Analysis of factors influencing hospitalization cost of patients with distal radius fractures: an empirical study based on public traditional Chinese medicine hospitals in two cities, China.

BACKGROUND: Distal radius fractures (DRFs) have become a public health problem for all countries, bringing a heavier economic burden of disease globally, with China's disease economic burden being even more acute due to the trend of an aging population. This study aimed to explore the influencing factors of hospitalization cost of patients with DRFs in traditional Chinese medicine (TCMa) hospitals to provide a scientific basis for controlling hospitalization cost. METHODS: With 1306 cases of DRFs patients hospitalized in 15 public TCMa hospitals in two cities of Gansu Province in China from January 2017 to 2022 as the study object, the influencing factors of hospitalization cost were studied in depth gradually through univariate analysis, multiple linear regression, and path model. RESULTS: Hospitalization cost of patients with DRFs is mainly affected by the length of stay, surgery and operation, hospital levels, payment methods of medical insurance, use of TCMa preparations, complications and comorbidities, and clinical pathways. The length of stay is the most critical factor influencing the hospitalization cost, and the longer the length of stay, the higher the hospitalization cost. CONCLUSIONS: TCMa hospitals should actively take advantage of TCMb diagnostic modalities and therapeutic methods to ensure the efficacy of treatment and effectively reduce the length of stay at the same time, to lower hospitalization cost. It is also necessary to further deepen the reform of the medical insurance payment methods and strengthen the construction of the hierarchical diagnosis and treatment system, to make the patients receive reasonable reimbursement for medical expenses, thus effectively alleviating the economic burden of the disease in the patients with DRFs.

Endoscopic-Assisted Forehead Augmentation with Polyetheretherketone (PEEK) Patient-Specific Implant (PSI) for Aesthetic Considerations.

BACKGROUND: Forehead augmentation have become popular aesthetic procedures among Asians in recent years. However, the use of polyetheretherketone (PEEK) patient-specific implant (PSI) in the facial contouring surgery for aesthetic considerations is not well documented in the existing studies. The purpose of this study was to develop a novel method for forehead augmentation and assess the clinical outcomes and complications in patients who underwent forehead augmentation with PEEK PSI assisted by endoscopy. METHODS: The PEEK PSIs were fabricated using the virtual surgical planning (VSP) and the computer-aided manufacturing (CAM) for each patient, preoperatively. The implant pockets were dissected in the subperiosteal plane, and PEEK PSIs were placed in their designed position and fixed assisting by endoscopy via small incision within the hairline. All patients were asked to complete the FACE-Q questionnaire before and 6 months after the operation. Pre- and postoperative demographics, photographs, and other clinical data of patients were collected and analyzed. RESULTS: 11 patients underwent forehead augmentation were enrolled in this study. All procedures were completed successfully with the help of endoscope. The average patient age was 30.63 ± 2.54 years. The mean thickness and size of PEEK PSI were 4.44 ± 1.77 mm and 38.43 ± 22.66 cm2, respectively. The mean operative time was 83.00 ± 29.44 min, and the mean postoperative follow-up period was 11.00 ± 6.50 months. No implant exposure, extrusion or removal were reported. The FACE-Q scores of patients in satisfaction with the forehead increased from 47.64 ± 7.15 to 78.81 ± 6.35. CONCLUSIONS: PEEK PSIs can be prefabricated to achieve accurate remodeling of the frontal contour with good esthetic outcomes. The endoscope provides direct and magnified vision, which allow easy access to the supraorbital rim and lateral edge of the eyebrow arch and confirming the position of the implants without damaging nerves and vessels. Endoscopic-assisted forehead augmentation with PEEK PSI is safe and effective. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .

Diethylaminoethyl-dextran and monocyte cell membrane coated 1,8-cineole delivery system for intracellular delivery and synergistic treatment of atherosclerosis.

