Associations between hyperuricemia and ultrasound-detected knee synovial abnormalities in middle-aged and older population: a cross-sectional study.

OBJECTIVES: Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample. METHODS: Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities. RESULTS: In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS. CONCLUSION: In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.

The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci.

Backgrounds: Glioma is a highly malignant brain tumor with a grim prognosis. Genetic factors play a role in glioma development. While some susceptibility loci associated with glioma have been identified, the risk loci associated with prognosis have received less attention. This study aims to identify risk loci associated with glioma prognosis and establish a prognostic prediction model for glioma patients in the Chinese Han population. Methods: A genome-wide association study (GWAS) was conducted to identify risk loci in 484 adult patients with glioma. Cox regression analysis was performed to assess the association between GWAS-risk loci and overall survival as well as progression-free survival in glioma. The prognostic model was constructed using LASSO Cox regression analysis and multivariate Cox regression analysis. The nomogram model was constructed based on the single nucleotide polymorphism (SNP) classifier and clinical indicators, enabling the prediction of survival rates at 1-year, 2-year, and 3-year intervals. Additionally, the receiver operator characteristic (ROC) curve was employed to evaluate the prediction value of the nomogram. Finally, functional enrichment and tumor-infiltrating immune analyses were conducted to examine the biological functions of the associated genes. Results: Our study found suggestive evidence that a total of 57 SNPs were correlated with glioma prognosis (p < 5 × 10-5). Subsequently, we identified 25 SNPs with the most significant impact on glioma prognosis and developed a prognostic model based on these SNPs. The 25 SNP-based classifier and clinical factors (including age, gender, surgery, and chemotherapy) were identified as independent prognostic risk factors. Subsequently, we constructed a prognostic nomogram based on independent prognostic factors to predict individualized survival. ROC analyses further showed that the prediction accuracy of the nomogram (AUC = 0.956) comprising the 25 SNP-based classifier and clinical factors was significantly superior to that of each individual variable. Conclusion: We identified a SNP classifier and clinical indicators that can predict the prognosis of glioma patients and established a prognostic prediction model in the Chinese Han population. This study offers valuable insights for clinical practice, enabling improved evaluation of patients' prognosis and informing treatment options.

Using machine learning techniques to predict the risk of osteoporosis based on nationwide chronic disease data.

Osteoporosis is a major public health concern that significantly increases the risk of fractures. The aim of this study was to develop a Machine Learning based predictive model to screen individuals at high risk of osteoporosis based on chronic disease data, thus facilitating early detection and personalized management. A total of 10,000 complete patient records of primary healthcare data in the German Disease Analyzer database (IMS HEALTH) were included, of which 1293 diagnosed with osteoporosis and 8707 without the condition. The demographic characteristics and chronic disease data, including age, gender, lipid disorder, cancer, COPD, hypertension, heart failure, CHD, diabetes, chronic kidney disease, and stroke were collected from electronic health records. Ten different machine learning algorithms were employed to construct the predictive mode. The performance of the model was further validated and the relative importance of features in the model was analyzed. Out of the ten machine learning algorithms, the Stacker model based on Logistic Regression, AdaBoost Classifier, and Gradient Boosting Classifier demonstrated superior performance. The Stacker model demonstrated excellent performance through ten-fold cross-validation on the training set and ROC curve analysis on the test set. The confusion matrix, lift curve and calibration curves indicated that the Stacker model had optimal clinical utility. Further analysis on feature importance highlighted age, gender, lipid metabolism disorders, cancer, and COPD as the top five influential variables. In this study, a predictive model for osteoporosis based on chronic disease data was developed using machine learning. The model shows great potential in early detection and risk stratification of osteoporosis, ultimately facilitating personalized prevention and management strategies.

[Two-stage Inhibition Effects of Burkholderia sp. Y4 Application on Cadmium Uptake and Transport in Wheat].

