1.Expression of collagen and salvage treatment for recurrent esophageal squamous cell carcinoma after radical chemoradiotherapy
Ning LU ; Hangjia ZHU ; Zhen HUANG ; Jing WANG ; Wei SHI ; Yi GONG ; Hu QIU ; Shaobo KE ; Yongshun CHEN
Chinese Journal of Radiation Oncology 2024;33(7):614-619
Objective:To investigate the change of collagen fibers in locally recurrent esophageal squamous cell carcinoma after radical chemoradiotherapy and the discrepancy of adverse effects and survival outcomes among groups with different salvage treatments, provide references for the options of salvage therapy.Methods:Medical records of 137 patients with esophageal squamous cell carcinoma who received radical chemoradiotherapy and had local recurrence admitted to Cancer Center of Renmin Hospital of Wuhan University from January 2015 to September 2022 were retrospectively collected. The expression of collagen fibers in paraffin samples of cases with different recurrence time was determined by Masson staining, and the differences of the average optical density were calculated. According to the salvage treatment after local recurrence, all cases were divided into the salvage surgery group, second-course chemoradiotherapy group and immunochemotherapy group. The differences of survival outcomes and incidence rates of esophageal tracheal fistula, hemorrhage, pericardial effusion, radiation pneumonitis, radiation esophagitis were analyzed among the three groups. The differences of survival rates were analyzed by Kaplan-Meier method and compared by log-rank test among groups.Results:The expression of collagen fibers in recurrent esophageal squamous cell carcinoma was significantly higher than that in primary esophageal squamous cell carcinoma. Collagen fiber expression was gradually down-regulated with the prolongation of recurrence time. The expression of collagen fibers in recurrent cases after 7 years was similar to that of primary esophageal squamous cell carcinoma. The 1-, 2- and 3-year survival rates of patients in the salvage surgery group, the second-course chemoradiotherapy group and the immunochemotherapy group were 47%, 30%, 20%; 50%, 27%, 15% and 72.5%, 50%, 50%, respectively; Immunochemotherapy was more effective in salvage treatment for recurrent esophageal squamous cell carcinoma, but there was no statistical difference.Conclusions:Collagen fibers are abundant in recurrent esophageal squamous cell carcinoma after radical chemoradiotherapy. With prolongation of recurrent interval, the expression of collagen fibers is down-regulated. The survival outcomes of patients in the immunochemotherapy group, salvage surgery group and second-course chemoradiotherapy group were comparable.
2.Research on the Improvement of Ferroptosis and Cognitive Function Impairment in APP/PS1 Alzheimer's Mice by Bingchan-gsan via the Nrf2/HO-1 Signaling Pathway
Shaobo GUO ; Wenhui ZHU ; Yu BAI ; Biao ZHANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):598-607
OBJECTIVE To explore whether inhaling Bingchangsan(BCS can modulate the Nrf2/HO-1 signaling pathway to improve ferroptosis and cognitive dysfunction in Alzheimer's Disease(AD mouse models.METHODS 30 APP/PS1 mice were ran-domly divided into three groups:a model group(APP/PS1 group,a low-dose Bingchangsan group(BCS-L group,and a high-dose Bingchangsan group(BCS-H group.10 age-matched wild-type(WT mice were used as a control group.The WT group and the APP/PS1 group were treated with nebulized pure water,while the BCS-L group received 0.5μL of Bingchangsan inhalation solution per day,and the BCS-H group received 1μL,both administered via nebulization for 10 min daily for 2 weeks.2 weeks post-treat-ment,spatial cognitive abilities of the mice were assessed using the Morris water maze test.Following the water maze experiment,the mice were euthanized,and their brain tissues were collected for Aβ1-42 immunofluorescence,P-tau immunohistochemistry,and Nissl staining.Hippocampal tissues were extracted for Western blot and qPCR analysis to measure the protein and mRNA expression levels of Keap1,Nrf2,HO-1,GPX4,SCL7A11,TFRC,DMT1,FTL,and FTH1.Additionally,brain tissues were used for glutathione(GSH content measurement using a GSH assay kit.RESULTS In the BCS groups,the latency period for escape shortened,and the time spent in the quadrant with the platform,as well as the number of times crossing the platform,increased.Compared to the APP/PS1 