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Background The aim of this study was to develop and validate a prediction model for predicting the risk of preoperative asymptomatic lower extremity venous thrombosis (LEVT) in patients with knee osteoarthritis (KOA). Methods Patients with KOA diagnosed at our hospital between March 2022 and July 2023 were included in this study. Five factors were identified as independent risk factors for the development of preoperative asymptomatic LEVT in patients with KOA by univariate and multivariate logistic regression analysis and a prediction model was constructed by analyzing the results. The performance of the model was evaluated using receiver operating characteristic (ROC) curves. The accuracy of the model and its predictive ability were evaluated using calibration curves. The clinical application value of the prediction model was evaluated using decision curve analysis (DCA). Results A total of 354 patients diagnosed with KOA were included in the study. Multivariate logistic regression analysis revealed HDL 0.55 mg/L ( P = 0.049 ) were the independent risk factors for the occurrence of preoperative asymptomatic LEVT in patients with KOA. The combined-variable ROC curve suggested greater predictability and accuracy (AUC = 0.843, specificity = 90.3%, sensitivity = 71.4%). The calibration curve showed good model agreement and DCA suggested good clinical value of the model. Conclusion Low HDL, high LDL, Na + , Ca 2+ , and D-dimer levels can be used as independent risk factors for the preoperative prediction of asymptomatic LEVT in patients with KOA, and the present study also provides a simple prediction model for clinicians and patients.

Lung cancer is the leading cause of cancer-related mortality worldwide with an increasing incidence in many countries. There were few studies on arterial and venous thromboembolism (ATE/VTE) in patients with metastatic lung cancer. Our study focused on the clinical characteristics of stage IV lung cancer patients with ATE or VTE to further explore the risk factors and prognosis. Patients diagnosed with metastatic lung cancer were enrolled from January 2011 to June 2019 at a tertiary hospital in Jiangyin, China. Log-rank test was used to reveal the survival for patients with ATE or VTE. Univariable analysis and multivariable logistic regression were used to study the risk factors for ATE. A total of 587 patients were enrolled in our study, including 52 patients with VTE and 48 with ATE. ATE occurred earlier than VTE. Patients with ATE had a worse prognosis. Multivariable logistic regression revealed that older age and a history of hypertension were independent risk factors for ATE. Patients with metastatic lung cancer were at high risk of VTE and ATE. ATE occurred earlier and was associated with a worse prognosis. Attention should be paid to metastatic lung cancer patients who may develop thromboembolism, especially ATE.

To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)–related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75 mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant ( P 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.

Abstract. Background:. The prognostic value of SPRY4-Intronic transcript 1 (SPRY4-IT1) in women suffering from breast carcinoma and malignant tumors of the reproductive system remains to be ascertained. Therefore, this paper attempted to assess the relationship between SPRY4-IT1 with the clinicopathological indicators and survival analysis in women suffering from breast carcinoma and malignant tumors of their reproductive organs through meta-analysis. Method:. Related literature retrieved from Cochrane Library, Ovid, Embase, PubMed, the CNKI, and the Web of Science databases were reviewed. The latest article search was updated to September 1, 2021. The outcome indicators included as effective measures in the study were hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI). The Stata 12.0 software was used to analyze the data. Results:. The elevated SPRY4-IT1 levels were indicative of poor overall survival (OS) [HR = 2.44, 95% CI = 1.35–4.43, P

