Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. Methods:Two children with 17β hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children′s Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools.Results:The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5: 1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c. 347G>A (p.R116Q) variant and a c. 274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c. 547G>A (p.G183R) and a c. 331G>C (p.A111P). Among these, the c. 274G>A (p.A92T) and c. 331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+ PM2_supporting) and likely pathogenic (PM3+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c. 274G>A (p.A92T) variant and the ACAT1: c. 331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

Objective:To identify and improve the weakness in different clinical practice teaching hospital,and enhance the quality of practical teaching.Methods:A total of 291 trainees majoring in clinical medicine in grade 2016 in a medical college in Shenyang who practiced in different clinical teaching hospitals and participated in the objective structured clinical examination(OSCE)were enrolled.The OSCE scores was analyzed with one way ANOVA and Kruskal-Wallis statistic methods to identify the weakness in clinical practice teaching and improve the teaching quality.Results:In the standardized patient consultation and physical examination results,the passing rate and average score of H hospital was the lowest.The average score of trainees in H hospital was statistically significant compared to that in A,B,F,G,K,and L hospitals(P＜0.01).In terms of skill operation scores,H hospital had the lowest pass rate and average score.The average score of interns in H hospital was statistically significant compared to that in A,D,E,F,G,I,J,K hospitals(P＜0.01).In the interpretation of auxiliary examination results,the passing rate and average score of H hospital was the lowest.The average score of interns in A and H hospital was significantly different from that of B and J hospitals(P＜0.01).Conclusions:There are great differences in the practice effect of students in different clinical teaching hospitals.Medical colleges and universities should strengthen the management of clinical teaching hospitals to ensure the homogeneity of clinical practice teaching quality.

Purpose To investigate the value of pre-treatment relative cerebral blood flow(rCBF)and relative cerebral blood volume histogram of dynamic susceptibility contrast-enhanced perfusion weighted imaging in predicting the chemotherapy response of primary central nervous system lymphoma(PCNSL)patients.Materials and Methods Thirty-eight PCNSL patients with fifty-seven lesions treated with high-dose methotrexate chemotherapy from September 2016 to October 2023 were retrospectively involved in the study.The patients were divided into response group of 30 patients and non-response group of 8 patients.Region of interest was drawn in cerebral blood flow and cerebral blood volume images,and histogram paraments were extracted.Univariate and multivariate Logistic regression analysis were performed to identify the independent predictors for chemotherapy response in PCNSL,and then combined prediction model was constructed.The area under the receiver operating characteristic curve was used to compare the predictive performance of different paraments and combined model.Results The number of lesions(OR=9.726,95％CI 1.070-88.397,P=0.043)and rCBF90(OR=0.224,95％CI 0.072-0.704,P=0.010)were the independent predictors for chemotherapy response with the area under the curve of 0.681 and 0.798,respectively.The combined model of rCBF90 and the numbers of lesions showed the best predictive performance with the area under the curve of 0.846.Conclusion The pre-treatment quantitative parameters rCBF and relative cerebral blood volume of dynamic susceptibility contrast-enhanced perfusion weighted imaging could be used for predicting the response to high-dose methotrexate chemotherapy in PCNSL patients,and the rCBF90 is an independent predictor of chemotherapy response.

Purpose To construct the model of differentiating primary central nervous system lymphoma(PCNSL)and atypical glioblastoma(GBM)by combining multi-parameter MRI radiomics and six machine learning algorithms,thus to compare the diagnostic efficacy of different machine learning algorithms.Materials and Methods The clinical and imaging data of 77(125 lesions)PCNSL and 90 atypical GBM(108 lesions)from PLA General Hospital and public databases were retrospectively analyzed from January 2013 to December 2023,and all patients were randomly divided into a training set(163 cases)and a validation set(70 cases)according to 7∶3.T1WI,T2WI and T1-weighted contrast-enhanced sequences were selected for tumor segmentation,and 1 132 radiomics features were extracted from each region of interest.The intraclass correlation coefficient(ICC)was used for the consistency test,and image features with ICC≥0.85 were selected.ICC and recursive feature elimination were used to select the best radiomics features.Six classifiers were used to train and verify three single sequence feature sets,three double-sequence sets and one multi-sequence set.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the model.Results The combination model of the support vector machine of radial basis function classifier and multi-sequence feature set were the best model for differentiating PCNSL and atypical GBM.The area under the curve of the training set and the validation set were 0.969 and 0.913,respectively;and the accuracy were both 0.886.Conclusion Noninvasive extraction of multiparametric MRI features combined with machine learning algorithms can effectively differentiate PCNSL and atypical GBM,which provides support for the development of individualized treatment plans for patients.

Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .