ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

Oculopharyngodistal myopathy （OPDM） is a hereditary neuromuscular disorder occurring in adolescence or early adulthood and is characterized by slowly progressive external ophthalmoplegia， facial muscle weakness， dysphagia， and distal limb weakness. This article reports a patient with OPDM type 4 who had the initial presentation of bilateral pyroptosis and external ophthalmoplegia and was misdiagnosed with thyrotoxic myopathy， and later the patient developed the clinical manifestations of bilateral masticatory and facial muscle weakness， bulbar paralysis， and limb weakness. Genetic testing revealed abnormal CGG repeat expansion in the RILPL1 gene. The clinical data of the patient was analyzed， and a literature review was performed， so as to improve the awareness of this condition among clinicians.

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

OBJECTIVE: To observe the neuroprotective effect of 6-shogaol (6-SH) in global cerebral ischemia/reperfusion injury (CIRI) following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in rats. METHODS: Computer-aided molecular docking was used to determine whether 6-SH could spontaneously bind to death-associated protein kinase 1 (DAPK1). SPF-grade male SD rats were randomly divided into a sham group (n = 5), a CPR group (n = 7), and a CPR+6-SH group (n = 7). The CPR group and CPR+6-SH group were further divided into 12-, 24-, and 48-hour subgroups based on observation time points. A rat model of global CIRI after CA-CPR was established by asphyxiation. In the sham group, only tracheal and vascular intubation was performed without asphyxia and CPR induction. The CPR group was intraperitoneally injected with 1 mL of normal saline immediately after successful modeling. The CPR+6-SH group received an intraperitoneal injection of 20 mg/kg 6-SH (1 mL) immediately after successful modeling, followed by administration every 12 hours until the endpoint. Neurological Deficit Score (NDS) was recorded at each time point after modeling. After completion of observation at each time point, rats were anesthetized and sacrificed, and brain tissue specimens were collected. Histopathological changes of neurons were observed under light microscopy after hematoxylin-eosin (HE) staining. Ultrastructural changes of hippocampal neurons and autophagy were observed by transmission electron microscopy (TEM). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression levels of DAPK1, vacuolar protein sorting 34 (VPS34), Beclin1, and microtubule-associated protein 1 light chain 3 (LC3) in brain tissues. Western blotting was used to detect protein expression levels of DAPK1, phosphorylated DAPK1 at serine 308 (p-DAPK1 ser308), VPS34, Beclin1, and LC3. Immunofluorescence was used to observe Beclin1 and LC3 expression in brain tissues under a fluorescence microscope. RESULTS: Molecular docking results indicated that 6-SH could spontaneously bind to DAPK1. Compared with the sham group, the NDS scores of the CPR group rats were significantly increased at all modeling time points; under light microscopy, disordered cell arrangement, widened intercellular spaces, and edema were observed in brain tissues, with pyknotic and necrotic nuclei in some areas; under TEM, mitochondria were markedly swollen with intact membranes, dissolved matrix, reduced or disappeared cristae, vacuolization, and increased autophagosomes. Compared with the CPR group, the NDS scores of the CPR+6-SH group rats were significantly decreased at all modeling time points; under light microscopy, local neuronal edema and widened perinuclear space were observed; under TEM, mitochondria were mostly mildly swollen with intact membranes, fewer autophagosomes, and alleviated injury. RT-qPCR results showed that compared with the sham group, mRNA expression levels of DAPK1, VPS34, Beclin1, and LC3 in brain tissues were significantly upregulated in all CPR subgroups, with the most pronounced changes at 24 hours. Compared with the CPR group, the CPR+6-SH group showed significantly lower mRNA expression of the above indicators at each time point [24 hours post-modeling (relative expression): DAPK1 mRNA: 3.41±0.68 vs. 4.48±0.62; VPS34 mRNA: 3.63±0.49 vs. 4.66±1.18; Beclin1 mRNA: 3.08±0.49 vs. 4.04±0.22; LC3 mRNA: 2.60±0.36 vs. 3.67±0.62; all P < 0.05]. Western blotting results showed that compared with the sham group, the protein expression levels of DAPK1, VPS34, Beclin1, and LC3 in all CPR subgroups were significantly increased, while the expression of p-DAPK1 ser308 was significantly decreased, with the most pronounced changes observed in the CPR 24-hour subgroup. Compared with the CPR group, the CPR+6-SH subgroups exhibited significantly reduced protein expression of DAPK1, VPS34, Beclin1, and LC3 [24-hour post-modeling: DAPK1/β-actin: 1.88±0.22 vs. 2.47±0.22; VPS34/β-actin: 2.55±0.06 vs. 3.46±0.05; Beclin1/β-actin: 2.12±0.03 vs. 2.87±0.03; LC3/β-actin: 2.03±0.24 vs. 3.17±0.23; all P < 0.05]. Conversely, the expression of p-DAPK1 ser308 was significantly upregulated in the CPR+6-SH group compared to the CPR group [24-hour post-modeling: p-DAPK1 ser308/β-actin: 0.40±0.02 vs. 0.20±0.07, P < 0.05]. Under the fluorescence microscope, fluorescence intensities of Beclin1 and LC3 in the CPR 24-hour group were significantly higher than those in the sham 24-hour group; compared with the CPR 24-hour group, the CPR+6-SH 24-hour group showed significantly reduced fluorescence intensities of Beclin1 and LC3. CONCLUSION 6-SH inhibited the expression of DAPK1, alleviated excessive autophagy after global CIRI following CA-CPR in rats, and exerted neuroprotective effects. The mechanism may be related to phosphorylation at the DAPK1 ser308 site.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; Cardiopulmonary Resuscitation ; Autophagy/drug effects* ; Heart Arrest/therapy* ; Death-Associated Protein Kinases/metabolism* ; Reperfusion Injury/metabolism* ; Disease Models, Animal ; Neuroprotective Agents/pharmacology* ; Brain Ischemia/metabolism*

