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OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.
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Humanos , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Exossomos/metabolismo , Proliferação de Células/genética , Neoplasias Colorretais/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.
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Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "
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OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.
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Objective@#To explore the intervention effect of 12 week spinal health exercise on adolescents high and low shoulders, in order to provide empirical evidence for exploring simple and feasible measures to intervene.@*Methods@#In February 2023, 60 high and low shoulder students from a vocational high school in a certain county of Luzhou City were randomly selected as the research subjects by convenient sampling method. Paired sampling was used to randomly divide participants into an intervention group and a control group with 30 students each group. The intervention group received spinal health gymnastics intervention during 12 weeks of morning exercises and large break exercises for twice a day, with two groups each time; the control group maintained their previous morning exercises and large break exercises. A follow up study was conducted on the height difference between the left and right shoulder peaks of the intervention group and the control group students before intervention, after 12 weeks intervention, at 4 weeks post intervention. The t-test was used to analyze the changes in shoulder peak height difference between the intervention group and the control group.@*Results@#Before intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(2.50±1.19)cm] and the control group [(2.49±1.20)cm] adolescents ( t=0.05, P > 0.05). After 12 weeks of intervention, the difference in shoulder height between the left and right sides of adolescents in the intervention group decreased, compared to that before intervention [(1.43±1.15, 2.50±1.19)cm], while the control group increased compared to that before intervention [(2.58±1.19, 2.49±1.20) cm], and the differences were both statistically significant ( t= -78.17 , 20.15, P <0.05). At 4 weeks post intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(1.44±1.15)cm] and the control group [(2.59±1.18)cm] compared to 12 weeks after the intervention ( t=1.80, 1.05, P >0.05). The intervention group [(2.49±1.26, 2.52±1.16) (1.43±1.21, 1.44±1.13) (1.44±1.21, 1.45±1.14)cm] and the control group [(2.45±1.24, 2.52±1.20) (2.55±1.24, 2.61±1.18) (2.55±1.22, 2.62±1.18)cm] showed no statistically significant difference in the height of the left and right shoulder peaks between males and females before intervention, after 12 weeks of intervention, and after stopping intervention for 4 weeks ( t =-0.08, -0.03, -0.02; -0.15, -0.12, -0.15, P >0.05).@*Conclusions@#Spinal health gymnastics has a good effect on correcting high and low shoulders in adolescents. Spinal health gymnastics should be promoted on campus to promote adolescent posture health.
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To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
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SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.
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From the perspective of cybernetics， this study investigated the fundamental principles of empirical thinking in traditional Chinese medicine， encompassing six stages： experience input and storage， experience extraction and activation， experience combination and reconstruction， judgment and decision-making based on experience， and experience evaluation and feedback. The potential limitations of empirical thinking in clinical applications were analyzed， mainly manifested as “individuality”， “superficiality”， “conservatism”， “prioritizing commonality over individuality”， and “cognitive inertia”. To overcome these limitations， this paper also explored strategies and methods for clinical error-correction from four points： the integration of rational and empirical thinking， the reinforcement of feedback mechanisms and transcendent correction， the integration of individualization and quantity-quality balance， and the management and transference of tacit knowledge under empirical thinking.
