Plasma steroid profiling combined with machine learning for the differential diagnosis in mild autonomous cortisol secretion from nonfunctioning adenoma in patients with adrenal incidentalomas.

BACKGROUND: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting (XGBoost) was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: 76 patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among five ML models evaluated, XGBoost demonstrated superior performance with an AUC of 0.77 using 24 steroid hormones. The SHAP method identified five steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone (DHEA), 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate (DHEAS). Upon incorporating clinical features into the model, the AUC increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, DHEA, LDL-c, BMI, and ACTH along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these two entities through a single blood collection.

Molecular characterization and functional roles of circulating cell-free extrachromosomal circular DNA.

Circular DNA segments isolated from chromosomes are known as extrachromosomal circular DNA (eccDNA). Its distinct structure and characteristics, along with the variations observed in different disease states, makes it a promising biomarker. Recent studies have revealed the presence of eccDNAs in body fluids, indicating their involvement in various biological functions. This finding opens up avenues for utilizing eccDNAs as convenient and real-time biomarkers for disease diagnosis, treatment monitoring, and prognosis assessment through noninvasive analysis of body fluids. In this comprehensive review, we focused on elucidating the size profiles, potential mechanisms of formation and clearance, detection methods, and potential clinical applications of eccDNAs. We aimed to provide a valuable reference resource for future research in this field.

Steroid profiling in adrenal disease.

The measurement of steroid hormones in blood and urine, which reflects steroid biosynthesis and metabolism, has been recognized as a valuable tool for identifying and distinguishing steroidogenic disorders. The application of mass spectrometry enables the reliable and simultaneous analysis of large panels of steroids, ushering in a new era for diagnosing adrenal diseases. However, the interpretation of complex hormone results necessitates the expertise and experience of skilled clinicians. In this scenario, machine learning techniques are gaining worldwide attention within healthcare fields. The clinical values of combining mass spectrometry-based steroid profiles analysis with machine learning models, also known as steroid metabolomics, have been investigated for identifying and discriminating adrenal disorders such as adrenocortical carcinomas, adrenocortical adenomas, and congenital adrenal hyperplasia. This promising approach is expected to lead to enhanced clinical decision-making in the field of adrenal diseases. This review will focus on the clinical performances of steroid profiling, which is measured using mass spectrometry and analyzed by machine learning techniques, in the realm of decision-making for adrenal diseases.

Patients with early-stage alcohol-associated liver disease are at increased risk of hospital readmission and death.

BACKGROUND AND AIMS: Patients with alcohol use disorder (AUD) can develop alcohol-associated fatty liver disease (AFLD). However, the impact of AFLD on outcomes remains unclear. We studied the impact of AFLD on readmission, 30-day mortality, and overall mortality in patients admitted with AUD. METHODS: Hospitalized patients with AUD between 2011 and 2019 at a tertiary medical center were retrospectively evaluated. Our population included patients with AUD with AFLD: AST and ALT elevation and serum bilirubin <3 mg/dl. Patients with AUD without evidence of liver disease served as control and were labeled as no ALD. Patients with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) were included for comparison. Kaplan-Meier survival analysis and multivariable regression for predictors of mortality and survival were performed. RESULTS: There were 7522 patients of which 32.44% were female with mean age of 51.86 ±â€…14.41 years. Patient distribution included no ALD (n = 3775), AFLD (n = 2192), AC (n = 1017) and AH (n = 538) groups. Compared to no ALD group, AFLD group was associated with significantly higher 30-day mortality [4.43% vs. 1.56%, hazard ratio (HR): 2.84; P  < 0.001], overall mortality [15.97% vs. 12.69%, HR 1.40, P  < 0.001], and 30-day readmission [21.85% vs. 18.49%, odds ratio: 1.21; P  < 0.01]. CONCLUSION: We demonstrated that AFLD is not a benign entity and poses significant mortality risk. Our results suggest that AFLD may be under-recognized and highlight the need for focused management and close follow-up after discharge.

