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Background/Aims@#Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. @*Methods@#Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. @*Results@#In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. @*Conclusions@#Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

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@#Objective To investigate the effects of β-sitosterol on the proliferation and apoptosis of colon cancer cell HCT116,and its regulation of on phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods Cultivated colon cancer cells HCT116 in vitro and divided them into β-sitosterol High(240μmol/L)、medium(120μmol/L)and low-dose(60μmol/L)groups,set control group(0μmol/L).Applied different concentrations of β-sitosterol treatment of HCT116 cells.And 24h later,the cell proliferation and activity were determined by cell counting kit-8(CCK-8)method,the morphological changes observed under a microscope;Cell apoptosis was observed by Hoechst 33342 nuclear staining;Used cell colony formation assy to detect the colony forming ability of HCT116 cells;and Western blot was used to evaluate the expression of PI3K,p-Akt,Akt,Bcl-2 and Bax in cells.Used AutoDock software for molecular docking of β-sitosterol with Akt and PI3K.Results Compared with the control group,β-sitosterol could inhibit the proliferation of colon cancer HCT116 cells in a concentration dependent manner,inhibit their colony forming ability and promote cell apoptosis and inhibit the expression of p-Akt、PI3K、and Bcl-2 proteins in HCT116 cells and promotes the expression of Bax protein.The binding of β-sitosterol with PI3K and Akt proteins is relatively stable.Conclusion β-sitosterol may regulate the proliferation and apoptosis of HCT116 through inhibiting PI3K/Akt signaling pathway.

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Objective:To evaluate the relationship between B-cell lymphoma/adenovirus E1B19 kDa-interacting protein 3-like protein (BNIP3L)/adenovirus E1B-interacting protein and mitochondrial dysfunction in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:One hundred and eighty C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=45 each) using a random number table method: control group (C group), sham operation group (Sham group), SAE group, and SAE+ BNIP3L agonist carfilzomib group (SC group). The sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized animals. In SC group, carfilzomib 2 mg/kg was intraperitoneally injected at 2 h after CLP. Twenty mice in each group were selected, and the survival at 7 days after operation was recorded. Eight surviving mice in each group were selected at 1 week after CLP for Morris water maze test. The remaining mice were sacrificed at 24 h after surgery, and the hippocampal tissues were harvested for determination of the expression of BNIP3L (by immunofluorescence) and BNIP3L in mitochondrial protein (by Western blot) and for microscopic examination of the morphological structure of mitochondria. The mitochondrial ATP content was measured by fluorescein-fluorescence enzyme luminescence method, and the mitochondrial membrane potential (MMP) was measured by fluorescence spectrophotometry. Results:Compared with C and Sham groups, the survival rate was significantly decreased, the escape latency was prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform region was decreased, the expression of BNIP3L in the hippocampal mitochondria was down-regulated, the MMP and content of mitochondrial ATP were decreased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was marked in SAE group. Compared with SAE group, the survival rate was significantly increased, the escape latency was shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform region was increased, the expression of BNIP3L in the hippocampal mitochondria was up-regulated, the MMP and content of mitochondrial ATP were increased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was attenuated in SC group. Conclusions:BNIP3L-mediated mitochondrial dysfunction may be involved in the mechanism of SAE developed in mice.

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Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.

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Objective To optimize the supercritical CO2 extraction conditions of volatile oil from Wenjing Huoxue cataplasm. Methods On the basis of single factor investigation on the comprehensive score of extraction yield , osthole content and isoimperatorin, the effects of extraction temperature, pressure and time on the comprehensive score of extracted volatile oil were optimized by orthogonal design. Results In the single factor experiment, the factors that had a great influence on the comprehensive score of the extracted volatile oil were extraction temperature, extraction pressure and extraction time. The orthogonal experiment results showed that the extraction temperature and extraction pressure had a significant influence on the comprehensive score of volatile oil. The optimized extraction process was as follows: extraction temperature at 55 ℃, extraction pressure as 30 MPa, and extraction time as 2 h. Conclusion The extraction process optimized in this experiment is stable and feasible, which could be used for the extraction and preparation of the volatile oil.