CHADS 2 and CHA 2 DS 2 -VASc scores have been used to assess the prognostic risk of thromboembolism in non-valvular atrial fibrillation patients. Recent studies have shown the utility of CHADS 2 and CHA 2 DS 2 -VASc scores for evaluating the severity of coronary artery disease (CAD). The newly defined CHA 2 DS 2 -VASc-HSF score evaluates atherosclerosis and is associated with CAD severity. This study investigated the association between the CHA 2 DS 2 -VASc-HSF score and acute coronary syndrome (ACS) severity as assessed by the Gensini score and the number of vessels. Furthermore, this study also compared the diagnostic value of the CHADS 2 , CHA2 DS2-VASc, and CHA 2 DS 2 -VASc-HSF score for ACS. A total of 2367 eligible inpatients (ACS group [ n = 2030]; non-CAD group [ n = 337]) were consecutively enrolled in this study. Receiver operating characteristic curve diagnostic tests and logistic regression models were used to analyze the risk factors for ACS. The CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HSF scores were significantly higher in the ACS group than those in the control group. After adjusting for numerous traditional CAD risk factors, an increased CHA 2 DS 2 -VASc-HSF score was found to be an independent risk factor for patients with ACS (odds ratio 1.401, 95% confidence interval 1.044, −1.879; P

Aldosterone-producing adenomas (APA) is one of the causative factors of primary aldosteronism. Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Cell proliferation and aldosterone secretion of H295 R cells in response to angiotensin Ⅱ (Agn Ⅱ) were analyzed. We found that CTNNB1 knockdown reduced β-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/β-catenin signaling pathway and downregulated expression of downstream genes including axin 2, lymphoid enhancer binding factor 1 ( LEF1 ), and cyclin D1. In addition, CTNNB1 knockdown decreased responses of H295 R cells to Agn Ⅱ and decreased aldosterone secretion. Our findings suggest that CTNNB1 knockdown can inhibit H295 R cell proliferation and decrease aldosterone secretion in the responses of H295 R cells to Ang II through inhibiting Wnt/β-catenin signaling pathway, indicating that targeting Wnt/β-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.

Glioma is a common type of tumor in human central nervous system, and it is characterized with high mobility and mortality. The prognosis of patients with advanced glioma remains poor. Thus, it is necessary to develop novel therapeutic approaches for the treatment of this disease. Circular RNAs are a group of noncoding RNAs which have been detected in eukaryotic cells. They are tissue-specific and characterized with a more stable structure compared with linear RNAs. Recently, studies have revealed that certain circular RNAs are involved in biological processes such as gene regulation; however, the functions of most circular RNAs remain unknown and require further investigation. Furthermore, circular RNAs can act as “sponges” of its target microRNA, consequently suppressing their activity. Additionally, impaired expression of circular RNAs is reported in different diseases including cancer. In our study, low expression of circular RNA Scm like with 4 Mbt domains 2 was detected in glioma samples. Furthermore, reduced circRNA Scm like with 4 Mbt domains 2 expression was observed in human glioma cell lines compared to normal astrocyte cells. Additionally, overexpression of circRNA Scm like with 4 Mbt domains 2 suppressed the growth and metastasis of glioma cells in vitro . Moreover, microRNA-182-5p could be a downstream molecule of circRNA Scm like with 4 Mbt domains 2. The influenced of microRNA-182-5p-induced proliferation, migration, and invasion of glioma cells could be abrogated by overexpressed circRNA Scm like with 4 Mbt domains 2. In addition, metastasis suppressor 1 was predicted as a novel target of microRNA-182-5p, and its expression was restored by circRNA Scm like with 4 Mbt domains 2. In summary, our findings provided novel insight into the roles of circRNA Scm like with 4 Mbt domains 2 in glioma. More importantly, circRNA Scm like with 4 Mbt domains 2/microRNA-182-5p/metastasis suppressor 1 axis could be a putative therapeutic target for the treatment of patients with glioma.

