1.Mechanisms of Mycobacterium tuberculosis-induced primary cilia degra-dation in monocytes-macrophages and promotion of osteoclast differentia-tion
Chengran ZHANG ; Qianfei LIU ; Nanjun XIONG ; Junbao CHEN ; Qile GAO ; Mingxing TANG ; Shaohua LIU
Chinese Journal of Infection Control 2025;24(9):1208-1214
Objective To explore the effect of Mycobacterium tuberculosis infection on the primary cilia of mono-cytse-macrophages and its potential mechanisms of promoting osteoclast differentiation.Methods Bone marrow-de-rived mononuclear cells(BMMCs)isolated from patients in control group and spinal tuberculosis group(TB group)were performed in vitro culture,and then cultured with Mycobacterium tuberculosis,infection model(Rv group)was constructed.Changes in cilia were observed by fluorescence staining and scanning electron microscopy tech-nique,a mouse spinal TB model was constructed for validating.Results Compared with the control group,the ex-pression of primary cili markers in the lesion of bone tissue of patients in TB group decreased significantly;After co-culturing with Mycobacterium tuberculosis,the ratio(48.56%±7.77%vs 9.58%±5.59%)and length(4.050[3.289,4.666]μm vs 0[0,0.676]μm)of primary cilia of monocytes-macrophages in the Rv group decreased sig-nificantly;The infiltration of osteoclasts in the bone marrow cavity of spinal TB mice was obvious,and the propor-tion and length of primary cilia decreased significantly.Conclusion Intracellular infection of Mycobacterium tuberculosis can induce degradation of primary cilia in monocytes-macrophages,promote osteoclast differentiation,and exacerbate vertebral bone resorption.
2.Autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture for anterior cruciate ligament tears
Ming TANG ; Qingsong ZHANG ; Hanqi WANG ; Huawei WEN ; Yushun FANG ; Ya'nan LI ; Shaohua ZHANG ; Du XIE
Chinese Journal of Orthopaedic Trauma 2025;27(5):417-424
Objective:To investigate the clinical effectiveness of autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture in the treatment of anterior cruciate ligament (ACL) tears.Methods:A retrospective study was conducted to analyze the clinical data of 38 patients with ACL tear who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan from January 2016 to July 2020. There were 30 males and 8 females, with an age of (25.4±7.2) years. By the typing of MRI Sherman tear locations (MSTL) for anterior cruciate ligament, 7 cases were Type I and 31 cases type II. A total of 18 patients underwent single bundle reconstruction of autologous hamstring tendon combined with remnant suture (group A), and the other 20 patients underwent conventional reconstruction to clean the synovial sheath of ACL (group B). The operation time,Tenger scores, Lysholm scores, International Knee Documentation Committee (IKDC) subjective score and side-to-side differences in relaxation at pre- operation, 1 year and 2 years after operation, as well as ACL healing of the affected knee at 2 years after operation, were observed and compared between the 2 groups. The graft synovial coverage was evaluated by secondary arthroscopy in some cases.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (38.5±8.4) months. No surgical site infection or knee stiffness occurred in the 2 groups after operation, and 2 patients in each group developed intermuscular venous thrombosis at a lower limb. There was no significant difference in operation time between the 2 groups ( P>0.05). There were significant differences in Tenger score [(6.3±1.6) points versus (4.7±1.7) points], Lysholm score [(93.4±4.2) points versus (85.9±4.3) points] and IKDC subjective score [(89.1±2.9) points versus (81.2±2.9) points] between group A and group B at 1 year after operation ( P<0.05), but there was no significant difference in Tenger score, Lysholm score or IKDC subjective score between the 2 groups at 2 years after operation ( P>0.05). There was no significant difference in side-to-side difference in relaxation between the 2 groups at 1 year or 2 years after operation ( P>0.05). MRI evaluation at 2 years after operation showed no recurrent rupture or no sign of impingement between the graft and the intercondylar fossa in either group. Conventional secondary arthroscopy for 2 patients in group A and 3 patients in group B revealed better synovial coverage in group A. Conclusion:In the treatment of ACL tears of MSTL types I and II, compared with conventional reconstruction to clean the synovial sheath of ACL, autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture can lead to better functional recovery at 1 year after operation, though there is no significant difference in function at 2 years after operation.