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Objective:To investigate the repair of the severe nasal deformity in the unilateral cleft lip secondary with the methods in the composite tissue Z-plasty and the nasolabial anatomical reconstruction.Methods:A total of 25 patients with severe nasal deformity due to secondary unilateral cleft lip underwent the reconstructive surgery using the technique of composite tissue Z-plasty and the nasolabial anatomical reconstruction for anatomical restoration of cartilage, muscle, and soft tissue layers. All patients were followed up for 3-24 months, with an average period of 7.6 months. The treatment outcomes were evaluated by a questionnaire in postoperative follow-up.Results:All the 25 patients had achieved satisfactory nostril shape and no other complications such as bleeding, infection and flap necrosis were recorded. A total of 25 patients were evaluated postoperatively. The average columella length was significantly improved from an average of 14.2 mm preoperatively to 20.2 mm postoperatively. The average ratio of the cleft side columella height to the alar base width was 0.18 preoperatively and 0.30 postoperatively. The postoperative basal and frontal views revealed a better shape of the nostrils, columella and nasal floor. GAIS questionnaires of 25 patients demonstrated that 20 patients reported great improvement, 4 patients reported moderate improvement, 1 patient had poor improvement in size and shape of the affected side nostril who undevwent the another repair of the rdure in 12 months postoperation. The ectopic muscles around the pear hole was completely released and the effect was good after repair. The satisfactory rate was 96%.Conclusions:Combining the composite tissue Z-plasty with the nasolabial anatomical reconstruction allows for thorough anatomical restoration of cartilage, muscle, and skin layers in unilateral cleftlip nasal deformities. This single-step approach is a safe and technically easy therapeutic option that is associated with high patients′ satisfaction. This method should be considered for promotion in clinic.

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Artemisia argyi is the leaves of compositae plants of A. argyi Lévl. et Vant.， which is a traditional Chinese medicine commonly used in China. The analysis was carried out by consulting traditional medical classics， modern standard norms and literature， and using Cytoscape software to sort out and visualize the evolution of the processing and the efficacy of processed products. The processing of A. argyi was first made in the Han dynasty and was popular in the Song and Ming dynasties. There were many processing methods in ancient times， including net processing， cutting， frying， processing with auxiliary material （vinegar， wine， salt， charcoal， rice water， sulfur， medicinal juice， jujube mud processing） and other processing methods （baking， winching， making herbs into wool）. Modern common processing methods included purification， vinegar processing， charcoal processing and making herbs into wool， which are relatively simple compared with ancient processing methods. There were obvious differences in the efficacy and application of raw and processed products of A. argyi. Although the processing effects of A. argyi in ancient and modern times were mainly to reduce toxic side effects and enhance the effects of warming meridians and hemostasis， only the purified A. argyi， vinegar-processed A. argyi and vinegar-processed A. argyi charcoal could be seen in the present studies， other processed products had not been inherited and studied， and the processing mechanism was still unclear. It is suggested that in the later exploration and research， researchers can establish a multi-dimensional standard research system based on the characteristics of the medicinal plant A. argyi and the processing characteristics of A. argyi decoction pieces in order to systematically explore the transformation rules before and after processing， and clearly explain the scientific connotation.