Alzheimer's disease and related dementias (ADRD) present a growing public health burden in the United States. One actionable risk factor for ADRD is air pollution: multiple studies have found associations between air pollution and exacerbation of ADRD. Our study builds on previous studies by applying modern statistical causal inference methodologies-generalized propensity score (GPS) weighting and matching-on a large, longitudinal dataset. We follow 50 million Medicare enrollees to investigate impacts of three air pollutants-fine particular matter (PM${}_{2.5}$), nitrogen dioxide (NO${}_2$), and summer ozone (O${}_3$)-on elderly patients' rate of first hospitalization with ADRD diagnosis. Similar to previous studies using traditional statistical models, our results found increased hospitalization risks due to increased PM${}_{2.5}$ and NO${}_2$ exposure, with less conclusive results for O${}_3$. In particular, our GPS weighting analysis finds IQR increases in PM${}_{2.5}$, NO${}_2$, or O${}_3$ exposure results in hazard ratios of 1.108 (95% CI: 1.097-1.119), 1.058 (1.049-1.067), or 1.045 (1.036-1.054), respectively. GPS matching results are similar for PM${}_{2.5}$ and NO${}_2$ with attenuated effects for O${}_3$. Our results strengthen arguments that long-term PM${}_{2.5}$ and NO${}_2$ exposure increases risk of hospitalization with ADRD diagnosis. Additionally, we highlight strengths and limitations of causal inference methodologies in observational studies with continuous treatments. Keywords: Alzheimer's disease and related dementias, air pollution, Medicare, causal inference, generalized propensity score., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients., Methods: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias., Results: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001)., Conclusions: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma. Methods: Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed. Results: There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients' median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated. Conclusions: Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

In recent years， regional compound air pollution events caused by fine particles （PM 2.5 ） and ozone （O 3 ） have occurred frequently in economically developed areas of China， in which atmospheric oxidizing capacity （AOC） has played an important role. In this study， the WRF-CMAQ model was used to study the impacts of anthropogenic emission reduction on AOC during the COVID-19 lockdown period. Three representative cities in eastern China （Shijiazhuang， Nanjing， and Guangzhou） were selected for an in-depth analysis to quantify the contribution of meteorology and emissions to the changes in AOC and oxidants and to discuss the impact of AOC changes on the formation of secondary pollutants. The results showed that， compared with that in the same period in 2019， the urban average AOC in Shijiazhuang， Nanjing， and Guangzhou in 2020 increased by 60%， 48.7%， and 12.6%， respectively. The concentrations of O 3 ， hydroxyl radical （·OH）， and nitrogen trioxide （NO 3 ·） increased by 1.6%-26.4%， 14.8%-73.3%， and 37.9%-180%， respectively. The AOC in the three cities increased by 0.06×10 -4 ， 0.12×10 -4 ， and 0.33×10 -4 min -1 ， respectively， due to emission reduction. The meteorological change increased AOC in Shijiazhuang and Nanjing by 20% and 17.9%， respectively， but decreased AOC in Guangzhou by -9.3%. Enhanced AOC led to an increase in the nitrogen oxidation ratio （NOR） and VOCs oxidation ratio （VOR） and promoted the transformation of primary pollutants to secondary pollutants. This offset the effects of primary emission reduction and resulted in a nonlinear decline in secondary pollutants compared to emissions during the COVID-19 lockdown.

In recent years， ozone （O 3 ） has become an increasingly important air pollutant in China. Identifying the sensitivity of O 3 to the precursors volatile organic compounds （VOCs） and nitrogen oxides （NO x ） can help make effective abatement strategies. This study compared three methods for determining O 3 -VOCs-NO x sensitivity： simulated photochemical indicator values and sensitivity coefficients derived from a three-dimensional air quality model and an observation-based model （OBM）， with a case study involving an O 3 pollution event that occurred in Nanjing in late July 2017. The results showed that O 3 sensitivity based on the photochemical indicator and sensitivity coefficients demonstrated similar spatial variations （over 50% of the grid cells of Nanjing exhibiting identical O 3 sensitivity）. However， sensitivity coefficients identified a larger number of areas within a transitional O 3 sensitivity regime， as opposed to the VOCs- or NO x -limited regime identified by the photochemical indicator. The determination of the latter was affected by the adopted threshold values. The OBM relied on the quality of the observational data. For example， positive biases in observed NO 2 could lead to an underestimation of O 3 sensitivity to NO x with the OBM. During the high pollution period， the three methods exhibited significant disparities. The photochemical indicator tended to suggest the VOCs-limited condition， whereas the OBM and sensitivity coefficients indicated the NO x -limited or transitional regimes.