We have developed a biomimetic delivery system termed the Monocyte Cell Membrane-Coated 1,8-Cineole Biomimetic Delivery System (MM-CIN-BDS or BDS), which integrates diethylaminoethyl-dextran (DEAE) and monocyte cell membrane (MM). This innovative approach enhances the cellular uptake efficiency of 1,8-cineole (CIN) and facilitates targeted therapy for atherosclerosis. Our findings demonstrate the successful modification of the drug carrier with DEAE and MM, as validated by measurements of particle size, zeta potential, microscopic morphology, and western blotting analyses. Notably, cellular uptake experiments unveil a significant enhancement in cellular uptake efficiency due to DEAE modification. However, the introduction of monocyte cell membranes diminishes this effect in normal human umbilical vein endothelial cells (HUVECs), although this efficiency is notably restored in HUVECs activated with lipopolysaccharide (LPS). Through in vivo imaging investigations, we observe that the MM coating augments distribution in the spleen, brain, and atherosclerotic plaques, while concurrently diminishing distribution in the heart and kidneys. Animal studies corroborate these findings, illustrating that MM-CIN-BDS treatment curtails lipid parameters, dampens the expression of inflammatory factors and proteins, mitigates vascular tissue damage, and ultimately reduces the extent of atherosclerotic lesion areas. To encapsulate, DEAE emerges as an especially adept agent for modifying drug carriers with suboptimal cellular uptake efficiency in the realm of cardiovascular diseases. The potential therapeutic promise of MM-CIN-BDS for atherosclerosis treatment is evident from our research.

A Retrospective Study of Transaxillary Endoscopic Breast Augmentation Using Ultrasonic Scalpel or Conventional Electrocautery for Implant Pocket Dissection.

BACKGROUND: Ultrasonic scalpel has been reported to be superior to conventional electrocautery in many studies. However, with respect to transaxillary endoscopic breast augmentation, few studies on the effect of ultrasonic scalpel are available in the literature. METHODS: The medical records of 173 female patients who underwent breast augmentation via endoscopic transaxillary approach from January 2018 to December 2020 were reviewed retrospectively. The patients were divided into two groups according to the implant pocket dissection instruments. In group A, the implant pockets were dissected with conventional electrocautery (EC group) on 81 patients, and in group B, ultrasonic scalpel (US group) was used for implant pockets on 92 patients. All operations were performed by the same senior plastic surgeon and the same surgical team. The operation time, intraoperative blood loss, postoperative total drainage volume, days of drainage, postoperative surgical site pain and hospital stay time of the two groups were compared and analyzed statistically. RESULTS: The average operation time of the US group (83.82 ± 11.57 min) was significantly shorter than that of the EC group (101.40 ± 14.36 min), intraoperative blood loss in the US group was significantly less than that of the EC group (18.67 ± 6.20 ml vs. 21.59 ± 6.44 ml), the mean hospital stay days (2.96 ± 0.69 vs. 4.30 ± 1.11), total drainage volume (122.24 ± 43.81 vs. 232.37 ± 99.15), and duration of drain (2.52 ± 0.54 vs. 3.77 ± 1.10), mean VAS score for surgical site pain on 3 postoperative days (5.08 ± 1.35 vs. 6.51 ± 1.36, 4.08 ± 1.16 vs. 5.40 ± 1.32, 3.04 ± 0.91 vs. 4.06 ± 1.11) were significantly lower in the US group compared to the EC group. CONCLUSIONS: The ultrasonic scalpel reduces operative time, intraoperative blood loss, postoperative drainage, postoperative pain, hospital stay time, and incidence of complications. The ultrasonic scalpel is safe and reliable for transaxillary endoscopic breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Histone methyltransferase enzyme enhancer of zeste homolog 2 counteracts ischemic brain injury via H3K27me3-mediated regulation of PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Epigenetic histone methylation plays a crucial role in cerebral ischemic injury, particularly in the context of ischemic stroke. However, the complete understanding of regulators involved in histone methylation, such as Enhancer of Zeste Homolog 2 (EZH2), along with their functional effects and underlying mechanisms, remains incomplete. METHODS: Here, we employed a rat model of MCAO (Middle cerebral artery occlusion) and an OGD (Oxygen-Glucose Deprivation) model of primary cortical neurons to study the role of EZH2 and H3K27me3 in cerebral ischemia-reperfusion injury. The infarct volume was measured through TTC staining, while cell apoptosis was detected using TUNEL staining. The mRNA expression levels were quantified through quantitative real-time polymerase chain reaction (qPCR), whereas protein expressions were evaluated via western blotting and immunofluorescence experiments. RESULTS: The expression levels of EZH2 and H3K27me3 were upregulated in OGD; these expression levels were further enhanced by GSK-J4 but reduced by EPZ-6438 and AKT inhibitor (LY294002) under OGD conditions. Similar trends were observed for mTOR, AKT, and PI3K while contrasting results were noted for UTX and JMJD3. The phosphorylation levels of mTOR, AKT, and PI3K were activated by OGD, further stimulated by GSK-J4, but inhibited by EPZ-6438 and AKT inhibitor. Inhibition of EZH2 or AKT effectively counteracted OGD-/MCAO-induced cell apoptosis. Additionally, inhibition of EZH2 or AKT mitigated MCAO-induced infarct size and neurological deficit in vivo. CONCLUSIONS: Collectively, our results demonstrate that EZH2 inhibition exerts a protective effect against ischemic brain injury by modulating the H3K27me3/PI3K/AKT/mTOR signaling pathway. The results provide novel insights into potential therapeutic mechanisms for stroke treatment.