3.Mechanisms of Mycobacterium tuberculosis-induced primary cilia degra-dation in monocytes-macrophages and promotion of osteoclast differentia-tion
Chengran ZHANG ; Qianfei LIU ; Nanjun XIONG ; Junbao CHEN ; Qile GAO ; Mingxing TANG ; Shaohua LIU
Chinese Journal of Infection Control 2025;24(9):1208-1214
Objective To explore the effect of Mycobacterium tuberculosis infection on the primary cilia of mono-cytse-macrophages and its potential mechanisms of promoting osteoclast differentiation.Methods Bone marrow-de-rived mononuclear cells(BMMCs)isolated from patients in control group and spinal tuberculosis group(TB group)were performed in vitro culture,and then cultured with Mycobacterium tuberculosis,infection model(Rv group)was constructed.Changes in cilia were observed by fluorescence staining and scanning electron microscopy tech-nique,a mouse spinal TB model was constructed for validating.Results Compared with the control group,the ex-pression of primary cili markers in the lesion of bone tissue of patients in TB group decreased significantly;After co-culturing with Mycobacterium tuberculosis,the ratio(48.56%±7.77%vs 9.58%±5.59%)and length(4.050[3.289,4.666]μm vs 0[0,0.676]μm)of primary cilia of monocytes-macrophages in the Rv group decreased sig-nificantly;The infiltration of osteoclasts in the bone marrow cavity of spinal TB mice was obvious,and the propor-tion and length of primary cilia decreased significantly.Conclusion Intracellular infection of Mycobacterium tuberculosis can induce degradation of primary cilia in monocytes-macrophages,promote osteoclast differentiation,and exacerbate vertebral bone resorption.
4.Autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture for anterior cruciate ligament tears
Ming TANG ; Qingsong ZHANG ; Hanqi WANG ; Huawei WEN ; Yushun FANG ; Ya'nan LI ; Shaohua ZHANG ; Du XIE
Chinese Journal of Orthopaedic Trauma 2025;27(5):417-424
Objective:To investigate the clinical effectiveness of autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture in the treatment of anterior cruciate ligament (ACL) tears.Methods:A retrospective study was conducted to analyze the clinical data of 38 patients with ACL tear who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan from January 2016 to July 2020. There were 30 males and 8 females, with an age of (25.4±7.2) years. By the typing of MRI Sherman tear locations (MSTL) for anterior cruciate ligament, 7 cases were Type I and 31 cases type II. A total of 18 patients underwent single bundle reconstruction of autologous hamstring tendon combined with remnant suture (group A), and the other 20 patients underwent conventional reconstruction to clean the synovial sheath of ACL (group B). The operation time,Tenger scores, Lysholm scores, International Knee Documentation Committee (IKDC) subjective score and side-to-side differences in relaxation at pre- operation, 1 year and 2 years after operation, as well as ACL healing of the affected knee at 2 years after operation, were observed and compared between the 2 groups. The graft synovial coverage was evaluated by secondary arthroscopy in some cases.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (38.5±8.4) months. No surgical site infection or knee stiffness occurred in the 2 groups after operation, and 2 patients in each group developed intermuscular venous thrombosis at a lower limb. There was no significant difference in operation time between the 2 groups ( P>0.05). There were significant differences in Tenger score [(6.3±1.6) points versus (4.7±1.7) points], Lysholm score [(93.4±4.2) points versus (85.9±4.3) points] and IKDC subjective score [(89.1±2.9) points versus (81.2±2.9) points] between group A and group B at 1 year after operation ( P<0.05), but there was no significant difference in Tenger score, Lysholm score or IKDC subjective score between the 2 groups at 2 years after operation ( P>0.05). There was no significant difference in side-to-side difference in relaxation between the 2 groups at 1 year or 2 years after operation ( P>0.05). MRI evaluation at 2 years after operation showed no recurrent rupture or no sign of impingement between the graft and the intercondylar fossa in either group. Conventional secondary arthroscopy for 2 patients in group A and 3 patients in group B revealed better synovial coverage in group A. Conclusion:In the treatment of ACL tears of MSTL types I and II, compared with conventional reconstruction to clean the synovial sheath of ACL, autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture can lead to better functional recovery at 1 year after operation, though there is no significant difference in function at 2 years after operation.
