Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein-protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management.

Association between diabetes mellitus and postoperative urinary retention after cerebral angiography.

AIMS: The aim of this study is to examine the association between diabetes mellitus and postoperative urinary retention on cerebral angiography (including intravascular interventional therapy). METHODS: We collected data on the demographic characteristics and comorbidities, imaging and routine laboratory data, surgical information, and medications of patients who underwent cerebral angiography. Multivariate logistic regression was used to explore the correlation between diabetes and the incidence of postoperative urinary retention. RESULTS: A total of 932 patients were included, with a mean age of 59.7 years (74.1% men). Postoperative urinary retention occurred in 40.8% of the diabetes mellitus group and 30.3% of the group without diabetes. Compared with the group without diabetes, those with diabetes were more likely to experience postoperative urinary retention. Patients with higher glycosylated hemoglobin A1c levels had a higher risk of developing postoperative urinary retention. CONCLUSIONS: Diabetes was independently linked to postoperative urinary retention following cerebral angiography and patients with glycosylated hemoglobin A1c levels > 6% were more likely to experience postoperative urinary retention. Therefore, clinically regulating blood glucose levels may help to reduce the likelihood of postoperative urinary retention after cerebral angiography.

Nitrous oxide inhalation-induced cerebral venous sinus thrombosis in a 20-year-old man: A case report.

Nitrous oxide is increasingly abused in the young population and has been verified to induce neuropathy, myelopathy, encephalopathy, and thrombosis. Nitrous oxide-related thrombosis was identified in the coronary artery, ascending aorta, pulmonary artery, and deep vein in the lower extremities. Cases with nitrous oxide abuse-related thrombosis in cerebral veins or cerebral venous sinus have rarely been reported, and confounding risk factors for thrombosis other than nitrous oxide exist in previous cases. Here, we report a case of probable nitrous oxide abuse-related cerebral venous sinus thrombosis without common confounding risk factors for thrombosis except for nitrous oxide.

Migraine and Risk of Breast Cancer: A Systematic Review and Meta-analysis.

Migraine and breast cancer are 2 prevalent diseases with high morbidity and mortality rates world-wide. There have been inconsistent reports regarding the association between migraine and risk of breast cancer. This systematic review and meta-analysis aimed to assess the risk of breast cancer in patients with migraine. By December, 1, 2022, we searched PubMed, Web of Science, Scopus, and Cochrane Library databases. Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (CIs) were extracted or assessed to determine the pooled risk estimate using a random-effects model. We use the Newcastle-Ottawa Scale (NOS) to evaluate the quality of studies. We included 9 studies involving 393,282 participants. The pooled analysis showed that patients with migraine had a slightly low risk of breast cancer (OR 0.82, 95% CI, 0.72-0.94; P = .003), especially in case-control studies (OR 0.69, CI: 0.60-0.81, I2 = 74.1%, p < .001), and hormone receptor-positive breast cancer (OR 0.76, CI: 0.63-0.91; I2 = 88.6%; p = .003). Our findings demonstrate a slightly low risk of breast cancer, especially hormone receptor-positive breast cancer, in patients with migraine.

Is endovascular treatment still good for acute ischemic stroke in the elderly? A meta-analysis of observational studies in the last decade.

Background: The lack of randomized evidence makes it difficult to establish reliable treatment recommendations for endovascular treatment (EVT) in elderly patients. This meta-analysis aims to evaluate the therapeutic effects of endovascular treatment for acute ischemic stroke in the elderly compared with younger patients. Methods: Comprehensive literature retrieval was conducted to identify studies that directly compared the outcomes of EVT in elderly patients and those aged <80 years. The primary outcome was functional independence, defined as mRS 0-2 at 90 days after EVT. The secondary outcomes were the rate of successful recanalization, symptomatic intracranial hemorrhage (sICH) and mortality. Odds ratios (ORs) were estimated using a random effects model. Results: In total, twenty-six studies with 9,492 enrolled participants were identified. Our results showed that, compared with patients aged <80 years undergoing EVT, EVT was associated with a lower rate of functional independence at 90 days (OR = 0.38; 95% CI, 0.33-0.45; p < 0.00001) and a higher mortality rate (OR = 2.51; 95% CI, 1.98-3.18; p < 0.00001) in the elderly. Furthermore, even without a significantly observed increase in sICH (OR = 1.19; 95% CI, 0.96-1.47; p = 0.11), EVT appeared to be associated with a lower rate of successful recanalization (OR = 0.81; 95% CI, 0.68-0.96; p = 0.02). Conclusion: Evidence from observational studies revealed that EVT has less functional outcomes in elderly patients with acute ischemic stroke. Further studies are needed to better identify patients aged ≥80 years who could potentially benefit from EVT.

