BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

OBJECTIVE: To analyze the short-term effectiveness and safety of personalized three-dimensional (3D) printed customized prostheses in severe Paprosky type Ⅲ acetabular bone defects. METHODS: A retrospective analysis was conducted on 8 patients with severe Paprosky type Ⅲ acetabular bone defects and met the selection criteria between January 2023 and June 2024. There were 3 males and 5 females, with an average age of 64.6 years ranged from 56 to 73 years. All primary replacement prostheses were non-cemented, including 1 ceramic-ceramic interface, 1 ceramic-polyethylene interface, and 6 metal-polyethylene interfaces. The time from the primary replacement to the revision was 4 days to 18 years. The reasons for revision were aseptic loosening in 5 cases, revision after exclusion in 2 cases, and repeated dislocation in 1 case. The preoperative Harris score was 39.5±3.7 and the visual analogue scale (VAS) score was 7.1±0.8. The operation time, intraoperative blood loss, hospital stay, and complications were recorded. The hip function was evaluated by Harris score, and the degree of pain was evaluated by VAS score. The acetabular cup abduction angle, anteversion angle, rotational center height, greater trochanter height, and femoral offset were measured on X-ray film. RESULTS: The operation time was 95-223 minutes, with an average of 151.13 minutes. The intraoperative blood loss was 600-3 500 mL, with an average of 1 250.00 mL. The hospital stay was 13-20 days, with an average of 16.88 days. All 8 patients were followed up 2-12 months, with an average of 6.4 months. One patient had poor wound healing after operation, which healed well after active symptomatic treatment. One patient had lower limb intermuscular vein thrombosis, but no thrombosis was found at last follow-up. No serious complications such as aseptic loosening, infection, dislocation, and periprosthetic fracture occurred during the follow-up. At last follow-up, the Harris score was 72.0±6.2 and the VAS score was 1.8±0.7, which were significantly different from those before operation ( t=-12.011, P<0.001; t=16.595, P<0.001). On the second day after operation, the acetabular cup abduction angle ranged from 40° to 49°, with an average of 44.18°, and the acetabular cup anteversion angle ranged from 19° to 26°, with an average of 21.36°, which were within the "Lewinneck safety zone". There was no significant difference in the rotational center height, greater trochanter height, and femoral offset between the healthy side and the affected side ( P>0.05). CONCLUSION The use of personalized 3D printed customized prostheses for the reconstruction of severe Paprosky type Ⅲ acetabular bone defects can alleviate pain and enhances hip joint function, and have good postoperative prosthesis position, without serious complications and have good safety.
Humans ; Printing, Three-Dimensional ; Male ; Female ; Middle Aged ; Acetabulum/surgery* ; Aged ; Retrospective Studies ; Hip Prosthesis ; Prosthesis Design ; Arthroplasty, Replacement, Hip/instrumentation* ; Reoperation ; Treatment Outcome

OBJECTIVE: To explore the role of antibiotic-eluting absorbable calcium sulfate in treating periprosthetic infection after one-stage revision of knee arthroplasty. METHODS: A retrospective analysis was performed on 36 patients(36 knees)who underwent phaseⅠrevision for periprosthesis infection after total knee arthroplasty from January 2018 to March 2022. All patients were underwent knee cavity puncture before operation and had positive results of aseptic body fluid culture, 21 patients received revision combined with antibiotic loaded calcium sulfate at stageⅠ(calcium sulfate group) during operation, and 15 patients underwent renovation at stageⅠ(revision group). There were 9 males and 12 females in calcium sulfate group, aged from 54 to 76 years old with an average of(67.6±6.2) years old. There were 15 patients in revision group, including 4 males and 11 females, aged from 60 to 75 years old with average of (69.6±4.1) years old. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6) at 7, 14, 30 and 90 days after operation were compared between two groups, and the rate of end-infection control at follow-up were compared. The systemic antibiotic application time, hospital stay and postoperative complications were observed between two groups. RESULTS: Calcium sulfate group were followed up for 12 to 29 months with an average of(18.9±4.2) months, and the infection control rate was 90.5%;while revision group were followed up 18 to 29 months with average of (21.6±3.7) months, and the infection control rate was 86.7% (13/15). There were no significant differences in follow-up time and infection control rate between two groups(P>0.05). Postoperative levels of CRP and IL-6 at 7, 14 and 30 days in calcium sulfate group were (32.79±11.48), (15.50±6.52), (9.36±3.32) mg·L^-1 and (17.31±6.15) pg·ml^-1, respectively;which were lower than those in revision group (40.65±11.32), (30.15±10.57), (18.97±5.86) mg·L^-1 and (25.54±6.73) pg·ml^-1, had statistical differences(P<0.05). There were no significant differences in IL-6 levels at 7 and 14 days after operation and CRP levels at 90 days after operation between two groups (P>0.05). The hospitalization time and systemic antibiotic application time in calcium sulfate group were (18.4±2.2) and (63.5±21.4) d, respectively;which were better than those in revision group (20.5±2.4) and (82.7±16.9) d, and had statistical differences(P<0.05). No significant wound complications and hypercalcemia were observed in calcium sulfate group. CONCLUSION Antibiotic eluted absorbable calcium sulfate could be used to treat periprosthetic knee infection, significantly reducing CRP levels in the early postoperative period, shortening hospital stay and systemic antibiotic application time, but it does not significantly improve the control rate of revision infection at stageⅠ.
Humans ; Male ; Female ; Aged ; Prosthesis-Related Infections/surgery* ; Middle Aged ; Calcium Sulfate/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use* ; Interleukin-6/blood* ; C-Reactive Protein/metabolism* ; Reoperation ; Knee Prosthesis/adverse effects*

