Enhanced SLC35B2/SAV1 sulfation axis promotes tumor growth by inhibiting Hippo signaling in HCC.

BACKGROUND AND AIMS: Protein tyrosine sulfation (PTS) is a common posttranslational modification that regulates a variety of physiological and pathological processes. However, the role of PTS in cancer remains poorly understood. The goal of this study was to determine whether and how PTS plays a role in HCC progression. APPROACH AND RESULTS: By mass spectrometry and bioinformatics analysis, we identified SAV1 as a novel substrate of PTS in HCC. Oxidative stress upregulates the transcription of SLC35B2, a Golgi-resident transporter of sulfate donor 3'-phosphoadenosine 5'-phosphosulfate, leading to increased sulfation of SAV1. Sulfation of SAV1 disrupts the formation of the SAV1-MST1 complex, resulting in a decrease of MST1 phosphorylation and subsequent inactivation of Hippo signaling. These molecular events ultimately foster the growth of HCC cells both in vivo and in vitro. Moreover, SLC35B2 is a novel transcription target gene of the Hippo pathway, constituting a positive feedback loop that facilitates HCC progression under oxidative stress. CONCLUSIONS: Our findings reveal a regulatory mechanism of the SLC35B2/SAV1 sulfation axis in response to oxidative stress, highlighting its potential as a promising therapeutic target for HCC.

The relationship between mentally active sedentary behavior and cognitive function across different educational levels.

INTRODUCTION: How education affects the relationship between sedentary behavior and cognitive function remains unclear. The aim of this study was to investigate the relationship between mentally active sedentary behavior and cognitive function in rural older Chinese across different levels of education. METHODS: Data from 517 participants aged 60 years and older in rural China at baseline, 4 weeks, 8 weeks, 6 months, 12 months, and 24 months were analyzed. Univariate analysis was carried out using descriptive statistical techniques and bivariate analysis was performed using Linear mixed effects models. RESULTS: Total mentally active sedentary behavior time and playing cards/mahjong time were significantly associated with global cognition (0.27 points (95% CI, 0.15 to 0.39), P＜0.001; 0.30 points (95% CI, 0.18 to 0.41), P＜0.001, respectively), the attention dimension (0.08 points (95% CI, 0.02 to 0.14), P = 0.005; 0.10 points (95% CI, 0.04 to 0.16), P = 0.001, respectively), and the memory dimension (0.18 points (95% CI, 0.05 to 0.31), P < 0.001; 0.19 points (95% CI, 0.13 to 0.25), P＜0.001, respectively). Such associations were more pronounced in illiterate participants. CONCLUSION: Our study suggested a positive association between mentally active sedentary behavior and cognitive function, with the association being more pronounced among illiterate older adults compared to the relatively well-educated. Future cognitive interventions should focus more on mentally active behavior. In addition, education-specific intervention strategy may be considered in cognitive interventions.

Ultrasound-guided caudal anaesthesia combined with epidural anaesthesia for caesarean section: a randomized controlled clinical trial.

BACKGROUND: Although epidural anaesthesia and spinal anaesthesia are currently the general choices for patients undergoing caesarean section, these two neuraxial anaesthesia methods still have drawbacks. Caudal anaesthesia has been considered to be more appropriate for gynaecological surgery. The purpose of this study was to compare epidural anaesthesia combined with caudal anaesthesia, spinal anaesthesia and single-space epidural anaesthesia for caesarean section with respect to postoperative comfort and intraoperative anaesthesia quality. METHODS: In this clinical trial, 150 patients undergoing elective caesarean section were recruited and randomized into three groups according to a ratio of 1:1:1to receive epidural anaesthesia only, spinal anaesthesia only or epidural anaesthesia combined with caudal anaesthesia. The primary outcome was postoperative comfort in the three groups. Secondary outcomes included intraoperative anaesthesia quality and the incidences of nausea, vomiting, postdural puncture headache, maternal bradycardia, or hypotension. RESULTS: More patients were satisfied with the intraoperative anaesthesia quality in the EAC group than in the EA group (P = 0.001). The obstetrician was more significantly satisfied with the intraoperative anaesthesia quality in the SA and EAC groups than in the EA group (P = 0.004 and 0.020, respectively). The parturients felt more comfortable after surgery in the EA and EAC groups (P = 0.007). The incidence of maternal hypotension during caesarean section was higher in the SA group than in the EA and EAC groups (P = 0.001 and 0.019, respectively). CONCLUSIONS: Epidural anaesthesia combined with caudal anaesthesia may be a better choice for elective caesarean section. Compared with epidural anaesthesia and spinal anaesthesia, it has a higher quality of postoperative comfort and intraoperative anaesthesia.

Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

Comparison of Easydo Activator, ultrasonic and needle irrigation techniques on sealer penetration and smear layer removal in vitro.

The effects of Easydo Activator (EA), a new sonic irrigation system, on sealer penetration at the root apex were compared to needle irrigation (NI) and passive ultrasonic irrigation (PUI) in this study. Forty-two single-rooted teeth were prepared and randomly divided into three groups (n = 14): group 1: NI; group 2: PUI; and group 3: EA. A solution of 3% sodium hypochlorite (NaOCl) was used for irrigation. Nine teeth in each group were filled with AH Plus sealer mixed with CY5 fluorescent dye and a single gutta-percha cone. The sealer penetration area, maximum penetration depth and percentage of sealer penetration at 5 mm and 1 mm from the apex were analyzed by confocal laser scanning microscopy (CLSM). The remaining 5 teeth in each group were subjected to test smear layer scores by scanning electron microscopy (SEM). The CLSM evaluation showed that increases in the area, depth and percentage of sealer penetration were detected at 1 and 5 mm from the root apex in the PUI group compared with the NI group, and greater increases were observed in the EA group (P < 0.05). The SEM experiment showed that the lowest scores for the smear layer and debris removal were achieved by the EA group when compared with the PUI and NI groups (P < 0.05). In conclusion, EA was superior to PUI and NI regarding sealer penetration at the root apex during endodontic treatment, and it could provide a new technical idea for clinical root canal therapy.

Adenosine deaminase from the cerebrospinal fluid for the diagnosis of tuberculous meningitis: A meta-analysis.

OBJECTIVE: To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase. METHODS: Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model. RESULTS: Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82-0.90), specificity of 0.89 (95% CI: 0.86-0.91), positive likelihood ratio of 7.70 (95% CI: 6.16-9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12-0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91-0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L. CONCLUSIONS: Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.

Gardenia (Gardenia jasminoides Ellis) fruit: a critical review of its functional nutrients, processing methods, health-promoting effects, comprehensive application and future tendencies.

Gardenia fruit (GF) is the mature fruit of Gardenia jasminoides Ellis, boasting a rich array of nutrients and phytochemicals. Over time, GF has been extensively utilized in both food and medicinal contexts. In recent years, numerous studies have delved into the chemical constituents of GF and their associated pharmacological activities, encompassing its phytochemical composition and health-promoting properties. This review aims to provide a critical and comprehensive summary of GF research, covering nutrient content, extraction technologies, and potential health benefits, offering new avenues for future investigations and highlighting its potential as an innovative food resource. Additionally, the review proposes novel industrial applications for GF, such as utilizing gardenia yellow/red/blue pigments in the food industry and incorporating it with other herbs in traditional Chinese medicine. By addressing current challenges in developing GF-related products, this work provides insights for potential applications in the cosmetics, food, and health products industries. Notably, there is a need for the development of more efficient extraction methods to harness the nutritional components of GF fully. Further research is needed to understand the specific molecular mechanisms underlying its bioactivities. Exploring advanced processing techniques to create innovative GF-derived products will show great promise for the future.

Advances on delta 5-unsaturated-polymethylene-interrupted fatty acids: Resources, biosynthesis, and benefits.

Though the knowledge on delta 5-unsaturated-polymethylene-interrupted fatty acids (Δ5-UPIFAs) is being updated, the issue of their integration still exists within the field. Thus, this review systematically summarizes the sources, biosynthesis and metabolism, analytical methods, preparation, and health-promoting roles of Δ5-UPIFAs. In plants, the content of Δ5-UPIFAs is higher, which is an ideal source. In animals, although the content of Δ5-UPIFAs is not high, there are many species, which is the possible source of some special Δ5-UPIFAs. At present, although the extraction of Δ5-UPIFAs is mainly from plants, the fermentation by organisms, especially for genetically modified microorganisms engineering maybe be a substitue of pepration of Δ5-UPIFAs. Δ5-UPIFAs have been proved to possess multi-beneficial effects, such as lipid lowering, anti-inflammation and so on, so it has a certain potential application value. However, related knowledge of the underlying molecular mechanisms regarding Δ5-UPIFAs limited, and how Δ5-UPIFAs work is not clear. Further clinical and human studies about Δ5-UPIFAs are also needed. Studies on tapping new resources, developing structured lipide rich in Δ5-UPIFA and enhancing delivery were quite deficient. This review emphasizes the further directions on Δ5-UPIFAs with scientific suggestions to pay more attention to the applications of Δ5-UPIFAs in food, pharmaceutical and cosmetic industries.