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Objective:To explore the relationship between platelet count (PLT) and organ dysfunction and prognosis in critically ill patients and its prognostic evaluation.Methods:A retrospective cohort study was conducted. The relevant records of 35 860 patients were extracted from the US Intensive Care Database (MIMIC-Ⅲ) from 2001 to 2012. According to the PLT count, patients were divided into the thrombocytopenia group (PLT<100×10 9/L), normal platelet group (100×10 9/L≤PLT≤300×10 9/L), and thrombocytosis group (PLT>300×10 9/L). This study included adult patients between 18 and 89 years old. Patients with survival time less than 24 h and lack of vital signs or PLT values were excluded. The outcome event was the hospital mortality of the patient. Survival was analyzed by the Kaplan-Meier method. The prognostic factors were identified by univariate and multivariate COX analyses. The nomogram to predict hospital mortality was built by the significant prognostic factors. In combination with the important prognostic factors, a nomogram was established to predict the prognosis of critically ill patients in hospital, and the AUC value under the ROC curve was used to assess the discriminative power of the nomogram. Results:Compared with the normal PLT group and the thrombocythemia group, organ dysfunction in the thrombocytopenia group was significantly worse; the SOFA score [3 (2, 5) vs. 2.0 (1, 5) vs. 7 (5, 9)], SAPS-Ⅱ score [31 (23, 41) vs. 32 (23, 42) vs. 38 (30, 50) ], hospital mortality (35.0% vs. 45.2% vs. 54.7%), the incidence of mechanical ventilation (50.3% vs. 41.4% vs. 62.8%), and renal replacement therapy (1.3% vs. 1.3% vs. 6.0%) were significantly higher (all P<0.05). COX regression analysis found that thrombocytopenia was an independent predictor of hospital mortality and was entered into a nomogram after final regressions ( HR=1.477, 95% CI: 1.347-1.691, P<0.01). When the above indicators were brought into the nomogram, the AUC of the nomogram was 0.744. Conclusions:Thrombocytopenia is an independent prognostic predictor of hospital mortality for critically ill patients. PLT-related nomograms have good discrimination, which may help clinicians evaluate the prognosis of hospitalized patients.

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Objective@#To analyze the spatio-temporal distribution characteristics of new HIV/AIDS cases at ages of 50 years and older in Wenzhou City from 2006 to 2020, so as to provide insights into precise control of AIDS. @*Methods @#The data of new HIV/AIDS cases aged 50 years and older in Wenzhou City from 2006 to 2020 were collected from the China Information System for Disease Control and Prevention. The temporal and spatial distribution characteristics of new HIV/AIDS cases at ages of 50 years and older were identified using global and local spatial autocorrelation analyses and spatial-temporal scan analysis.@*Results@#Totally 1 917 new HIV/AIDS cases aged 50 years and older were detected in Wenzhou City from 2006 to 2020, and there were 179 new HIV/AIDS cases in 58 townships ( streets ) from 2006 to 2010, 643 cases in 113 townships ( streets ) from 2011 to 2015 and 1 095 cases in 147 townships ( streets ) from 2016 to 2020, respectively. The distribution of new HIV/AIDS cases appeared positive spatial autocorrelations from 2006 to 2010 ( Moran's I value=0.05, Z=1.976, P=0.046 ), from 2011 to 2015 ( Moran's I value=0.08, Z=2.314, P=0.028) and from 2016 to 2020 (Moran's I value=0.18, Z=3.956, P=0.003 ). Spatial-temporal scan analysis identified two clusters. The primary cluster mainly covered 70 towns ( streets ) in Lucheng Distrct, Ouhai District, Longwan District, Economic and Technical Development Region, Rui' an City and Pingyang County of Wenzhou City from January 1, 2014 to December 31, 2020, with a cluster radius of 34.30 km [log likelihood ratio ( LLR )=192.84, RR=2.60, P<0.001], and the secondary cluster was located in Hongqiao Township of Yueqing City from January 1, 2009 to December 31, 2015, with a cluster radius of 0 ( LLR=90.60, RR=7.27, P<0.001 ).@*Conclusions@#The number of new HIV/AIDS cases aged 50 years and older appeared a tendency towards a rise in Wenzhou City from 2006 to 2020, with spatial clusters that were predominantly identified in urban areas, Rui' an City and Pingyang County of Wenzhou City.

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In order to further promote hierarchical medical system and enhance the capacity of primary healthcare services, China began to build compact county medical community. At present, the development of China′s compact county community still exists such problems as the construction of service system, the basic institutional mechanism, the quality of supply capacity and the core guarantee mechanism. In order to solve the existing problems, the authors took Shaxian District of Sanming City, Fujian Province, Dancheng County of Zhoukou City, Henan Province, and Yangqu County, Taiyuan City, Shanxi Province as examples to summarize the experience of the advanced pilot areas of the policy. In the future, the construction of compact county community in China should be based on the construction of " single-core multi-layer" system, starting from the five levels of collaborative management, practical operation, system construction, basic guarantee and multi-party supervision, to comprehensively enhance the healthcare services, and finally achieve the goal of the strategy of hierarchical medical and Healthy China.

