The impact of air pollution on hospitalization for COPD patients in China.

BACKGROUND: With the rapid development of the global economy and the acceleration of urbanization, air pollution has become a major environmental problem threatening human health. There is limited evidence on the acute effects of air pollution on chronic obstructive pulmonary disease (COPD). METHODS: From 2014 to 2019, we collected data on daily admissions for COPD patients from a city in China. We used the generalized additive model together with distributed lag models to fit the associations of air pollutants with hospital admissions. RESULTS: We observed significant increments in the number of daily admissions (0.086-0.109%) for COPD for a unit range increase in air quality index, PM2.5 and PM10 over four lag days. The impact of air pollution on the number of daily admissions was mainly reflected in the COPD patients who were hospitalized through outpatient departments and tertiary hospitals. DISCUSSION: Short-term exposure to outdoor air pollution may induce the occurrence or exacerbation of COPD patients; therefore, government departments should strengthen the management of air pollution, improve supervision and control mechanisms, pay attention to the quality of medical services, and reduce the adverse effects of air pollution on patients' health.

USP39 interacts with SIRT7 to promote cervical squamous cell carcinoma by modulating autophagy and oxidative stress via FOXM1.

BACKGROUND: Sirtuin 7 (SIRT7) is an oncogene that promotes tumor progression in various malignancies, however, its role and regulatory mechanism in cervical squamous cell carcinoma (CSCC) is unknown. Herein, we attempted to investigate the functional role and molecular mechanism of SIRT7 underlying CSCC progression. METHODS: SIRT7 expression was evaluated in CSCC cells using various assays. We then used a series of function gain-and-loss experiments to determine the role of SIRT7 in CSCC progression. Furthermore, mechanism experiments were conducted to assess the interaction between SIRT7/USP39/FOXM1 in CSCC cells. Additionally, rescue assays were conducted to explore the regulatory function of USP39/FOXM1 in CSCC cellular processes. RESULTS: SIRT7 was highly expressed in CSCC patient tissues and cell lines. SIRT7 deficiency showed significant repression on the proliferation, and autophagy of CSCC cells in vitro and tumorigenesis in vivo. Similarly, apoptosis and ROS production in CSCC cells were accelerated after the SIRT7 knockdown. Moreover, SIRT7 and USP39 were found colocalized in the cell nucleus. Interestingly, SIRT7 was revealed to deacetylate USP39 to promote its protein stability in CSCC cells. USP39 protein was also verified to be upregulated in CSCC tissues and cells. USP39 silencing showed suppressive effects on CSCC cell growth. Mechanistically, USP39 was revealed to upregulate SIRT7 by promoting the transcriptional activity of FOXM1. Rescue assays also indicated that SIRT7 promoted autophagy and inhibited ROS production in CSCC cells by regulating USP39/FOXM1. CONCLUSION: The SIRT7/USP39/FOXM1 positive feedback network regulates autophagy and oxidative stress in CSCC, thus providing a new direction for CSCC-targeted therapy.

Elucidating the Multimodal Anticancer Mechanism of an Organometallic Terpyridine Platinum(II) N-Heterocyclic Carbene Complex against Triple-Negative Breast Cancer In Vitro and In Vivo.

Treatment of triple-negative breast cancer (TNBC) has long been a medical challenge because of the lack of effective therapeutic targets. Targeting lipid, carbohydrate, and nucleotide metabolism pathways has recently been proven as a promising option in view of three heterogeneous metabolic-pathway-based TNBC subtypes. Here, we present a multimodal anticancer platinum(II) complex, named Pt(II)caffeine, with a novel mode of action involving simultaneous mitochondrial damage, inhibition of lipid, carbohydrate, and nucleotide metabolic pathways, and promotion of autophagy. All these biological processes eventually result in a strong suppression of TNBC MDA-MB-231 cell proliferation both in vitro and in vivo. The results indicate that Pt(II)caffeine, influencing cellular metabolism at multiple levels, is a metallodrug with increased potential to overcome the metabolic heterogeneity of TNBC.