Anti-diabetic effects of Inonotus obliquus extract in high fat diet combined streptozotocin-induced type 2 diabetic mice / Efectos antidiabéticos del extracto de Inonotus obliquus en ratones diabéticos tipo 2 inducidos por estreptozotocina combinada con una dieta rica en grasas

Introduction: type 2 diabetes (T2DM) is a complex disease affected by lifestyle and genetic factors. Although the drugs currently used to treat T2DM have certain curative effects, they still have some adverse side effects. Therefore, it is urgent to find new effective drugs with few side effects to cure T2DM. Objective: to study the role of Inonotus obliquus (IO) in diabetic model mice. Methods: we used high-fat diet (HFD) combined with streptozocin (STZ) to establish a diabetic mouse model. Mice were divided into non-high-fat diet group (ND), diabetes model group (HFD + STZ) and IO-treated diabetes model group (IO). The mice in the IO group were orally treated with IO (150 mg/kg) at 10 ml/kg for five weeks. Body weight, glucose level, food intake and water consumption, glucose tolerance and insulin tolerance were evaluated in all mice. The pathological sections of liver, kidney and pancreas were observed by hematoxylin-eosin staining. Results: after IO administration, the blood glucose level, water consumption, low-density lipoprotein (LDL) and triacylglycerol (TG) levels of mice decreased. Compared with the HFD + STZ group, the number of normal islet iiiiiiii cells increased and focal necrosis of the liver was significantly reduced in the IO administration group. Conclusions: IO reduced the levels of blood glucose, restored body weight, and enhanced insulin sensitivity along with insulin tolerance and glucose tolerance in diabetic mice. Additionally, IO also reversed HFD and STZ-induced organ injury. (AU)

Introducción: la diabetes mellitus tipo 2 (T2DM) es una enfermedad compleja influenciada por el estilo de vida y los factores genéticos. En la actualidad, aunque los medicamentos para la diabetes tipo 2 tienen cierto efecto curativo, todavía tienen algunos efectos secundarios. Por lo tanto, es urgente encontrar nuevos medicamentos para la diabetes tipo 2 que tengan un buen efecto curativo y menos efectos secundarios. Objetivo: estudiar el papel del Inonotus obliquus (IO) en ratones diabéticos. Métodos: se estableció un modelo de ratón diabético con dieta de alto contenido en grasas (HFD) y estreptozocina (STZ). Los ratones se dividieron en el grupo de dieta no alta en grasas (ND), el grupo modelo de diabetes mellitus (HFD + STZ) y el grupo modelo de diabetes mellitus tratado con IO. Los ratones del grupo IO recibieron 10 ml/kg de IO (150 mg/kg) durante cinco semanas. Se observaron el peso corporal, el nivel de azúcar en sangre, la ingesta de alimentos, la ingesta de agua potable, la tolerancia a la glucosa y la tolerancia a la insulina de los ratones de cada grupo, y se estudiaron muestras de biopsias hepáticas, renales y pancreáticas mediante tinción de hematoxilina eosina. Resultados: los niveles de glucosa en sangre, el consumo de agua, la lipoproteína de baja densidad (LDL) y los triglicéridos (TG) disminuyeron después de la administración de IO. En comparación con el grupo HFD+STZ, el número de células β pancreáticas normales y la necrosis focal hepática disminuyeron significativamente en el grupo IO. Conclusiones: el IO redujo el nivel de glucosa en sangre, ayudó a recuperar el peso corporal y mejorar la sensibilidad a la insulina, la tolerancia a la insulina y la tolerancia a la glucosa en ratones diabéticos. Además, el IO revirtió el daño orgánico inducido por HFD y STZ. (AU)

Anti-diabetic effects of Inonotus obliquus extract in high fat diet combined streptozotocin-induced type 2 diabetic mice.