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Objective:To explore the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio(PLR)and NLR-PLR score for carcinoma(HCC)patients undergoing liver transplantation(LT).Methods:From July 2015 to October 2021, clinical data are retrospectively reviewed for 110 HCC patients undergoing orthotopic LT at Third Hospital of Hebei Medical University.The values of NLR and PLR were calculated.And the cut-off values of NLR and PLR were obtained by receiver operating characteristic (ROC) curve and then grouped according to the cut-off values.Survival time is analyzed by Kaplan-Meier method and Log-rank test performed for inter-group comparison.Univariate and multivariate analyses are performed based on Cox proportional risk regression model.NLR <3.37 and PLR <105.96 are denoted as 0 point while NLR ≥3.37 and PLR ≥105.96 as 1 point.Two points are added up as NLR-PLR score.According to NLR-PLR score, they are divided into 3 groups of 0, 1 and 2.Results:Median overall survival(OS)is 27 months in patients with NLR-PLR score 0, 26.5 months in patients with NLR-PLR score 1 and 6 months in patients with NLR-PLR score 2.Median OS in patients with NLR-PLR score 2 is significantly shorter than that in those with NLR-PLR score 0/1.And the difference is statistically significant( P<0.001).Median disease-free survival(DFS)is 24.5 months in NLR-PLR 0 group, 24 months in NLR-PLR 1 group and 6 months in NLR-PLR 2 group.The difference is statistically significant( P=0.002).Univariate analysis show that Child-Pugh grade, MELD score, NLR/PLR level, NLR-PLR score, complying with University of California San Francisco Criteria(UCSF)criteria and absence/presence of microvascular invasion(MVI)have an impact on patient survival.Further multivariate analysis show that NLR-PLR score, complying with UCSF criteria and MELD score are independent risk factors affecting patients' prognosis and survival. Conclusions:NLR, PLR and NLR-PLR score may predict long-term survival of patients.And NLR-PLR score is an independent risk factor for patient survival.It has more predictive value than NLR/PLR.
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Objective:To evaluate the risk of HBV recurrence after liver transplantation in patients with end-stage hepatitis B related liver disease, and to explore the indications for antiviral therapy withdrawal.Methods:The data of HBV DNA, cccDNA in liver puncture tissues and peripheral blood in 31 patients after liver transplantation was retrospectively analyzed.Results:Among the 31 patients, 15 (48%) had detectable and quantified HBV DNA in liver biopsy tissue, while their HBV related serological indicators were negative, suggesting an occult HBV infection in some patients. The study found 15 out of 19 cases who were taking Entecavir were cccDNA negative (78.9%), compared to 5 out of 12 cases (41.6%) in Lamivudine regiment ( P=0.03). Conclusions:Hidden HBV infection can be detected by amplifying cccDNA and HBV DNA in liver puncture tissue by using ddPCR. Entecavir is superior to lamivudine in the clearance of cccDNA.
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Objective:To evaluate the efficacy of total laparoscopic surgery vs. open surgery for hilar cholangiocarcinoma. Methods:The clinical data of 45 patients undergoing laparoscopic radical resection of hilar cholangiocarcinoma and 42 patients by open surgery from Mar 2017 to Mar 2021 were retrospectively analyzed.Results:There was no significant difference in demographics, Bismuth classification and excision extension between the two groups (all P>0.05). The laparoscopic surgery used longer time ( t=-1.366, P<0.05). The intraoperative blood loss, number of lymph node dissection and postoperative hospital stay favored laparoscopic method( t=0.043, t=0.026, t=-1.852, P<0.05). R 0 radical resection rate，postoperative complications were also in favor of laparoscopic surgery ( χ2=3.216, χ2=2.566, all P<0.05). There was no significant difference in postoperative pathology and in hospital expenses (all P>0.05). The 1- and 3-year survival rate of the laparoscopic group was superior (all P<0.05). Conclusions:In spite of longer operational time，patients in laparoscopic hilar cholangiocarcinoma radical resection group have shorter postoperative in hospital stay and longer postoperative survival time.
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Objective:To construct three image recognition models of manikin′s glottis using visual laryngoscopy based on deep-learning algorithm.Methods:The tracheal intubation manikin′s epiglottis was visualized using a videolaryngoscope, and then epiglottis was elevated to expose the glottis and acquire glottic images. A total of 149 images were obtained from various angles and orientations and randomly divided into training set and test set, and the annotation of image data was completed. Three glottal image recognition models of CenterNet, YOLOv3 and YOLOv4 were developed. The training set was used to complete the training of the models, and finally the test set was used to evaluate the model performance.Results:CenterNet, YOLOv3 and YOLOv4 three models were successfully constructed, the mean average precision of CenterNet, YOLOv3 and YOLOv4 was 92.33%, 89.52% and 89.02% respectively, the recall rates were 87.50%, 90.00% and 90.00% respectively, the precision rates reached 97.22%, 94.74% and 94.74% respectively, and the accuracy rates were 90.91%, 85.11% and 88.89% respectively. All three algorithms demonstrated an identical F1 score of 91.00%.Conclusions:The CenterNet, YOLOv3 and YOLOv4 models are successfully constructed, and three recognition models can accurately identify the glottis in the image, with the CenterNet model demonstrating the highest recognition precision.