Predictive model for the intraoperative unresectability of hilar cholangiocarcinoma: Reducing futile surgical exploration.

INTRODUCTION: Surgical exploration is widely performed in hilar cholangiocarcinoma (HCCA), but the intraoperative resectability rate is only 60%-80%. Exploration substantially increases pain and mental stress, and the costs and length of hospital stay are considerably increased. Identifying preoperative risk factors associated with unresectability could decrease unnecessary exploration. MATERIALS AND METHODS: In total, 440 HCCA patients from multiple centers were enrolled. Those receiving surgical exploration were divided into the resected and unresected groups. Morphological variables including Bismuth classification, lymph node metastasis and vessel invasion were obtained from radiological exams. Logistic regression for the training cohort was used to identify risk factors for unresectability, and a nomogram was constructed to calculate the unresectability rate. A calibration curve assessed the power of the nomogram. RESULTS: Among 311 patients receiving surgical exploration, 45 (14.7%) were unresectable by intraoperative judgment. Compared with the resected group, unresected patients had similar costs (p = 0.359) and lengths of hospital stay (p = 0.439). Multivariable logistic regression of the training cohort (235 patients) revealed that CA125, Bismuth-Corlette type IV, lymph node metastasis and hepatic artery invasion were risk factors for unresectability. Liver atrophy (p = 0.374) and portal vein invasion (p = 0.114) were not risk factors. The nomogram was constructed based on the risk factors. The concordance index (C-index) values of the calibration curve for predicting the unresectability rate of the training and validation (76 patients) cohorts were 0.900 (95% CI, 0.835-0.966) and 0.829 (95% CI, 0.546-0.902), respectively. CONCLUSION: Analysis of preoperative factors could reveal intraoperative unresectability and reduce futile surgical explorations, ultimately benefiting HCCA patients.

Retracted: Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Jianping Zhou, Fengxue Yang, Xiaolin Xu, Gang Feng, Jun Chen, Jinglin Song, Hongwei Dai. Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography. Med Sci Monit, 2018; 24: 8306-8314. DOI: 10.12659/MSM.912470.

Trading quality for quantity? Evidence from patient level data in China.

In China, overcrowding at hospitals increases the workload of medical staff, which may negatively impact the quality of medical services. This study empirically examined the impact of hospital admissions on the quality of healthcare services in Chinese hospitals. Specifically, we estimated the impact of the number of hospital admissions per day on a patient's length of stay (LOS) and hospital mortality rate using both ordinary least squares (OLS) and instrumental variable (IV) methods. To deal with potential endogeneity problems and accurately identify the impact of medical staff configuration on medical quality, the daily air quality index was selected as the IV. Furthermore, we examined the differential effects of hospital admissions on the quality of care across different hospital tiers. We used the data from a random sample of 10% of inpatients from a city in China, covering the period from January 2014 to June 2019. Our final regression analysis included a sample of 167 disease types (as per the ICD-10 classification list) and 862,722 patient cases from 517 hospitals. According to our results, the LOS decreased and hospital mortality rate increased with an increasing number of admissions. Using the IV method, for every additional hospital admission, there was a 6.22% (p < 0.01) decrease in LOS and a 1.86% (p < 0.01) increase in hospital mortality. The impact of healthcare staffing levels on the quality of care varied between different hospital tiers. The quality of care in secondary hospitals was most affected by the number of admissions, with the average decrease of 18.60% (p < 0.05) in LOS and the increase of 6.05% (p < 0.01) in hospital mortality for every additional hospital admission in our sample. The findings suggested that the supply of medical services in China should be increased and a hierarchical diagnosis and treatment system should be actively promoted.

Analysis of influencing factors of economic burden and medical service utilization of diabetic patients in China.