Introduction: Introduction: type 2 diabetes (T2DM) is a complex disease affected by lifestyle and genetic factors. Although the drugs currently used to treat T2DM have certain curative effects, they still have some adverse side effects. Therefore, it is urgent to find new effective drugs with few side effects to cure T2DM. Objective: to study the role of Inonotus obliquus (IO) in diabetic model mice. Methods: we used high-fat diet (HFD) combined with streptozocin (STZ) to establish a diabetic mouse model. Mice were divided into non-high-fat diet group (ND), diabetes model group (HFD + STZ) and IO-treated diabetes model group (IO). The mice in the IO group were orally treated with IO (150 mg/kg) at 10 ml/kg for five weeks. Body weight, glucose level, food intake and water consumption, glucose tolerance and insulin tolerance were evaluated in all mice. The pathological sections of liver, kidney and pancreas were observed by hematoxylin-eosin staining. Results: after IO administration, the blood glucose level, water consumption, low-density lipoprotein (LDL) and triacylglycerol (TG) levels of mice decreased. Compared with the HFD + STZ group, the number of normal islet ß cells increased and focal necrosis of the liver was significantly reduced in the IO administration group. Conclusions: IO reduced the levels of blood glucose, restored body weight, and enhanced insulin sensitivity along with insulin tolerance and glucose tolerance in diabetic mice. Additionally, IO also reversed HFD and STZ-induced organ injury.

Introducción: Introducción: la diabetes mellitus tipo 2 (T2DM) es una enfermedad compleja influenciada por el estilo de vida y los factores genéticos. En la actualidad, aunque los medicamentos para la diabetes tipo 2 tienen cierto efecto curativo, todavía tienen algunos efectos secundarios. Por lo tanto, es urgente encontrar nuevos medicamentos para la diabetes tipo 2 que tengan un buen efecto curativo y menos efectos secundarios. Objetivo: estudiar el papel del Inonotus obliquus (IO) en ratones diabéticos. Métodos: se estableció un modelo de ratón diabético con dieta de alto contenido en grasas (HFD) y estreptozocina (STZ). Los ratones se dividieron en el grupo de dieta no alta en grasas (ND), el grupo modelo de diabetes mellitus (HFD + STZ) y el grupo modelo de diabetes mellitus tratado con IO. Los ratones del grupo IO recibieron 10 ml/kg de IO (150 mg/kg) durante cinco semanas. Se observaron el peso corporal, el nivel de azúcar en sangre, la ingesta de alimentos, la ingesta de agua potable, la tolerancia a la glucosa y la tolerancia a la insulina de los ratones de cada grupo, y se estudiaron muestras de biopsias hepáticas, renales y pancreáticas mediante tinción de hematoxilina eosina. Resultados: los niveles de glucosa en sangre, el consumo de agua, la lipoproteína de baja densidad (LDL) y los triglicéridos (TG) disminuyeron después de la administración de IO. En comparación con el grupo HFD+STZ, el número de células ß pancreáticas normales y la necrosis focal hepática disminuyeron significativamente en el grupo IO. Conclusiones: el IO redujo el nivel de glucosa en sangre, ayudó a recuperar el peso corporal y mejorar la sensibilidad a la insulina, la tolerancia a la insulina y la tolerancia a la glucosa en ratones diabéticos. Además, el IO revirtió el daño orgánico inducido por HFD y STZ.

CD36 aggravates podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy in lupus nephritis.