Cross-cultural adaptation and psychometric properties of the Mainland Chinese version of the manchester orofacial pain disability scale (MOPDS) among college students.

BACKGROUND: Orofacial pain (OFP) is a highly prevalent disorder in mainland China that predisposes to an associated physical and psychological disability. There is lack of a good properties mainland Chinese version of instrument to examine OFP. This study aims to cross-cultural adaptation and evaluate psychometrics properties of the Manchester Orofacial Pain Disability Scale (MOPDS) in mainland Chinese Mandarin context. METHODS: Translation and cross-cultural adaption of the mainland Chinese version MOPDS were conducted following accepted guidelines of self-report measures. Chinese college students (N = 1039) completed the mainland Chinese version of the MOPDS for item analysis, reliability and validity tests, and measurement invariance analysis, and after a one-month interval, around 10% of the sample (n = 110) were invited to retest. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 26 software were used for all additional studies. RESULTS: We found that the mainland Chinese version of MOPDS contains 25 items, divided into two categories: physical disability and psychological disability. The scale demonstrated excellent internal reliability, test-retest reliability, and validity. The measurement invariance results proved that the scale could be applied to people of different gender, age, and health consultation status. CONCLUSIONS: The results demonstrated the mainland Chinese version of MOPDS has good psychometric properties and can be used to measure the level of physical and psychological disability of Chinese OFP peoples.

Clinical observation of phacoemulsification under the low perfusion pattern and low negative pressure in patients with low corneal endothelial cell density.

BACKGROUND: To observe the safety and effect of phacoemulsification combined with intraocular lens (IOL) implantation in patients with low corneal endothelial cell density (CD) under the low perfusion pattern with low negative pressure. METHODS: In this retrospective case series study, a total of 16 patients (17 eyes) were studied. They had all been diagnosed with low corneal endothelial (CD) and cataracts in the First Affiliated Hospital of Fujian Medical University from December 2019 to October 2021. They underwent phacoemulsification combined with IOL implantation under the low perfusion pattern with low negative pressure. The variations of corneal endothelial( CD), coefficient of variation (CV) of the cell area, central corneal thickness (CCT), visual acuity, and intraocular pressure before and after the operation were observed and assessed. Then a paired t-test, repeated measures analysis of variance, and Pearson correlation analysis were adopted for data analysis. RESULTS: The mean intraocular pressure of the 17 eyes was 16.88 ± 6.47 mmHg before the operation and 14.41 ± 3.10 mmHg after the operation, showing a statistically significant difference of t = 2.222, and p = 0.041. Before the operation, the mean visual acuity was 0.16 ± 0.09, and after the operation, it was 0.45 ± 0.16, displaying a statistically significant difference of t = -9.917, p < 0.001. Before and after the operation, four of the 17 eyes had no detectable CD. The mean CD of the other 13 eyes at one month after the operation (644.308 ± 106.24 cells/mm2) was lower than that before the operation (709.62 ± 119.19 cells/mm2), and the differences were statistically significant (F = 20.044, p < 0.001). However, no statistically significant differences were found in the mean CV before the operation (31.23 ± 4.21), and at one month after the operation (32.62 ± 3.80; F = 2.130, p = 0.157). Moreover, the mean CCT of 14 eyes at one month after the operation (562.72 ± 27.82 µm) was larger than that before the operation (534.79 ± 24.69 µm). CONCLUSIONS: The low perfusion pattern with low negative pressure is safe and effective for corneal endothelial dysfunction patients complicated with cataracts.

Quantitative evaluation of the infrapatellar fat pad in knee osteoarthritis: MRI-based radiomic signature.