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Objective:To observe the technique of using the random flap with a subcutaneous pedicle forone-stage reconstuction of anterior auricular conchal defect and its efficancy.Methods:Ten cases were involved in this study, including 3 cases of carcinoma, 6 cases of nevus, and one with iatrogenic detect. Six patients were men, and 4 were women. Their ages were 2 months to 68 years (mean 57 years). Surgical defect size ranged from 1.0 cm×1.0 cm to 2.5 cm×1.5 cm. They were resected and reconstructed using the retroauricular random flap of the subcutaneous pedicle.Results:10 wounds were healed by first intention. The appearance and functionality of the flap matched well with the receiptive site. During 6 to 24 months of follow-up, no tumor or nevus recurred. All patients were satisfied with the aesthetic results of the POSAS assessment scale.Conclusions:Aesthetic results are achieved with satisfactory appearance and functionality by this easy-to-learn technique in comparative short surgical time.

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Objective:To evaluate the value of Facial Emotion Recognition Test (FERT) in the early diagnosis of behavioral variant frontotemporal dementia (bvFTD).Methods:A total of 27 patients with mild bvFTD, 27 patients with mild Alzheimer′s disease (AD) and 54 normal controls were successively collected in the Memory Clinic of Department of Neurology,Xuanwu Hospital, Capital Medical University from January 2018 to July 2019. The subjects were assessed by the FERT and a battery of neuropsychological background tests including Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Auditory Verbal Learning Test (AVLT), etc. The discriminatory power of the FERT was evaluated using the receiver operating characteristic curve (ROC).Results:The average FERT scores of bvFTD, AD and control groups were 18.00 (14.00, 21.00), 25.00 (21.00, 28.00) and 28.00 (26.00, 30.00) respectively. The FERT scores of bvFTD group were significantly lower than those of control groups ( H=-55.278, P<0.001) and AD groups ( H=-28.407, P=0.002). ROC results showed that the FERT had a high discriminatory power for differentiating bvFTD from the controls, with an area under the curve (AUC) value of 0.969 (95% CI 0.931-1.000, P<0.001). Both the sensitivity and specificity were 92.6% with a cut-off value at 24. For differentiating bvFTD group from AD group, the AUC value for the FERT was 0.850 (95% CI 0.749-0.951, P<0.001), with sensitivity of 81.5% and specificity of 71.4% with a cut-off value of 22. Compared with the AUC values for the FAB and AVLT-Delayed Recall (0.776 and 0.714), the AUC value for the FERT was slightly higher, though the differences among them were not statistically significant. Conclusions:Disturbance of emotion processing is presented in the early stage of bvFTD. FERT is one of the sensitive and specific neuropsychological indicators for the early diagnosis of bvFTD.

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Objective@#To retrospectively analyze the characteristics of nasopharyngeal carcinoma, long-term efficacy, adverse reactions of intensity-modulated radiotherapy (IMRT) in non-endemic northwest China and summarize the experience of IMRT in the treatment of nasopharyngeal carcinoma in the past decade.@*Methods@#Clinical data of 658 patients newly diagnosed with nasopharyngeal carcinoma without distant metastasis admitted to First affiliated hospital from January 2006 to December 2016 were retrospectively analyzed. All patients were treated with IMRT. The survival analysis was performed by Kaplan-Meier method. The multivariate analysis was conducted with Cox’s regression model.@*Results@#In non-endemic northwest China, a large proportion of patients were newly diagnosed with locally advanced nasopharyngeal carcinoma, and a majority of them were pathologically characterized as differentiated subtypes. The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) rates were 75.7%, 70.1%, 91.2%, 97.0% and 81.0%, respectively. Multivariate analysis showed that age, pathological type, nasopharyngeal tumor volume>23 cm3 and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DFS (all P<0.05). Age, pathological type, neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of OS (all P<0.05). N stage and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DMFS (both P<0.05).@*Conclusions@#Similar clinical efficacy has been achieved in terms of IMRT for nasopharyngeal carcinoma in non-endemic northwest China compared with that in endemic area. Induction chemotherapy combined with concurrent radiochemotherapy can provide clinical benefits for patients with locally advanced nasopharyngeal carcinoma in non-endemic area.