In order to evaluate the feasibility of using Burkholderia sp. Y4 as a cadmium （Cd）-reducing bacterial agent in contaminated wheat fields， the changes in the rhizosphere soil microbial community and Cd available state， as well as the content and transport characteristics of Cd in the wheat root， basal node， internode， and grain under the treatment of strain Y4 were tested using microbial high-throughput sequencing， step-by-step extraction， subcellular distribution， and occurrence analyses. The results showed that root application of strain Y4 significantly reduced the root and grain Cd content of wheat by 7.7% and 30.3%， respectively， compared with that in the control treatment. The Cd content and Cd transfer factor results in wheat vegetative organs showed that strain Y4 reduced the Cd transfer factor from basal node to internode by 79.3%， and Cd content in the wheat internode stem also decreased by 50.9%. The study of Cd occurrence morphology showed that strain Y4 treatment increased the proportion of residual Cd in roots and basal ganglia， decreased the contents of inorganic and water-soluble Cd in roots， and increased the content of residual Cd in basal ganglia. Further examination of the subcellular distribution of Cd showed that the Cd content in root cell walls and basal ganglia cell fluid increased by 21.3% and 98.2%， respectively， indicating that the Cd fixation ability of root cell walls and basal ganglia cell fluid was improved by the strain Y4 treatment. In the rhizosphere soil， it was found that the microbial community structure was changed by strain Y4 application. Under the Y4 treatment， the relative abundance of Burkholderia increased from 9.6% to 11.5%， whereas that of Acidobacteriota decreased. Additionally， the relative abundance of Gemmatimonadales， Pseudomonadales， and Chitinophagales were also increased by strain Y4 treatment. At the same time， the application of strain Y4 increased the pH value of rhizosphere soil by 8.3%. The contents of exchangeable Cd， carbonate-bound Cd， and iron-manganese oxide-bound Cd in the soil decreased by 44.4%， 21.7%， and 15.9%， respectively， whereas the proportion of residual Cd reached 53.6%. Root application of strain Y4 increased the contents of nitrate nitrogen and ammonium nitrogen in the soil by 22.0% and 21.4%， respectively， and the contents of alkaline nitrogen also increased to a certain extent. In conclusion， the root application of strain Y4 not only improved soil nitrogen availability but also inhibited Cd transport and accumulation from contaminated soil to wheat grains in a "two-stage" manner by reducing Cd availability in rhizosphere soil and improving Cd interception and fixation capacity of wheat roots and basal nodes. Therefore， Burkholderia Y4 has application potential as a Cd-reducing and growth-promoting agent in wheat.

METTL3-mediated the m6A modification of SF3B4 facilitates the development of non-small cell lung cancer by enhancing LSM4 expression.

BACKGROUND: Splicing factor B subunit 4 (SF3B4) has been confirmed to participate in the progression of many cancers and is considered to be a potential target for non-small cell lung cancer (NSCLC). Thus, the role and molecular mechanism of SF3B4 in NSCLC progression deserves further study. METHODS: Quantitative real-time PCR and western blot were employed to detect the mRNA and protein levels of SF3B4, Sm-like protein 4 (LSM4) and methyltransferase-like 3 (METTL3). Cell proliferation, apoptosis, invasion, migration and stemness were tested by cell counting kit-8, colony formation, flow cytometry, transwell, wound healing, and sphere formation assays. The interaction between SF3B4 and METTL3 or LSM4 was confirmed by MeRIP, RIP and Co-IP assays. Mice xenograft models were constructed to assess the effects of METTL3 and SF3B4 on NSCLC tumorigenesis. RESULTS: SF3B4 had high expression in NSCLC tissues and was associated with the shorter overall survival of NSCLC patients. Knockdown of SF3B4 suppressed NSCLC cell proliferation, invasion, migration and stemness, while inducing apoptosis. METTL3 promoted SF3B4 mRNA stability by m6A modification, and its knockdown inhibited NSCLC cell growth, metastasis and stemness by downregulating SF3B4. SF3B4 could interact with LSM4, and sh-SF3B4-mediated the inhibition on NSCLC cell functions could be reversed by LSM4 overexpression. In addition, reduced METTL3 expression restrained NSCLC tumor growth, and this effect was reversed by SF3B4 overexpression. CONCLUSION: METTL3-stablized SF3B4 promoted NSCLC cell growth, metastasis and stemness via positively regulating LSM4.

Ag2 O-TiO2 -NTs enhance osteogenic activity in vitro by modulating TNF-α/ß-catenin signaling in bone marrow-derived mesenchymal stem cells.

