1.Ilizarov bone transport combined with antibiotic bone cement promotes junction healing of large tibial bone defect
Zhibo ZHANG ; Zhaolin WANG ; Zhigang WANG ; Peng LI ; Jianhao JIANG ; Kai ZHANG ; Shuye YANG ; Gangqiang DU
Chinese Journal of Tissue Engineering Research 2025;29(10):2038-2043
BACKGROUND:Ilizarov bone transport is very effective in the treatment of open large tibial bone defects,but there are still complications,among which the difficulty of junction healing is one of the difficult points in treatment. OBJECTIVE:To investigate the effect of Ilizarov bone transport combined with antibiotic bone cement on junction healing after operation of open large tibial bone defect. METHODS:Totally 51 patients with open large tibial bone defect(bone defect>4 cm)admitted to Binzhou Medical University Hospital from August 2010 to January 2022 were selected,of which 28 received Ilizarov bone transport alone(control group)and 23 received Ilizarov bone transport combined with antibiotic bone cement treatment(trial group).External fixation time,bone healing time,bone healing index,visual analog scale score during bone removal,bone defect limb function,junction healing and complications at the final follow-up were statistically compared between the two groups. RESULTS AND CONCLUSION:(1)All the 51 patients were followed up for a mean of(22.53±5.77)months.External fixation time,bone healing time,bone healing index,postoperative infection rate,and non-healing rate of junction were less in the trial group than those in the control group(P<0.05).There was no significant difference between the two groups in visual analog scale scores at 6 months after the second surgery and in the functional excellence and good rate of limb with bone defect at the final follow-up(P>0.05).(2)These findings indicate that compared with the Ilizarov bone transport alone,Ilizarov bone transport combined with antibiotic bone cement treatment can promote the healing of open tibial fracture junction and increase the rate of bone healing.
2.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
3.In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum
Leijia CHEN ; Mengyi CUI ; Xiangyu SONG ; Kai WANG ; Zhibo JIA ; Liupu YANG ; Yanghui DONG ; Haochen ZUO ; Jiaxiang DU ; Dengke PAN ; Wenjing XU ; Hongbo REN ; Yaqun ZHAO ; Jiang PENG
Organ Transplantation 2024;15(3):415-421
Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.
4.Value of dual-layer detector spectral CT quantitative parameters in evaluating treatment response of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer
Wenjing YUAN ; Zhiqing HUANG ; Ziqi JIA ; Hanliang ZHANG ; Jianye LU ; Xiaohua DU ; Zhibo WEN ; Xian LIU ; Weicui CHEN
Chinese Journal of Radiology 2024;58(2):194-200
Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.
5.Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation
Shujun YANG ; Hao WEI ; Yong XU ; Heng'en WANG ; Xiangyu SONG ; Zhibo JIA ; Jiang PENG ; Mengyi CUI ; Boyao YANG ; Leijia CHEN ; Aitao GUO ; Xiaoli ZHANG ; Dengke PAN ; Jiaxiang DU ; Panfeng SHANG ; Shengkun SUN
Organ Transplantation 2023;14(4):521-
Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.
6.Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia.
Sisi DU ; Xiaojing WU ; Binbin LI ; Yimin WANG ; Lianhan SHANG ; Xu HUANG ; Yudi XIA ; Donghao YU ; Naicong LU ; Zhibo LIU ; Chunlei WANG ; Xinmeng LIU ; Zhujia XIONG ; Xiaohui ZOU ; Binghuai LU ; Yingmei LIU ; Qingyuan ZHAN ; Bin CAO
Frontiers of Medicine 2022;16(3):389-402
Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2 = 0.033; P = 0.018), followed by acute kidney injury (AKI; R2 = 0.032; P = 0.011) and plasma MIP-1β level (R2 = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications*
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Bacteria/classification*
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Chemokine CCL4/blood*
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Community-Acquired Infections/microbiology*
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Humans
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Lung
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Microbiota/genetics*
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Pneumonia, Bacterial/diagnosis*
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Prognosis
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RNA, Ribosomal, 16S/genetics*
7.Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China.
Zhiqiang WANG ; Zhibo ZHANG ; Yong LI ; Li SUN ; Dezhen PENG ; Danyu DU ; Xian ZHANG ; Luwei HAN ; Liwen ZHAO ; Ligong LU ; Hongzhi DU ; Shengtao YUAN ; Meixiao ZHAN
Acta Pharmaceutica Sinica B 2021;11(6):1526-1540
Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.
