephrotoxicity of Alismatis Rhizoma, Lycopi Herba could be considered as an alternative treatment for HF, especially in patients with renal insufficiency or in the early stages of HF.
7.The surgical treatment progress of proximal femoral deformity caused by fibrous dysplasia of bone
Chengkuo CAI ; Jingyu ZHANG ; Shuzhen DENG ; Yancheng LIU ; Yongcheng HU
Chinese Journal of Orthopaedics 2024;44(15):1040-1047
Fibrous dysplasia of bone (FD) is a tumorlike disease characterized by intramedullary fibrosis, in which the development of the bone in the lesion area stops at the stage of immature braided bone, with the inability to form a normal bone trabecula, resulting in structural changes and reduced mechanical strength of the bone. Repeated pathological fractures often occur with weight bearing, followed by curvature of the affected bone, limb shortening, and abnormal gait. The proximal femur is often involved in FD limb malformations, with complex types and degrees, most of which are manifested as gradually aggravating hip varus and diaphysial curvature. The proximal femur is a common site of limb deformity caused by FD, the types and severity of malformations are complex and varied, which is usually manifested as gradually aggravated varus hip joint and diaphysis bending deformity. The purpose of deformity correction is to restore the normal mechanical axis and length of the femur, thereby restoring the function of the limb, avoiding the progression of deformity and relieving the pain symptoms caused by repeated pathological microfractures, which is more important than the treatment of the lesion itself. The preoperative treatment plan should be made individually for each patient according to the location and extent of the lesion and the type of the lesion. The patients need to be followed up for a long time to adjust the correction plan. Whether the lesion should be curette and bone graft and the type of bone graft material used are still controversial. The femoral deformity of FD should be analyzed based on the principles of deformity correction, the type of deformity and the location of the apex of the deformity should be determined, the osteotomy plan should be designed, and the preoperative simulation should be performed. Both intramedullary and extramedullary fixation after osteotomy can provide sufficient biological stability. The choice of fixation device should be determined according to the specific situation during the operation. There is no obvious abnormality in bone healing and regeneration in FD patients, but dysplastic bone tissue is included in the callus formation. The limb deformity of FD patients is prone to relapse after treatment, long-term close follow-up is needed to adjust the correction plan.
8.Design of an anatomic plate of ulna coronoid process by 3D printing and computer software
Yanxi YANG ; Shijie ZHANG ; Yi LIU ; Yongcheng CHEN ; Bei LIU ; Rongrui YANG ; Maogeng YANG ; Di WU
Chinese Journal of Orthopaedic Trauma 2023;25(2):154-160
Objective:To design an anatomical plate of ulna coronoid process using 3D printing and computer model design software based on a collection of CT scanning data of the ulna coronoid process.Methods:The CT scans of the elbow joint with no obvious anatomic variation, no fracture, or no history of elbow operation were collected which had been taken at Trauma Center, The First Affiliated Hospital of Kunming Medical University from September 2017 to January 2022. There were 52 males and 50 females. RadiAnt DICOM Viewer and Mimics Medical 21.0 were used to visualize the CT data of the elbow joint of 102 volunteers. The software was used to measure the angle between the tip of the ulna coronoid process and the tuberosity of the ulna, the width at 1/2 height of the ulna coronoid process, the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity, and the safety angle for screw placement. After the values were measured, Siemens Ungraphics NX12.0 software was used to design the anatomical plate and the screw guide device of the ulna coronoid process. After the plate model was designed, a 1:1 actual plate model of the ulna coronoid process was produced by 3D printing. The actual plate model was placed onto an adult model of the ulna coronoid process and an adult cadaveric specimen of the ulna coronoid process to verify its matching degree. An in vitro operation was simulated using the plate model to verify its operability. Results:There were no significant differences between the left and right sides in the angle between the tip of the ulna coronoid process and the tuberosity of the ulna, the width at 1/2 height of the ulna coronoid process, the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity, or the safety angle for screw placement in either males or females ( P>0.05). There were no significant differences between males and females in the angle between the tip of the ulna coronoid process and the tuberosity of the ulna or in the safety angle for screw placement ( P>0.05). There were statistically significant differences between males and females in the width of 1/2 height of the ulna coronoid process and the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity ( P<0.05). However, the experiments on computer simulative adaptation and plate model simulative adaptation found that the anatomical plates of the ulna coronoid process designed on various parameters of males and females were exchangeable, leading to similarly good marching degrees and safe angles for screw placement. Conclusions:The anatomical plate of the ulna coronoid process designed in this study demonstrates a good fit and a safe angle for screw placement, basically achieving the goal expected to provide a basis for fabrication of a titanium alloy plate. In design of an anatomical plate of ulna coronoid process, it is not necessary to differentiate males from females or to differentiate the left side from the right one, because only a general plate can be used for both males and females and for both the left and the right sides.