Case report and mini-review: Sarcina ventriculi in the stomach of an 80-year-old female.

Sarcina ventriculi, also known as Zymosarcina ventriculi and, incorrectly, as Clostridium ventriculi, is rarely encountered in clinical settings. A patient with a complicated gastrointestinal (GI) history, who was acutely presenting with small-bowel obstruction, was found to be colonized by S. ventriculi. The distinctive morphology of this species, with large Gram-variable cocci (up to 3 µm) arranged in two-by-two cuboid clusters reaching up to 20 µm, was key in identifying this bacterium in a stomach biopsy specimen. Sarcina ventriculi appears to be ubiquitously found in nature, and related bacterial species can cause GI-related disease in various animals. Clinical manifestations in humans are broad and often related to other underlying comorbidities. Isolation of S. ventriculi in the laboratory requires anaerobic culture on select media but its absence from standard MALDI-TOF databases complicates identification. Susceptibility data do not exist, so empiric treatment is the only option for this rare pathogen.

Study on the reversal of epileptic drug resistance by tetramethylpyrazine in combination with carbamazepine through modulation of P-Glycoprotein expression in rat brain microvessel endothelial cell.

The purpose of this study was to detect the changes of P-Glycoprotein (P-GP) expression in rat brain microvessel endothelial cell line RBE4 after the action of Tetramethylpyrazine (TMP) on Carbamazepine (CBZ), so as to clarify the potential mechanism of TMP combined with CBZ against intractable epilepsy drug resistance. The RBE4 cell line was utilized for in vitro analysis. Cells were divided into control, CBZ, and CBZ-TMP group. The expression of P-GP was assessed using Western blot and reverse transcription polymerase chain reaction (RT-PCR). Intracellular concentration of CBZ was measured through high-performance liquid chromatography (HPLC). The differential expression of mRNA was evaluated by RNA sequencing. The intracellular concentration of CBZ in the CBZ-TMP group was significantly higher than that in other groups. The expression of P-GP in the CBZ group was significantly higher than that in the control group, while in the CBZ&TMP group, it was significantly lower than that in the other groups. Comparative analysis also revealed some differentially expressed genes. Compared with the CBZ group, FAM106A, SLC3A2, TENM2, etc. were upregulated most significantly in the CBZ&TMP group. ZBTB10, WDR7, STARD13, etc. were downregulated most significantly. Results suggest that TMP increases the intracellular concentration of CBZ, downregulates the expression of P-GP increased by CBZ, and modulates related cellular metabolism and signaling pathways, thus reversing the drug resistance mechanism of intractable epilepsy, providing a theoretical basis for the combination of traditional Chinese medicine and antiepileptic drugs.

Opioid Free Total Intravenous Anesthesia With Dexmedetomidine-Esketamine-Lidocaine for Patients Undergoing Lumpectomy.