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Objective:To evaluate the effect of esketamine on long-term cognitive dysfunction induced by propofol anesthesia in the developing rats and the role of phosphatidylinositol-3-kinase (PI3K)/serine-threonine protein kinase (Akt) signaling pathway.Methods:Forty-eight clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 10-15 g, were divided into 4 groups ( n=12 each) using a random number table method: fat emulsion group (C group), propofol group (P group), esketamine + propofol group (EP group), and PI3K inhibitor LY294002 + esketamine + propofol group (LYEP group). Medium/long-chain fat emulsion injection 100 mg/kg was intraperitoneally injected in C group. Propofol was intraperitoneally injected at a dose of 50 mg/kg, followed by an additional dose of 50 mg/kg after the righting reflex was restored (40-60 min later) in P group. In group EP, esketamine 10 mg/kg was intraperitoneally injected, followed by propofol administration using the same method as previously described in P group. In LYEP group, LY294002 25 μg was injected via the lateral ventricle, 30 min later ketamine 10 mg/kg was intraperitoneally injected, and then propofol was given using the same method as previously described in P group. Six rats in each group were randomly sacrificed at 2 h after emergence for microscopic examination of pathological changes of hippocampal neurons and for determination of Akt, phosphorylated Akt (p-Akt), Bax, and cleaved caspase-3 in the hippocampal tissues (using Western blot). The remaining 6 rats in each group were subjected to Y-maze test to evaluate their learning and memory abilities at 30 days after birth. The p-Akt/Akt ratio was calculated. Results:Compared with C group, the p-Akt/Akt ratio in the hippocampal tissues was significantly decreased, the expression of Bax and cleaved caspase-3 was up-regulated, the number of training sessions required for learning was increased, the correct response rate was decreased ( P<0.05), and the pathological damage to neurons in hippocampal CA1 region was found in P, EP and LYEP groups. Compared with P group, the p-Akt/Akt ratio in the hippocampal tissues was significantly increased, the expression of Bax and cleaved caspase-3 was down-regulated, the number of training sessions required for learning was decreased, the correct response rate was increased ( P<0.05), and the pathological damage to neurons in hippocampal CA1 region was significantly attenuated in EP and LYEP groups. Compared with EP group, the p-Akt/Akt ratio in the hippocampal tissue was significantly decreased, and the expression of Bax and cleaved caspase-3 was up-regulated, the number of training sessions required for learning was increased, the correct response rate was decreased ( P<0.05), and the pathological damage to neurons in hippocampal CA1 region was aggravated in LYEP group. Conclusions:Esketamine can alleviate long-term cognitive impairment caused by propofol anesthesia in the developing rats, and the mechanism may be related to activation of the PI3K/Akt signaling pathway and inhibition of apoptosis in neurons.