This study applied a de-weather method based on a machine learning technique to quantify the contribution of meteorology and emission changes to air quality from 2015 to 2021 in four cities in the Yangtze River Delta Region. The results showed that the significant reductions in PM 2.5 , NO 2 , and SO 2 emissions(57.2%-68.2%, 80.7%-94.6%, and 81.6%-96.1%, respectively) offset the adverse effects of meteorological conditions, resulting in lower pollutant concentrations. The meteorological contribution of maximum daily 8-h average O 3 (MDA8&#95;O 3 ) showed a stronger effect than that of others(23.5%-42.1%), and meteorological factors promoted the increase in MDA8&#95;O 3 concentrations(4.7%); however, emission changes overall resulted in a decrease in MDA8&#95;O 3 concentrations(-3.2%). NO 2 and MDA8&#95;O 3 decreased more rapidly from 2019 to 2021, mainly because the emissions played a stronger role in reducing pollutant concentrations than from 2015 to 2018. However, emissions changes had weaker reduction effects on PM 2.5 and SO 2 from 2019 to 2021 than from 2015 to 2018. De-weather methods could effectively seperate the effects of meteorology and emission changes on pollutant trends, which helps to evaluate the real effects of emission control policies on pollutant concentrations.

The medical imaging community has embraced Machine Learning (ML) as evidenced by the rapid increase in the number of ML models being developed, but validating and deploying these models in the clinic remains a challenge. The engineering involved in integrating and assessing the efficacy of ML models within the clinical workflow is complex. This paper presents a general-purpose, end-to-end, clinically integrated ML model deployment and validation system implemented at UCSF. Engineering and usability challenges and results from 3 use cases are presented. A generalized validation system based on free, open-source software (OSS) was implemented, connecting clinical imaging modalities, the Picture Archiving and Communication System (PACS), and an ML inference server. ML pipelines were implemented in NVIDIA's Clara Deploy framework with results and clinician feedback stored in a customized XNAT instance, separate from the clinical record but linked from within PACS. Prospective clinical validation studies of 3 ML models were conducted, with data routed from multiple clinical imaging modalities and PACS. Completed validation studies provided expert clinical feedback on model performance and usability, plus system reliability and performance metrics. Clinical validation of ML models entails assessing model performance, impact on clinical infrastructure, robustness, and usability. Study results must be easily accessible to participating clinicians but remain outside the clinical record. Building a system that generalizes and scales across multiple ML models takes the concerted effort of software engineers, clinicians, data scientists, and system administrators, and benefits from the use of modular OSS. The present work provides a template for institutions looking to translate and clinically validate ML models in the clinic, together with required resources and expected challenges., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NVIDIA provided 4 T4 cards as a grant to UCSF., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The objective of this study was to evaluate factors associated with postoperative opioid use after open treatment of distal radius fractures., Methods: The Humana insurance claims database was queried for open treatment of distal radius fractures by Current Procedural Terminology codes. The search was further refined to identify patients who filled an opioid prescription within 6 weeks after their surgery. The study's outcomes were: (1) limited postoperative opioid use, defined as filling a prescription once in the 6-week to 6-month period after surgery; and (2) persistent postoperative opioid use, defined as filling a prescription more than once in the 6-week to 6-month period after surgery. Logistic regression models were performed to identify factors associated with limited and persistent postoperative opioid use. Subgroup analyses were performed among opioid-naïve patients and those with open fractures., Results: This study identified 9141 of 19 220 total patients with limited and persistent opioid use. Significant risk factors included nonhome discharge, inpatient surgical setting, long-term pain, tobacco abuse, and age less than 65 years. Of note, both preoperative opioid use within 1 month before surgery (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.2-2.9) and preoperative opioid use between 1 and 6 months before surgery (OR, 4.0; 95% CI, 3.7-4.4) were significantly associated with persistent postoperative opioid use., Conclusions: This study has identified numerous risk factors associated with postoperative opioid use after open treatment of distal radius fractures. Understanding these risk factors is the first step toward reducing postoperative opioid use.

