ObjectiveTo explore the potential mechanism of Erchen Decoction （二陈汤， ECD） in improving metabolic syndrome （MS） with phlegm syndrome. MethodsForty mice were randomly divided into a blank group of 10 mice and a modeling group of 30 mice. The MS model with phlegm syndrome was induced in the modeling group by high-fat diet. Thirty successfully modeled mice were randomly divided into a model group， a ECD group， and a metformin group， with 10 mice in each group. The ECD group was given 0.4 g/（kg·d） of ECD， while the metformin group was intervened with 11.1 g/（kg·d） of metformin solution， and the blank group and the model group were given 0.02 ml/（g·d） of sterilized drinking water， all by gavage， once daily for 4 weeks. Body weight， abdominal circumfe-rence， body length， Lee's index and food intake were recorded. Blood glucose and blood lipid levels including fasting blood glucose， triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. ELISA was used to detect serum leptin levels， while HE staining was used to observe liver pathological changes. Western Blot and q-PCR were used to detect protein and mRNA expression of hypothalamic leptin receptor （LepR）， pro melanocortin （POMC）， and neuropeptide Y （NPY） in the hypothalamus. Immunofluorescence was used to detect fluorescence expression of POMC and NPY in the hypothalamic arcuate nucleus region. ResultsPathological results showed that the mice in the model group had numerous fat vacuoles in hepatocytes and significant liver fat deposition， while the ECD and metformin groups showed reduced fat vacuoles and less liver fat deposition. Compared to those in the blank group， the mice in the model group mice showed liver fat deposition， increased body weight， abdominal circumference， Lee's index and food intake； fasting blood glucose， TG， TC， LDL-C， and serum leptin levels were elevated， while HDL-C was decreased； the expression of LepR， POMC protein levels and their mRNA expression decreased， while the protein level and mRNA expression of NPY increased； the fluorescence expression of POMC in the arcuate nucleus was reduced， while NPY fluorescence expression increased （P＜0.05 or P＜0.01）. Compared to the model group， the ECD group and metformin group showed significant improvements in the above indicators （P＜0.05 or P＜0.01）. Compared to the ECD group， the metformin group showed a reduction in body weight and NPY fluorescence expression， and an increase in HDL-C levels （P＜0.05 or P＜0.01）. ConclusionECD can downregulate serum leptin levels and improve glucose and lipid metabolism in the MS of phlegm syndrome. Its mechanism of action may be to reduce liver fat deposition and thereafter affect the expression of neuropeptides related to feeding activity in the hypothalamus.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

BACKGROUND:In endodontics,revascularization and effective control of bacterial infection are prerequisite for regenerative repair of tissues and further development of the root apex.Ornidazole,carried in pulp-capping materials or vascularized scaffolding materials may control pulpal infections,but its effect on vascularization need to be investigated.OBJECTIVE:To investigate the residual concentration pattern of ornidazole in root canals and to evaluate the effects of ornidazole on endothelial cell proliferation,migration,and differentiation,as well as on vascular irritation.METHODS:(1)Ornidazole was encapsulated in the isolated pulp cavity and then immersed in Hank's balanced salt solution for 7 days.Ornidazole was then removed from the pulp cavity,reencapsulated in sterile water,and again immersed in Hank's balanced salt solution.The mass concentration of ornidazole in the pulp cavity fluid was measured periodically by colorimetric method.(2)Human umbilical vein endothelial cells were inoculated into well plates.Adherent cells were stimulated by the addition of lipopolysaccharide for 24 hours,and then co-cultured by the addition of 0,1,2,5,8,10 μg/mL ornidazole,to detect the cellular activity and migratory ability.Human umbilical vein endothelial cells were inoculated in well plates and co-cultured with different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole or stimulated by lipopolysaccharide for 24 hours followed by the addition of different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole.The gene expression of vascular endothelial growth factor and basic fibroblast growth factor as well as the protein expression of vascular endothelial growth factor was detected.(3)The chorioallantoic membrane assay was employed to assess the vascular irritation of 2 and 10 μg/mL ornidazole.RESULTS AND CONCLUSION:Residual ornidazole in exfoliated teeth was rapidly released within the initial 6 days,with a subsequent decrease in release rate,maintaining a concentration of approximately 2 μg/mL at the root apex after 8 days.Under lipopolysaccharide-induced inflammatory conditions,cell counting kit-8 and cell live-dead fluorescence staining showed that ornidazole(1-10 μg/mL)had no significant effect on the activity of human umbilical vein endothelial cells,and the cell scratch assay showed that ornidazole(1-10 μg/mL)had no obvious effect on the migratory ability of human umbilical vein endothelial cells.RT-qPCR assay showed that,after co-cultivation with ornidazole alone,the mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells showed an overall decreasing trend.After co-culturing with ornidazole under lipopolysaccharide-induced inflammation,the mRNA expression of the two factors showed a rising trend in human umbilical vein endothelial cells.Western blot assay showed that vascular endothelial growth factor protein expression had an elevating trend in human umbilical vein endothelial cells after co-culture with ornidazole under lipopolysaccharide-induced inflammatory conditions.The chorioallantoic membrane assay showed that 2 and 10 μg/mL ornidazole were non-vascular irritating.To conclude,1-10 μg/mL ornidazole is non-cytotoxic and non-vascular irritating,promotes the expression of angiogenesis-related genes and proteins in inflammatory endothelial cells,and serves as a potential therapeutic agent for pulpal infection control.