The toxic effects of nanoparticles-silver oxide (Ag2 O) limited its use. However, loading Ag2 O nanoparticles into titanium dioxide (TiO2 ) nanotubes (Ag2 O-TiO2 -NTs) has more efficient biological activity and safety. The aim of this study was to observe the effect of Ag2 O-TiO2 -NTs on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and its mechanism. The enzyme activity of lactate dehydrogenase (LDH) and the expression of RUNX family transcription factor 2 (Runx2), OPN, OCN in BMSCs were detected by quantitative real time polymerase chain reaction. At 14 days of induction, the mineralization ability and alkaline phosphatase (ALP) activity of cells in each group were observed by Alizarin Red S staining and ALP staining. In addition, the protein levels of tumor necrosis factor-α (TNF-α) and ß-catenin in BMSCs of each group were observed by western blot. After 14 days of the induction, the mineralization ability and ALP activity of BMSCs in the Ag2 O-TiO2 -NTs group were significantly enhanced compared with those in the Ag2 O and TiO2 groups. Western blot analysis showed that the BMSCs in the Ag2 O-TiO2 -NTs group exhibited much lower protein level of TNF-α and higher protein level of ß-catenin than those in the Ag2 O and TiO2 groups.Ag2 O-TiO2 -NTs enhance the osteogenic activity of BMSCs by modulating TNF-α/ß-catenin signaling.

Current trends and emerging patterns in the application of nanomaterials for ovarian cancer research: a bibliometric analysis.

Introduction: Ovarian cancer remains to be a significant cause of global cancer-related mortality. In recent years, there has been a surge of studies in investigating the application of nanomaterials in the diagnosis and treatment of ovarian cancer. This study aims to conduct a comprehensive bibliometric analysis regarding nanomaterial-based researches on ovarian cancer to evaluate the current state and emerging patterns in this field. Methods: A thorough literature search on the Web of Science Core Collection database was conducted to identify articles focused on nanomaterial-based ovarian cancer researches. The studies that met the inclusion criteria were selected for further analysis. VOSviewer and CiteSpace were applied for the bibliometric and visual analyses of the selected publications. Results: A total of 2,426 studies were included in this study. The number of annual publications showed a consistent upward trend from 2003 to 2023. Notably, China, the United States, and India have emerged as the leading contributors in this field, accounting for 37.39%, 34.04%, and 5.69% of the publications, respectively. The Chinese Academy of Sciences and Anil K. Sood were identified as the most influential institution and author, respectively. Furthermore, the International Journal of Nanomedicine was the most frequently cited journal. In terms of the research focus, significant attention has been directed towards nanomaterial-related drug delivery, while the exploration of immunogenic cell death and metal-organic frameworks represented recent areas of interest. Conclusion: Through comprehensive analyses, an overview of current research trends and emerging areas of interest regarding the application of nanomaterials in ovarian cancer was illustrated. These findings offered valuable insights into the status and future directions of this dynamic field.

Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer.

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.

SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl- concentration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl- transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl- transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl- concentration ([Cl-]i) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl-]i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

[Clinical outcomes and bone resection analysis of unilateral double-channel endoscopic technique in treating lumbar disc herniation].

OBJECTIVE: To explore clinical outcomes and bone resection of interlaminar fenestration decompression and unilateral biportal endoscopic (UBE) technique in treating lumbar disc herniation(LDH). METHODS: A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021. Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3) years old,were treated with UBE,29 patients with L4,5 and 25 patients with L5S1. There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of (39.9±10.0) years old,were treated with small fenestration,25 patients with L4,5 and 26 patients with L5S1. Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups. Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between two groups before operation and 1,3,6 and 12 months after operation,respectively;and modified MacNab evaluation criteria was used to evaluate clinical efficacy. Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups. RESULTS: All 105 patients were successfully completed operation. Both of two groups were followed up from 6 to 12 months with an average of (10.69±2.49) months. Operation time,postoperative time of getting out of bed and hospital stay were (58.20±5.54) min,(2.40±0.57) d and (3.80±0.61) d in UBE group,and (62.90±7.14) min,(4.40±0.64) d and (4.40±0.64) d in small fenestrum group,respectively;and had statistically difference between two groups(P<0.05). Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery (P<0.05). VAS of lumbar pain in UBE group (1.37±0.49) score was lower than that of small fenestration group (2.45±0.64) score,and had statistically difference (t=9.745,P<0.05). Postoperative ODI in UBE group at 1 and 3 months were (28.54±3.31) % and (22.87±3.23) %,respectively,which were lower than those in small fenestra group (36.31±9.08) % and (29.90±8.36) %,and the difference was statistically significant (P<0.05). There were no significant difference in VAS and ODI between two groups at other time points (P>0.05). According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group. In small fenestration group,35 patients got excellent,12 good,and 4 fair. In UBE group,amount of bone resection on L4,5 segment was (0.45±0.08) cm3 and (0.31±0.08) cm3 on the segment of L5S1. In small fenestration group,amount of bone resection on L4,5 segment was (0.57±0.07) cm3 and (0.49±0.04) cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group (P<0.05). In UBE group,retention rate of laminoid complex on L4,5 segment was (0.73±0.04) and L5S1 segment was (0.83±0.03),while L4,5 segment was(0.68±0.06) and L5S1 segment was (0.74±0.04) in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P<0.05). CONCLUSION: Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher efficiency,faster postoperative recovery and less damage to bone structure.