This study aims to compare perioperative events following total knee arthroplasty (TKA) amongst various degrees of preoperative opioid use. In total, 84,569 patients undergoing TKA were identified from a Humana Claims Dataset, and stratified by their preoperative opioid use based on number of prescriptions filled within 6 months of surgery (naïve 0 [50,561]; sporadic 1 [12,411]; chronic 2 or greater [21,687]). Outcomes of interest included Center for Medicare and Medicaid Services (CMS)-reportable complications, need for postoperative supplemental oxygen, 90-day readmission, and hospital length of stay. Complication rates (9.8% vs 8.9% vs 12.6%; p < 0.01), need for supplemental oxygen (3.0% vs 3.1% vs 5.3%; p = 0.03), mean length of stay (2.1 vs 2.8 vs 3.5; p < 0.01), and 90-day readmission (9.7% vs 10.8% vs 16.4%; p < 0.01) significantly differed amongst groups. On logistic regression, only the chronic opioid use group was associated with significantly increased likelihood of complications, need for supplemental oxygen, and readmission. (Journal of Surgical Orthopaedic Advances 31(2):100-103, 2022).

Purpose: The purpose of this study was to determine whether patients who had an intra-articular corticosteroid injection into the thumb carpometacarpal (CMC) joint for the treatment of arthritis within the 3 months before CMC joint arthroplasty or arthrodesis were at increased risk for wound complication/infection and/or repeat surgery for wound complication/infection in comparison with patients who did not receive an injection within 6 months or who received an injection between 3 and 6 months before surgery., Methods: We identified 5,046 patients in the Humana claims database who underwent surgery for CMC joint arthritis. The patients were stratified into 3 groups: (1) no thumb injection within 6 months of CMC joint surgery, (2) thumb injection between 3 and 6 months before CMC joint surgery, and (3) thumb injection within 3 months before CMC joint surgery. The primary outcome was wound complication/infection within 90 days after surgery. The secondary outcome was repeat surgery for wound complication/infection within 90 days after surgery. Multivariable logistic regression was performed to assess the associations between the timing of injection and wound complication/infection and repeat surgery for wound complication/infection., Results: The rates of wound complication/infection within 90 days after surgery were similar among the 3 study groups. However, patients who received an intra-articular corticosteroid injection within 3 months before surgery had a 2.2 times greater likelihood of repeat surgery for a wound complication/infection compared with patients who did not have an injection within 6 months before surgery., Conclusions: Patients who receive an intra-articular corticosteroid injection within the 3 months before surgery for CMC joint arthritis may be at increased risk of repeat surgery to treat a wound complication/infection in the 90-day postoperative period., Type of Study/level of Evidence: Prognostic II., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Xanthoceraside is a component obtained in the husks of Xanthoceras sorbifolia Bunge. Series of researches proved that xanthoceraside had functions of anti-inflammation and anti-tumor effects. However, the mechanisms of xanthoceraside against bladder cancer are unclear. Accordingly, we proposed to investigate xanthoceraside's impacts and potential mechanisms in cells of bladder cancer., Methods: By using the CCK-8 assay, we measured the viability of cells. With the use of 4,6-diamidino-2-phenylindole (DAPI) staining, we examined nuclear fragmentation and chromatin condensation in the nuclei of apoptotic cells. By using flow cytometry, we measured cell apoptosis. By using Western blotting, we tested the expressions of Caspase-9, Caspase-8, Caspase-3, Bcl-xL, P53, and PI3K/Akt/Bcl-2/Bax., Results: The proliferation of cell lines of human bladder cancer T24 and 5637 was suppressed by xanthoceraside significantly in a time- and concentration-dependent way. When cell lines 5637 and T24 were incubated as the xanthoceraside dose increased, the rates of cell apoptosis were upregulated, which was dependent on dose. According to further analysis, xanthoceraside induced apoptosis by upregulating Bax and downregulating the expression of Bcl-xL and Bcl-2. However, xanthoceraside did not change the expression of Caspase-9, Caspase-8, and Caspase-3. Interestingly, xanthoceraside also downregulated the expression of p-PI3K and p-Akt, and upregulated P53., Conclusions: Xanthoceraside induces cell apoptosis through downregulation of the PI3K/Akt/Bcl-2/Bax signaling pathway in cell lines of human bladder cancer., Competing Interests: None

