ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by synovial inflammation, cartilage loss. Often manifesting as joint pain and limited mobility, it severely affects the quality of life of patients. Traditional treatment methods such as pharmacological injections and surgical interventions primarily aim to alleviate symptoms but have limited effects on cartilage repair. Human umbilical cord mesenchymal stem cells (hUC-MSCs), due to their anti-inflammatory and chondrogenic capabilities, is considered a new hope for the treatment of KOA. This article synthesizes the latest research findings from both domestic and international sources to discuss the theoretical basis for the clinical application of hUC-MSCs in treating KOA, clinical study design, and efficacy evaluation. It also addresses the challenges in the clinical application of hUC-MSCs and explores future directions, in the hope of providing feasible theoretical support for the treatment of KOA with hUC-MSCs.

BACKGROUND:Streptococcus mutans is an important pathogen of dental caries,and timely detection of its levels is of great significance for early detection and treatment of dental caries. OBJECTIVE:To evaluate the effect of loop-mediated isothermal amplification(FTA-LAMP)direct extraction of Streptococcus mutans DNA. METHODS:(1)Bacterial suspensions containing ATCC standard strains(Streptococcus mutans)were prepared and inoculated into the brain-heart leachate medium.After mixed thoroughly,the mixture was then diluted in a 10-fold gradient into seven concentrations(4.2×107,4.2×106,4.2×105,4.2×104,4.2×103,4.2×102,4.2×10 CFU/mL),two parallel controls were made for each dilution level,and sterile water was used as a blank control.(2)The DNA of Streptococcus mutans was extracted using FTA Elute card,boiling method,kit extraction and lysate extraction methods separately and then amplified using LAMP technology was amplified.A specificity test was also performed to compare the differences between the four DNA extraction methods.RESULTS AND CONCLUSION:The DNA extracted by all four methods met the requirements for LAMP amplification.Specificity test results showed that only Streptococcus mutans could specifically amplify the target gene.The detection limit value of the DNA concentration was 4.2×103 CFU/mL for the lysate method,4.2×104 CFU/mL for the FTA Elute card extraction method,4.2×106 CFU/mL for the kit extraction method,and 4.2×107 CFU/mL for the boiling method.In the other aspects of the four extraction methods,the kit extraction method had the highest experimental cost,number of steps and time;the other three methods had the same number of steps,with the FTA Elute card method requiring the least amount of instruments,the boiling method having the lowest single cost,and the lysate extraction method taking the least amount of time.Only a small amount of bacteria were needed for successful extraction using both the FTA Elute card and lysate extraction methods.Compared with the FTA Elute card method,the lysate extraction method was superior in terms of time,but it had a high single cost and required more equipment.To conclude,the FTA-LAMP technology established in this study has the advantages of ease of operation,high specificity,high sensitivity,and visualization,which is expected to be a new way for efficient extraction and detection of Streptococcus mutans.

BACKGROUND:Developmental dysplasia of the hip often leads to limb deformities in children,and the research related to its diagnosis and treatment has been gradually clarified.Recently,the finite element method has been paid attention to by scholars in the research related to developmental dysplasia of the hip because of its advantages. OBJECTIVE:Through literature search and review of the relevant research progress of finite element method in children's developmental dysplasia of the hip and treatment,analyze and summarize its advantages and disadvantages,and explore the direction of further research in the future. METHODS:PubMed,SCI,CBM,and CNKI were searched for relevant articles published from January 2014 to November 2023 with the key words of"developmental dysplasia(dislocation)of the hip,dysplasia of the hip,finite element analysis(method),pavlik harness,fixation in herringbone position,biomechanics,pelvic osteotomies,pemberton,salter,dega,periacetabular osteotomy,children"in Chinese and English.A small number of long-term articles were included,and 62 articles were finally included for analysis through screening. RESULTS AND CONCLUSION:(1)The mechanical environment of hip joint in children with developmental dysplasia of the hip was abnormal.The pressure in acetabulum was uneven.The stress increased and concentrated;the joint contact area decreased,and the local stress concentrated in femoral neck.(2)In the Pavlik sling and herringbone fixation,the mechanical environment of the hip was improved;the concentrated high stress area disappeared and the joint contact area increased,but the excessive abduction angle led to the increase of stress in the acetabulum and the lateral femoral head.(3)After pelvic osteotomy,the stress environment of hip joint and sacroiliac joint was improved.There was no single hinge in the three kinds of osteotomy,and the stress load position was different according to the age of the children.(4)After peri-acetabular osteotomy,the joint contact pressure was close to normal,but it was difficult to recover in patients with non-spherical femoral head.(5)The postoperative X-ray film findings could not show that the joint contact mechanics was the best.(6)It is indicated that the information that cannot be measured in the body can be obtained by using the finite element method,which can be operated in a virtual environment without the limitation of time and ethics.It can directly see the stress change area of normal and developmental dysplasia of the hip,explain the effectiveness of treatment from the point of view of mechanics,establish a specific finite element model and tailor-made operation plan for patients who need osteotomy.There is no standard or unified standard for the finite element modeling of developmental dysplasia of the hip and the material characteristic parameters of children's hip joint.Due to the inherent limitations of finite element method,it is impossible to analyze the model that contains bone,cartilage,ligament,muscle and other elements at the same time.The operation of finite element analysis is difficult,although it has advantages,it is not universal,and the current research sample size is small,which needs to be further expanded and verified.

Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: The treatment of asymmetric maxillary hypoplasia and dental crowding secondary to unilateral cleft lip and palate (UCLP) is often challenging.This study introduced an asymmetric tooth-borne distractor in anterior maxillary segmental distraction osteogenesis and used three-dimensional finite element analysis to evaluate its potential for clinical application in cases of asymmetrical maxillary hypoplasia. Methods: A cone-beam computed tomography scan of a late adolescent with UCLP was used to construct a three-dimensional finite element model of the teeth and maxillary structures. An asymmetric distractor model was used to simulate conventional distraction osteogenesis and asymmetric distraction osteogenesis (ADO) to evaluate the resultant stress distribution and displacement. Results: Postoperatively, both distraction methods resulted in anterior maxillary segment advancement with a slight upward movement. ADO yielded a greater increase in the dental arch length on the cleft side and induced rotation of the anterior maxillary segment, potentially improving midline deviation. Both methods showed similar stress distributions, with higher stress concentrations on the cleft side. Conclusions ADO may offer clinical advantages in correcting asymmetrical maxillary hypoplasia in patients with UCLP by facilitating asymmetrical expansion and rotation of the maxilla. Further research is needed to generalize these findings to other clinical presentations.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.