BACKGROUND: This study analyzed factors that affect the financial burden and utilization of medical services of patients with diabetes in a city of China. METHODS: We randomly sampled 10% of the information on the front page of diabetic inpatient medical records in the city from January 2014 to September 2019. Total cost of hospitalization, length of hospitalization and the number of hospitalization were analyzed. Descriptive statistical analysis and multiple linear regression analysis were adopted. RESULTS: Understanding the current financial burden of diabetic patients and the use of medical services, the results show that the direct economic burden of diabetic patients per hospitalization was approximately 8,000 Yuan, and the indirect economic burden was approximately 2,000 Yuan. Age, medical payment methods, admission channels, and medical institution grades are all important factors affecting medical expenses and medical service utilization of diabetic patients. In addition, the inequality of medical service utilization of patients is increased due to different types of medical insurance. CONCLUSIONS: To reduce the economic burden on patients and society, governments should strengthen supervision, the advancement of diagnosis and treatment systems, the service conditions of primary medical institutions, the management of medical services, and the use of medical resources. To create a more impartial medical and health environment where the value of medical staff are truly reflected, financial investments should be attained to improve medical technologies and labor costs.

Association of interleukin-10-1082 (-1087) A > G polymorphisms and periodontitis risk: An updated meta-analysis based on 26 case-control studies.

BACKGROUND: The association between interleukin-10 (IL-10)-1082 (-1087) A > G polymorphism and either chronic (CP) or aggressive periodontitis (AgP) susceptibility was conflicting. This meta-analysis aimed to quantitatively estimate the association. METHODS: Pubmed, Embase, Web of Science, and WANFAN databases were searched for relevant studies that were submitted prior to January 31, 2018, and meta-analyses were performed using STATA 14.0. RESULTS: Database mining yielded 26 studies of interest. For the IL-10-1082 (-1087) A > G (rs1800896) polymorphism and its relation to CP susceptibility, the overall analysis showed no significant estimates, but subgroup analysis revealed significant associations in the AA versus GG + GA model in the Caucasian population (odds ratio [OR] = 1.274, 95% confidence interval [CI] = 1.069-1.518, P = 0.007; I2  = 0.0%, P = 0.483) and in the GG versus AA + AG model in the Han population (OR = 6.66, 95% CI = 7.72-9.41, P = 0.000; I2  = 0.0%, P = 0.82), which all showed no obvious publication bias by Egger's linear regression test. For the association between an IL-10-1082 (-1087) A > G polymorphism and AgP susceptibility, the overall analysis and Caucasian subgroup analysis yielded nonsignificant estimates. CONCLUSIONS: Our meta-analysis indicated that the IL-10-1082 (-1087) AA genotype in the Caucasian population, and the GG genotype in the Han population might be putative risk factors for CP. PRACTICAL IMPLICATIONS: The IL-10-1082 (-1087) AA genotype and the GG genotype might be potential biomarkers for Caucasian CP and for Han CP, respectively. However, additional research will be required to validate the findings of this meta-analysis.

Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography.

BACKGROUND The aim of this study was to dynamically evaluate tooth movement, root resorption, and remodeling of alveolar bone using different forces to cause tooth movement in rats. MATERIAL AND METHODS 12-week-old male Sprague-Dawley rats were selected. Nickel-titanium (Ni-Ti) coil springs (20 g, 50 g, and 100 g forces) were placed for mesial movement of the left first maxillary molar teeth. Tooth movement, root resorption, and microarchitectural parameters of the trabecular bone were evaluated by in vivo micro-CT. Histological examination was used to observe the root resorption, alveolar bone remodeling, and changes in osteoclasts from day 0 to day 14. RESULTS The tooth movement distance increased significantly over the initial 3 days in the 3 groups. The 20 g force group showed more tooth movement than in the 50 and 100 g force groups after 14 days (P<0.05). From days 7 to 10, root resorption lacunae appeared in the 3 groups and then stabilized, and the 100 g force group produced more lacunar resorption than in the anther 2 groups (P<0.05). Compared to day 0, the trabecular thickness and bone volume fraction on the pressure side gradually decreased from day 7 to day 14. The structure model index increased significantly from day 3 to day 14. Histological examination showed remarkable root resorption craters and osteoclasts positive for tartrate-resistant acid phosphatase in the root resorption lacunae in the 50 g and 100 g groups from day 7 to day 14. CONCLUSIONS A 100 g heavy force can be used to establish a root resorption model in rats.