A major cause of proteinuria in lupus nephritis (LN) is podocyte injury, and determining potential therapeutic targets to prevent podocyte injury is important from a clinical perspective in the treatment of LN. CD36 is involved in podocyte injury in several glomerulopathies and was reported to be a vital candidate gene in LN. Here, we determined the role of CD36 in the podocyte injury of LN and the underlying mechanisms. We observed that CD36 and NLRP3 (NLR family pyrin domain containing 3) were upregulated in the podocytes of lupus nephritis patients and MRL/lpr mice with renal impairment. In vitro, CD36, NLRP3 inflammasome, and autophagy were elevated accompanied with increased podocyte injury stimulated by IgG extracted from lupus nephritis patients compared that from healthy donors. Knocking out CD36 with the CRISPR/cas9 system decreased the NLRP3 inflammasome levels, increased the autophagy levels and alleviated podocyte injury. By enhancing autophagy, NLRP3 inflammasome was decreased and podocyte injury was alleviated. These results demonstrated that, in lupus nephritis, CD36 promoted podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy by enhancing which could decrease NLRP3 inflammasome and alleviate podocyte injury.

Factors Associated With the Utilization of Outpatient Virtual Clinics: Retrospective Observational Study Using Multilevel Analysis.

BACKGROUND: Although the COVID-19 pandemic has accelerated the adoption of telemedicine and virtual consultations worldwide, complex factors that may affect the use of virtual clinics are still unclear. OBJECTIVE: This study aims to identify factors associated with the utilization of virtual clinics in the experience of virtual clinic service implementation in Taiwan. METHODS: We retrospectively analyzed a total of 187,742 outpatient visits (176,815, 94.2%, in-person visits and 10,927, 5.8%, virtual visits) completed at a large general hospital in Taipei City from May 19 to July 31, 2021, after rapid implementation of virtual outpatient clinic visits due to the COVID-19 pandemic. Data of patients' demographic characteristics, disease type, physicians' features, and specialties/departments were collected, and physicians' opinions regarding virtual clinics were surveyed and evaluated using a 5-point Likert scale. Multilevel analysis was conducted to determine the factors associated with the utilization of virtual clinics. RESULTS: Patient-/visit-, physician-, and department-level factors accounted for 67.5%, 11.1%, and 21.4% of the total variance in the utilization of virtual clinics, respectively. Female sex (odds ratio [OR] 1.27, 95% CI 1.22-1.33, P<.001); residing at a greater distance away from the hospital (OR 2.36, 95% CI 2.15-2.58 if distance>50 km, P<.001; OR 3.95, 95% CI 3.11-5.02 if extensive travel required, P<.001); reimbursement by the National Health Insurance (NHI; OR 7.29, 95% CI 5.71-9.30, P<.001); seeking care for a major chronic disease (OR 1.33, 95% CI 1.24-1.42, P<.001); the physician's positive attitude toward virtual clinics (OR 1.50, 95% CI 1.16-1.93, P=.002); and visits within certain departments, including the heart center, psychiatry, and internal medicine (OR 2.55, 95% CI 1.46-4.46, P=.004), were positively associated with the utilization of virtual clinics. The patient's age, the physician's age, and the physician's sex were not associated with the utilization of virtual clinics in our study. CONCLUSIONS: Our results show that in addition to previously demonstrated patient-level factors that may influence telemedicine use, including the patient's sex and distance from the hospital, factors at the visit level (insurance type, disease type), physician level (physician's attitude toward virtual clinics), and department level also contribute to the utilization of virtual clinics. Although there was a more than 300-fold increase in the number of virtual visits during the pandemic compared with the prepandemic period, the majority (176,815/187,742, 94.2%) of the outpatient visits were still in-person visits during the study period. Therefore, it is of great importance to understand the factors impacting the utilization of virtual clinics to accelerate the implementation of telemedicine. The findings of our study may help direct policymaking for expanding the use of virtual clinics, especially in countries struggling with the development and promotion of telemedicine virtual clinic services.

Evaluating the comparative efficiency of medical centers in Taiwan: a dynamic data envelopment analysis application.