BACKGROUND: The infrapatellar fat pad (IFP) may have bilateral influence on knee osteoarthritis (KOA). IFP evaluation may be a key contributor to the diagnostic and clinical management of KOA. Few studies have evaluated KOA-related IFP alteration with radiomics. We investigated radiomic signature for the assessment of IFP for KOA progression in older adults. METHODS: A total of 164 knees were enrolled and grouped based on Kellgren-Lawrence (KL) scoring. MRI-based radiomic features were calculated from IFP segmentation. The radiomic signature was developed using the most predictive subset of features and the machine-learning algorithm with minimum relative standard deviation. KOA severity and structure abnormality were assessed using a modified whole-organ magnetic resonance imaging score (WORMS). The performance of the radiomic signature was evaluated and the correlation with WORMS assessments was analyzed. RESULTS: The area under the curve of the radiomic signature for diagnosing KOA was 0.83 and 0.78 in the training and test datasets, respectively. Rad-scores were 0.41 and 2.01 for the training dataset in the groups with and without KOA (P < 0.001) and 0.63 and 2.31 for the test dataset (P = 0.005), respectively. WORMS significantly and positively correlated with rad-scores. CONCLUSIONS: The radiomic signature may be a reliable biomarker to detect IFP abnormality of KOA. Radiomic alterations in IFP were associated with severity and knee structural abnormalities of KOA in older adults.

Tooth ultrastructure changes induced by a nonsense mutation in the FAM83H gene: insights into the diversity of amelogenesis imperfecta.

OBJECTIVES: The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient's teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods. RESULTS: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient's dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site. CONCLUSIONS: This study expands the understanding of the effects of FAM83H mutations on tooth structure. CLINICAL RELEVANCE: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.

Factorial structure and measurement invariance of the Chinese version of the Oral Health Impact Profile-14 among clinical populations and non-clinical populations: an evidence for public oral investigations.

OBJECTIVE: Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations. METHODS: The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses. RESULTS: We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach's α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p = 0.030, d = 0.125), physical pain (t = 7.880, p < 0.001,d = 0.436), psychological discomfort (t = 8.993, p < 0.001, d = 0.514), physical disability (t = 6.343, p < 0.001, d = 0.358), psychological disability (t = 5.592, p < 0.001, d = 0.315), social disability (t = 5.301, p < 0.001,d = 0.304), social handicap (t = 4.452, p < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p = 0.002, d = 0.280), psychological discomfort (t = 2.478, p = 0.014, d = 0.222), and psychological disability (t = 2.067, p = 0.039, d = 0.188). CONCLUSION: This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations.

Comparison of EASYDO ACTIVATOR, passive ultrasonic, and needle irrigation techniques on the treatment of apical periodontitis: a study in rats.

OBJECTIVES: To evaluate the long-term therapeutic effect of EASYDO ACTIVATOR, passive ultrasonic irrigation, and needle irrigation in experimental apical periodontitis in rats. MATERIALS AND METHODS: Sprague-Dawley male rats were used to produce periapical lesions. The pulp chambers of the bilaterally first mandibular molars were exposed and left open for 21 days. The rats were divided into four groups according to different irrigation protocols. Seven days after irrigation, the mandibles were removed for micro-CT, histological, and immunohistochemical analysis. Serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme-linked immunosorbent assays (ELISA). Statistical data were analyzed by one-way analysis of variance (ANOVA) with LSD tests. RESULTS: The passive ultrasonic irrigation and EASYDO ACTIVATOR groups had the smallest apical lesions compared to the other groups (P < 0.05), while the needle irrigation group had smaller lesions than the control group (P < 0.05). The EASYDO ACTIVATOR group had less inflammation infiltration compared to the control and needle irrigation groups (P < 0.05). The control and needle irrigation groups had more TNF-α expression compared to the passive ultrasonic irrigation and EASYDO ACTIVATOR groups (P < 0.05). The lowest IL-6 expression was observed in the EASYDO ACTIVATOR group. The EASYDO ACTIVATOR group had the lowest serum level of TNF-α than other groups (P < 0.05). IL-6 expression was significantly lower in the EASYDO ACTIVATOR group in comparison with the control and needle irrigation groups (P < 0.05). CONCLUSIONS: EASYDO ACTIVATOR can significantly reduce the apical lesions and decrease the inflammatory response around the periapical area. CLINICAL RELEVANCE: EASYDO ACTIVATOR is recommended for clinical application.

Role of NOD2 and hepcidin in inflammatory periapical periodontitis.