group,the expression levels of Aβ1-42 and P-tau in the hippocampal CA1 region and cortex of mice in the BCS groups were signifi-cantly reduced(P<0.05,P<0.01.Nissl staining revealed a denser arrangement of neurons with more Nissl bodies in the BCS groups.In the hippocampal tissue,compared to untreated APP/PS1 mice,significant increases in the protein and mRNA levels of Nrf2,HO-1,SLC7A11,GPX4,and FTL were observed in all BCS groups(P<0.05,P<0.01.While the BCS-L group showed in-creased levels of FTH1 protein and mRNA,these changes were not statistically significant.Furthermore,the expression levels of TFRC,DMT1,and Keap1 were significantly downregulated in the BCS groups(P<0.05,P<0.01.Additionally,treatment with BCS effectively restored the glutathione(GSH content in the brain(P<0.01.CONCLUSION Inhalation of BCS can improve cognitive dysfunction in APP/PS1 mice.BCS activates the Nrf2/HO-1 pathway,increases the expression of GPX4,and enhances Nrf2 tran-scriptional activity by inhibiting Keap1.This leads to an upregulation of SLC7A11 and restoration of GSH levels,effectively countering ferroptosis.Additionally,BCS effectively inhibits TFRC and DMT1,while upregulating FTL and FTH1 expression,thereby maintaining intracellular iron homeostasis.This contributes to mitigating the impact of ferroptosis on APP/PS1 mice,subsequently enhancing their cognitive functions.
3.Three fixation methods in the revision of medial defective intertrochanteric fractures with failed treatment: a finite element analysis
Lin QI ; Wei ZHANG ; Zhengguo ZHU ; Shaobo NIE ; Jiaqi LI ; Hua CHEN ; Peifu TANG
Chinese Journal of Orthopaedics 2023;43(5):308-315
Objective:To compare the biomechanical differences of dynamic condylar screw (DCS), locking compression plate (LCP) combined with DCS and medial anatomic buttress plate (MABP) combined with DCS in the revision of medial defective intertrochanteric fractures by finite element analysis.Methods:The femoral CT imaging data provided by a healthy adult volunteer were used to reconstruct the solid three-dimensional model of femur by Mimics 21.0 and Geomagics Studio 12. Evans-Jensen II B intertrochanteric fracture was established by Ansys Workbench18.0. The three-dimensional models of proximal femoral nail antirotation (PFNA), DCS, LCP and MABP were reconstructed in Solidworks 2015. The PFNA was assembled with the fracture model, and then the PFNA was removed to establish the postoperative failure model of femoral intertrochanteric fracture and then simulated the fixation in the hip-preserving revision surgery of femoral intertrochanteric fractures: non-medial support reconstruction group (DCS); indirect medial support reconstruction group (DCS+LCP) and partial direct medial support reconstruction group (DCS+MABP). Finally, the forces on the hip joint of 70 kg normal people during standing (700 N), slow walking (1,400 N), brisk walking (1,750 N) and going up and down stairs (2,100 N) were simulated in Abaqus 6.14, the relative displacement and stress peak value of fracture end and stress distribution and stress peak value of internal fixation in different models were recorded.Results:At 700 N axial load, the relative displacement of fracture end fixed by DCS, DCS+LCP and DCS+MABP was 0.28, 0.13 and 0.09 mm; the peak stress of the fracture end was 49.01, 15.29 and 1.35 MPa; the peak stress of internal fixation was 230, 220 and 174 MPa, respectively. At 1,400 N axial load, the relative displacement of the fracture end of the three internal fixation methods was 0.56, 0.24 and 0.16 mm; the peak stress of fracture end was 108.49, 28.96 and 3.12 MPa; the peak stress of internal fixation was 469, 352 and 324 MPa, respectively. At 1,750 N axial load, the relative displacement of the fracture end of the three group was 0.70, 0.30 and 0.20 mm; the peak stress of the fracture end was 139.59, 37.57 and 4.17 MPa; the peak stress of internal fixation was 594, 421 and 393 MPa, respectively. At 2,100 N axial load, the relative displacement of the fracture end of the three internal fixation methods was 0.85, 0.35 and 0.23 mm; the peak stress of the fracture end was 170.05, 46.36 and 5.24 MPa; the peak stress of internal fixation was 724, 504 and 460 MPa, respectively.Conclusion:The partial direct reconstruction of medial support under the neck by DCS+MABP may have better biomechanical properties in the revision of medial defective intertrochanteric fractures.