Correcting the Broad, Flat and Short Chin Using Modified M-genioplasty.

BACKGROUND: Several genioplasty techniques can narrow the width of the chin. Nevertheless, patients with a broad and short chin who received these methods were unsatisfied with the outcomes. The goal of this study was to analyze the clinical outcomes of modified M-shaped genioplasty for broad, flat and short chin deformity. METHODS: Thirty-eight patients with broad, flat and short chins were included in this study from January 2019 to December 2021. The preoperative design was performed individually according to the data of the chin and the patient's desire of final chin shape. Narrowing and vertical elongating genioplasty was performed for all the patients with modified M-shaped genioplasty under general anesthesia according to the preoperative designs. All patients have completed the FACE-Q preoperatively and 3 months postoperatively. The results were evaluated by clinical appearances and FACE-Q scores. RESULTS: The vertical lengthening of the chin was 2-5 mm, with an average of 3.02 mm. The horizontal narrowing width was 3-6 mm, with an average of 5.6 mm. FACE-Q scores in satisfaction with the chin increased significantly from 35.34 ± 9.57 to 72.95 ± 6.81. There were no severe complications took place during the time frame of 3-24 months postoperatively. CONCLUSIONS: The modified M-shaped genioplasty preserved the bone structure in the midsymphyseal area and suprahyoid muscular attachments as far as possible, and the bone segments may be repositioned quickly. This technique produced reliable and esthetically satisfying results in correcting a short, flat and broad chin, with altered vertical length, slope, width and protrusion three-dimensionally. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

TAK1 deficiency promotes liver injury and tumorigenesis via ferroptosis and macrophage cGAS-STING signalling.

Background & Aims: Oxidative stress-mediated ferroptosis and macrophage-related inflammation play an important role in various liver diseases. Here, we explored if and how hepatocyte ferroptosis regulates macrophage stimulator of interferon genes (STING) activation in the development of spontaneous liver damage, fibrosis, and tumorigenesis. Methods: We used a transforming growth factor-beta-activated kinase 1 (TAK1) deficiency-induced model of spontaneous liver damage, fibrosis, and tumorigenesis to investigate hepatocyte ferroptosis and its impact on macrophage STING signalling. Primary hepatocytes and macrophages were used for in vitro experiments. Results: Significant liver injury and increased numbers of intrahepatic M1 macrophages were found in hepatocyte-specific TAK1-deficient (TAK1ΔHEP) mice, peaking at 4 weeks and gradually decreasing at 8 and 12 weeks. Meanwhile, activation of STING signalling was observed in livers from TAK1ΔHEP mice at 4 weeks and had decreased at 8 and 12 weeks. Treatment with a STING inhibitor promoted macrophage M2 polarisation and alleviated liver injury, fibrosis, and tumour burden. TAK1 deficiency exacerbated liver iron metabolism in mice with a high-iron diet. Moreover, consistent with the results from single-cell RNA-Seq dataset, TAK1ΔHEP mice demonstrated an increased oxidative response and hepatocellular ferroptosis, which could be inhibited by reactive oxygen species scavenging. Suppression of ferroptosis by ferrostatin-1 inhibited the activation of macrophage STING signalling, leading to attenuated liver injury and fibrosis and a reduced tumour burden. Mechanistically, increased intrahepatic and serum levels of 8-hydroxydeoxyguanosine were detected in TAK1ΔHEP mice, which was suppressed by ferroptosis inhibition. Treatment with 8-hydroxydeoxyguanosine antibody inhibited macrophage STING activation in TAK1ΔHEP mice. Conclusions: Hepatocellular ferroptosis-derived oxidative DNA damage promotes macrophage STING activation to facilitate the development of liver injury, fibrosis, and tumorigenesis. Inhibition of macrophage STING may represent a novel therapeutic approach for the prevention of chronic liver disease. Impact and implications: The precise mechanism by which hepatocyte ferroptosis regulates macrophage STING activation in the progression of liver damage, fibrosis, and tumorigenesis remains unclear. Herein, we show that deletion of TAK1 in hepatocytes caused oxidative stress-mediated ferroptosis and macrophage-related inflammation in the development of spontaneous liver injury, fibrosis, and hepatocellular carcinoma.

Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis.

Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent.

The Accuracy of a Patient-Specific Three-Dimensional Digital Ostectomy Template for Mandibular Angle Ostectomy.

BACKGROUND: Although three-dimensional (3D)-printed digital ostectomy templates (DOTs) can help surgeons perform mandibular angle ostectomy (MAO) more precisely and safely, the clinical application of such templates is problematic. OBJECTIVES: The aim of this study was to evaluate the accuracy of a novel DOT and improve the precision of MAO. METHODS: A total of 20 patients with a prominent mandibular angle (PMA) were allocated into 2 groups (10 patients per group). A conventional DOT and a novel DOT were applied to guide MAO in Groups A and B, respectively. The mean time taken for curved osteotomy and the volume of postoperative drainage on 1 side within 24 hours were recorded. The deviations between the simulated and postoperative lower border of the mandible were measured on both sides. RESULTS: All the patients were satisfied with the cosmetic outcomes. Statistical results showed that the mean time taken for curved osteotomy was shorter in Group B than in Group A, and that the volume of postoperative drainage on 1 side within 24 hours was similar between the 2 groups. The deviations at the anterior and posterior parts of the inferior border showed that the accuracy of osteotomy was higher in Group B than in Group A, and that there was no significant difference between the 2 groups in the middle part. CONCLUSIONS: The novel DOT is easy to locate and fix tightly, which reduced the operating time and increased the safety and precision of the procedures.

A botanical medicine dragon's blood exhibited clinical antithrombosis efficacy similar to low molecular weight heparin.

Deep vein thrombosis (DVT) is a common complication following traumatic fracture with a 0.5%-1% annual incidence. Low molecular weight heparin (LMWH) is the most commonly used anticoagulation drug for DVT prevention, but treatment with LMWH is invasive. Our aim is to compare the antithrombotic effect of dragon's blood, an oral botanical anticoagulant medicine approved by the Chinese FDA, with LMWH in patients undergoing hip fracture surgery and to explore the molecular mechanisms of anticoagulation treatment. Our study recruited patients and divided them into LMWH and dragon's blood treatment group. Coagulation index tests, Doppler ultrasound and mRNA sequencing were performed before and after anticoagulation therapy. There was no significant difference in postoperative DVT incidence between the two groups (23.1% versus 15.4%, P=0.694). D-dimer (D-D) and fibrinogen degradation product (FDP) showed significant reductions in both groups after anticoagulation treatments. We identified SLC4A1, PROS1, PRKAR2B and seven other genes as being differentially expressed during anticoagulation therapy in both groups. Genes correlated with coagulation indexes were also identified. Dragon's blood and LMWH showed similar effects on DVT and produced similar gene expression changes in patients undergoing hip fracture surgery, indicating that dragon's blood is a more convenient antithrombosis medicine (oral) than LMWH (hypodermic injection).

SIRT1/FOXO3a axis plays an important role in the prevention of mandibular bone loss induced by 1,25(OH)2D deficiency.