Purpose: To compare rates of procedural intervention for arthrofibrosis following anterior cruciate ligament reconstruction (ACLR) among patients who were not prescribed any pharmacologic thromboprophylaxis compared with patients who were prescribed aspirin and to patients who were prescribed other agents., Methods: A search of a national insurance claims database was performed to identify all patients who underwent ACLR from 2007 to 2017 who were active within the database at a minimum of 6 months before and 18 months after their surgery. The primary outcome studied was a subsequent procedure for arthrofibrosis, manipulation under anesthesia, and lysis of adhesions (MUA/LOA). Patients who filled a prescription for aspirin, low-molecular weight heparin, direct factor Xa inhibitors, fondaparinux, and warfarin within 2 days after their surgery were included and those who filled a prescription within 3 months before surgery were excluded. Thromboprophylaxis status was defined as no thromboprophylaxis, aspirin, and any agent other than aspirin. Logistic regression analysis was performed to determine the association between prophylaxis status and MUA/LOA., Results: Of the 14,081 patients in our final surgical population, 191 patients had MUA/LOA and 13,890 patients did not. In total, 499 patients were prescribed pharmacologic prophylaxis. Rates of MUA/LOA across groups were 1.3% in the group with no thromboprophylaxis, 1.9% in the group prescribed aspirin, and 4.3% in the group prescribed any agent other than aspirin. Only the group prescribed an agent other than aspirin was significantly associated with subsequent procedure for arthrofibrosis (odds ratio 2.6, 95% confidence interval 1.3-4.8, P = .004)., Conclusions: Patients who were prescribed a pharmacologic agent other than aspirin had a 2.6 times greater likelihood of requiring a procedural intervention for arthrofibrosis following ACLR compared with patients who were not prescribed a thromboprophylaxis agent LEVEL OF EVIDENCE: III, Retrospective Cohort Study., (Published by Elsevier Inc.)

Anlotinib is a novel molecular targeted agent targeting the vascular endothelial growth factor receptor, which differs from the other currently available non-small cell lung cancer (NSCLC) molecular targeted drugs targeting this receptor. Although the application of anlotinib may bring new hope for patients with advanced NSCLC, the cost of treatment is high. The results of this study showed that microRNA-6077 (miR-6077) represses the expression of GLUT1 (glucose transporter 1) and enhances the sensitivity of patient-derived lung adenocarcinoma (AC) cells to anlotinib. The miR-6077, which potentially binds to the 3'untranslated region of GLUT1, was identified and screened by miRDB, an online tool; sequences of miR-6077 were prepared as lentivirus particles. A549 cells (a lung adenocarcinoma cell line) and five patient-derived AC cell lines were infected with control miRNA or miR-6077, and subsequently treated with the indicated concentration of anlotinib. The expression of proteins, such as GLUT1, was determined by western blotting. The antitumor effect of anlotinib was identified through in-vitro (e.g., MTT) or in-vivo methods (e.g., subcutaneous tumor model). Overexpression of miR-6077 repressed the expression of GLUT1 and decreased the glucose uptake, lactate production, or ATP generation in AC cells. In addition, MiR-6077 may enhance the antitumor effect of anlotinib on A549 or patient-derived AC cell lines. Therefore, our results indicated that miR-6077 represses the expression of GLUT1 and enhances the sensitivity of patients-derived lung AC cells to anlotinib., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells., Methods: Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i., Results: Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637., Conclusions: Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.