8.Comparative experiment study of two kinds of methods for establishing SD rat chloasma model
Zhibo DENG ; Shiyi HE ; Qianli WANG ; Yuntao LI ; Qiaoli HU ; Yonghong DU
Chongqing Medicine 2018;47(15):1993-1996
Objective To comparatively analyze the SD rat chloasma model established by using the two methods of progesterone injection and ultraviolet radiation.Methods The rat chloasma model was established by adopting the high and low doses of progesterone injection and ultraviolet irradiation.The plaque area was observed and the skin section was observed by light microscope.The SOD and MDA levels closely related with chloasma melanin deposition were detected.Results The significant pigment deposition on the back skin in the high dose progesterone group was seen by naked eye and the scattered pigment deposition was seen in the low dose progesterone group;significant pigment deposition could be found in the ultraviolet group.Compared with the control group,the MDA level of various tissues in the high dose progesterone group was increased,while the SOD level was decreased,serum and skin SOD level in the low dose progesterone group was decreased,the difference was statistically significant(P<0.05).Serum and skin SOD level in the high dose ultraviolet group was decreased,while the MDA level was increased,the skin SOD level in the low dose ultraviolet group was decreased(P<0.05),but the difference between the two groups was not statistically significant (P>0.05).The melanin grains were heaped up as the small black body under light microscope,which in the progesterone group showed the clutter distribution,the difference between the high dose group and low dose group was significant;which in the ultraviolet group showed the linear dense arrangement and the intergroup had no significant difference.Conclusion Progesterone injection and ultraviolet irradiation all can successfully establish the SD rat chloasma model,and the constructing model effect and stability of ultraviolet irradiation are better.
9.Characteristic prenatal MRI signs in diagnosis of placenta accreta
Jinchao DU ; Furong LYU ; Zhibo XIAO ; Bo SHENG ; Fajin LYU ; Ziyu LIU
Chinese Journal of Medical Imaging Technology 2018;34(3):412-415
Objective To explore the value of prenatal MRI signs in diagnosis of placenta accreta.Methods MRI data of 163 pregnant women with suspected placenta accreta were retrospectively reviewed.According to the results of cesarean section,they were divided into placenta accreta group (n =136) or without placenta accreta group (n =27).The differencesof MRI signs between the two groups were compared.Taking cesarean section results as the gold standard,the sensitivity,specificity,positive and negative predictive value of MRI signs were calculated,respectively.Results Uterine bulging,abnormal vessels and hypointense T2WI bands at junction of placental and myometrium,as well as uterine recess had statistical differences between the two groups (all P<0.05).No statistical difference of placental heterogeneity,focal interruptions in myometrial wall,uterine penetration and parametrium implantation nor protrusion of placenta into cervix was found between the two groups (all P>0.05).The MRI signs of uterine penetration and parametrium implantation,uterine recess,protrusion of placenta into cervix yielded a specificity and positive predictive value of 100%,respectively.Conclusion Prenatal MRI has high efficacy in the diagnosis of placenta accrete.Placenta accrete should be highly suspected especially in the presence of uterine penetration and parametrium implantation,uterine recess and protrusion of placenta into the cervix.
10.Diagnostic value of fast imaging employing steady state acquisition and single shot fast spin echo sequences in diagnosis of normal fetal thymuses: Comparative study
Jinchao DU ; Zhibo XIAO ; Furong LYU ; Bo SHENG ; Fajin LYU ; Ziyu LIU
Chinese Journal of Medical Imaging Technology 2017;33(10):1526-1530
Objective To compare the diagnostic value of MR examination with fast imaging employing steady state acquisition (FIESTA) and single shot fast spin echo (SSFSE) sequences for normal fetal thymuses.Methods Totally 366 normal fetuses were examined using MRI with FIESTA and SSFSE sequences,and the anatomy and MR manifestations of thymuses were observed.Kappa analysis and x2 test were performed.The transverse area (TA) and transverse diameter (TD) were measured on the "three vessel" level,while the superoinferior diameter (SID) was measured on the sagittal level.The mean value of these parameters at different gestational were calculated,and the regression equations of each parameter and gestational age were fitted.Results Two doctors had good agreements with the images of FIESTA and SSFSE sequences (Kappa=0.745,0.802,both P<0.01).The clear rate of FIESTA and SSFSE sequences was 86.34% (632/732) and 37.70% (276/732) respectively,and the differences were significant (x2 =367.520,P<0.001).The thymic size increased with the gestational age,and the regression equations and correlation coefficients were:TA =-5.80 + 0.35 ×gestational (r=0.820,P<0.01),TD=-14.59+1.63×gestational (r=0.817,P<0.01),and SID=-9.63+1.44×gestational (r=0.778,P<0.01).Conclusion The subtle structure and contour of fetal thymus showed with FIESTA sequence are clearer than those of SSFSE sequence.MRI can clearly show fetal thymus after 22 weeks of pregnancy.

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