5.Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction
Juan YAO ; Rui DING ; Xiangyang LI ; Tongjuan TANG ; Wanwan WU ; Kedong WEI ; Shaohua XU ; Liang WANG ; Peng ZHOU ; Jinling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):1-9
ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3(Sirt3)/adenosine monophosphate dependent protein kinase (AMPK) signaling pathway in chronic heart failure (CHF) rats after myocardial infarction (MI). MethodSD rats randomly divide into sham operation group (normal saline ,thread only without ligature), model group (normal saline, ligation of the left anterior descending coronary artery proximal to the heart), Linggui Zhugantang group (4.8 g·kg-1) and Captopril group (0.002 57 g·kg-1), with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin (HE) staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species (ROS). JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate (ATP), superoxide dismutase (SOD), malondialdehyde (MDA), mitochondrial respiratory chain complex activity (Ⅰ-Ⅳ). TdT-mediated dUTP nick end labeling (TUNEL) staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3, phosphorylated AMPK (p-AMPK), phosphorylated dynamic-related protein 1(p-Drp1), mitochondrial fission protein 1(Fis1), mitochondrial fission factor (MFF), optic atrophy protein 1(OPA1). ResultCompared to the sham group, the left ventricular end diastolic diameter (LVIDd) and left ventricular end systolic diameter (LVIDs) were significantly increased in model group (P<0.01), while the left ventricular short axis shortening rate (LVFS) and left ventricular ejection fraction (LVEF) were significantly decreased (P<0.01). There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS, MDA levels and myocardial cell apoptosis rate were significantly increased (P<0.01), SOD level, ATP content, and membrane potential were significantly decreased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) was significantly decreased (P<0.01). Levels of p-Drp1, Fis1, MFF proteins were significantly up-regulated (P<0.01), while Sirt3, p-AMPK, OPA1 proteins level were significantly down-regulated (P<0.01). Compared with model group, LVIDd and LVIDs were significantly decreased (P<0.01), LVEF and LVFS were significantly increased (P<0.01). Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS, MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group (P<0.01), SOD level, ATP content, and membrane potential significantly increased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) increased significantly (P<0.01),and p-Drp1, Fis1, MFF protein levels were significantly down-regulated (P<0.01), Sirt3, p-AMPK, OPA1 protein were significantly up-regulated (P<0.01). ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells, maintain mitochondrial function stability, and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
6.Logistic regression analysis and risk model construction of choroidopathy sec-ondary to high myopia
Recent Advances in Ophthalmology 2024;44(1):52-57
Objective To analyze the influencing factors of choroidopathy(choroidal atrophy and choroidal neovas-cularization)secondary to high myopia based on Logistic regression analysis and to construct a Nomogram risk prediction model based on the related factors,so as to provide guidance for clinical treatment.Methods A total of 340 patients(680 eyes)with high myopia admitted to Beijing Jishuitan Hospital from January 2021 to January 2023 were selected and di-vided into group A(170 patients,340 eyes)and group B(170 patients,340 eyes).The incidence of choroidopathy in the two groups was compared.The groups A and B were divided into two subgroups,subgroup a and subgroup b,according to whether choroidopathy occurred or not.Multivariate Logistic regression analysis was carried out to explore the influencing factors of choroidopathy secondary to high myopia.A Nomogram risk prediction model for choroidopathy secondary to high myopia was constructed based on the influencing factors and externally validated.Results In groups A and B,the age,proportion of diabetes mellitus,axial length,and level of seruim transforming growth factor β1(TGF-β1)of patients in subgroup a were higher than those in the subgroup b,and the diopter was lower than that in the subgroup b(all P<0.05).The Logistic regression analysis showed that age,diabetes mellitus,axial length and serum TGF-β1 level were independent risk factors for choroidopathy secondary to high myopia,and diopter was a protective factor(all P<0.05).Age,diabetes mellitus,axial length and serum TGF-β1 level were positively correlated risk factors for choroidopathy secondary to high myopia,and diopter was a negatively correlated risk factor(all P<0.05).The area under the curve of the Nomogram risk prediction model for predicting choroidopathy secondary to high myopia was 0.818,and the calibration was good.Con-clusion Age,diabetes mellitus,axial length,diopter and serum TGF-β1 level are the influential factors for choroidopa-thy secondary to high myopia.The Nomogram risk prediction model established based on these factors has a certain value for predicting choroidopathy secondary to high myopia.The clinical therapeutic schedules should be made based on this model to reduce the risk of secondary choroidopathy.