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Objective@#To investigate the change and association of glioma-associated oncogene homolog 1 (Gli1) and β-catenin on bone formation in rats with chronic fluorosis which were inhibited by cyclopamine (Cycl).@*Methods@#Forty-eight Sprague-Dawley rats were evenly divided to four groups, including control, F, F+Cycl and F+DMSO groups. The control group were fed with tap water (NaF<1 ppm). The F, F+Cycl and F+DMSO groups were exposed to NaF (50 ppm) in drinking water as the chronic fluorosis model. Then the rats in F+Cycl or F+DMSO groups were injected by Cycl or DMSO after 6 months, respectively. Urine fluoride concentration was detected using fluorine ion selective electrode. The enzyme-linked immunosorbent assay (ELISA) was used to detect bone alkaline phosphatase (BALP). Bone tissues were stained with hematoxylin-eosin. The mRNA and protein expression of Gli1 and β-catenin in bone tissue were detected using real-time PCR, immunohistochemistry and Western blot.@*Results@#Compared with the controls, the urine fluoride concentration and the width and volume of bone trabeculae were increased in the F, F+Cycl and F+DMSO groups, but no statistical difference among the 3 fluorosis groups. The concentration of BALP was increased in the F group and decreased in F+Cycl group (P<0.05). The expression of Gli1 and β-catenin mRNA and protein was higher in the F and F+Cycl groups than controls, but lower in the F+Cycl group than in the F group. There was positive correlation between the expression of Gli1 and β-catenin (r=0.476, P<0.05). The expression of Gli1 and β-catenin was also associated with BALP concentration and volume of bone trabeculae, respectively (r1=0.457, r2=0.466, r3=0.581, r4=0.554, respectively, P<0.05 for all).@*Conclusions@#The expression of Gli1 can be inhibited by Cycl. It may be involved in the bone formation of rats with chronic fluorosis. It may also affect the expression of β-catenin, which is an osteogenesis factor.

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Objective:To investigate the expression changes of Hedgehog related factors (Ihh, Shh and Smo) in bone of rats with chronic fluorosis, and the significance.Methods:Thirty-six healthy SD rats were divided to three groups with the method of random digits table by body weight (100 - 120 g), 12 rats in each group, half male and half female. The rats of control were fed with tap water (NaF < 1 mg/L), and the experimental rats were exposed to NaF (low dose fluoride group: 5 mg/L, high dose fluoride group: 50 mg/L) added to the drinking water to establish the chronic fluorosis model. After the rats were raised for six months, 24-hour urine samples were collected and the femoral metaphysis of the rats was taken. Urine fluoride and bone fluoride were detected by fluorin ion selective electrode method. Bone tissues were stained with hematoxylin-eosin and observed under light microscope. The content of bone alkalinephosphatase (BALP) in rats' serum was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Ihh, Shh and Smo mRNA and protein in bone were detected by Real-time PCR and immunohistochemistry (IHC).Results:The contents of urine fluoride, bone fluoride and serum BALP were increased gradually in the control, low and high doses fluoride groups [urine fluoride: (1.37 ± 0.44), (5.96 ± 0.56), (7.60 ± 0.61) mg/L; bone fluoride: (306.04 ± 12.58), (652.91 ± 51.83), (1 094.11 ± 126.34) mg/kg; BALP: (27.78 ± 4.09), (46.59 ± 5.75), (57.45 ± 3.99) U/L, P < 0.05]. It could observed that bone sclerosis by light microscope in low and high doses fluoride groups. The expressions of Ihh, Shh and Smo mRNA in high dose fluoride group (1.39 ± 0.36, 0.56 ± 0.23, 0.40 ± 0.15) were higher than those of the control and low dose fluoride groups (0.73 ± 0.19, 0.92 ± 0.34; 0.19 ± 0.04, 0.36 ± 0.16; 0.14 ± 0.04, 0.24 ± 0.13; P < 0.05). The expression of Shh mRNA in low dose fluoride group was higher than that of the control group ( P < 0.05). The expressions of Ihh and Smo protein in high dose fluoride group (138.89 ± 3.72, 149.29 ± 7.63) were higher than those of the control and the low dose fluoride groups (127.39 ± 2.69, 134.81 ± 3.53; 129.64 ± 12.62, 139.07 ± 9.30), and the low dose fluoride group were higher than those of the control group ( P < 0.05). The expression of Shh protein in high dose fluoride group (141.26 ± 7.49) was higher than that of the control group (130.96 ± 11.10, P < 0.05). Conclusion:The expression of Hedgehog signaling pathway related factors in bone of rats with chronic fluorosis is changed, which indicates that bone formation can be affected by activation of Hedgehog signaling pathway induced by fluoride.