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Objective:To investigate the clinical efficacy of trigeminal neuralgia treatment in elderly patients with percutaneous balloon compression assisted by a robotic surgical navigation and positioning planning system.Methods:Eleven elderly patients with trigeminal neuralgia admitted to the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University between August 2021 and August 2022 were retrospectively analyzed.Three-dimensional time-of-flight magnetic resonance angiography, a three-dimensional fast spin-echo sequence with variable flip angles and thin-slice CT scans were performed before the procedure, and multimodal image fusion was performed by a robot workstation.The volume of Meckel's cave was calculated.Two paths were set up in the surgical planning: an actual puncture path, targeting the anterior inner quadrant of the internal foramen ovale, and a virtual path, used to plan the insertion depth of the balloon.The actual puncture path was completed under the guidance of the robotic arm adapter, and the virtual path for depth measurement was completed under lateral X-ray views of digital subtraction angiography.The balloon was placed at the predetermined depth and was inflated to form a pear shape to complete the procedure.The visual analogue scale(VAS)score was used to evaluate preoperative pain, and the Barrow Neurological Institute(BNI)facial numbness score was used to evaluate postoperative facial numbness.The patients were followed up for 1-12 months and the results were analyzed.Results:In all of the 11 patients, puncturing the foramen ovale and entry into the Meckel's cave were successfully conducted and the balloon was inflated to form a pear shape.Ten patients(90.9%)achieved complete remission immediately after the procedure, and 1 patient had delayed healing at 5 days after the procedure.There were no serious complications related to the procedure.There was no recurrence of pain during the follow-up, and the BNI numbness grading was between 2-3.The ratio between the inflated balloon volume and the preoperative volume of the Meckel's cave was approximately 1.7.Conclusions:Robot-assisted percutaneous balloon compression is safe and effective for the treatment of trigeminal neuralgia in elderly patients.
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Objective:To investigate the clinical significance of a new classification system for atlas fractures based on pre- and post-treatment CT features, with a focus on diagnosis and treatment.Methods:A retrospective analysis was conducted on 75 cases of cervical vertebra fractures treated at the Sixth Hospital of Ningbo City between January 2015 and December 2020. The study included 44 males and 31 females, with an average age of 53.3±13.0 years (range: 27-81 years). The fractures were classified according to the Landells classification, resulting in 12 cases of type I, 13 cases of type II, 33 cases of type III, 9 cases that were difficult to classify due to fracture lines located at anatomical junctions, and 8 cases that could not be classified using the Landells classification due to diverse injury mechanisms. To establish a new preliminary classification for cervical vertebra fractures, the researchers considered whether the fracture line in the CT images involved the facet joint surface of the atlas, the impact on bilateral half-rings, and the displacement distance of the fracture ends. Five spinal surgeons were randomly selected to classify the CT images of the 75 patients using the new classification method. After one month, the imaging data of the 75 cases of cervical vertebra fractures were randomized and reclassified to assess the reliability and repeatability of the classification.Results:The new cervical vertebra fracture classification method comprised three types based on whether the fracture line involved the facet joint surface of the atlas: type A (no involvement of the facet joint surface of the atlas), type B (involvement of one side of the facet joint surface with intact contralateral half-ring), and type C (involvement of one side of the facet joint surface with fractured contralateral half-ring). Additionally, based on the maximum displacement distance between the fracture ends (>4 mm), six subtypes were identified: subtype 1 (≤4 mm displacement) and subtype 2 (>4 mm displacement). Consequently, the subtypes were classified as A1, A2, B1, B2, C1, and C2. According to the new classification method, the 75 patients included 17 cases of A1, 12 cases of A2, 7 cases of B1, 13 cases of B2, 12 cases of C1, and 14 cases of C2. The classification demonstrated excellent consistency, as assessed by the five doctors, with Kappa values of 0.85 and 0.91 for reliability and repeatability, respectively. At the final follow-up, all conservatively treated patients achieved bone healing, while four surgically treated patients experienced non-union of the fracture ends but exhibited good fusion between the atlas and axis. The remaining surgically treated patients achieved bony union without complications such as loosening or fracture of internal fixation.Conclusion:The new cervical vertebra fracture classification method, based on CT imaging features, comprehensively covers common clinical cases of cervical vertebra fractures and demonstrates excellent consistency. It provides valuable clinical guidance for the diagnosis and treatment of cervical vertebra fractures.
