1.Distribution and drug resistance characteristics of Acinetobacter baumannii in the environment of a general hospital in Xuhui District of Shanghai from 2018 to 2023
Yan WANG ; Jing WANG ; Yuqing YAO ; Junjie ZHANG ; Zhiyao TENG ; Bingqing YAN ; Congcong ZHANG ; Lufang JIANG ; Liang TIAN
Shanghai Journal of Preventive Medicine 2025;37(6):476-483
ObjectiveTo analyze the distribution, drug resistance characteristics, and changing trends of Acinetobacter baumannii (AB) isolated from environmental surfaces and healthcare workers’ hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023, and to provide reference for infection control in the hospital. MethodsEnvironmental samples were collected quarterly from critical surfaces and healthcare workers’ hands in the intensive care unit (ICU), geriatrics, and respiratory departments from 2018 to 2023. Clinical isolates were obtained from all patients with AB infections in ICU, geriatrics, respiratory department, rehabilitation department, infectious diseases department, emergency department, cardiology department, and orthopedics of the hospital from 2018 to 2023. Retrospective analyses were performed on AB detection rates, strain origins, resistance rates to commonly used antimicrobial agents, and resistance gene features, comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains. ResultsFrom 2018 to 2023, a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected, with a positive detection rate of 19.21%. The detection rate gradually decreased year-on-year (χ2trend=45.290, P<0.001). The majority of samples originated from patient-contacted items (34.56%, 94/272), followed by shared items (26.84%, 73/272) and healthcare worker-contacted items (15.07%, 41/272). From 2018 to 2023, the resistance rate of AB on environmental surfaces and healthcare workers’ hands to commonly tested antibiotics in the hospital ranged from 10% to 40%. The resistance rates to cefotaxime (42.52%) and piperacillin (38.58%) were relative high, while the resistance to polymyxin E (1.57%), polymyxin B (2.36%), and doxycycline (3.94%) maintained low. The annual fluctuations in resistance to cefotaxime, piperacillin, ceftriaxone, tobramycin, doxycycline, minocycline and cotrimoxazole were statistically significant (all P<0.05). There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam, cefepime, ceftazidime, subamphetamine, meropenem, piperacillin, aztreonam, gentamicin, tobramycin, minocycline, ciprofloxacin, levofloxacin, and cotrimoxazole in the hospital from 2018 to 2023 (all P<0.05). The resistance rate of clinical isolates was generally high, especially to β-lactam and quinolone drugs, which were mostly above 80% [such as cefepime (93.86%), cefotaxime (97.37%), imipenem (98.25%), and ciprofloxacin (99.12%)]. The resistance rate of environmental isolated strains to similar antibiotics was relatively lower, mostly concentrated at 10%‒30%. The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps (51.97%), followed by changes in target sites (32.46%). Among the 34 CRAB strains, carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains (17.65%), while genes such as KPC, IMP, VIM, and SIM were not detected. ConclusionFrom 2018 to 2023, AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes, indicating a potential transmission risk. It is necessary to further strengthen bacterial resistance monitoring and hospital infection control, and use antibiotics reasonably.
2.Integrating radiology and histology via co-attention deep learning for predicting progression-free survival in patients with metastatic prostate cancer.
Yuanshen ZHAO ; Feng LIU ; Chaofan ZHU ; Chongzhe YAN ; Bangkang FU ; Junjie HE ; Xin XIE ; Rongpin WANG ; Zhicheng LI
Chinese Medical Journal 2025;138(22):3013-3015
3.Application of functional perforator flap transplantation with chimeric iliac bone flap in reconstruction of composite tissue defects of hand or foot.
Junjie LI ; Huihui GUO ; Bin LUO ; Huihai YAN ; Mingming MA ; Tengfei LI ; Tao NING ; Wei JIAO
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(9):1098-1105
OBJECTIVE:
To evaluate the effectiveness of functional perforator flaps utilizing the superficial circumflex iliac artery as a vascular pedicle, as well as chimeric iliac bone flaps, in the reconstruction of composite tissue defects in the hand and foot.