BACKGROUND: People in Taiwan enjoy comprehensive National Health Insurance coverage. However, under the global budget constraint, hospitals encounter enormous challenges. This study was designed to examine Taiwan medical centers' efficiency and factors that influence it. METHODS: We obtained data from open sources of government routine publications and hospitals disclosed by law to the National Health Insurance Administration, Ministry of Health and Welfare, Taiwan. The dynamic data envelopment analysis (DDEA) model was adopted to estimate all medical centers' efficiencies during 2015-2018. Beta regression models were used to model the efficiency level obtained from the DDEA model. We applied an input-oriented approach under both the constant returns-to-scale (CRS) and variable returns-to-scale (VRS) assumptions to estimate efficiency. RESULTS: The findings indicated that 68.4% (13 of 19) of medical centers were inefficient according to scale efficiency. The mean efficiency scores of all medical centers during 2015-2018 under the CRS, VRS, and Scale were 0.85, 0.930, and 0.95,respectively. Regression results showed that an increase in the population less than 14 years of age, assets, nurse-patient ratio and bed occupancy rate could increase medical centers' efficiency. The rate of emergency return within 3-day and patient self-pay revenues were associated significantly with reduced hospital efficiency (p < 0.05). The result also showed that the foundation owns medical center has the highest efficiency than other ownership hospitals. CONCLUSIONS: The study results provide information for hospital managers to consider ways they could adjust available resources to achieve high efficiency.

Potentially preventable hospital readmissions after patients' first stroke in Taiwan.

Readmission is an important indicator of the quality of care. The purpose of this study was to explore the probabilities and predictors of 30-day and 1-year potentially preventable hospital readmission (PPR) after a patient's first stroke. We used claims data from the National Health Insurance (NHI) from 2010 to 2018. Multinomial logistic regression was used to assess the predictors of 30-day and 1-year PPR. A total of 41,921 discharged stroke patients was identified. We found that hospital readmission rates were 15.48% within 30-days and 47.25% within 1-year. The PPR and non-PPR were 9.84% (4123) and 5.65% (2367) within 30-days, and 30.65% (12,849) and 16.60% (6959) within 1-year, respectively. The factors of older patients, type of stroke, shorter length of stay, higher Charlson Comorbidity Index (CCI), higher stroke severity index (SSI), regional hospital, public and private hospital, and hospital in the lower urbanized area were associated significantly with the 30-day PPR. In addition, the factors of male, hospitalization year, and monthly income were associated significantly with 1-year PPR. The ORs of long-term PPR showed a decreasing trend since implementing the national health insurance post-acute care (PAC) program in 2014 and a dramatic drop in 2018 after the government expanded the long-term care plan-LTC 2.0 in 2017. The results showed that better discharge planning, implementing post-acute care programs and long-term care plan-LTC 2.0 may benefit the care of stroke patients and help reduce long-term readmission in Taiwan.

Cost-effectiveness of immune checkpoint inhibitors in the treatment of non-small-cell lung cancer as a second line in Taiwan.

Objectives: To evaluate the cost-effectiveness of immune checkpoint inhibitors versus docetaxel in patients with advanced non-small-cell lung cancer. Methods: A Markov model was constructed to simulate the clinical outcomes and costs of advanced non-small-cell lung cancer. Clinical outcomes data were derived from randomized clinical trials. Drug acquisition cost and other health resource use were obtained from the claim data of a tertiary hospital and the National Health Insurance. The outcome was an incremental cost-effectiveness ratio expressed as cost per quality-adjusted life year gained. One-way and probabilistic sensitivity analyses were performed to evaluate the uncertainty of the model parameters. Results: In the base case, patients treated with immunotherapies in the second line were associated with higher costs and higher mean survival. The incremental costs per quality-adjusted life year gained for pembrolizumab, nivolumab, or atezolizumab compared to docetaxel were NT$416,102, NT$1,572,912 and NT$1,580,469, respectively. Conclusion: The results showed that pembrolizumab was more cost effective than nivolumab and atezolizumab compared with docetaxel as a second-line regimen for patients with previously treated advanced non-small-cell lung cancer at willingness to pay threshold in Taiwan.