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Objective To retrospectively analyze the characteristics of nasopharyngeal carcinoma,long-term efficacy,adverse reactions of intensity-modulated radiotherapy (IMRT) in non-endemic northwest China and summarize the experience of IMRT in the treatment of nasopharyngeal carcinoma in the past decade.Methods Clinical data of 658 patients newly diagnosed with nasopharyngeal carcinoma without distant metastasis admitted to First affiliated hospital from January 2006 to December 2016 were retrospectively analyzed.All patients were treated with IMRT.The survival analysis was performed by Kaplan-Meier method.The multivariate analysis was conducted with Cox's regression model.Results In non-endemic northwest China,a large proportion of patients were newly diagnosed with locally advanced nasopharyngeal carcinoma,and a majority of them were pathologically characterized as differentiated subtypes.The 5-year overall survival (OS),disease-free survival (DFS),local recurrence-free survival (LRFS),regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) rates were 75.7％,70.1％,91.2％,97.0％ and 81.0％,respectively.Multivariate analysis showed that age,pathological type,nasopharyngeal tumor volume＞23 cm3 and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DFS (all P＜0.05).Age,pathological type,neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of OS (all P＜0.05).N stage and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DMFS (both P＜0.05).Conclusions Similar clinical efficacy has been achieved in terms of IMRT for nasopharyngeal carcinoma in non-endemic northwest China compared with that in endemic area.Induction chemotherapy combined with concurrent radiochemotherapy can provide clinical benefits for patients with locally advanced nasopharyngeal carcinoma in non-endemic area.

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OBJECTIVES@#To evaluate the application value of CT-based radiomics features for the ascending and descending types of nasopharyngeal carcinoma (NPC).@*METHODS@#A total of 217 NPC patients (48 ascending type and 169 descending type), who obtained CT images before radiotherapy in Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from February 2015 to October 2017, were analyzed retrospectively. All patients were randomly divided into a training set (=153) and a test set (=64). Gross tumor volume in the nasopharynx (GTVnx) was selected as regions of interest (ROI) and was analyzed by radiomics. A total of 1 300 radiomics features were extracted via IBEX. The least absolute shrinkage and selection operator (LASSO) logistic regression was performed to choose the significant features. Support vector machine (SVM) and random forest (RF) classifiers were built and verified.@*RESULTS@#Six features were selected by the LASSO from 1 300 radiomics features. Compared with SVM classifier, RF classifier showed better classification performance. The area under curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were 0.989, 0.941, 1.000, and 0.924, respectively for the training set; 0.994, 0.937, 1.000, and 0.924, respectively for the validation set.@*CONCLUSIONS@#CT-based radiomics features possess great potential in differentiating ascending and descending NPC. It provides a certain basis for accurate medical treatment of NPC, and may affect the treatment strategy of NPC in the future.