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Objective:To preliminarily investigate the effects of tumor treating field (TTF) arrays on the positioning accuracy of radiotherapy setup in the treatment of glioblastoma.Methods:The kilovolt cone-beam CT (CBCT) and an X-ray volumetric imaging (XVI) system were used to verify the radiotherapy setup of 29 patients treated with conventional radiotherapy and 12 patients treated with TTF concurrent radiotherapy, respectively. The errors of radiotherapy position isocenter and treatment plan isocenter were evaluated in six directions, namely lateral (Lat), head pin (Lng), dorsoventral (Vrt), roll, pitch, and rotation (Rtn). Then, the plan isocenter was redetermined according to the setup error data. Moreover, the dose distribution was recalculated without changing the radiation field parameters. Finally, the V40, Dmean, D98% and D2% of both PTV and CTV and the Dmean, D20 cm 3, and D30 cm 3 of scalp tissue were evaluated. Results:When patients were treated with TTF concurrent radiotherapy wearing TTF arrays, the setup errors increased by 2 mm and 1.3 mm on average (maximum: 3.5 mm and 2.7 mm) toward the foot and dorsal directions, respectively. In addition, the setup errors in both Roll and Rtn directions increased by about 1.1° toward one side. The V40 and D98% of PTV decreased by up to 4.78% and 6%, respectively. The Dmean, D20 cm 3, and D30 cm 3 to scalp tissue increased by up to 2.6%, 3.2%, and 3.5%, respectively. The errors of other dose parameters for both CTV and PTV were within 2%. Conclusions:TTF arrays have significant effects on the setup errors of patients in the Lng and Vrt directions and increase the setup difficulty in the Roll and Rtn directions, while there is no significant error in the Lat and Pitch directions. Moreover, too large setup errors can significantly reduce the dose to PTV.
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Objective:To detect the expression of N6-methyladenosine (m 6A) regulators in colorectal tumor samples and its clinical significance. Methods:From September to December 2021, the data regarding the expression of m 6A regulators in colorectal tumor samples were collected using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and the expression of m 6A regulators was compared between different clinical pathological characteristics and between different molecular subtypes. Survival analysis was conducted in patients with colorectal cancer with different m 6A expression levels. Results:In TCGA, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) were higher in colorectal tumor samples than normal tissue samples (TCGA-COAD: IGF2BP3: 12.80 vs. 204.46, logFC = 4.00, P = 0.003; YTHDF1: 2 347.56 vs. 3712.77, logFC = 0.66, P < 0.001; TCGA-READ: IGF2BP1: 6.20 vs. 359.32, logFC = 5.82, P = 0.007; YTHDF1: 2 470.10 vs. 4 369.09, logFC = 0.82, P = 0.020). The intersection of TCGA and GEO databases showed that methyltransferase like 14 (METTL14), YTH domain m 6A RNA binding protein 3 (YTHDF3), and α-ketoglutarate dependent dioxygenase AlkB homolog 5 (ALKBH5) were downregulated in colorectal tumor samples compared with normal tissue samples (TCGA-COAD: METTL14: 1 051.56 vs. 711.40, logFC = -0.56, P < 0.001; YTHDF3:4 613.85 vs. 3 155.05, logFC = -0.55, P < 0.001, ALKBH5: 4 250.10 vs. 2 555.55, logFC = -0.73, P < 0.001; TCGA-READ vs. METTL14: 1 113.3 vs. 674.36, logFC = -0.72, P < 0.001; YTHDF3: 5 034.30 vs. 3 331.95, logFC = -0.60, P = 0.004; ALKBH5: 4 902.20 vs. 2 529.71, logFC = -0.95, P < 0.001; GEO-CRC vs. METTL14: 6.58 vs. 6.33, logFC = -0.06, P < 0.001; YTHDF3: 6.28 vs. 6.20, logFC = -0.02, P = 0.002; ALKBH5: 5.07 vs. 4.98, logFC = -0.02, P < 0.001). In colorectal tumor samples of different molecular subtypes, IGF2BP2, HNRNPC, TP53 and YTHDF2 expression was low in KRAS (IGF2BP2: 48.53 vs. 44.04, t = 2.64, P = 0.008; HNRNPC: 121.30 vs. 112.60, t = 2.32, P = 0.020; TP53: 65.30 vs. 60.26, t = 2.11, P = 0.034; YTHDF2: 54.07 vs. 51.19; t = 1.97, P = 0.048). Different clinical pathological characteristics showed that IGF2BP1 was higher in colorectal cancer with positive lymph nodes (8.97 vs. 6.11, W = 20 008, P = 0.002), distant metastasis (8.94 vs. 6.41, W = 19 104, P = 0.009), or stage Ⅲ-Ⅳ (7.46 vs. 7.13, W = 8 779, P = 0.025) than normal tissue. ALKBH5 overexpression, advanced age, presence of vascular invasion, and late pathological staging were significantly related to a short survival period (high ALKBH5 expression vs. low ALKBH5 expression: 5.85 years vs. not available, HR: 1.63, 95% CI: 1.071-2.491, P = 0.021; > 68 years vs. < 68 years: 6.78 years vs. not available, HR: 1.59, 95% CI: 1.049-2.422, P = 0.047; stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 4.55 years vs. 8.33 years, HR: 2.89, 95% CI: 1.895-4.425, P < 0.001; presence of vein invasion vs. absence of vein invasion: 5.48 years vs. not available, HR: 2.82, 95% CI: 1.672-4.783, P < 0.001). Conclusion:Some of the m 6A regulators are associated with the biological characteristics and prognosis of colorectal cancer.
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Objective:To dynamically observe the changes in iodine level in residents' drinking water after the change of regional water supply mode (2020) in Jiangsu Province.Methods:The survey of water iodine level was conducted from June to October 2020 in administrative villages of Jiangsu Province with a median water iodine ≥40 μg/L in 2017. The survey mainly covered 1 537 administrative villages in 21 counties (cities and districts) of 5 cities, including Huaian City, Lianyungang City, Suqian City, Yancheng City, and Xuzhou City. Based on the standard of "Definition and Demarcation of Iodine Deficient Areas and Iodine Adequate Areas" (WS/T 669-2020), the administrative villages with a median water iodine of 40 - 100 μg/L were classified as iodine adequate areas. Water iodine testing was conducted using the "Method for Water Iodine Testing in Iodine Deficient and High Iodine Areas" recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:Totally 1 498 administrative villages in Jiangsu Province were monitored in 2020, all of which had centralized water supply. The minimum value of water iodine in all administrative villages was 1.2 μg/L and the maximum value was 606.7 μg/L, and the median water iodine was 35.2 μg/L. Among them, 206 administrative villages had median water iodine < 10 μg/L, accounting for 13.75% (206/1 498); 610 administrative villages had median water iodine from 10 to < 40 μg/L, accounting for 40.72% (610/1 498); 635 administrative villages had median water iodine from 40 to 100 μg/L, accounting for 42.39% (635/1 498); and 47 administrative villages with median water iodine > 100 μg/L, accounting for 3.14% (47/1 498). Except for Sucheng District in Suqian City, Xinyi City and Gulou District in Xuzhou City, Qingjiangpu District and Xuyi County in Huaian City, and Guannan County in Lianyungang City, the median water iodine in the administrative villages of the remaining 15 counties (cities and districts) in 2020 decreased significantly compared to 2017, and the differences were statistically significant ( P < 0.05). Conclusion:After change of regional water supply mode in 2020, in most monitored counties (cities and districts) of Jiangsu Province, the water iodine level of administrative villages has decreased significantly compared to 2017.