4.Analysis on the Selection of Acupoints and the Application of Manipulation in the Treatment of Diabetes Peripheral Neuropathy with Tuina
Huixin YAN ; Hongyi GUAN ; Jiabao SUN ; Shaobo ZHANG ; Haiyu ZHU ; Xingquan WU ; Bailin SONG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):2942-2949
Objective To explore the rules of acupoint selection and manipulation application of Tuina in the treatment of diabetes peripheral neuropathy(DPN)with data mining technology.Methods The clinical research literature of Tuina for DPN from October 2022 was selected by searching four Chinese databases that CNKI,WanFang,VIP and Chinese Biomedical Literature Database.Using the traditional Chinese medicine inheritance assistance platform software,analyze and summarize the rules of selecting acupoints and applying manipulations in the treatment of DPN with Tuina.Results A total of 110 articles were included,including 65 acupoints and 33 manipulations.The acupoints with the highest frequency are Zusanli(ST 36),Sanyinjiao(SP 6),Taixi(KI 3),Yongquan(KI 1),Taichong(LR 3),Yanglingquan(GB 34),etc.The meridians mainly include Taiyin Spleen Meridian of Foot,Yangming Stomach Meridian of Foot,Taiyang Bladder Meridian of Foot and Shaoyin Kidney Meridian of Foot.Five-shu Points,Lower He-sea Points and Yuan-primary Points are commonly used specific points.The acupoints are mostly distributed in the lower limbs.The categories of Tuina manipulations mainly include squeezing-pressing manipulations,pushing rolling manipulations and composite manipulations.The Tuina manipulations mainly include kneading manipulation,pressing manipulation,point-pressing manipulation,pressing-kneading manipulation and twisting manipulation with both palms.Conclusion The acupoint selection and manipulation application of Tuina in treating DPN have certain rules,and the main treatment principles are to regulate the organs and dredge collaterals,and to replenish qi and promote blood circulation,which can provide objective basis for clinical treatment.
5.Efficacy of surgical management for esophageal squamous cell carcinoma in pathological stage T1b
Duojie ZHU ; Cheng WANG ; Xiaoping WEI ; Jianbao YANG ; Yuqi MENG ; Tieniu SONG ; Shaobo ZHANG ; Haiming FENG ; Tao JING ; Peng JIANG ; Bin LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(06):696-700
Objective To investigate the prognostic survival status and influence factors for surgical treatment of esophageal squamous cell carcinoma (ESCC) in pathological stage T1b (pT1b). Methods The patients with ESCC in pT1b undergoing Ivor-Lewis or McKeown esophagectomy in Lanzhou University Second Hospital from 2012 to 2015 were collected, including 78 males (78.3%) and 17 females (21.7%) with an average age of 61.4±7.4 years. Results The most common postoperative complications were pneumonia (15.8%), anastomotic leakage (12.6%) and arrhythmia (8.4%). Ninety-three (97.9%) patients underwent R0 resection, with an average number of lymph node dissections of 14.4±5.6. The rate of lymph node metastasis was 22.1%, and the incidence of lymph vessel invasion was 13.7%. The median follow-up time was 60.4 months, during which 25 patients died and 27 patients relapsed. The overall survival rate at 3 years was 86.3%, and at 5 years was 72.7%. Multivariate Cox regression analysis showed that lymph node metastasis (P=0.012, HR=2.60, 95%CI 1.23-5.50) and lympovascular invasion (P=0.014, HR=2.73, 95%CI 1.22-6.09) were independent risk factors for overall survival of pT1b ESCC. Conclusion Esophagectomy via right chest approach combined with two-fields lymphadenectomy is safe and feasible for patients with pT1b ESCC. The progress of pT1b ESCC with lymph node metastasis or lymphovascular invasion is relatively poor.