The immunological response occurring during periapical inflammation includes expression of nucleotide binding oligomerization domain containing 2 and hepcidin. Nucleotide binding oligomerization domain containing 2 deficiency increases infiltration of inflammatory cells close to alveolar bone. Hepcidin has an important role in iron metabolism affecting bone metabolism.We investigated the role of nucleotide binding oligomerization domain containing 2 and hepcidin in inflammatory periapical periodontitis. Periapical periodontitis was induced in rats and confirmed by micro-computed tomography. Nucleotide binding oligomerization domain 2 and hepcidin were evaluated through immunohistochemistry. Bioinformatics analysis was undertaken usingthe Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Micro-computer tomography revealed alveolar bone resorption in the periapical region and furcation area of mandibular molars in rats of the periapical periodontitis group. Immunohistochemistry showed increased expressionof nucleotide binding oligomerization domain containing 2 and hepcidin around root apices in rats of the periapical periodontitis group. Bioinformatics analysis of differentially expressed genes in inflamed and non-inflamed tissues revealed enrichment in the NOD-like receptor signaling pathway. Our data suggest that nucleotide binding oligomization domain contain2 and hepcidin have important roles in periapical periodontitis severity because they can reduce alveolar bone loss.They could elicit new perspectives for development of novel strategies for periapical periodontitis treatment.

Comparison of sealer penetration of sonic activation versus conventional needle irrigation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Most existing studies comparing the efficiency of sonic irrigation (SI) and conventional needle irrigation (CNI) in increasing the penetration of sealers into dentine tubules are controversial; and this study aimed to determine whether the use of SI can lead to greater sealing ability than CNI, during the root canal treatment. METHODS: The EMBASE, PubMed, and Cochrane Library databases were used to find confocal laser scanning microscopy studies evaluating percentage and maximum depth of sealer penetration following the use of SI or CNI in mature permanent teeth until October 2022. The critical estimative checklist of randomized controlled trials of the standardized Joanna Briggs Institute was adopted to independently score the quality of each study. The random-effect model for meta-analysis was used to analyse for each canal segment (apical, middle, coronal). The results are shown in the forest plots as weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). RESULTS: Ninety-seven articles were included in the preliminary screening, and nine of them were included in this study. Eight studies were included in the meta-analysis.The meta-analysis exhibited great increases in the coronal (WMD: 8.09, 95% CI 2.78-13.40/WMD: 165.32, 95% CI 128.85-201.80), and middle segments (WMD: 8.81, 95% CI 5.76-11.87/WMD: 132.98, 95% CI 68.71-197.25) for the percentage and maximum depth of sealer penetration, respectively. The percentage of sealer penetration in the apical thirds region was nonsignificant (WMD: 4.73, 95% CI - 2.34-11.80). However, the maximum depth of sealer penetration in the apical thirds region was significant (WMD: 121.46, 95% CI 86.55-156.38). Chi-squared analysis revealed heterogeneity scores of 0.0-70.0% and 44.0-90.0% for the percentage and maximum depth of sealer penetration, respectively. DISCUSSION: This review verified that SI significantly improves tubular dentin sealer penetration in most areas of the root canal; thus, SI may lead to better filling efficiency and anti-reinfection effects than CNI during and after the root canal therapy. Nevertheless, a large heterogeneity in the current data comparing the irrigation efficiency of SI versus CNI in the apical third of the root canal was found, implying the necessity to standardize root canal irrigation procedures and obtain more accurate results in this area. TRIAL REGISTRATION: INPLASY database (INPLASY202270116).

The Chinese version of the Oral Health Impact Profile-14 (OHIP-14) questionnaire among college students: factor structure and measurement invariance across genders.

BACKGROUND: The Oral Health-related Quality of Life (OHRQoL) is a multi-dimensional concept commonly used to examine the impact of health status on quality of life, and the Oral Health Impact Profile-14 (OHIP-14) questionnaire is a good self-assessment tool. This study was designed to investigate the factor structure of the OHIP-14 scale Chinese version, measurement invariance and latent mean differences across genders among college students. METHODS: The online survey was completed by 919 college students. This study used confirmatory factor analysis (CFA) to check the structural models of the OHIP-14 scale, The correlation of each item with the scale total score could test homogeneity, and Cronbach's alpha (Cronbach's α) could evaluate internal consistency. Multi-group CFA was used to explore whether the Chinese version of the OHIP-14 scale was used in male and female populations for measurement consistency. T-test compared scores between men and women. Regression analyses were used to evaluate the relationship between age, gender, education, subject, and the score on the OHIP-14 scale. RESULTS: We found that the 7-factor structure had the best fit index in the sample. According to Cronbach's α, the overall score of OHIP was 0.958, and Cronbach's α for 7 factors was: functional limitation was 0.800, physical pain was 0.854, psychological discomfort was 0.902, physical disability was 0.850, psychological disability was 0.768, social disability was 0.862, social handicap was 0.819 and the test-retest reliability interval was 0.723. Multi-group confirmatory factor analysis supported residual measurement invariance across gender. T-test for scores showed that females scored higher significantly than men as did the overall score, in terms of physical pain (p<0.001), physical disability (p<0.001), and psychological disability (p<0.001). CONCLUSIONS: This study found the OHIP-14 Chinese version to be a good tool for assessing the college students' OHRQoL in China, allowing people to conduct self-assessments.