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Objective:To learn about the implementation of prevention and control measures in drinking water-borne endemic fluorosis areas and the trend of the disease change in Jiangsu Province.Methods:In March to October 2021, a general survey was carried out in 1 972 villages with drinking water-borne endemic fluorosis in 27 counties (cities and districts) of Jiangsu Province, the operation of water improvement projects in the villages was monitored, and the water fluoride content was determined. The prevalence of dental fluorosis among children aged 8 to 12 years in all the villages was investigated.Results:The 1 972 villages with drinking water-borne endemic fluorosis had completed water improvement, and all water improvement projects were operating normally and the water was qualified. Among them, 1 774 villages in the disease affected areas had achieved the control goal, accounting for 89.96%; and there were 198 villages in the disease affected areas with control measures up to the standard, accounting for 10.04%. A total of 47 water improvement projects were monitored, including 2 small-scale water improvement projects, accounting for 4.26%. There were 45 large-scale water improvement projects, accounting for 95.74%. A total of 125 790 children aged 8 to 12 years were examined, and 12 625 cases of dental fluorosis were detected. The detection rate of dental fluorosis was 10.04%, and the dental fluorosis index was 0.19. The detection rate of dental fluorosis in children aged 8 to 12 years was 9.98% (1 854/18 579), 10.27% (2 704/26 323), 9.48% (2 765/29 152), 9.73% (2 835/29 145) and 10.92% (2 467/22 591), respectively, with statistically significant difference (χ 2 = 10.51, P = 0.015). Among the 198 villages with control measures up to standard, according to the historical water fluoride, the detection rate of dental fluorosis in children in each water fluoride range (1.20-2.00, 2.01-3.00, 3.01-4.00, > 4.00 mg/L) was 37.73% (698/1 850), 43.17% (1 176/2 724), 45.50% (769/1 690) and 55.20% (802/1 453), respectively, with a statistically significant difference (χ 2 = 104.15, P < 0.001). Conclusion:The water improvement measures in drinking water-borne endemic fluorosis areas in Jiangsu Province have achieved significant results, which still need to be further consolidated.
RESUMO
Objective:To analyze the influencing factors of dental fluorosis of children in the drinking-water-borne endemic fluorosis (referred to as drinking-water-borne fluorosis) areas with qualified drinking water.Methods:In 2020 and 2021, the cluster sampling method was used to select the children aged 8 to 12 years old from the drinking-water-borne fluorisis areas with qualified drinking water in Tianjin City for water and urine fluoride detection, dental fluorosis examination and questionnaire survey, and logistic regression and classification tree model were used to analyze the influencing factors of dental fluorosis in children.Results:A total of 3 795 cases children aged 8 to 12 years old were investigated, and 1 001 cases of dental fluorosis were detected, and the detection rate of dental fluorosis was 26.38% (1 001/3 795). The results of logistic analysis showed that age [odds ratio ( OR) = 1.193, 95% confidence interval ( CI): 1.115 - 1.277], high urinary fluoride (1.84 - 19.40 mg/L, OR = 1.510, 95% CI: 1.169 - 1.952) and the number of permanent residents at home ≥6 ( OR = 1.377, 95% CI: 1.090 - 1.739) were risk factors of dental fluorosis in children; and the mother's with higher education level (college degree or above, OR = 0.664, 95% CI: 0.441 - 0.999), the years of water improvement ≥5 years (5 - < 10 years, OR = 0.193, 95% CI: 0.157 - 0.238; ≥10 years, OR = 0.254, 95% CI: 0.193 - 0.333) were protective factors of dental fluorosis in children. The results of classification tree model analysis showed that the years of water improvement contributed the most to the prevalence of dental fluorosis among children in the drinking-water-borne fluorisis areas with qualified drinking water, followed by age, number of permanent residents at home and urinary fluoride. The area under the receiver operating characteristic curve (AUC) of logistic regression model and classification tree model were 0.730 (95% CI: 0.711 - 0.748) and 0.721 (95% CI: 0.702 - 0.739), respectively, with good fitting effect. Conclusion:The detection rate of children's dental fluorosis in the drinking-water-borne fluorosis areas with qualified drinking water is mainly related to the years of water improvement, age, the number of permanent residents at home and urinary fluoride.