OBJECTIVES: To evaluate the value of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT imaging at our hospital from August, 2020 to March, 2023, including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment. GEP-NEN were classified into G1, G2, and G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) based on pathological typing. The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers: ⁶⁸Ga-DOTATATE>¹⁸F-FDG (A); ⁶⁸Ga-DOTATATE=¹⁸F-FDG (B); ⁶⁸Ga-DOTATATE<¹⁸F-FDG (C); and complementation (D). The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis. RESULTS: In the 49 patients with GEP-NEN, ⁶⁸Ga-DOTATATE PET/CT was superior to ¹⁸F-FDG PET/CT for detecting systemic tumor lesions (P<0.001) and more sensitive for detecting primary/recurrent lesions, lymph node metastasis, liver metastasis, and bone metastasis (P<0.05), while ¹⁸F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis (P<0.05). In terms of the detection efficiency, Pattern A was found in 46.9% (23/49) patients, Pattern B in 38.8% (19/49), Pattern C in 12.2% (6/49), and Pattern D in 2.0% (1/49). The complementary value of ¹⁸F-FDG PET/CT to ⁶⁸Ga-DOTATATE PET/CT was 0% in G1 NET patients (0/13), 8.3% in G2 NET patients (2/24), 50% in G3 NET patients (3/6), and 33.3% in NEC patients (2/6). 12.2% (6/49) of the patients had their staging confirmed or changed due to additional lesions detected by ¹⁸F-FDG PET/CT imaging, resulting subsequently in establishment or adjustment of their treatment plans. CONCLUSIONS ⁶⁸Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients. Additional ¹⁸F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2, G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Neuroendocrine Tumors/therapy* ; Pancreatic Neoplasms/therapy* ; Retrospective Studies ; Organometallic Compounds ; Stomach Neoplasms/therapy* ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Intestinal Neoplasms/therapy* ; Female ; Male ; Middle Aged ; Aged ; Adult

Objective:To study the effects of the apical dentin surface morphology resected with Er∶YAG laser on the proliferation of human periodontal ligament cells(hPDLCs).Methods:66 single premolars were randomly divided into 3 groups(n=22),and the api-cal root slices were made by resection perpendicular to the root long axis 3 mm from the apex using high-speed handpiece(group A),piezosurgery(group B)and Er∶YAG laser(group C),respectively.SEM was used to observe the apical dentin surface in the aspects of debris,smear layer,dentinal tubules,cracks,ablation characteristics and the dentin surface roughness was measured.hPDLCs were clutured on the surface of the slices of the groups,CCK-8 method was used to detect cell proliferation on the samples at 24,48 and 72 h of culture,respectively.Results:The surface preparition time of group A was shorter than that of group B and C(P＜0.001).SEM observation showed that in group C,there was no residual debris or stained layer,and dentin tubule was visible on the dention sur-faces.Detritus and stained layers were observed in group A and B,and dentin tubule was not observed in group A.Cracks were observed in all the groups,but less in group C.Roughness(nm)of group C(1 487.13±295.90)was higher than that of group A and B(P＜0.001).CCK-8 assay showed that the cell proliferation(A value)of all groups increased gradually with the culture time after 24,48 and 72 h of hPDLCs seeded on the root surface.And the cell proliferation in group C was the most significant than that in group A and B(P＜0.05)at 48 and 72 h.Conclusion:The morphological performance of the apical dentin surface resected with Er∶YAG laser is more conducive to hPDLCs growth than that with the ultrasound and burs.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