Objective:To evaluate the diagnostic value of MRI findings in differentiating between tophus and giant cell tumors of the tendon sheath (GCTTS) in the knee.Methods:The study was a case-control study. The clinical and MRI data of patients diagnosed with knee tophus or GCTTS was retrospectively analyzed at the Affiliated Hospital of Qingdao University from September 2018 to September 2024. The study included 23 cases of tophus and 22 cases of GCTTS. MRI sequences, including T 1WI, fat-suppressed T 2WI, and proton density weighted imaging, were evaluated. Parameters including lesion signal intensity and homogeneity, margin, maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, synovial hyperplasia, joint effusion, and periarticular soft tissue swelling were recorded. Independent sample t-tests, χ2 tests, or Fisher exact tests were used to compare MRI findings between the two groups. Multivariate logistic regression was performed to identify independent predictive factors. Results:Significant differences in terms of maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, and periarticular soft tissue swelling between the two groups were found (all P<0.05). No significant differences for other parameters were observed (all P>0.05). Lesion location and ligament/tendon parenchymal involvement demonstrated the highest sensitivity and specificity for distinguishing the two diseases. The sensitivity and specificity values for lesion location were 0.78 and 0.95. The sensitivity and specificity values for ligament/tendon involvement were 0.78 and 1.00. Multivariate logistic regression identified lesion location (inside or outside the synovial cavity) as an independent predictor for differentiating tophus from GCTTS ( OR=31.48, 95% CI 1.58-625.69, P=0.024). Conclusion:The location of the lesion (inside or outside the synovial cavity) and involvement of ligament/tendon parenchyma are critical factors in differentiating knee tophus from GCTTS. Additionally, lesion location serves as an independent predictor for distinguishing between the two conditions.

Objective To observe the efficacy of nomogram model based on enhanced MRI radiomics,deep learning(DL)and clinical features for differentiating spinal tuberculosis and pyogenic spondylitis.Methods Totally 59 cases of spinal tuberculosis and 66 of pyogenic spondylitis were retrospectively enrolled.Radiomics,DL and clinical features relevant to differentiating spinal tuberculosis and pyogenic spondylitis were selected.Then a predictive model was constructed using logistic regression based on the selected optimal features,and a comprehensive nomogram model was developed through combination of the above features.The effectiveness of these models for distinguishing spinal tuberculosis from pyogenic spondylitis were visualized based on receiver operating characteristic curves,calidration curves and decision curves.Results The nomogram model demonstrated the highest area under the curve(AUC)in both training set and test set,with AUC of 0.997 and 0.920,respectively.In test set,DeLong test indicated that the difference of AUC between the nomogram model and clinical model was significant(P=0.002),while no significant difference was observed between the nomogram model and the other models(all P＞0.05).The nomogram model provided the highest overall net benefit and exhibited good calibration for distinguishing spinal tuberculosis from pyogenic spondylitis.Conclusion Nomogram model based on enhanced MRI radiomics,DL and clinical features demonstrated high efficacy for differentiating spinal tuberculosis from pyogenic spondylitis.

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.

BACKGROUND:In endodontics,revascularization and effective control of bacterial infection are prerequisite for regenerative repair of tissues and further development of the root apex.Ornidazole,carried in pulp-capping materials or vascularized scaffolding materials may control pulpal infections,but its effect on vascularization need to be investigated.OBJECTIVE:To investigate the residual concentration pattern of ornidazole in root canals and to evaluate the effects of ornidazole on endothelial cell proliferation,migration,and differentiation,as well as on vascular irritation.METHODS:(1)Ornidazole was encapsulated in the isolated pulp cavity and then immersed in Hank's balanced salt solution for 7 days.Ornidazole was then removed from the pulp cavity,reencapsulated in sterile water,and again immersed in Hank's balanced salt solution.The mass concentration of ornidazole in the pulp cavity fluid was measured periodically by colorimetric method.(2)Human umbilical vein endothelial cells were inoculated into well plates.Adherent cells were stimulated by the addition of lipopolysaccharide for 24 hours,and then co-cultured by the addition of 0,1,2,5,8,10 μg/mL ornidazole,to detect the cellular activity and migratory ability.Human umbilical vein endothelial cells were inoculated in well plates and co-cultured with different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole or stimulated by lipopolysaccharide for 24 hours followed by the addition of different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole.The gene expression of vascular endothelial growth factor and basic fibroblast growth factor as well as the protein expression of vascular endothelial growth factor was detected.(3)The chorioallantoic membrane assay was employed to assess the vascular irritation of 2 and 10 μg/mL ornidazole.RESULTS AND CONCLUSION:Residual ornidazole in exfoliated teeth was rapidly released within the initial 6 days,with a subsequent decrease in release rate,maintaining a concentration of approximately 2 μg/mL at the root apex after 8 days.Under lipopolysaccharide-induced inflammatory conditions,cell counting kit-8 and cell live-dead fluorescence staining showed that ornidazole(1-10 μg/mL)had no significant effect on the activity of human umbilical vein endothelial cells,and the cell scratch assay showed that ornidazole(1-10 μg/mL)had no obvious effect on the migratory ability of human umbilical vein endothelial cells.RT-qPCR assay showed that,after co-cultivation with ornidazole alone,the mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells showed an overall decreasing trend.After co-culturing with ornidazole under lipopolysaccharide-induced inflammation,the mRNA expression of the two factors showed a rising trend in human umbilical vein endothelial cells.Western blot assay showed that vascular endothelial growth factor protein expression had an elevating trend in human umbilical vein endothelial cells after co-culture with ornidazole under lipopolysaccharide-induced inflammatory conditions.The chorioallantoic membrane assay showed that 2 and 10 μg/mL ornidazole were non-vascular irritating.To conclude,1-10 μg/mL ornidazole is non-cytotoxic and non-vascular irritating,promotes the expression of angiogenesis-related genes and proteins in inflammatory endothelial cells,and serves as a potential therapeutic agent for pulpal infection control.

Objective To observe the efficacy of nomogram model based on enhanced MRI radiomics,deep learning(DL)and clinical features for differentiating spinal tuberculosis and pyogenic spondylitis.Methods Totally 59 cases of spinal tuberculosis and 66 of pyogenic spondylitis were retrospectively enrolled.Radiomics,DL and clinical features relevant to differentiating spinal tuberculosis and pyogenic spondylitis were selected.Then a predictive model was constructed using logistic regression based on the selected optimal features,and a comprehensive nomogram model was developed through combination of the above features.The effectiveness of these models for distinguishing spinal tuberculosis from pyogenic spondylitis were visualized based on receiver operating characteristic curves,calidration curves and decision curves.Results The nomogram model demonstrated the highest area under the curve(AUC)in both training set and test set,with AUC of 0.997 and 0.920,respectively.In test set,DeLong test indicated that the difference of AUC between the nomogram model and clinical model was significant(P=0.002),while no significant difference was observed between the nomogram model and the other models(all P＞0.05).The nomogram model provided the highest overall net benefit and exhibited good calibration for distinguishing spinal tuberculosis from pyogenic spondylitis.Conclusion Nomogram model based on enhanced MRI radiomics,DL and clinical features demonstrated high efficacy for differentiating spinal tuberculosis from pyogenic spondylitis.

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.