This study aimed to explore the relationship of loneliness, perceived stress, and depressive symptoms among the Chinese rural empty nest elderly. The role of sense of coherence (SOC) as a moderating variable was investigated in a representative sample of older adults in Henan, China, from November 2016 to February 2017. Results indicated that perceived stress mediated the relationship between loneliness and depressive symptoms, and SOC acted as a moderator on this mediating model. The mediation effect of perceived stress was significant only when SOC was lower. The results emphasized the importance of perceived stress in older adults. SOC was a protective factor with regard to depressive symptoms, and improving SOC should be a focus of health promotion with the elderly.

Aims: The study is aimed at studying the incidence of acute kidney injury (AKI) and exploring the potential predictor for AKI in patients with acute pancreatitis., Methods: A retrospective study adopting a stratified cohort sampling design was performed in a cohort of patients ( n = 237) diagnosed with acute pancreatitis without any renal injury. The following information including age, gender, serum creatinine, serum urea nitrogen, serum uric acid, serum cystatin C, fasting serum glucose, serum amylase, serum lipase, serum choline esterase, total protein, albumin, globulin, total bilirubin, direct bilirubin, total bile acids, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, gamma glutamyl transpeptidase, and alkaline phosphatase were collected from each patient when they were diagnosed with acute pancreatitis. Student t -test was conducted to figure out the difference between patients with and without AKI. Univariate and multivariate logistic regression analyses were used for investigating the predictors for AKI in patients with acute pancreatitis., Results: 18 (7.6%) patients in total had developed AKI among the study group. Compared with patients without AKI (1.01 ± 0.26 mg/L), the level of baseline serum cystatin C (CYS-C) was significantly higher in patients with AKI (3.64 ± 2.17 mg/L, P < 0.001). Baseline serum CYS-C (OR = 203.594, P < 0.001) was the independent and significant predictor for AKI in patients with acute pancreatitis. AKI in patients with acute pancreatitis could be identified with a sensitivity of 88.9% at specificity of 100% (AUC = 0.948, 95% CI 0.879-1.000) by baseline serum CYS-C (cut-off value = 1.865 mg/L)., Conclusions: Baseline serum CYS-C shall be adopted to predict the potential risk of AKI in patients with acute pancreatitis.

Objectives: This study aimed to examine the role of falls efficacy in the relationship between the locomotive function and quality of life., Methods: From March to May in 2016, we conducted a cross-sectional survey among 830 community residents aged ≥60 years from Jinzhou,China.GLFS-25 (25-question Geriatric Locomotive Function Scale), FES-I(International edition of Falls Efficacy Scale),and SF-12 (12-item Short Form Health Survey) were used to estimate locomotive function, falls efficacy and quality of life, respectively. The higher score of GLFS-25, the worse the locomotive function., Results: Median age was 68.69 years (ranges 60-88). Locomotive function, falls efficacy and quality of life all presented a linear relationship within each other, locomotive function score was negatively correlated with falls efficacy score (-0.461, P < 0.01). locomotive function score was negatively correlated with quality of life score (-0.523, P < 0.01).Falls efficacy score was positively correlated with quality of life score (0.415, P < 0.01).Falls efficacy exerted both a mediating and moderating role between locomotive function and quality of life, and the mediation effect accounted for 45.5% of the total effect., Conclusions: Poorer locomotive function was associated with poorer quality of life, and greater falls efficacy was associated with better quality of life. In addition, falls efficacy was demonstrated to be both a mediator and moderator variable in the linkage between locomotive function and quality of life. Aged care professional practitioners and our policy makers should strengthen the awareness of the psychological role of the elderly falls efficacy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Effective vaccines against malaria caused by Plasmodium falciparum are still lacking, and the molecular mechanism of the host-parasite interaction is not fully understood. Here we demonstrate that the interaction of RAP2, a parasite-secreted rhoptry protein that functions in the parasitophorous vacuole formation stage of the invasion, and CD147 on the host erythrocyte is essential for erythrocyte invasion by P falciparum and is independent from all previously identified interactions involved. Importantly, the blockade of the CD147-RAP2 interaction by HP6H8, a humanized CD147 antibody, completely abolished the parasite invasion with both cure and preventative functions in a humanized mouse model. Together with its long half-life on human red blood cells and its safety profile in cynomolgus monkeys, HP6H8 is the first antibody that offers an advantageous approach by targeting a more conserved late-stage parasite ligand for preventing as well as treating severe malaria., (© 2018 by The American Society of Hematology.)