Objective: To analyze effect of fractured file removal from the middle third root canal on root fracture resistance using finite element analysis, which provides a theoretical basis for clinical prognosis evaluation. Methods: Two finite-element models were established, the fractured file removal model (fractured file located in the middle third of root canals, followed by ultrasonic file removal and root canal preparation) and the control model (root canal preparation only), and compressive displacement dependencies on compressive force was computed and compared with experimental data for validation. The validated finite-element models were used to analyze the stress distribution differences during the initiation, propagation and completion of the crack between fractured file removal specimen and control one. Results: The critical breaking force of the fractured file removal specimen was 406 N, and the finite element simulation result was 396 N. The critical breaking force of the control specimen was 502 N, and the finite element simulation result was 483 N. The position of crack initiation in the finite element simulation was basically consistent with that in the experiment. The experimental data of compressive test and the results of finite-element computation were in agreement, thus validating the finite-element model. In the process of continuous pressure, the stress distribution of the control root is relatively uniform, and the location of crack initiation and the direction of propagation have a certain unpredictability. Compared with the control root, the stress concentration on the root with fracture file removal was obvious, especially on edges, and the number of cracks are much more. Because of the thinner radicular wall, the crack propagation rate is faster too. Therefore, the overall root fracture resistant is decreased obviously. Conclusions During the fractured file removal procedure, amount of dentine removed should be minimized, and the edges and corners which caused by fractured file removal should be shaped to smooth in order to reduce the stress concentration and prevent the root from fracture.

Objective To investigate the effect of hyperbaric oxygen preconditioning on syngeneic kidney transplantation in rats and to explore the potential mechanism. Methods Forty male SD rats were randomly divid-ed into control group(Sham group),kidney transplantation group(KTx group)and hyperbaric oxygen precondi-tioning group(HBO+KTx group). Kidney transplantation was performed 24 h after hyperbaric preconditioning. Rats were sacrificed 24 h after the transplantation.Serum creatinine(Scr)and blood urea nitrogen(BUN)were de-tected.The level of superoxide dismutase(SOD),malondialdehyde(MDA)and heme oxygenase-1(HO-1)in the graft was examined. Kidney pathological examination was performed after renal tissue fixed. Results Compared with the KTx group,HBO + KTx group showed lower Scr and BUN level. The MDA level was decreased and the SOD activity was increased significantly after hyperbaric oxygen preconditioning in HBO+KTx group.Renal tubu-lar necrosis was significantly reduced in HBO+KTx group.HO-1 level in HBO+KTx group was significantly high-er than that of KTx group. Conclusion Hyperbaric oxygen preconditioning can reduce lipid peroxidation,en-hance antioxidant enzyme activity and improve the level of HO-1 in graft tissue,thus attenuating kidney injury.

Objective: To investigate the association between the frequency and filling rate of lateral canals and the sealing quality in the apical third roots of the permanent teeth with failed endodontic treatments, so as to explore the failure factors of root canal therapy. Methods: Clinical records of the permanent teeth with failed endodontic treatments were collected from the Department of Endodontics, Capital Medical University School of Stomatology during a period of 2 years. The teeth were diagnosed as chronic apical periodontitis and then undergone endodontic microsurgery. The sealing quality of the apical root canal was observed by means of periapical radiographs. The surgical treatments were performed and the resected root apices were collected. The samples were scanned by micro-computed tomography and the 3D volume rendered images of the resected root apices were reconstructed. Moreover, the frequency and the filling rate of lateral canals in the apical third roots were calculated. The potential relationship between tooth position and the presence of lateral canals was evaluated. Results: Totally 89 teeth with 89 root apices met the inclusion criteria and were included in the present study. The rate of correct-filling, underfilling and overfilling was 40% (36/89), 32% (28/89), and 28% (25/89), respectively, examined by periapical radiographs. Amongst all of the 89 samples, lateral canals were found in 44 samples. The incidence of apices with lateral canals was 49% (44/89). Furthermore, 3 out of 44 samples were fully filled with material in the lateral canals, and the rest 41 samples showed no filling materials. The filling rate of the lateral canals was 7% (3/44). However, no significant difference was detected between the tooth position and the presence of lateral canals (P>0.05). Conclusions The sealing quality of the apical third roots in permanent teeth with failed endodontic treatments was not good enough. The incidence of apices with lateral canals was high, but the filling rate of the canals was low. Further studies are needed to explore the relationship between lateral canals and the failure of endodontic treatment.