Objective:To explore the application of the suspension culture method in pancreatic cancer organoid construction.Methods:Cell suspensions obtained from 8 pancreatic cancer tissue samples at the Second Hospital of Lanzhou University between July 2023 and March 2024, were prepared by digested pancreatic cancer tumor tissues using mixed enzymes, inoculated into ultra-low adsorption culture plates for suspension culture, and when the organoids were cultured to a certain size, passaging and freezing were initiated, and their structural morphology was observed by inverted microscope. Hematoxylin-eosin (HE) staining showed that pancreatic cancer organoids were lumpy or irregularly tubular, with obvious nuclear atypia, and were remarkably similar in tissue structure to pancreatic cancer tissue.Results:Among the 8 pancreatic cancer tissue samples, pancreatic cancer organoids were successfully constructed in three patients, and HE staining showed that pancreatic cancer organoids had a high degree of structural similarity with tumor tissues. Immunohistochemistry suggested that CK7, CK19, P53, and Ki-67 were expressed in the pancreatic cancer organoids and tumor tissues of case origin in more or less the same way.Conclusion:The suspension culture method is able to construct pancreatic cancer-like organs that are approximately the same as the originating tumor tissues at the tissue level.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a serious but underdiagnosed condition. Demand for the gold standard diagnostic polysomnogram (PSG) far exceeds its availability. More efficient diagnostic methods are needed, even in tertiary settings. Machine learning (ML) models have strengths in disease prediction and early diagnosis. We explored the use of ML with oximetry, demographic and anthropometric data to diagnose OSA. METHODS: A total of 2,996 patients were included for modelling and divided into test and training sets. Seven commonly used supervised learning algorithms were trained with the data. Sensitivity (recall), specificity, positive predictive value (PPV) (precision), negative predictive value, area under the receiver operating characteristic curve (AUC) and F1 measure were reported for each model. RESULTS: In the best performing four-class model (neural network model predicting no, mild, moderate or severe OSA), a prediction of moderate and/or severe disease had a combined PPV of 94%; one out of 335 patients had no OSA and 19 had mild OSA. In the best performing two-class model (logistic regression model predicting no-mild vs. moderate-severe OSA), the PPV for moderate-severe OSA was 92%; two out of 350 patients had no OSA and 26 had mild OSA. CONCLUSION Our study showed that the prediction of moderate-severe OSA in a tertiary setting with an ML approach is a viable option to facilitate early identification of OSA. Prospective studies with home-based oximeters and analysis of other oximetry variables are the next steps towards formal implementation.
Humans ; Oximetry/methods* ; Sleep Apnea, Obstructive/diagnosis* ; Male ; Female ; Middle Aged ; Machine Learning ; Polysomnography ; Adult ; Anthropometry ; ROC Curve ; Aged ; Algorithms ; Predictive Value of Tests ; Sensitivity and Specificity ; Neural Networks, Computer ; Demography

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.