Plain language summary Lung cancer is the first leading cause of cancer death in Taiwan. About 75% of patients have advanced disease at the time of diagnosis (stage III/IV) with a median survival of 13.2 months. Most non-small-cell lung cancer (NSCLC) patients are usually diagnosed at a late stage. The conventional chemotherapy, surgery or radiation regimens may not be of significant benefits. Fortunately, newer immunotherapies or targeted therapies have improved the 5-year survival rates of advanced NSCLC from 15 to 50% with high cost. This study aimed to assess if the newer targeted therapies are cost effective and provide 'value for money' compared with chemotherapy in NSCLC patients with advanced stage. A cost­effectiveness model was created based on the data from the real-world and published phase III randomized controlled trials. The results showed that pembrolizumab is more cost effective than nivolumab and atezolizumab compared with docetaxel as a second-line regimen for patients with previously treated advanced NSCLC at willingness to pay threshold in Taiwan.

Cost-effectiveness analysis of olaparib and niraparib as maintenance therapy for women with recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: We evaluated the cost-effectiveness of olaparib and niraparib as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer.Methods: A decision analysis model compared the costs and effectiveness of olaparib and niraparib versus placebo for patients with or without germline BRCA mutations. Resource use and associated costs were estimated from the 2020 National Health Insurance Administration reimbursement price list. Clinical effectiveness was measured in progression-free survival per life-years (PFS-LY) based on the results of clinical trials SOLO2/ENHOT-Ov21 and ENGOT-OV16/NOVA. The incremental cost-effectiveness ratio (ICER) was estimated from a single-payer perspective. RESULTS: In the base case, olaparib was the more cost-effective treatment regimen. The ICERs for olaparib and niraparib compared to placebo were NT$1,804,785 and NT$2,340,265 per PFS-LY, respectively. Tornado analysis showed that PFS and the total resource use cost of niraparib regimen for patients without gBRCA were the most sensitive parameters impacting the ICER. The ICERs for both drugs in patients with a gBRCA mutation were lower than in patients without a gBRCA mutation. Probabilistic sensitivity analysis indicated that olaparib was more cost-effective than niraparib at the willingness-to-pay threshold of NT$2,602,404 per PFS life-year gained. CONCLUSION: Olaparib was estimated to be less cost and more effective compared to niraparib as maintenance therapy for patients with recurrent platinum-sensitive ovarian cancer.

[Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report of One Case].

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.

Short-, Mid-, and Long-Term Associations Between PM2.5 and Stroke Incidence in Taiwan.

OBJECTIVE: To investigate the association between the risk of stroke and exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) over various exposure periods. METHODS: This was a nationwide population-based case-control study in which 10,035 incident patients with a primary diagnosis of ischemic stroke each were matched with two randomly selected controls for sex, age, Charlson Comorbidity Index, year of stroke diagnosis, and level of urbanization. Multiple logistic models adjusted for potential confounders were used to assess the association of PM2.5 with ischemic stroke incidence. RESULTS: There were significant short-term, medium-term, and long-term relationships between PM2.5 exposure and ischemic stroke incidence. CONCLUSIONS: This study supports existing evidence that PM2.5 should be considered a risk factor for ischemic stroke.

The ZNF76 rs10947540 polymorphism associated with systemic lupus erythematosus risk in Chinese populations.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease with a strong genetic disposition. Genetic studies have revealed that single-nucleotide polymorphisms (SNPs) in zinc finger protein (ZNF)-coding genes are associated with susceptibility to autoimmune diseases, including SLE. The objective of the current study was to evaluate the correlation between ZNF76 gene polymorphisms and SLE risk in Chinese populations. A total of 2801 individuals (1493 cases and 1308 controls) of Chinese Han origin were included in this two-stage genetic association study. The expression of ZNF76 was evaluated, and integrated bioinformatic analysis was also conducted. The results showed that 28 SNPs were associated with SLE susceptibility in the GWAS cohort, and the association of rs10947540 was successfully replicated in the independent replication cohort (Preplication = 1.60 × 10-2, OR 1.19, 95% CI 1.03-1.37). After meta-analysis, the association between rs10947540 and SLE was pronounced (Pmeta = 9.62 × 10-6, OR 1.29, 95% CI 1.15-1.44). Stratified analysis suggested that ZNF76 rs10947540 C carriers were more likely to develop relatively high levels of serum creatinine (Scr) than noncarriers (CC + CT vs. TT, p = 9.94 × 10-4). The bioinformatic analysis revealed that ZNF76 rs10947540 was annotated as an eQTL and that rs10947540 was correlated with decreased expression of ZNF76. Remarkably, significantly reduced expression of ZNF76 was confirmed by expression data from both our laboratory and an array-based expression database. Taken together, these results suggest that ZNF76 rs10947540 is a possible susceptibility factor associated with SLE susceptibility. The mechanism underlying the relationship between ZNF76 and SLE pathogenesis still requires further investigation.