METHODS:
A retrospective review of the clinical data from 13 patients suffering from severe hand or foot injuries, treated between May 2019 and January 2025, was conducted. The cohort comprised 8 males and 5 females, with ages ranging from 31 to 67 years (mean, 48.5 years). The injuries caused by mechanical crush incidents (n=9) and traffic accidents (n=4). The distribution of injury sites included 8 cases involving the hand and 5 cases involving the foot. Preoperatively, all patients exhibited bone defects ranging from 2.0 to 6.5 cm and soft tissue defects ranging from 10 to 210 cm2. Reconstruction was performed using functional perforator flaps based on the superficial circumflex iliac artery and chimeric iliac bone flaps. The size of iliac bone flaps ranged from 2.5 cm×1.0 cm×1.0 cm to 7.0 cm×2.0 cm×1.5 cm, while the size of the soft tissue flaps ranged from 4 cm×3 cm to 15 cm×8 cm. In 1 case with a significant hand defect, a posterior interosseous artery perforator flap measuring 10.0 cm×4.5 cm was utilized as an adjunct. Likewise, an anterolateral thigh perforator flap measuring 25 cm×7 cm was combined in 1 case involving a foot defect. All donor sites were primarily closed. Postoperative flap survival was monitored, and bone healing was evaluated through imaging examination. Functional outcomes were assessed based on the location of the defects: for hand injuries, grip strength, pinch strength, and flap two-point discrimination were measured; for foot injuries, the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, Maryland Foot Score, plantar pressure distribution and gait symmetry index (GSI) were evaluated.
RESULTS:
All flaps survived completely, with primary healing observed at both donor and recipient sites. All patients were followed up 6-18 months (mean, 12.2 months). No significant flap swelling or deformity was observed. Imaging examination showed a bone callus crossing rate of 92.3% (12/13) at 3 months after operation, and bone density recovered to more than 80% of the healthy side at 6 months. The time required for bone flap integration ranged from 2 to 6 months (mean, 3.2 months). One patient with a foot injury exhibited hypertrophic scarring at the donor site; however, no major complication, such as infection or bone nonunion, was noted. At 6 months after operation, grip strength in 8 patients involving the hand recovered to 75%-90% of the healthy side (mean, 83.2%), while pinch strength recovered to 70%-85% (mean, 80%). Flap two-point discrimination ranged from 8 to 12 mm, approaching the sensory capacity of the healthy side (5-8 mm). Among the 5 patients involving the foot, the AOFAS score at 8 months was 80.5±7.3, VAS score was 5.2±1.6. According to the Maryland Foot Score, 2 cases were rated as excellent and 3 as good. Gait analysis at 6 months after operation showed GSI above 90%, with plantar pressure distribution closely resembling that of the contralateral foot.
CONCLUSION
The use of functional perforator flaps based on the superficial circumflex iliac artery, combined with chimeric iliac bone flaps, provides a reliable vascular supply and effective functional restoration for the simultaneous repair of composite bone and soft tissue defects in the hand or foot. This technique represents a viable and effective reconstructive option for composite tissue defects in these anatomical regions.
Humans
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Male
;
Middle Aged
;
Female
;
Perforator Flap/transplantation*
;
Adult
;
Plastic Surgery Procedures/methods*
;
Hand Injuries/surgery*
;
Aged
;
Retrospective Studies
;
Foot Injuries/surgery*
;
Ilium/transplantation*
;
Iliac Artery/surgery*
;
Soft Tissue Injuries/surgery*
;
Bone Transplantation/methods*
;
Treatment Outcome
4.Compound Centella asiatica formula alleviates Schistosoma japonicum-induced liver fibrosis in mice by inhibiting the inflammation-fibrosis cascade via regulating the TLR4/MyD88 pathway.
Liping GUAN ; Yan YAN ; Xinyi LU ; Zhifeng LI ; Hui GAO ; Dong CAO ; Chenxi HOU ; Jingyu ZENG ; Xinyi LI ; Yang ZHAO ; Junjie WANG ; Huilong FANG
Journal of Southern Medical University 2025;45(6):1307-1316
OBJECTIVES:
To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice.
METHODS:
The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting.
RESULTS:
We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver.