Background: The aim of the study was to evaluate the feasibility of the opioid-free anesthesia (OFA) technique with dexmedetomidine, esketamine, and lidocaine among patients diagnosed with benign breast mass and scheduled for lumpectomy. Methods: We enrolled 80 female patients who were aged from 18 to 60 years, graded with American Society of Anesthesiologists physical status I or II, diagnosed with benign breast mass, and scheduled for lumpectomy. These patients were randomly treated with OFA or opioid-based anesthesia (OBA). Dexmedetomidine-esketamine-lidocaine and sufentanil-remifentanil were administered in OFA and OBA group, respectively. We mainly compared the analgesic efficacy of OFA and OBA technique, as well as intraoperative hemodynamics, the quality of recovery, and satisfaction score of patients. Results: There was no significant difference between the two groups with regard to visual analogue scale (VAS) score at 2, 12, and 24 h after extubation. However, the time to first rescue analgesic was prolonged in OFA group than that in OFB group (6.18 ± 1.00 min vs. 7.40 ± 0.92 min, P = 0.000). Further, mean arterial pressure and heart rate at T0 (entering operating room), T1 (before anesthesia induction), T2 (immediately after intubation), T3, T4, and T5 (1, 5, and 10 min after surgical incision, respectively) were significantly higher in OFA group than that in OBA group. Incidence of hypotension and bradycardia was lower in OFA group. Consistently, fewer patients in OFA group consumed atropine (8% vs. 32%, P = 0.019) and ephedrine (5% vs. 38%, P = 0.001) compared to OBA group. Furthermore, patients in OFA group had a longer awakening time (7.14 ± 2.63 min vs. 4.54 ± 1.14 min, P = 0.000) and recovery time of orientation (11.76 ± 3.15 min vs. 6.92 ± 1.19 min, P = 0.000). Fewer patients in the OFA group experienced postoperative nausea and vomiting (PONV) (11% vs. 51%, P = 0.000) and consumed ondansetron (5% vs. 35%, P = 0.003) compared to OBA group. And patients in OFA group had a higher satisfaction score than those in OBA group (9 (8 - 9) vs. 7 (7 - 8), P = 0.000). Conclusion: For patients undergoing lumpectomy, OFA technique with dexmedetomidine-esketamine-lidocaine showed a better postoperative analgesic efficacy, a more stable hemodynamics, and a lower incidence of PONV. However, such advantage of OFA technique should be weighed against a longer awakening time and recovery time of orientation in clinical practice.

Saliva sampling strategies affecting the salivary glucose measurement.

Characterized by sustained elevated blood glucose levels, diabetes mellitus has become one of the largest global public health concerns by imposing a heavy global burden on socio-economic development. To date, regular blood glucose level check by performing a finger-prick test has been a routine strategy to monitor diabetes. However, the intrusive nature of finger blood prick tests makes it challenging for individuals to maintain consistent testing routines. Recently, salivary glucose measurement (SGM) has increasingly become a non-invasive alternative to traditional blood glucose testing for diabetes. Despite that, further research is needed to standardize the collection methods and address the issues of variability to ensure accurate and reliable SGM. To resolve possible remaining issues in SGM, we here thoroughly explored saliva sampling strategies that could impact the measurement results. Additionally, the effects of supplements taken, mouth washing, gum chewing, and smoking were collectively analyzed, followed by a continuous SGM over a long period, forming the stepping stone for the practical transitional development of SGM in non-invasive diabetes monitoring.

The effect of maternal vitamin D deficiency during pregnancy on glycolipid metabolism of offspring rats and the improvement of vitamin D intervention after weaning.

Background: Vitamin D deficiency during pregnancy is common, but whether maternal vitamin D status affects glycolipid metabolism of offspring remains unclear. Objective: To evaluate the effect of maternal vitamin D deficiency during pregnancy on the glycolipid metabolism of offspring at different life-cycles (from birth to adulthood) and to explore the improvement of different dosages of vitamin D supplementation. Methods: Sprague-Dawley rats were fed vitamin D-deprived (VDD group) or standard vitamin D diets (SC group) during pregnancy, and their diets were changed to standard vitamin D diets during lactation (the offspring were sorted into VDDoffspring and SCoffspring groups). After weaning, rats in the VDDoffspring group were randomly assigned to the VDDoffspring, VDDoffspring-S3300 and VDDoffspring-S10000 groups with diets containing standard, medium and high dosages of vitamin D for 12 wk. Serum was collected for biochemical analyses at postnatal Day 21, postnatal Day 56 and postnatal Day 84. Oral glucose tolerance test (OGTT) was performed at postnatal Day 70. Results: Compared to SCoffspring, rats in the VDDoffspring group had significantly lower birth weight with faster weight gain and higher levels of lipid metabolism in early life. After near adulthood, the differences in weight and lipid metabolism between the two groups disappeared. OGTT showed significantly higher blood glucose levels in the VDDoffspring group at 30 min, 60 min, and 90 min. The continuation of vitamin D supplementation at medium and high dosages after weaning did not cause any obvious changes in weight or glycolipid metabolism (except for postprandial hyperglycemia). OGTT demonstrated that the glucose levels in the VDDoffspring-S3300 group were lowest at all the time points and that those in the VDDoffspring-S10000 group were the highest at 30 min, 60 min, and 90 min among the three groups. Conclusion: The adverse effects of vitamin D deficiency during pregnancy on glycolipid metabolism in offspring vary in different stages. Over a long time period, adequate vitamin D supplementation is beneficial to glycolipid metabolism for the offspring of subjects with vitamin D deficiency during pregnancy; however, further improvement is required.