Cost-utility analysis of stereotactic body radiotherapy plus cetuximab in previously irradiated recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: This study aimed to estimate the cost-utility of stereotactic body radiotherapy (SBRT) plus cetuximab for patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. METHODS: We constructed a Markov health-state transition model to simulate costs and clinical outcomes of recurrent squamous cell carcinoma of the head and neck. Model parameters were derived from the published literature and the National Health Insurance Administration reimbursement price list. Incremental cost-effectiveness ratio and the net monetary benefit were calculated from a health payer perspective. The impact of uncertainty was modeled with one-way and probabilistic sensitivity analyses. RESULTS: In the base-case, SBRT plus cetuximab compared to SBRT alone resulted in an ICER of NT$ 840,455 per QALY gained. In the one-way sensitivity analysis, the utility of progression-free state for patients treated with SBRT plus cetuximab or SBRT alone and the cost of progression-free survival for SBRT+Cet were the most sensitive parameters in the model. Probabilistic sensitivity analysis showed that the probability of cost-effectiveness at a willingness-to-pay threshold of NT$ 2,252,340 per QALY was 100% for SBRT plus cetuximab but 0% for SBRT alone. CONCLUSIONS: This study showed that SBRT+Cet was cost-effective and benefited patients with previously irradiated rSCCHN.

Evaluating the Operational Efficiency and Quality of Tertiary Hospitals in Taiwan: The Application of the EBITDA Indicator to the DEA Method and TOBIT Regression.

This study estimates the efficiency of 19 tertiary hospitals in Taiwan using a two-stage analysis of Data Envelopment Analysis (DEA) and TOBIT regression. It is a retrospective panel-data study and includes all the tertiary hospitals in Taiwan. The data were sourced from open information hospitals legally required to disclose to the National Health Insurance (NHI) Administration, Ministry of Health and Welfare. The variables, including five inputs (total hospital beds, total physicians, gross equipment, fixed assets net value, the rate of emergency transfer in-patient stay over 48 h) and six outputs (surplus or deficit of appropriation, length of stay, the total relative value units [RVUs] for outpatient services, total RVUs for inpatient services, self-pay income, modified EBITDA) were adopted into the Charnes, Cooper and Rhodes (CCR) and Banker, Charnes and Cooper (BCC) model. In the CCR model, the technical efficiency (TE) from 2015-2018 increases annually, and the average efficiency of all tertiary hospitals is 96.0%. In the BCC model, the highest pure technical efficiency (PTE) was in 2018 and the average efficiency of all medical centers is 99.1%. The average scale efficiency of all medical centers was 96.8% in the BBC model, meaning investment can be reduced by 3.2% and the current production level can be maintained with a fixed return to scale. Correlation coefficient analysis shows that all variables are correlated positively; the highest was the number of beds and the number of days in hospital (r = 0.988). The results show that TE in the CCR model was similar to PTE in the BCC model in four years. The difference analysis shows that more hospitals must improve regarding surplus or deficit of appropriation, modified EBITDA, and self-pay income. TOBIT regression reveals that the higher the bed-occupancy rate and turnover rate of fixed assets, the higher the TE; and the higher number of hospital beds per 100,000 people and turnover rate of fixed assets, the higher the PTE. DEA and TOBIT regression are used to analyze the other factors that affect medical center efficiency, and different categories of hospitals are chosen to assess whether different years or different types of medical centers affect operational performance. This study provides reference values for the improvable directions of relevant large hospitals' inefficiency decision-making units through reference group analysis and slack variable analysis.

Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report of One Case / 中国医学科学院学报

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.