PDLIM1 Inhibits Tumor Metastasis Through Activating Hippo Signaling in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.

Human drug efflux transporter ABCC5 confers acquired resistance to pemetrexed in breast cancer.

AIM: Pemetrexed, a new generation antifolate drug, has been approved for the treatment of locally advanced or metastatic breast cancer. However, factors affecting its efficacy and resistance have not been fully elucidated yet. ATP-binding cassette (ABC) transporters are predictors of prognosis as well as of adverse effects of several xenobiotics. This study was designed to explore whether ABC transporters affect pemetrexed resistance and can contribute to the optimization of breast cancer treatment regimen. METHODS: First, we measured the expression levels of ABC transporter family members in cell lines. Subsequently, we assessed the potential role of ABC transporters in conferring resistance to pemetrexed in primary breast cancer cells isolated from 34 breast cancer patients and the role of ABCC5 in mediating pemetrexed transport and apoptotic pathways in MCF-7 cells. Finally, the influence of ABCC5 expression on the therapeutic effect of pemetrexed was evaluated in an in vivo xenograft mouse model of breast cancer. RESULTS: The expression levels of ABCC2, ABCC4, ABCC5, and ABCG2 significantly increased in the pan-resistant cell line, and the ABCC5 level in the MCF-7-ADR cell line was 5.21 times higher than that in the control group. ABCC5 expression was inversely correlated with pemetrexed sensitivity (IC50, r = 0.741; p < 0.001) in breast cancer cells derived from 34 patients. Furthermore, we found that the expression level of ABCC5 influenced the efflux and cytotoxicity of pemetrexed in MCF-7 cells, with IC50 values of 0.06 and 0.20 µg/mL in ABCC5 knockout and over-expression cells, respectively. In the in vivo study, we observed that ABCC5 affected the sensitivity of pemetrexed in breast tumor-bearing mice, and the tumor volume was much larger in the ABCC5-overexpressing group than in the control group when compared with their own initial volumes (2.7-fold vs. 1.3-fold). CONCLUSIONS: Our results indicated that ABCC5 expression was associated with pemetrexed resistance in vitro and in vivo, and it may serve as a target or biomarker for the optimization of pemetrexed regimen in breast cancer treatment.

BRAF V600E as an accurate marker to complement fine needle aspiration (FNA) cytology in the guidance of thyroid surgery in the Chinese population: evidence from over 1000 consecutive FNAs with follow-up.

BACKGROUND: Currently, several commercial molecular tests have been developed for reclassifying thyroid nodules with indeterminate fine needle aspiration cytology. These tests are quite expensive and not available in China. Previous studies demonstrated a very high prevalence of the BRAF V600E mutation in Asian people. A high incidence may result in a robust sensitivity. We conducted this study to determine the prevalence of BRAF V600E mutation and its ability to reclassify cytologically indeterminate thyroid nodules in the Chinese population. METHODS: Between January 2016 and October 2018, consecutive patients who underwent a fine needle aspiration procedure and agreed to provide materials for molecular analysis in our hospital were recruited in this study. All were followed up until they had a thyroidectomy and a final pathological diagnosis or until January 2019 (those did not have surgery). RESULTS: A total of 1960 patients were included in this study. Until January 2019, 1240 patients underwent surgery. Using histopathological diagnosis as a gold standard, the overall sensitivity and specificity of the BRAF V600E mutational analysis for the discrimination of benign nodules from cancer in thyroid fine needle aspiration samples were 83.3% (81.0-85.3%) and 96.0% (77.7-99.8%), respectively, with an area under the ROC curve of 0.90 (95% CI 0.85-0.95, P < 0.001). Among cases with indeterminate cytology, BRAF-positive cases were showing malignancy in the final pathology, and BRAF-negative cases were showing safer to be followed up. CONCLUSION: The BRAF V600E mutation is highly prevalent in the Chinese population and can accurately complement cytopathology in the guidance of thyroid surgery.Mini-abstract: The BRAF V600E mutation has both high specificity and sensitivity to predict thyroid malignancy in the Chinese population. It can accurately complement cytopathology in the guidance of thyroid surgery.