CONCLUSIONS
CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals
;
Toll-Like Receptor 4/metabolism*
;
Mice
;
Myeloid Differentiation Factor 88/metabolism*
;
Schistosoma japonicum
;
Liver Cirrhosis/parasitology*
;
Schistosomiasis japonica
;
Signal Transduction
;
Molecular Docking Simulation
;
Inflammation
;
Centella/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Tumor Necrosis Factor-alpha/metabolism*
5.Effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen levels in rats with polycystic ovary syndrome
Junjie CHEN ; Xuemei XU ; Yan LI ; Jinying FU
Tianjin Medical Journal 2024;52(2):154-161
Objective To study the regulation effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen level in rats with polycystic ovary syndrome.Methods The rat model of polycystic ovary syndrome was established by subcutaneous injection of human chorionic gonadotropin(HCG)combined with insulin.Rats were randomly divided into the polycystic ovary syndrome group,the Baizhu Fuzi Tang group(6.4 g/kg),the Bazhen Tang group(9.2 g/kg),the Bazhen Tang combined with Baizhu Fuzi Tang group(11.55 g/kg)and the diethylstilbestrol group(0.5 mg/kg).A blank control group(unmodulated rats)was set up with 10 rats in each group.The uterine index of rats was determined and calculated.Fasting blood glucose(FBG),2 h postprandish blood glucose(2 h PBG)and fasting insulin(FINS)were determined and insulin sensitivity index(ISI)and insulin resistance index(IR)were calculated.Serum estradiol(E2),testosterone(T),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),anti-Mullerian tube hormone(AMH)and insulin-like growth factor 1(IGF-1),C-reactive protein(CRP),interleukin(IL)-6,tumor necrosis factor(TNF)-α,total peroxidase activity(T-AOC),superoxide dismutase(SOD)and malondialdehyde(MDA)levels in ovarian tissue were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of ovarian tissue were detected by hematoxylin-eosin(HE)staining.Real-time quantitative polymerase chain reaction(qPCR)was used to determine mRNA levels of ARA70,CBP,SCR1 and HOXA10 in endometrium and mRNA expressions of AMPK,GLUT4 and PPARγ in ovarian tissue.Western blot assay was used to determine expression levels of AMPK,GLUT4 and PPARγ in ovarian tissue.Results Compared with the polycystic ovary syndrome group,uterine index,FINS,FBG,2 h PBG,IR levels,serum T,LH,FSH,PRL,AMH,IGF-1 levels,ovarian tissue CRP,IL-6,TNF-α,T-AOC and MDA level,endometrial ARA70,CBP,SCR1 mRNA level of rats decreased significantly in the Baizhu Fuzi decoction group,the Bazhen decoction group and the Bazhen decoction combined with Baizhu Fuzi decoction group(P<0.05).ISI level,serum E2 level,ovarian tissue SOD level,endometrial HOXA10 mRNA level,ovarian tissue AMPK,GLUT4 and PPARγ mRNA and protein levels were significantly increased(P<0.05).The above indexes were significantly changed in the Bazhen decoction and Bazhu Fuzi decoction group than those of the Bazhu Fuzi decoction group and the Bazhen decoction group(P<0.05).Conclusion Bazhen Decoction combined with Baizhu Fuzi Decoction can regulate glucose metabolism,inhibit ovarian tissue oxidation and inflammatory damage,improve endometrium tolerance,regulate estrogen level,and improve the progression of polycystic ovary syndrome in rats.The mechanism may be related to the regulation of AMPK/GLUT4/PPARγ pathway.