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For resectable elderly esophageal cancer,neoadjuvant chemoradiotherapy combined with surgery is still the preferred treatment under the condition of fully measuring the patient's physical function.Definitive chemoradiation is the first choice for patients with inoperable esophageal cancer,and may be a good alternative for elderly operable patients with good response to tumor regression.For older patients (＞80 years old),radiotherapy alone may be mild and conservative enough to be the preferred option.At the same time,compared with conventional radiation dose (50.4 Gy),selective regional lymph node irradiation,standard PF regimen (cisplatin + 5-fluorouracil),radiotherapy of high dose (≥60 Gy),involving field irradiation combined with single-drug chemotherapy (such as tegio) can bring better prognosis.

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Conventional imaging techniques and gastrointestinal endoscopy cannot accurately predict the early clinical efficacy of chemoradiotherapy in the treatment of esophageal cancer,whereas the functional imaging of PET-CT,MRI-DWI and radiomics can reflect the functional metabolism of the tumors prior to the morphological changes,which can compensate for the limitations of conventional diagnostic methods.In this article,the current application of imaging techniques in predicting the early response of chemoradiotherapy for esoohageal cancer was reviewed.

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Objective To explore the features of connected speech produced by Chinese mild Alzheimer's disease (AD) patients.Methods Thirty Chinese mild AD patients (eight males and 22 females,and the age was (72.73 ± 7.78) years) and 30 age and education matched normal controls from three communities were recruited in Xuanwu Hospital from January 2018 to May 2018.All subjects completed tasks of picture naming,semantic fluency (animal),and Cookie Theft picture description.Picture description was analyzed for speech production (total word output,speech rate,sound errors),lexical content (number of nouns and verbs,proportion of pronouns and verbs,semantic errors),information content (information unit,idea density,efficiency),syntactic structure and complexity (mean length of utterance,words in sentences,syntactic errors).Differences between groups were calculated.Association between picture naming,semantic fluency,and measures in picture descriptions was analyzed.Results Compared with the controls,mild AD patients achieved lower scores on the picture naming task (74.45±8.04 vs 79.60± 1.73,t=-2.800,P=0.010) as well as on the semantic fluency task (10.35±3.08 vs 18.50±4.66,t=-6.520,P＜0.01) and produced lower speech rate (131.80±36.40 vs 149.64±26.69,t=-2.095,P=0.041),less number of nouns (7.52±2.55 vs 9.67±3.58,t=-2.509,P=-0.015) and verbs (4.40±2.24 vs 5.73±1.92,t=-2.375,P=0.021),increased proportion of pronouns (0.286 (0.319) vs 0.039 (0.122),Z=3.602,P＜0.01) and semantic errors (0.629 (1.396) vs 0 (0.779),Z=2.386,P=0.017),less information units (11.00±3.63 vs 13.70±3.53,t=-2.787,P=0.007),decreased idea density (0.11±0.04 vs 0.16±0.05,t=-3.946,P＜0.01),decreased efficiency (14.23±7.56 vs 22.95±7.14,t=-4.738,P＜0.01),shorter mean length of utterance (6.64± 1.27 vs 8.25± 1.70,t=-3.928,P＜0.01),and less words in sentence (0.84±0.10 vs 0.95±0.06,t=-4.625,P＜0.01).Group differences in total word output,sound errors,proportion of verbs,and syntactic errors did not reach statistical significance.Scores on picture naming task were negatively associated with the proportion of pronouns (r=-0.737,P=0.003),and positively associated with the idea density (r=0.540,P=0.046) and efficiency (r=0.592,P=0.026) in the AD group.Scores on semantic fluency task were negatively associated with the proportion of pronouns (r=-0.554,P=0.011).Conclusions Connected speech in mild AD patients was characterized by decreased naming accuracy,decreased sematic fluency,decreased content words,information units,conciseness,efficiency,and syntactic complexity,but motoric aspects of speech and sentence structure remained relatively preserved.Decreased content words and increased pronouns in mild AD may relate to semantic impairment.