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.

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.

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.

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.

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.

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.

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.

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.

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.

Objective To investigate the clinical efficacy of three-stage Masquelet technique in the treatment of infective bone defects of foot and ankle.Methods A retrospective case series study was conducted on the clinical data of 19 patients with infective bone defects of foot and ankle admitted to Zhongnan Hospital of Wuhan University from December 2014 to October 2017.There were 15 males and four females,aged 18-68 years [(39.6 ± 12.3)years].Among the patients,16 patients were infected with bacteria and three patients were infected with Mycobacterium tuberculosis.The infection involved humeral end,talus and surrounding joints in 14 patients,internal hemorrhoids in two patients,midfoot and interphalangeal joints in one patient,and humerus and metatarsophalangeal joints in two.The operation included three stages:the first stage was thorough debridement,supplemented with negative pressure closed drainage (VSD) and continuous washing to clarify the pathogenic bacteria;the second stage was to fill the bone defect with targeted antibiotic bone cement to prevent or treat infection;in the third stage,after filling the antibiotic bone cement for 3 months with no sign of local wound infection,the bone cement was taken out,and the bone reconstruction operation was performed by means of internal fixation and bone grafting.The flap survival and wound healing were observed,and the time of fracture healing was recorded.The American Orthopaedic Foot and Ankle Society (AOFAS) score and the Visual Analogue Score (VAS) were used to evaluate the improvement of the function of the foot and ankle before operation and at the last follow-up,and the bone healing was evaluated according to the radiographic union scale in tibial (RUST) fractures.Results The patients were followed up for 9-12 months [(11.1 ±1.0) months].Two patients with soft tissue defects caused by preoperative infection and necrosis received posterior tibial artery perforator flap and anterolateral thigh flap repair in the second stage,and the flaps all survived.The postoperative bone healing time was 3 7 months [(3.5 ± 1.4)months].Nineteen patients underwent three-stage surgery,and the ankle and foot wound or sinus tract were all healed,with no infection recurrence during follow-up.At the last follow-up,the AOFAS score was improved significantly from preoperative (36.3 s-12.1) points to (71.4 ± 5.7) points (P ＜ 0.05).The VAS was decreased significantly from preoperative (5.3 ± 1.2) points to (1.4 ± 0.9) points (P ＜ 0.05).The RUST bone healing score at the last follow-up was 8-12 points [(10.2 ± 1.1) points].Conclusion In treating the infective bone defects of foot and ankle,the three-stage Masquelet technique can effectively control infection,facilitate wound healing,promote bone union,and improve foot and ankle function.