The status and childcare management of overweight and obesity among preschool children in Hangzhou.

OBJECTIVES: This study aims to investigate the prevalence of overweight and obesity in preschool children in Hangzhou and assess the impact of childcare management. By examining the characteristics and predicting the trends of overweight and obesity, we hope to emphasize the significance of childcare management in primary community health service centers and the use of Electronic Health-care System in kindergartens. This study also seeks to provide evidence for intervention measures and effective prevention and control management of childhood obesity. METHODS: From 2020 to 2022, kindergarten children aged 3-6 years old were selected as the research objects in kindergartens in Hangzhou. The Electronic Health-care System will be utilized to facilitate the management of childhood obesity and provide guidance and training to pediatricians and Primary Care Physicians. RESULTS: The overall detection rates of overweight and obesity were 7.27 % and 3.55 %, respectively, among children aged 3-6 years in Hangzhou. The rates of simple obesity in Hangzhou preschool children aged 3-6 years were 4.25 , 3.42, and 3.04 % from 2020 to 2022, respectively; the overweight detection rates of children were 8.27 , 7.28, and 6.34 %, respectively, and the difference was statistically significant (p<0.05). The detection rates of overweight and obesity in 2022 were significantly lower than those in 2020 (p<0.05). The prevalence of obesity in children increased with age. Boys had a significantly higher incidence rate of obesity than girls (p<0.05). The proportion of children with moderate and severe obesity showed a downward trend. Intervention measures for childhood obesity in primary community health service centers and kindergartens are constantly being implemented. CONCLUSIONS: The prevalence of obesity in preschool children aged 3-6 years in Hangzhou exhibited a decreasing tendency. This research has identified that child care administration, particularly the implementation of the Electronic Health-care System, demonstrates effectiveness in handling overweight and obesity amongst children.

Factors and Molecular Mechanisms of Vitamin A and Childhood Obesity Relationship: A Review.

Childhood obesity has become a public health concern. As the importance of vitamin A (VA) in the body has become increasingly acknowledged, there is limited clinical trial evidence to substantiate the association between VA and childhood obesity. Vitamin A deficiency (VAD) increases the risk of childhood obesity, a finding consistently reported in pregnant women. VA could regulate the adipogenic process, inflammation, oxidative stress and metabolism-related gene expression in mature adipocytes. VAD disrupts the balance of obesity-related metabolism, thus affecting lipid metabolism and insulin regulation. Conversely, VA supplementation has a major impact on efficacy in obesity, and obese individuals typically have a lower VA status than normal-weight individuals. Several studies have attempted to identify the genetic and molecular mechanisms underlying the association between VA and obesity. In this review, we summarize and discuss recent new developments focusing on retinol, retinoic acid, and RBP4 and elucidate and provide an overview of the complex interrelationships between these critical components of VA and childhood obesity. However, the causal relationship between VA status and childhood obesity remains unclear. It is also unknown whether VA supplementation improves the overall obesogenic metabolic profile.

[Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC].

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 µm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

Ovarian Granulosa Cell Tumor Initially Presenting as a Giant Liver Mass Radiologically Mimicking Primary Cystic Cholangiocarcinoma.