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.

BACKGROUND: Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. METHODS: We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. RESULTS: Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. CONCLUSIONS: Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.

Conditional Survival of Patients with Limited-Stage Small Cell Lung Cancer After Surgery: A National Real-World Cohort Study.

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

Application of pedobarographic analysis in neglected congenital clubfoot patients following Ponseti treatment for recurrence prediction.

Background: Neglected congenital clubfoot (NCCF) is a birth deformity that remains untreated until the child begins to walk. Irrespective of the treatment protocols employed, children with NCCF face an elevated risk of recurrence following the initial correction. Predicting this recurrence could enable early intervention for high-risk children, ultimately diminishing the likelihood of invasive surgery. Methods: From January 2006 to January 2022, a total of 33 unilateral NCCF patients were enrolled in this study at Xijing Hospital. Pedobarographic tests were performed at three distinct time points: after the initial Ponseti treatment, before recurrence treatment, and after recurrence treatment. Four derivative parameters were developed for predicting recurrence, namely the difference of the contact time% (DCT%), difference of the contact area% (DCA%), difference of the peak pressure (DPP), and difference of the pressure-time integral (DPTI) between the two feet. ROC curves, Kaplan-Meier survival analysis, and Cox regression were employed to identify potential prognostic factors. Results: Out of the 33 unilateral NCCF patients, recurrence occurred in 8 individuals, with an average follow-up period of 109.8 months. The predictive parameter for recurrence is the midfoot (MF) zone's DCT% (MF-DCT%). When the contact time (CT)% of the affected side was 20.69% higher than that of the unaffected side, the hazard ratio (HR) of recurrence increased by 7.404 times. Another predictive plantar pressure parameter is the DPP in the MF zone (MF-DPP). If the PP of the affected side was 159% higher than that of the unaffected side, the HR of recurrence increased by 9.229 times. The MF-DCT% and MF-DPP of recurrence patients were assessed at three time points for comparisons, further validating their predictive ability for recurrence. Conclusion: Although satisfactory clinical outcomes were achieved in patients with unilateral NCCF after the initial Ponseti treatment, the plantar pressure distribution does not return to normal levels, which may indicate future recurrence. DCT% and DPP in the MF zone can be used as plantar pressure predictors of recurrence in patients with NCCF.

Trends and benefits of early hip arthroplasty for femoral neck fracture in China: a national cohort study.

BACKGROUND: Limited studies have examined the benefits of early arthroplasty within 48 h from admission to surgery for femoral neck fractures (FNFs). Using the national inpatient database, the authors aimed to investigate the trends in early arthroplasty within 48 h for FNFs in China and to assess its effect on in-hospital complications and 30-day readmission patterns. MATERIALS AND METHODS: This was a retrospective cohort study. Patients receiving primary total hip arthroplasty (THA) or hemiarthroplasty (HA) for FNFs in the Hospital Quality Monitoring System between 2013 and 2019 were included. After adjusting for potential confounders with propensity score matching, a logistic regression model was performed to compare the differences in in-hospital complications [i.e. in-hospital death, pulmonary embolism, deep vein thrombosis (DVT), wound infection, and blood transfusion], rates and causes of 30-day readmission between early and delayed arthroplasty. RESULTS: During the study period, the rate of early THA increased from 18.0 to 19.9%, and the rate of early HA increased from 14.7 to 18.4% ( P <0.001). After matching, 11 731 pairs receiving THA and 13 568 pairs receiving HA were included. Compared with delayed THA, early THA was associated with a lower risk of pulmonary embolism [odds ratio (OR) 0.51, 95% CI: 0.30-0.88], DVT (OR 0.59, 95% CI: 0.50-0.70), blood transfusion (OR 0.62, 95% CI: 0.55-0.70), 30-day readmission (OR 0.82, 95% CI: 0.70-0.95), and venous thromboembolism-related readmission (OR 0.50, 95% CI: 0.34-0.74). Similarly, early HA was associated with a lower risk of DVT (OR 0.70, 95% CI: 0.61-0.80) and blood transfusion (OR 0.74, 95% CI: 0.68-0.81) than delayed HA. CONCLUSION: Despite a slight increase, the rate of early arthroplasty remained at a low level in China. Given that early arthroplasty can significantly improve prognosis, more efforts are needed to optimize the procedure and shorten the time to surgery.

Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function.

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide, and therefore the identification of the modifiable risk factors [such as exposure to vapors, gases, dust and fumes (VGDF)] for accelerate disease progression has important significance. Methods: We conducted COPD surveillance in six cities of southern China between 2014 and 2019. We recorded the diagnosis of chronic bronchitis, respiratory symptoms, occupational exposure to VGDF and other covariates by using a structured questionnaire. Logistic regression and multivariate linear regression model were adopted for analysis. We performed sensitivity analyses based on two methods of propensity score (PS) methods to evaluate the robustness of our results. Results: A total of 7,418 participants were included. Cough [odds ratios (ORs): 1.60, 95% confidence interval (CI): 1.22 to 2.08] and phlegm (OR: 1.49, 95% CI: 1.19 to 1.85) correlated significantly with exposure to dust. There was an increased risk of cough (OR: 1.53, 95% CI: 1.11 to 2.07) for occupational exposure to gas/vapor/fume. Dual exposure to dust and gas/vapor/fume was associated with a significantly increased risk of chronic bronchitis (OR: 1.74, 95% CI: 1.20 to 2.52), cough (OR: 1.43, 95% CI: 1.15 to 1.79) and phlegm (OR: 1.49, 95% CI: 1.24 to 1.79). In 5,249 participants with complete data of spirometry, gas/vapor/fume was associated with a decreased ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) (ß: -1.05, 95% CI: -1.85 to -0.26) and maximal mid-expiratory flow (MMEF) (ß: -0.15, 95% CI: -0.23 to -0.07). Dual exposure to dust and gas/vapor/fume was significantly associated with decreased FEV1/FVC (ß: -0.74, 95% CI: -1.28 to -0.20) and MMEF (ß: -0.06, 95% CI: -0.12 to -0.01). Results of sensitivity analysis were not materially changed. Conclusions: VGDF exposure is associated with chronic bronchitis, respiratory symptoms and decreased lung function, suggesting that VGDF contributes to the pathogenesis and progression of COPD.

Effect of moxibustion for "nourishing the kidney and benefiting the marrow" on knee osteoarthritis. / "补肾益髓"æ³•è‰¾ç¸æ²»ç–—è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žçš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To compare the clinical effect between two acupoint regimens of moxibustion on knee osteoarthritis (KOA), and observe the influences on the serum content of interleukin 1α (IL-1α), interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α), bone gla protein (BGP) and osteoprotegerin (OPG). METHODS: KOA patients were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 3 cases dropped off). In the observation group, moxibustion was applied to Xiyan (EX-LE5), Dubi (ST35), Zusanli (ST36), Dazhu (BL11), Xuanzhong (GB39) and Yongquan (KI1) on the affected side. In the control group, EX-LE5, ST35 and ST36 were selected on the affected side. One session of treatment took 30 min in each group, delivered 3 times a week and the duration of treatment was 4 weeks. The scores of Western Ontario and McMaster University (WOMAC) and visual analogue scale (VAS) were observed and the serum content of IL-1α, IL-17A, TNF-α, BGP and OPG of the two groups were measured before and after treatment. RESULTS: Compared with those before treatment, the WOMAC score, VAS score and the serum content of IL-1α, IL-17A and TNF-α were decreased (P<0.05), and the content of BGP and OPG were increased (P<0.05) after treatment. Compared with the control group, the WOMAC score, VAS score and the serum content of IL-1α and TNF-α in the observation group were lower (P<0.05), and the content of BGP and OPG were higher (P<0.05). The total effective rate of the observation group was 89.5% (34/38), and that of the control group was 83.8% (31/37), with no statistically significant difference. CONCLUSIONS: Moxibustion therapy of "nourishing the kidney and benefiting the marrow" can relieve joint pain, improve joint function, reduce the level of inflammatory factors and ameliorate bone metabolic indicators. The effect of the acupoint regimen in this moxibustion therapy is better than that of the local acupoint selection.