It has been reported that 1,25 dihydroxyvitamin D [1,25(OH)2D] deficiency leads to the loss of mandibular bone, however the mechanism is unclear. We investigated whether the Sirt1/FOXO3a signaling pathway is involved in this process. Using a 1,25(OH)2D deficiency model induced by genetic deletion in mice of 25-hydroxyvitamin D-1α hydroxylase [1α(OH)ase-/- mice]. We first documented a sharp reduction of expression levels of Sirt1 in the 1α(OH)ase-/- mice in vivo. Next, we demonstrated dose-dependent upregulation of Sirt1 by treatment with exogenous 1,25(OH)2D3in vitro. We then identified a functional VDR binding site in the Sirt1 promoter. By crossing Prx1-Sirt1 transgenic mice with 1α(OH)ase-/- mice we demonstrated that the overexpression of Sirt1 in mesenchymal stem cells (MSCs) greatly improved the 1α(OH)ase-/- mandibular bone loss phenotype by increasing osteoblastic bone formation and reducing osteoclastic bone resorption. In mechanistic studies, we showed, in 1α(OH)ase-/- mice, decreases of Sirt1 and FoxO3a, an increase in oxidative stress as reflected by a reduction of the antioxidant enzymes peroxiredoxin1 (Prdx1), SOD1 and SOD2 expression, and an increase of markers for osteocyte senescence and senescence associated secretory phenotypes (SASP), including ß-galactosidase (ß-gal), p16, p53 and p21. The targeted overexpression of Sirt1 in the 1α(OH)ase-/- mice restored the expression levels of these molecules. Finally, we demonstrated that a Sirt1 agonist can upregulate FOXO3a activity by increasing deacetylation and nuclear translocation. Overall, results from this study support the concept that targeted increases in Sirt1/FOXO3a signaling levels can greatly improve the bone loss caused by 1,25(OH)2D deficiency.

Characterization of outdoor air pollution from solid fuel combustion in Xuanwei and Fuyuan, a rural region of China.

Outdoor air pollution is a growing public health concern, particularly in urban settings. However, there are limited epidemiological data on outdoor air pollution in rural areas with substantial levels of air pollution attributed to solid fuel burning for household cooking and heating. Xuanwei and Fuyuan are rural counties in China where the domestic combustion of locally sourced bituminous ("smoky") coal has been associated with the highest lung cancer rates in China. We previously assessed indoor and personal air pollution exposures in this area; however, the influence of indoor coal combustion and household ventilation on outdoor air pollution has not been assessed. Therefore, we measured outdoor fine particulate matter (PM2.5), species of polycyclic aromatic hydrocarbons (PAHs) including naphthalene (NAP) and the known carcinogen benzo(a)pyrene (BaP), sulfur dioxide (SO2), and nitrogen dioxide (NO2) over two consecutive 24-h sampling periods in 29 villages. Just over half of the villages were revisited two to nine months after the initial sampling period to repeat all measurements. The overall geometric mean (GM) of outdoor PM2.5, BaP, NAP, and NO2 were 45.3 µg/m3, 9.7 ng/m3, 707.7 ng/m3, and 91.5 µg/m3, respectively. Using linear mixed effects models, we found that burning smoky coal was associated with higher outdoor BaP concentrations [GM ratio (GMR) = 2.79] and lower outdoor SO2 detection rates (GMR = 0.43), compared to areas burning smokeless coal. Areas with predominantly ventilated stoves (> 50% of stoves) had higher outdoor BaP (GMR = 1.49) compared to areas with fewer ventilated stoves. These results show that outdoor air pollution in a rural region of China was associated with the type of coal used for cooking and heating indoors and the presence of stove ventilation. Our findings suggest that efforts of household stove improvement to reduce indoor air pollution have resulted in higher outdoor air pollution levels. Further reducing adverse health effects in rural villages from household coal combustion will require the use of cleaner fuel types.

Differential distribution of N- and O-Glycans and variable expression of sialyl-T antigen on HeLa cells-Revealed by direct fluorescent glycan imaging.