The present study investigated the influences of three metabolic uncouplers (pCP, oCP and oNP) on excess activated sludge reduction and microbial products of extracellular polymeric substances (EPS) and intracellular storage product (polyhydroxybutyrate, PHB) in short-term tests. Results showed sludge was reduced 58.2%, 59.8% and 80.8%, respectively, at pCP, oCP and oNP concentrations of 20mg/L. The dosage of three uncouplers had no obviously influences on COD removal and sludge settleability, but had significant inhibition effect on ammonia removal, especially for oNP. Low concentration of pCP and oNP (5mg/L) dosing resulted in protein and polysaccharide content increased in EPS, however, they were decreased at high pCP and oNP concentrations (>5mg/L). To oCP, the protein content in EPS was increased linearly with oCP concentration. Furthermore, metabolic uncouplers addition stimulated the production of PHB. Among three uncouplers, oCP could be an alternative uncoupler for sludge reduction in activated sludge process., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The identification of the autonomous or transposase-encoding element of the Mutator (Mu) transposable element system of maize is necessary to the characterization of the system. We reported previously that a transcript homologous to the internal region of the MuA element is associated with activity of the Mutator system. We describe here the cloning of another Mu element, designated MuA2, that cosegregates with Mutator activity as assayed by somatic instability of the a1-Mum2 allele. The MuA2 element has features typical of the transposable elements of the Mutator family, including the 210-bp terminal inverted repeats. Several lines of evidence suggest that MuA2 is an autonomous or transposase-encoding element of the Mu family: (1) MuA2 cosegregates with a genetically defined element that regulates somatic mutability of the a1-Mum2 allele; (2) MuA2 is hypomethylated while most other MuA2-hybridizing sequences in the genome are extensively methylated; (3) the increase of the copy number of MuA2 is concomitant with the increase of regulator elements; (4) MuA2-like elements are found in Mutator lines but not in non-Mutator inbreds. We propose that autonomous or transposase-encoding elements of the Mu family may be structurally conserved and MuA2-like.

A Mu element, which we designated MuA, was cloned from a maize line with a Mutator background by its homology to the terminal inverted repeats of Mu1. Like other Mu elements, MuA has terminal inverted repeats of approximately 200 bp which are homologous to those of Mu1, but the internal region is different. MuA is unique in several aspects, being approximately 5.5 kb in size and the largest Mu element reported to date. It is flanked by 8 bp duplications instead of the 9 bp duplications found in most other Mu insertions. The internal sequences of MuA hybridize to restriction fragments that cosegregate with Mutator activity in maize lines showing 1:1 segregation for somatic mutability. The most interesting observation is that a transcript of approximately 3.5 kb identified by the internal sequences of MuA is both qualitatively and quantitatively associated with Mutator activity. This transcript is present in maize lines containing germinal Mutator activity but is undetectable in maize inbreds with no known Mutator activity. The amount of the transcript is decreased in lines that have lost germinal Mutator activity. Northern analysis of maize a1-Mum mutant lines that segregate 1:1 for mutability shows that a transcript of the same size is associated with somatic Mutator activity. These data suggest that the 3.5 kb transcript is produced by the autonomous element that confers both germinal and somatic Mutator activity. The possibility that MuA is an autonomous or regulator element of the Mu family is discussed.