6.Anterolateral thigh perforator flap combined with fascia lata transfer in reconstruction of complex tissue defects of hand or foot
Junjie LI ; Wei JIAO ; Huihui GUO ; Wei HE ; Bin LUO ; Qiwei SONG ; Mingming MA ; Huihai YAN ; Tao NING
Chinese Journal of Microsurgery 2024;47(4):423-429
Objective:To investigate the clinical effect of anterolateral thigh perforator flap (ALTPF) combined with transfer of fascia lata in reconstruction of complex tissue defects of hand and foot.Methods:From July 2021 to October 2023, 9 patients with complex tissue defects of hand and foot were treated with ALTPF combined with fascia lata in the Department of Orthopaedic Microsurgical Repair and Reconstruction of Fuyang People's Hospital Affiliated to Anhui Medical University. There were 2 males and 7 females with an average age of 28.1 (range, 4-65) years old. Three patients had extensor tendon defects in 6 digits of dorsal hands, 5 had extensor tendon defect in 10 toes of dorsal foot, 1 had a defect of anterior tibial tendon and 1 had Achilles tendon defect in posterior ankles. The sizes of soft tissue defect ranged from 8.0 cm×6.0 cm to 15.0 cm×10.0 cm, and the lengths of tendon defect ranged from 6.0 to 13.0 cm. Preoperative Doppler ultrasound was used to locate the distribution of perforating branches in the anterolateral thigh region. According to the characteristics of wound, ALTPFs and fascia lata were designed and harvested. Fascia lata with an appropriate size of 1.5 cm×8.0 cm-4.5 cm×15.0 cm were taken to bridge the defects of the tendon and the Achilles tendon. The wounds were reconstructed with flaps sized 9.0 cm×6.5 cm-18.0 cm×7.5 cm. Nine fascia lata donor sites and 8 flap donor sites were sutured directly. One donor site was treated with a skin graft of ipsilateral ilioinguinal region. The survival and complications of the flaps and donor sites were observed through outpatient follow-up visits, WeChat reviews and home visits, etc. The hand function was assessed according to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, and the foot and ankle function was assessed according to the Mazur score standard of joint range of motion and motor function.Results:All patients were included in follow-up for 4-24 (mean, 13.4) months with complete clinical data being collected. All 9 ALTPFs survived and healed primarily. A linear scar left in donor sites in 8 patients, and mild lamellar scar at skin graft in 1 patient. Texture and colour of the flaps were similar to the surrounding tissue without secondary flap thinning surgery. Combined with postoperative rehabilitation training, satisfactory function recoveries were achieved. Hand function of 3 patients were evaluated according to Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, 2 patients were excellent and 1 was good. Ankle and foot functions in 6 patients were evaluated according to the range of motion of ankle and foot and Mazur score standard for motor function, 4 patients were excellent and 2 were good.Conclusion:ALTPF combined with fascia lata transfer can reconstruct the complex tissue defects of hand and foot. Of which, 1 donor site can meet the requirements of 2 types of tissues reconstruction at the same time, and with minimal damage to the donor site as well as an precise reconstruction of the recipient site. It avoids staged surgery, shortens the treatment time and reduces the cost of treatment.
7.Research progress in the evaluation of adult spinal deformities associated with osteoporosis and prevention of proximal junctional kyphosis or failure after corrective surgery
Dawei SONG ; Junjie NIU ; Jinning WANG ; Qi YAN ; Xiao SUN ; Huilin YANG ; Jun ZOU
Chinese Journal of Orthopaedics 2024;44(11):778-786
With the aging population, the increasing incidence of adult spinal deformity (ASD) associated with osteoporosis (OP) presents new challenges for evaluation and management. Although reasonable and standardized non-surgical treatment remains the first choice in the early stages of this disease, surgical treatment is necessary for patients with severe deformities and significant symptoms to achieve further improvement. Proximal junctional kyphosis/failure (PJK/PJF) is one of the most serious postoperative complications of ASD. Careful and comprehensive preoperative evaluation of bone quality and body sagittal alignment is crucial for the successful implementation of the operation. The Hounsfield unit (HU) based on CT imaging and the vertebral bone quality (VBQ) score based on MRI have proven to be reliable, effective, simple, and widely used in evaluating local vertebral bone quality in recent years. For the evaluation and prediction of PJF after ASD, the bone quality of the upper instrumented vertebra (UIV) can be assessed using HU values to identify high-risk patients and implement preventive measures. The VBQ score is predictive of the incidence of PJK/PJF in patients undergoing ASD surgery, with a high VBQ score being one of the risk factors for PJK/PJF after ASD correction. Patients with high VBQ scores can delay surgery and use anti-osteoporosis drugs before surgery to reduce the occurrence of PJK/PJF. Meanwhile, reasonable and personalized recovery parameters of ASD patients' sagittal sequence can help balance the benefits of efficacy and complications, maximizing the overall benefits. The prevention of PJK/PJF is challenging due to the stress gap between the internal fixation area and the original unfixed tissue area in the postoperative proximal junctional area, which is increasingly significant in OP patients. It is necessary to improve the fixation strength and bone riveting strength of the proximal junction area properly and to gradually decrease the fixed strength in the proximal junctional area to achieve a smooth transition of stress and avoid stress concentration resulting in failure. Relevant strategies include: 1. Enhanced proximal junction fixation, such as vertebral cement-enhanced pedicle screw fixation. 2. Strategies to cushion the stress in the proximal junction, such as Topping-off technology, which includes laminar/transverse hooks, dynamic rods, multi-segment stabilization screws, and multiple ligament-binding straps. 3. Minimally invasive technology can better protect the soft tissues such as the posterior ligament complex and muscles, reduce iatrogenic injury, and thus reduce the incidence of PJK/PJF. Currently, there are many controversies about the optimal treatment for ASD with OP, but the goal is to achieve maximum efficacy while minimizing complications. Additionally, attention should be paid to reasonable and standard anti-osteoporosis treatment in the perioperative period. This paper summarizes the relevant studies used to evaluate PJK/PJF after ASD in patients with OP and reviews the research progress on PJK/PJF prevention strategies, providing reference and ideas for reducing postoperative proximal junctional complications in adult spinal deformity patients with osteoporosis.