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Objective To systematically evaluate the effect of threshold inspiratory muscle training on pulmonary rehabilitation in postoperative lung cancer patients,with a focus on exploring the difference in efficacy under different interven-tion modes.Methods Randomized controlled trials on the effect of threshold inspiratory muscle training on pulmonary rehabilitation in postoperative lung cancer patients were retrieved from PubMed,Cochrane Library,Embase,Web of Science,CNKI,Wanfang data,VIP and China Biomedical Literature Database.Meanwhile,gray literature from ProQuest and clinicaltrials.gov was searched as supplements.The retrieval period was from the establishment of each data-base to May 9,2025.Cochrane 5.1.0 was used to evaluate the quality of literature,and a meta-analysis was per-formed using RevMan 5.4.Results Twelve studies involving 701 patients were included,all of which were of moderate to high quality.Threshold inspiratory muscle training could reduce the pulmonary complications of postoperative lung cancer patients(OR=0.45,95%CI 0.29 to 0.68,P<0.001),shorten the hospital stay(MD=-1.85,95%CI-3.29 to-0.42,P=0.010),improve the inspiratory muscle strength(MD=5.84,95%CI 0.96 to 10.71,P=0.020),enhance their ex-ercise endurance(SMD=0.40,95%CI 0.10 to 0.71,P=0.010),and did not increase the risk of pulmonary air leakage(OR=0.88,95%CI 0.47 to 1.63,P=0.680).Subgroup analysis revealed that shortening of hospital stay(MD=-2.98,95%CI-5.87 to-0.09,P=0.040)and the improvement in exercise endurance(SMD=0.57,95%CI 0.14 to 1.00,P=0.009)were significant only when threshold inspiratory muscle training was combined with aerobic exercise.However,standalone threshold inspiratory muscle training showed no statistical signifi-cance in these two outcomes.Conclusion Threshold inspiratory muscle training can effectively reduce postoperative pulmonary complications and im-prove inspiratory muscle strength in postoperative lung cancer patients with good safety.Threshold inspiratory muscle training could shorten hospital stay and improve exercise endurance only when combining with aerobic exercise.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.