7.Fascia lata autograft bridging combined with long head of biceps tendon transposition for irreparable massive rotator cuff tear
Ming TANG ; Huawei WEN ; Shaohua ZHANG ; Yushun FANG ; Tao LI ; Yanan LI ; Qingsong ZHANG
Chinese Journal of Orthopaedics 2023;43(4):238-246
Objective:To investigate the early clinical effect of fascia lata autograft bridging combined with the long head of biceps tendon transposition for treatment of irreparable massive rotator cuff tear.Methods:All of 31 cases of massive irreparable rotator cuff tear treated in our hospital from March 2016 to March 2020 were analyzed retrospectively. Among them, 17 cases (10 males, 7 females) were repaired with fascia lata autograft bridging under arthroscopy (patch group), the average age was 61.47±6.63 (ranging from 51 to 72) and 14 cases (4 males, 10 females) were repaired with fascia lata autograft bridging combined with the long head of biceps tendon transposition (combined group), the average age was 62.57±6.11 (ranging from 53 to 71). The operation time, intraoperative blood loss, postoperative complications, visual analogue scale (VAS) of pain before operation, at 1 week and 12 months after operation, Constant-Murley score of shoulder joint and American Association of shoulder and elbow Surgeons (ASES) score before operation, at 6 months and 12 months after operation were compared between the two groups. The outcome of rotator cuff healing was evaluated by MRI 1 year after operation.Results:All patients were followed up for 12-27 months (mean 18.33 ±6.8 months). There was no perioperative complication, and there was no significant difference in operation time between the two groups ( P>0.05) . The VAS score in the patch group was significantly higher than the combined group 1 week after operation ( t=2.09, P=0.048) , and there was no significant difference in VAS score 12 months after operation between the two groups. Constant-Murley score and ASES score in the combined group were significantly higher than the patch group at 6 months after operation ( t=5.23, P<0.001; t=4.45, P<0.001) , and there was no significant difference in Constant score and ASES score between the two groups at 12 months after operation. Constant score and ASES score in the two groups were significantly higher than those before operation. One year after operation, the MRI of the affected shoulder showed that the incidence of autograft patch thinning (Sugaya grade III) was 52.94%, the autograft patch structure failure rate (Sugaya grade IV and V) was 17.65% in the patch group, the autograft patch thinning rate (Sugaya grade III) was 35.71%, and the structural failure rate (Sugaya grade IV and V) was 7.14% in the combined group. The difference was statistically significant (χ 2=7.12, P=0.028) . Conclusion:Fascia lata autograft patch bridging combined with long head of biceps tendon transposition technique for treatment of irreparable massive rotator cuff tear has less pain 1 week after operation and better recovery of shoulder function half a year after operation. MRI showed better patch healing 1 year after operation.
8.Study of 68Ga-NODAGA-RGD PET/CT in predicting short-term efficacy of tyrosine kinase inhibitor in the treatment of distant metastatic differentiated thyroid cancer
Jun WANG ; Jingjing FU ; Xiaowei TANG ; Xiaochen YAO ; Liang SHI ; Shaohua LI ; Feng WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(8):459-464
Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.
9.Analysis of the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis
Taiji XIE ; Ling GUO ; Ruoyan GONG ; Qianlong TANG ; Run XIANG ; Wei DAI ; Shaohua XIE ; Ke ZHOU ; Tianpeng XIE ; Qiang LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(10):1407-1414
Objective To analyze the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis. Methods Thymoma patients who received treatment in Sichuan Cancer Hospital from March 2015 to March 2021 were collected. Clinical data of the patients were analyzed using Kaplan-Meier and Cox regression analyses. Results A total of 177 patients were included. There were 89 males and 88 females aged 17-88 (52.3±13.0) years, including 160 surgical patients and 17 non-surgical patients. There were 160 patients survived, 17 died of thymoma, and 5 had recurrence and metastasis. Overall, the 1-year, 3-year and 5-year progression-free survival rates were 94.4%, 88.7%, 88.1%, respectively; the 1-year, 3-year and 5-year overall survival rates were 94.9%, 91.5%, 91.0%, respectively. The Kaplan-Meier analysis showed that World Health Organization classification, clinical symptoms, Masaoka-Koga staging, treatment methods and surgery were statistically associated with progression-free survival; clinical symptoms, age, treatment methods and surgery were statistically associated with overall survival (P<0.05). Patients with younger age (P=0.018), without clinical symptoms (P=0.039), and with surgical treatment (P=0.004) had higher overall survival rates; those patients undergoing surgery had a higher progression-free survival rate (P=0.002). Conclusion Age, clinical symptoms and surgical treatment are independent factors influencing the prognosis of patients with thymoma.
10.A randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients
Xiang ZHENG ; Weijie ZHANG ; Hua ZHOU ; Ronghua CAO ; Zhangfei SHOU ; Shuwei ZHANG ; Ying CHENG ; Xuchun CHEN ; Chenguang DING ; Zuofu TANG ; Ning LI ; Shaohua SHI ; Qiang ZHOU ; Qiuyuan CHEN ; Gang CHEN ; Zheng CHEN ; Peijun ZHOU ; Xiaopeng HU ; Xiaodong ZHANG ; Ning NA ; Wei WANG
Chinese Medical Journal 2022;135(13):1597-1603
Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

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