9.Treatment of iliac fracture combined anterior dislocation of the sacroiliac joint by the "ladder reduction method"
Lei WEN ; Ge CHEN ; Kaiyu HOU ; Jianhua JI ; Changshun CHEN ; Kun LIU ; Yongcheng DENG ; Zhong CHEN ; Changyou ZHENG
Chinese Journal of Orthopaedics 2023;43(15):1007-1012
Objective:To investigate the clinical effect of "ladder reduction method" in the treatment of iliac fracture combined anterior dislocation of sacroiliac joint.Methods:The retrospective analysis was performed on 10 cases of iliac fracture combined anterior sacroiliac joint dislocation admitted to the Affiliated Hospital of Yunnan University from February 2010 to January 2022, among which 5 cases were males and 5 cases were females, aged ranging from 22 to 52 years, with an average age of 38.8 years. All patients were injured in car accidents including 5 cases of C1.2, 3 cases of C2, and 2 cases of C3 fractures according to Tile classification. All patients were treated with the "ladder reduction method" with plate and screw fixation. In the first step, 1-2 Schanz pins were inserted into the iliac crest to control the ilium, and the Schanz pins were appropriately pulled laterally; in the second step, the periosteal stripper was used to pry the reduction between the sacrum and ilium; in the third step, for the patients who still could not be reduced, a 2.5 mm diameter Kirschner wire was placed on the sacrum close to the iliac crest, and a periosteal stripper was inserted between the sacrum and iliac crest, with its tip against the Kirkner wire, and the iliac crest as the fulcrum for pry pulling to separate the two. In the fourth step, the pry was maintained, and then another 2.5 mm diameter Kirschner wire was placed on the sacrum close to the internal margin of the iliac bone. The periosteal stripper was continued to pry between the sacrum and the iliac bone, and the operation was repeated. At the same time, the anterior dislocation of the sacroiliac joint was reduced with traction of the lower limb. Postoperatively, the quality of reduction was evaluated by the Matta score, and the degree of functional recovery after pelvic fracture was evaluated by the Majeed score.Results:Four patients completed the reduction through the first and second steps, and 6 cases of refractory sacroiliac joint anterior dislocation were successfully reduced through the first to fourth steps. The fracture reduction time of 6 patients with refractory anterior sacroiliac joint dislocation was 39.67±3.09 min (range, 35-44 min), with intraoperative blood loss of 300.00±141.42 ml (range, 150-600 ml); in the other 4 cases, the fracture reduction time was 36.75±4.38 min (range, 30-42 min), and the intraoperative blood loss was 225.00±44.30 ml (range, 200-300 ml). All 10 patients were followed up for 12.9±3.7 months (range, 9-20 months). The anterior and posterior pelvic ring fractures were healed in all patients, and the fracture healing time was 12.77±1.62 weeks (range, 10.71-15.28 weeks). At the last follow-up, Matta evaluation was excellent in 5 cases, good in 1 case, and excellent in the other 4 cases. The Majeed scores of 6 cases were 86.50±6.08 points (range, 74-92 points), of which 5 cases were excellent and 1 case was good. The other 4 cases were 81.5±9.39 scores (range, 71-94), of which 2 were excellent and 2 were good.Conclusion:The "ladder reduction method" is a safe, effective and easy-to-operate method for the treatment of iliac fracture combined anterior dislocation of the sacroiliac joint, especially for refractory anterior dislocation of the sacroiliac joint, which can still obtain satisfactory curative effects.

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