6.Radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET in patients with hepatobiliary tumor
Haiqun XING ; Wenjia ZHU ; Chengyan DONG ; Jingnan WANG ; Ximin SHI ; Meiqi WU ; Shaobo YAO ; Fang LI ; Li HUO
Chinese Journal of Radiological Medicine and Protection 2021;41(4):293-298
Objective:To investigate the radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET/CT in patients with hepatobiliary tumor. Methods:A total of six patients with hepatic lesions who underwent PET/CT examination in Peking Union Medical College Hospital were enrolled. After intravenous injection of radiotracer 68Ga-FAPI-04 at (170.57 ± 14.43) MBq, whole-body imaging were performed at the time points of 3, 10, 15, 20, 30 and 60 min, respectively. Biodistribution pattern was observed. Regions of interest were manually delineated. Radiation dosimetry of all target organs were calculated by Olinda/EXM software. Results:The radioactive uptake dissipated gradually in liver whereas it was relatively stable in tumor lesions. The average SUV max of tumor lesions reached the maximum value (13.87± 2.55) at 20 min after injection. The target-to-background ratio increased with time, reaching the maximum value (10.09 ± 8.17) at 30 min after injection. The average effective dose in total body was (0.020 ± 0.002) mSv/MBq and organ with the highest effective dose was bladder wall at (0.146 ± 0.035) mSv/MBq. Conclusions:The effective dose in total body of 68Ga-FAPI-04 was similar to that of 18F-FDG. 68Ga-FAPI-04 is expected to be a PET/CT radiotracer for hepatobiliary tumors in consideration of rapid tumor uptake, low accumulation of liver background, and no influence of blood sugar levels.
7.Preclinical and clinical translation research of 68Ga-labeled fibroblast activation protein inhibitor for PET imaging
Haiqun XING ; Ximin SHI ; Chengyan DONG ; Xuezhu WANG ; Xiaona JIN ; Yonghong DANG ; Wenjia ZHU ; Shaobo YAO ; Fang LI ; Li HUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(8):480-485
Objective:To prepare 68Ga-fibroblast activation protein inhibitor (FAPI)-04, and evaluate its biodistribution and imaging characteristics in animals and healthy volunteers, in order to investigate the clinical translation potential. Methods:68Ga-FAPI-04 was synthesized by a manual method and its radiolabeling yield, radiochemical purity, and stability ( in vivo and in vitro) were analyzed. ICR mice ( n=16) were scarified at 5, 30, 60 and 120 min postinjection of 68Ga-FAPI-04 (1.11 MBq) to measure radioactive counts in main organs. The dynamic mircoPET imaging was acquired for 60 min on 3 ICR mice, and tumor imaging capabilities were examined with nude mice bearing HepG2 tumors. Furthermore, 2 healthy volunteers (1 male with age of 64 years, 1 female with age of 56 years) were recruited for the investigation of probe biodistribution in humans. A serial whole-body dynamic PET/CT scan was performed immediately following injection. Results:68Ga-FAPI-04 was synthesized within 20 min with the radiochemical yield of (68.7±4.0)% (decay corrected). The radiochemical purities of 68Ga-FAPI-04 were over 99% and the products were stable for 180 min in vitro and for 90 min in blood. 68Ga-FAPI-04 was mainly cleared through urinary tracts, while other organs only showed mild tracer accumulation. MicroPET imaging showed high uptake of 68Ga-FAPI-04 in the tumor tissue of mice, and the ratio of tumor/liver was 2.14±0.01 (35 min). The PET/CT imaging results of healthy volunteers revealed 68Ga-FAPI-04 could be quickly cleared. Conclusion:68Ga-FAPI-04 has many advantages for PET imaging, such as easy labeling, good stability, quick clearance and low background signals in the liver, which can be used as an attractive PET tracer for detection hepatocellular carcinoma.