Contribution of Interleukin-10-592 (-590, -597) C>A Polymorphisms to Periodontitis Susceptibility: An Updated Meta-Analysis Based on 18 Case-Control Studies.

INTRODUCTION: The association between interleukin-10- (IL-10-) 592 (-590, -597) C>A polymorphisms and susceptibility to chronic or aggressive periodontitis (CP or AgP) is conflicting. This meta-analysis is aimed at quantitatively estimating the association. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and WANFAN were searched for studies performed prior to January 31, 2018, to collect data for our research. Meta-analysis was performed using RevMan 5.3 or STATA 14.0. RESULTS: In total, 18 studies that met our criteria were included. Overall or HWE subgroup analysis of individuals with this polymorphism revealed that in terms of CP susceptibility, there was a significant difference between case groups and control groups in the A allele versus C allele model (OR = 1.38, 95% CI = 1.17-1.64 or OR = 1.38, 95% CI = 1.12-1.70), in the AA versus CC+CA model (OR = 1.49, 95% CI =1.06-2.10 or OR = 1.42, 95% CI = 1.13-1.78), and in the CC versus CA+AA model (OR = 0.69, 95% CI = 0.51-0.92 or OR = 0.68, 95% CI = 0.49-0.93); subgroup analysis based on a nonsmoking population also displayed significance in the A allele versus C allele model (OR = 1.43, 95% CI = 1.15-1.79) and CC versus CA+AA model (OR = 0.62, 95% CI = 0.44-0.87). For this polymorphisms and AgP susceptibility, our analyses revealed a significant association in both the A allele versus C allele model (OR = 1.29, 95% CI = 1.01-1.63) and the AA versus CC+CA model (OR = 1.93, 95% CI = 1.30-2.89); subgroup analysis based on Caucasian or nonsmoking populations showed significant differences in the AA versus CC+CA model (OR = 6.29, 95% CI = 1.78-22.21 or OR = 3.24, 95% CI = 1.59-6.61). CONCLUSIONS: IL-10-592 (-590, -597) A allele and the associated AA genotype may be risk factors for the onset of CP or AgP-particularly for the AA genotype and the increased risk of AgP in Caucasian or nonsmoking populations. Conversely, the CC genotype may act as a protective factor against the onset of CP.

Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in Dental Tissue Engineering.

Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

A novel two-step QSAR modeling work flow to predict selectivity and activity of HDAC inhibitors.

A two-step modeling approach was employed to study the selectivity and activity of histone deacetylase inhibitors. First, according to the activity difference against HDAC1 and HDAC6, a binary classification model was established to classify two kinds of inhibitors. Then two continuous models were built for each subclass to predict the activity value of HDAC1 and HDAC6 inhibitors. The three models were all built with the GA-kNN method combined with dragon descriptors. They were external validated by using external prediction set and Y-randomization test. The highly predictive models were generated for all three data sets. For the classification model, the classification accuracies of the models were as high as 100% for the external test set. For HDAC1 and HDAC6 inhibitor consecutive models, external R(2) values are 0.947 and 0.911, respectively. The results proved the reliability of these models. All models were used to screen 1000 compounds included in PubMed dataset. Virtual screening resulted in 8 and 13 structurally unique consensus hits that were considered novel putative HDAC1 and HDAC6 inhibitors, respectively.