BACKGROUND: Ovarian granulosa cell tumor (GCT) is a rare type of malignant sex-cord stromal tumor, with adult and juvenile types. The ovarian GCT initially presented as a giant liver mass clinically mimicking primary cholangiocarcinoma is exceedingly rare. CASE REPORT: We report such a case of a 66-year-old woman who presented with right upper quadrant pain. Abdominal magnetic resonance imaging (MRI) and a subsequently fused positron emission tomography/computed tomography (PET/CT) showed a solid and cystic mass with hypermetabolic activity concerning intrahepatic primary cystic cholangiocarcinoma. A fine-needle core biopsy of the liver mass showed coffee-bean-shaped tumor cells. The tumor cells were positive for Forkhead Box L2 (FOXL2), inhibin, Wilms tumor protein 1 (WT-1), steroidogenic factor 1 (SF1), vimentin, estrogen receptor (ER), and smooth muscle actin (SMA). The histologic features and immunoprofile supported a metastatic sex-cord stromal tumor favoring granulosa cell tumor, adult type. Strata next-generation sequencing test was performed on the liver biopsy and FOXL2 c.402C>G (p.C134W) mutation was present, consistent with granulosa cell tumor. CONCLUSION: To the best of our knowledge, this is the first documented case of ovarian granulosa cell tumor with FOXL2 mutation initially presenting as a giant liver mass clinically mimicking primary cystic cholangiocarcinoma.

Effect of individualised nutritional intervention on the postpartum nutritional status of patients with gestational diabetes mellitus and the growth and development of their offspring: a quasi-experimental study.

This study explored the effect of individualised nutritional intervention on the postpartum nutritional status of patients with the growth and development of their offspring. This study included pregnant women with gestational diabetes mellitus (GDM) at Hangzhou Women's Hospital in 2019. At 42 days after childbirth, the HbA1c (95% CI: 0.44-0.56%, p < 0.001), the FPG (95% CI: 0.01-0.26 mmol/L, p < 0.05), 2HPG (95% CI: -0.01-0.73 mmol/L, p < 0.05) and TCH (95% CI: -0.34-0.00 mmol/L, p < 0.05) level of the control group were 0.14, 0.36, and 0.17 mmol/L higher than in the intervention group. There were no differences in TG and HGB between the two groups (all p > 0.05). There were significant differences in the number of macrosomia and neonatal weight between the two groups (both p < 0.05). Differences in WHZ after childbirth were not statistically significant between the two groups (all p > 0.05). Individualised nutritional intervention could improve blood glucose levels 42 days after childbirth and reduce macrosomia incidence in pregnant women with GDM.Impact statementWhat is already known on this subject? Individualised nutrition intervention can improve blood glucose status and complications during pregnancy, thus improving pregnancy outcomes.What the results of this study add? Individual nutrition intervention improved the blood glucose and nutritional status of patients at 42 days postpartum, but there was no difference in the growth and development indicators of their offspring at 0-24 months.What the implications are of these findings for clinical practice and/or further research? Improve nutritional intervention programs for gestational diabetes, improve blood glucose during pregnancy and postpartum, to improve pregnancy outcomes and reduce the occurrence of type 2 diabetes and other metabolic diseases; Extend the monitoring range of the growth and development of the offspring of gestational diabetes, find the problems and timely carry out the nutritional intervention, to improve the development of the offspring.

Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC / 中国中药杂志

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 μm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

Endodontic management of a fused left maxillary second molar and two paramolars using cone beam computed tomography: A case report.