Cells are covered with glycans. The expression and distribution of specific glycans on the surface of a cell are important for various cellular functions. Imaging these glycans is essential to aid elucidation of their biological roles. Here, utilizing methods of direct fluorescent glycan imaging, in which fluorescent sialic acids are directly incorporated into substrate glycans via recombinant sialyltranferases, we report the differential distribution of N- and O-glycans and variable expression of sialyl-T antigen on HeLa cells. While the expression of N-glycans tends to be more peripheral at positions where cell-cell interaction occurs, O-glycan expression is more granular but relatively evenly distributed on positive cells. While N-glycans are expressed on all cells, sialyl-T antigen expression exhibits a wide spectrum of variation with some cells being strongly positive and some cells being almost completely negative. The differential distribution of N- and O-glycans on cell surface reflects their distinctive roles in cell biology.

Internal biomarkers and external estimation of exposure to polycyclic aromatic hydrocarbons and their relationships with cancer mortality in a high cancer incidence area.

This study aimed to evaluate internal biomarkers and external estimation of exposure to polycyclic aromatic hydrocarbons (PAH) in a high cancer mortality area in southeast China and identify which of these showed a stronger association of PAH with cancer mortality. A retrospective death survey was conducted to determine the mortality rate of cancer. Cumulative and aggregate external exposures to PAHs of local residents were estimated by field sampling. Three regions in southwest China with gradient PAH exposure levels from high to low (H, M, and L) were selected in this study. Research participants were selected from these three regions using a statistical sampling method. To determine the internal exposure, urinary OH-PAHs were measured using the first morning urine samples. From the retrospective death survey, the highest age-standardized lung cancer mortality rate occurred in Region H (78 per 100,000 person-years), followed by that in Regions M (33 per 100,000 person-years) and L (15 per 100,000 person-years), and the rate was nearly four times China's national mortality rate (20 per 100,000 person-years). Residents estimated daily aggregate exposure doses per unit body weight to carcinogenic benzo(a)pyrene equivalent concentration were 159 ±â€¯14 ng-kg-1-day-1, 7.41 ±â€¯2.76 ng-kg-1-day-1, and 6.13 ±â€¯2.89 ng-kg-1-day-1 in Region H, M, and L, respectively. The participants in Region M had the greatest urinary OH-PAH concentration (9.10 ±â€¯4.92 µg-g-1 crt), followed by Region H (8.01 ±â€¯4.22 µg-g-1 crt) and L (7.12 ±â€¯3.10 µg-g-1 crt). The spatial difference in the total OH-PAHs was not statistically significant. Aggregate and cumulative exposure to 16 PAHs from external routes were found, and external exposure had a stringer relationship with lung cancer mortality than internal exposure.

The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural china.

We previously reported that bacterial diversity in sputum samples from never-smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never-smoking women from Xuanwei, China. DNA from sputum samples of cases (n = 45) and controls (n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1-V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of never-smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: ORhigh = 1.00 [reference], ORmedium = 3.84 [1.02-14.48], ORlow = 3.78 [1.03-13.82]; observed species: ORhigh = 1.00 [reference], ORmedium = 2.37 [0.67-8.48], ORlow = 2.01 [0.58-6.97]; Phylogenetic Diversity (PD) whole tree: ORhigh = 1.00 [reference], ORmedium = 3.04 [0.85-10.92], ORlow = 2.53 [0.72-8.96]), as well as a decreased relative abundance of Fusobacteria (ORhigh = 1.00 [reference], ORmedium = 1.24 [0.42-3.66], ORlow = 2.01 [0.63-6.44], ptrend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Preparation and protective effects of 1,8-cineole-loaded self-microemulsifying drug delivery system on lipopolysaccharide-induced endothelial injury in mice.