8.Preparation and properties of 177Lu-labeled HER2 affibody
Hongxia GUO ; Donghui PAN ; Chen SU ; Yuping XU ; Lizhen WANG ; Junjie YAN ; Xinyu WANG ; Chongyang CHEN ; Hui YANG ; Min YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(6):330-336
Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.
9.Synthesis of 177Lu-labeled liquid metal-based ROS radiosensitizer and preliminary study of its therapeutic efficacy on breast cancer in mice
Junjie YAN ; Chen SU ; Jianhan LIN ; Xinyu WANG ; Donghui PAN ; Yuping XU ; Lizhen WANG ; Chongyang CHEN ; Min YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(6):343-348
Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.
10.Synthesis of a 68Ga-labeled bicyclic peptide targeting Nectin-4 and its application research in breast cancer imaging
Liqi LI ; Yue XU ; Donghui PAN ; Junjie YAN ; Xinyu WANG ; Chongyang CHEN ; Lizhen WANG ; Min YANG ; Yuping XU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):741-747
Objective:To prepare a novel 68Ga-labeled bicyclic peptide targeting poliovirus receptor related protein 4 (PVRL4, Nectin-4), and evaluate its feasibility for breast cancer imaging via in vitro and in vivo experiments. Methods:A Biotin-modified bicyclic peptide targeting Nectin-4, Biotin-BMIC, was synthesized, and its targeting properties were preliminarily evaluated by in vitro cell staining experiments. BMIC was modified by 1, 4, 7-triazonane-1, 4-diacetic acid (NODA) and the labeling precursor NODA-BMIC was prepared. A potential PET probe targeting Nectin-4, 68Ga-NODA-BMIC was prepared by one-step labeling strategy. The imaging properties of the probe were investigated by in vivo microPET imaging and in vitro experiments in mice bearing breast tumors. Data were analyzed by independent-sample t test and repeated measures analysis of variance. Results:Fluorescence staining of the cells showed that the fluorescently labeled bicyclic peptide, Biotin-BMIC, was highly aggregated in Nectin-4 positive BT474 breast cancer cells compared to those in Nectin-4 negative MDA-MB-231 cells. The uncorrected yield of 68Ga-NODA-BMIC was (71.5±2.2)% and the radiochemical purity was greater than 95%. The specific activity was greater than 3 GBq/μmol. After incubation 10, 30, 60 and 120 min, higher radioactivity uptakes were found in BT474 breast cancer cells compared to those in MDA-MB-231 breast cancer cells respectively ( F=1 302.00, P<0.001). MicroPET imaging showed that the BT474 xenograft tumors were clearly visible with favorable contrast. A significant statistical difference in uptakes between BT474 and MDA-MB-231 xenograft tumor uptake at 10, 30, 60, and 120 min after probe injection respectively was existed ( F=1 826.00, P<0.001). At 60 min postinjection, the uptake value of BT474 tumors was (5.03±0.14) percentage activity of injection dose per gram of tissue (%ID/g), which was significantly higher than that of MDA-MB-231 tumors ((0.19±0.04) %ID/g; t=79.40, P<0.001). Meanwhile, the tumor-to-muscle ratios in the former were also greater than those in the latter ( F=222.00, P<0.001). At 60 min postinjection, the tumor-to-muscle ratio in the former was significantly higher than that in the latter (24.75±3.10 vs 1.30±0.15; t=14.31, P=0.002). The results were consistent with the immunohistochemistry staining. Conclusions:A novel bicyclic peptide PET probe targeting Nectin-4, 68Ga-NODA-BMIC, is easy to be synthesized and owns satisfactory labeling yield and radiological purity. The imaging performance is good and the target tissues could be visualized. It may play a unique role in the diagnosis and treatment of breast cancer.

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