8.Study on the application of artificial intelligence system in the detection and differentiation of benign and malignant pulmonary nodules
Ci YIN ; Wenjie MAO ; Bin LI ; Cheng WANG ; Peng JIANG ; Duojie ZHU ; Jianbao YANG ; Yuqi MENG ; Xiaoping WEI ; Tao JING ; Haiming FENG ; Shaobo ZHANG ; Junping LIN
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(9):553-556
Objective:To evaluate the efficacy of artificial intelligence assisted pulmonary nodule diagnosis system in detection pulmonary nodule and predicting the malignant probability of pulmonary nodule.Methods:A retrospectively analyze the clinical data of 199 patients with lung nodules in the Thoracic Surgery Department of Lanzhou University Second Hospital from May 2016 to July 2020. The preoperative chest CT was imported into the artificial intelligence system to record the detected lung nodules, to measure nodal diameter and density classification and malignant probability prediction value of each nodule. The detection rate of pulmonary nodules by artificial intelligence system was calculated, and the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of artificial intelligence system in the differential diagnosis of benign and malignant pulmonary nodules were calculated and compared with manual film reading. and the sensitivity and specificity in the differential diagnosis of benign and malignant pulmonary nodules under the condition of different size and density of pulmonary nodules.Results:A total of 204 pulmonary nodules were pathologically diagnosed by surgical resection, and the detection rate of pulmonary nodules by artificial intelligence system was 100%. The artificial intelligence system can distinguish benign and malignant pulmonary nodules with a sensitivity of 95.83%(95% CI: 0.8967-0.9883), specificity 25.00%(95% CI: 0.1717-0.3425), and a positive likelihood ratio of 1.27(95% CI: 1.14-1.44), negative likelihood ratio 0.17(95% CI: 0.06-0.46), Manual reading for the differentiation of benign and malignant pulmonary nodules has a sensitivity of 87.36%(95% CI: 0.7850-0.9352), specificity 72.17%(95% CI: 0.6214-0.8079), and a positive likelihood ratio of 3.14(95% CI: 2.26-4.37), the negative likelihood ratio is 0.18(95% CI: 0.10-0.31). 5mm≤diameter of pulmonary nodule<10 mm, sensitivity 100%(95% CI: 0.6637-1.0000), specificity 50.00%(95% CI: 0.01258-0.98740), 10 mm≤diameter of pulmonary nodule <20 mm, sensitivity 94.29%(95% CI: 0.8084-0.9930), specificity 29.83%(95% CI: 0.1843-0.4340), 20 mm≤ diameter of pulmonary nodule ≤30 mm, sensitivity 96.15%(95% CI: 0.8679-0.9953), specificity 18.37%(95% CI: 0.0876-0.9953), sensitivity of subsolid lung nodules: 100%(95% CI: 0.9051-1.0000), specificity 20.00%(95% CI: 0.0051-0.7164), solid lung nodule sensitivity 93.22%(95% CI: 0.8354-0.9812), specificity 25.24%(95% CI: 0.1720-0.3476). Conclusion:The artificial intelligence assistant diagnosis system of pulmonary nodules has a strong performance in the detection of pulmonary nodules, but it can not meet the clinical requirements in the differentiation of benign and malignant pulmonary nodules. At present, the artificial intelligence system can be used as an auxiliary tool for doctors to detect pulmonary nodules and assist in the diagnosis of benign and malignant pulmonary nodules.