An optimised 1,8-cineole-loaded self-microemulsifying drug delivery system (CIN-SMEDDS) with a mean droplet size, polydispersity index, mean zeta potential and encapsulation efficiency of 38.14 ±â€¯1.47 nm, 0.208 ±â€¯0.036, -9.312 ±â€¯1.764 mV and 95.35% ±â€¯1.13%, respectively, successfully ameliorated the lipopolysaccharide (LPS)-induced endothelial injury in mice. Acute toxicity assay in mice through the oral administration of CIN-SMEDDS showed that the median lethal dose of CIN-SMEDDS was 2998.9 mg/kg. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated that the cytotoxicity of CIN-SMEDDS to Caco-2 cells may be ascribed to the surfactant/co-surfactant mixture. In particular, CIN-SMEDDS remarkably inhibited inflammatory cytokines IL-1ß, IL-6 and IL-8 with a simultaneous increase in IL-10 in LPS-treated mice. Haematoxylin-eosin staining results showed that CIN-SMEDDS attenuated LPS-induced vascular endothelial injury. Western blot results showed that the vascular protective effects of CIN-SMEDDS were associated with the NF-κB and peroxisome proliferator-activated receptor γ signalling pathways. These findings indicated that CIN-SMEDDS can attenuate LPS-induced endothelial injury and thus was proposed as a promising agent for the treatment of inflammatory cardiovascular disease.

VSIG-3 as a ligand of VISTA inhibits human T-cell function.

B7 family members and their receptors play a central role in the regulation of T-cell responses through T-cell co-stimulation and co-inhibition pathways that constitute attractive targets for the development of immunotherapeutic drugs. In this study, we report that VSIG-3/IGSF11 is a ligand of B7 family member VISTA/PD-1H and inhibits human T-cell functions through a novel VSIG-3/VISTA pathway. An extensive functional ELISA binding screening assay reveals that VSIG-3 binds to the new B7 family member VISTA but does not interact with other known members of the B7 family. Under the same experimental conditions, we did not observe any significant interaction between VSIG-8 and VISTA. In addition, VSIG-3 inhibits human T-cell proliferation in the presence of T-cell receptor signaling. Furthermore, VSIG-3 significantly reduces cytokine and chemokine production by human T cells including IFN-γ, IL-2, IL-17, CCL5/Rantes, CCL3/MIP-1α, and CXCL11/I-TAC. Anti-VISTA neutralization antibodies attenuate the binding of VSIG-3 and VISTA, as well as VSIG-3-induced T-cell inhibition. Hence, we have identified a novel ligand for VISTA that is able to inhibit human T-cell proliferation and cytokine production. This unique VSIG-3/VISTA co-inhibitory pathway may provide new strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may aid in the design of better vaccines.

Health risk from dietary exposure to polycyclic aromatic hydrocarbons (PAHs) in a typical high cancer incidence area in southwest China.

This study was designed to test whether the dietary intake of polycyclic aromatic hydrocarbons (PAHs) is a potential exposure source relating to the high cancer incidence area in southwest China. Duplicate plate method was used to collect food samples in rural and urban sites in the region. Questionnaire surveys were conducted among 300 local residents to obtain their dietary habits and 50 subjects were chosen to collect the samples. The 16 priority PAHs (PAH16) in composite food samples for each individual subject were measured, and non-carcinogenic and carcinogenic risks were analyzed based on the results of Monte Carlo method. The average concentration of the PAH16 in food samples was 12.04 ±â€¯8.52 ng g-1. The life time average daily benzo(a)pyrene equivalent (BaPeq) exposure dose was 6.07 × 10-6 mg kg-1 day-1. Although non-carcinogenic risk was found to be within a controllable range, the average incremental lifetime cancer risk (ILCR) was 3.7 × 10-5 for rural subjects and 6.1 × 10-5 for urban subjects, which is comparable with other regions in China. The serious risk level of 10-4 was exceeded by 10.7% of urban residents and 2.1% of rural residents. This study implies that dietary exposure to PAHs is a potential exposure source to the high cancer in the region, and further cancer risk control strategies need to be formulated.

[The development and recent status of the craniomaxillofacial surgery in China during past three decades].

The authors made a profound review on the development and the recent status of craniomaxillofacial surgery in China during past three decades. The emphases were placed on the following aspects: the modifications of the reconstructive procedure and minimal invasive mode, the researches on molecular genetic characteristics of the congenital craniofacial malformations, the clinical applications of three-dimensional digital computer-aided techniques (including three-dimensional printing and prefabricated template for precious osteotomies), the craniomaxillofacial defects reconstructing by using the distraction osteogenesis and osseous integrated titanium implant and prothesis, etc. Finally, the authors outlooked prospectively the future trends of the craniomaxillofacial surgery.