BACKGROUND: Fused teeth usually involve several complications, such as the development of caries in the groove between fused crowns, tooth impaction, diastemas, aesthetic and periodontal problems, and pulpal pathosis, due to the complex anatomical structure of fused teeth. A thorough diagnosis is paramount to forming an accurate treatment plan and obtaining a favourable prognosis. With the advent of cone-beam computed tomography (CBCT), accurate 3-dimensional images of teeth and their surrounding dentoalveolar structures can now be readily obtained, and the technology can accurately provide a minimally invasive approach to acquire detailed diagnostic information. Therefore, we utilize CBCT data herein to generate a digital model for the infected region in a patient, and this model enables us to better plan the management of his case. CASE SUMMARY: This report details the diagnosis and endodontic treatment of a rare case involving a fused maxillary second molar and two paramolars with apical periodontitis. The patient experienced pain upon biting and cold sensitivity in the area of the maxillary left molar. No caries or other defects were identified in these teeth, and a normal response to a pulp electric viability test was observed. With the aid of CBCT and digital model technology, we initially suspected that the infection originated from the isthmus between the maxillary second molar and two paramolars. Therefore, we only treated the isthmus by an endodontic approach and did not destroy the original tooth structure; furthermore, the vital pulp was retained, and good treatment outcomes were observed at the 24-month follow-up. CONCLUSION: This finding may provide new insights and perspectives on the diagnosis and treatment of fused teeth.

Mechanism of dact2 gene inhibiting the occurrence and development of liver fibrosis.

There are few reports about the relationship between dact2 and liver fibrosis. The inhibitory mechanism of dact2 in liver fibrosis is not clear, we need to further explore it. In this study has been shown that the dact2 gene can inhibit liver fibrosis. In this experiment, we used lentivirus as a vector to construct a lentivirus vector carrying the dact2 gene and packaged dact2 recombinant lentivirus and its control vector. HSC-T6 infected cells were observed. The effect of dact2 gene expression was activated by Wnt3a HSC-T6 cells. Immunoblot was used to detect α - SMA expression, TGF - ß 1, Smad3, Smad7, ß - Catenin and CyclinD1. The expression of MMP-2 and TIMP-1 was detected by real-time PCR. At the same time, dact2 recombinant lentivirus was injected into the tail vein. Carbon tetrachloride was used to establish the liver fibrosis model. After 7 weeks of modeling, the staining was used to observe the pathological changes of liver tissue, hydroxyproline was used to analyze the changes of collagen content in liver tissue, the expression of the protein was observed by immunohistochemistry, and the expression of fibrosis-related genes was detected by real-time PCR. Results showed that the dact2 gene expression could inhibit the activation of HSC-T6 cells and reduce the expression of TGF - ß 1. The percentage of Smad3, ß - Catenin and cyclinD1 protein was 50.02%, 46.73%, 47.58% and 37.50% respectively (P < 0.05).

lncRNA ZNF674-AS1 inhibits the migration, invasion and epithelial-mesenchymal transition of thyroid cancer cells by modulating the miR-181a/SOCS4 axis.

Thyroid cancer (TC) is a very common endocrine cancer worldwide. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. Long non-coding RNAs (lncRNAs), a series of non-coding RNAs with a length of >200 nts, have been regarded as crucial regulators of many cancers playing a tumor suppressive or oncogenic role, depending on circumstances. lncRNA ZNF674-AS1 was reported to be abnormally expressed in TC, but the exact mechanism remains unclear. This study aims to probe the mechanism and roles of ZNF674-AS1 in TC. The expression patterns of RNAs and proteins were determined via qRT-PCR and western blotting, respectively. Cell proliferation, migration and invasion were detected using MTT and Transwell assays. ZNF674-AS1 and SOCS4 expression were remarkably reduced while miR-181a was upregulated in TC tissues and cells. Enforced expression of ZNF674-AS1 inhibited proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and reduced tumour growth in vivo. Mechanistic assays verified that ZNF674-AS1 directly interacted with miR-181a to increase SOCS4 expression. In addition, miR-181a overexpression aggravated proliferation, metastasis and EMT by inhibiting SOCS4. Interestingly, inhibition of miR-181a diminished the promoting effects of ZNF674-AS1 silencing on the malignant behaviours of TC cells. These data illustrated that ZNF674-AS1 alleviated TC progression by modulating the miR-181a/SOCS4 axis (graphical abstract), further suggesting that ZNF674-AS1 might be used as a therapheutic target in TC treatment.