9.One-stage repair of ankle fracture combined with grade Ⅲ injury to lateral ligament
Li YU ; Bing WANG ; Zhe XIE ; Linglong DENG ; Chong ZHANG ; Chi WEI ; Kai DENG ; Guorong YU ; Shaobo ZHU
Chinese Journal of Orthopaedic Trauma 2019;21(7):581-585
Objective To investigate the surgical outcomes of one-stage repair of the ankle fracture combined with grade Ⅲ injury to the lateral ligament.Methods From April 2015 to December 2017,23 patients with ankle fracture and lateral ligament injury were treated at Department of Traumatic Reconstruction Surgery/Foot and Ankle Surgery,Zhongnan Hospital.There were 15 males and 8 females,aged from 18 to 65 years (average,37.8 years).After intraoperative treatment of their fractures,22 ruptures of the ligamentous insertion were repaired with suture anchor and one rupture of the middle ligament with Internal Brace.Routine postoperative X-rays,physical examination and Sefton grading system were used to evaluate the stability of the ankle joint and the subtalar joint.The Karlsson-Peterson and American Orthopedic Foot and Ankle Society (AOFAS) scores were used to evaluate the function and pain of the ankle.Results The follow-up for this cohort ranged from 12 to 24 months (average,13.9 months).The bone union time ranged from 6 to 24 weeks,averaging 10.1 weeks.There was no chronic instability of lateral ankle or subtalar joint in all the cases.Two cases developed osteochondral lesion of the medial talus which was treated with micro-fracture surgery one year after injury;one case suffered subtalar arthritis which was treated by subtalar arthrodesis 14 months after injury.Their Karlsson-Peterson scores averaged 84.6 points and AOFAS ankle-hindfoot scores 93.7 points with 19 excellent and 4 good cases.The Sefton grading system gave 9 cases of grade Ⅰ and 14 ones of grade Ⅱ.Conclusion One-stage repair of the ankle fracture combined with grade Ⅲ injury to the lateral ligament can lead to the stability of the ankle joint and the subtalar joint and improved function of the ankle.
10.Application of muscular flap and induced membrane technique in the emergency treatment for limb salvage for Gustilo type Ⅲ B and Ⅲ C open fracture of lower leg
Li YU ; Yong ZHAO ; Zhe XIE ; Bing WANG ; Ling-Long DENG ; Chi WEI ; Kai DENG ; Guorong YU ; Shaobo ZHU
Chinese Journal of Microsurgery 2018;41(6):538-543
Objective To investigate the clinical effectivity of the muscular flap transposition and induced membrane technique in the emergency treatment for the limb salvage of Gustilo type Ⅲ B/C open fracture of lower leg. Methods From July, 2015 to December, 2017, 10 cases of Gustilo type Ⅲ B/C fracture of lower leg with bone defects were performed limb salvage surgery. Induced membrane technique was used to fill the bone defects in the emergency room.The gastrocnemius and/or soleus muscular flaps were transposed to cover the bone cement or ex-posed bone simultaneously in emergence treatment. After the wound healed completely, traditional bone grafting was used to repair the bone defects. There were 4 cases of Gustilo type Ⅲ B and 6 cases of Gustilo type Ⅲ C. The aver-age length of bone defect was (5.25±1.70) cm ranging from 3.0 cm to 11.0 cm. The gastrocnemius medial head flaps were performed in 5 cases, the combined application with the gastrocnemius medial head flaps and the medial hemimuscular flaps of soleus were performed in 2 cases, and medial hemimuscular flaps of soleus were transposed in 3 cases. Results The wounds in 6 cases were healed at one stage, but 2 cases healed by dressing because the exudate after skin grafting.In 1 case, the cross-leg flap was used to cover the exposed bone cement due to the necro-sis of soleus flap. The other 1 was performed the transposition of the lateral gastrocnemius flaps because the exposure of bone cement after the necrosis of the upper and lateral muscles in lower leg. In the second-stage, the bone defects were reconstructed by traditional bone grafting. The average healed time of bone was 7.2 months ranging from 5 months to 9 months. At the last followed-up time, all patients recovered their function of weight-bearing. The Paley's score of the adjacent joints: excellent in 8 cases and good in 2 cases. Conclusion The combination with induced membrane technique and local muscular flap transposition in emergency surgery is an effective method to limb salvage for the Gustilo type Ⅲ B/C open fracture of lower leg.

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