Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways.

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNß treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.

Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system.

Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these epitopes have poor immunogenicity and stimulate insufficient CD8+ T cell responses, which motivated us to develop a new method to deliver and enhance their effectiveness. Bacterial outer membrane vesicles (OMVs) can serve as immunoadjuvants and act as a delivery vector for tumor antigens. In the current study, we engineered a new OMV platform for the co-delivery of ESC-derived tumor antigens and immune checkpoint inhibitors (PD-L1 antibody). An engineered Staphylococcal Protein A (SpA) was created to non-specifically bind to anti-PD-L1 antibody. SpyCatcher (SpC) and SpA were fused into the cell outer membrane protein OmpA to capture SpyTag-attached peptides and PD-L1 antibody, respectively. The modified OMV was able to efficiently conjugate with ESC-derived TAAs and PD-L1 antibody (SpC-OMVs + SpT-peptides + anti-PD-L1), increasing the residence time of TAAs in the body. The results showed that the combination therapy of ESC-based TAAs and PD-L1 antibody delivered by OMV had significant inhibitory effects in mouse tumor model. Specifically, it was effective in reducing tumor growth by enhancing IFN-γ-CD8+ T cell responses and increasing the number of CD8+ memory cells and antigen-specific T cells. Overall, the new OMV delivery system is a versatile platform that can enhance the immune responses of ESC-based TAA cancer vaccines.

Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract.

BACKGROUND: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood. METHODS: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3-4 weeks), adult (8-10 weeks), and aged (10-12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells. FINDINGS: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2. INTERPRETATION: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations. FUNDING: The full list of funding can be found at the Acknowledgements section.

The relationship between the radiation dose of pelvic-bone marrow and lymphocytic toxicity in concurrent chemoradiotherapy for cervical cancer.

OBJECTIVE: The purpose of this study is to verify the correlation between medium and low radiation doses of the pelvic-bone marrow and the incidence of lymphocytic toxicity during concurrent chemoradiotherapy for cervical cancer. MATERIALS AND METHODS: This research included 117 cervical cancer patients, who received concurrent chemoradiotherapy. Radiotherapy included external-beam radiation therapy and brachytherapy. The dosimetry parameters include the Volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and the mean dose (D mean) of the bone marrow. Lymphocytic toxicity was calculated from lowest lymphocytic count after two cycles of concurrent chemotherapy. RESULTS: During concurrent chemoradiotherapy, the incidence of lymphocytic toxicity is 94.88%. The incidence of grade 3-4 toxicity is 68.38%. Multivariate analysis findings show that the dosimetry parameters V5, V10, V20, and V30 are significantly correlated with lymphocytic toxicity. The patients are divided into small-volume subgroups and large-volume subgroups based on the cutoff values. The relative risk of both grade 1-4 and grade 3-4 lymphocytic toxicity is significantly lower in the small-volume subgroups than in the large-volume subgroups (P < 0.05). Kaplan-Meier analysis shows that the incidence of both grade 1-4 and grade 3-4 lymphocytic toxicity of the small-volume subgroups is significantly lower than that of the large-volume subgroups (P < 0.05). CONCLUSION: There is a significant correlation between a medium and low dose of pelvic-bone-marrow radiation and incidence of lymphocytic toxicity. Reducing the volume of medium and low radiation doses could effectively reduce incidence of lymphocytic toxicity.

The Epitope Basis of Embryonic Stem Cell-Induced Antitumor Immunity against Bladder Cancer.

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) share many cellular and molecular features with cancer cells. Taking advantage of these similarities, stem cells are effective vaccines against cancers in animal models. However, the molecular basis is not well understood, which hinders the development of effective cancer vaccines. Here, prophylactic and therapeutic bladder cancer vaccines composed of allogeneic ESCs and CpG with or without granulocyte macrophage colony stimulating factor are tested. The ESC-based cancer vaccines are able to induce specific antitumor immunity including stimulating cytotoxic CD8+ T cells and memory CD4+ T cells, reducing myeloid-derived suppressor cells, and preventing bladder cancer growth in mouse models. Furthermore, several genes that are overexpressed in both ESCs and tumors are identified. An epitope-based vaccine designed with shared overexpressed proteins induces specific antitumor immunity and reduces bladder cancer growth. Functional epitopes underlying the action of stem cell-based vaccines against bladder cancer are identified and it is confirmed that ESC-based anticancer vaccines have great potential. A systematic approach is provided here to developing novel effective epitope-based cancer vaccines in the future.

The effect of chronoradiotherapy on cervical cancer patients: A multicenter randomized controlled study.

Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity.

BACKGROUND: Staphylococcus aureus is a common human pathogen capable of causing diverse illnesses with possible recurrent infections. Although recent studies have highlighted the role of cellular immunity in recurrent infections, the mechanism by which S. aureus evades host responses remains largely unexplored. METHODS: This study utilizes in vitro and in vivo infection experiments to investigate difference of pro-inflammatory responses and subsequent adaptive immune responses between adsA mutant and WT S. aureus strain infection. FINDINGS: We demonstrated that adenosine synthase A (AdsA), a potent S. aureus virulence factor, can alter Th17 responses by interfering with NLRP3 inflammasome-mediated IL-1ß production. Specifically, S. aureus virulence factor AdsA dampens Th1/Th17 immunity by limiting the release of IL-1ß and other Th polarizing cytokines. In particular, AdsA obstructs the release of IL-1ß via the adenosine/A2aR/NLRP3 axis. Using a murine infection model, pharmacological inhibition of A2a receptor enhanced S. aureus-specific Th17 responses, whereas inhibition of NLRP3 and caspase-1 downregulated these responses. Our results showed that AdsA contributes to recurrent S. aureus infection by restraining protective Th1/Th17 responses. INTERPRETATION: Our study provides important mechanistic insights for therapeutic and vaccination strategies against S. aureus infections. FUNDING: This work was supported by grants from Shenzhen Peacock project (KQTD2015033-117210153), and Guangdong Science and Technology Department (2020B1212030004) to J.H. and China Postdoctoral Science Foundation (2019M663167) to BZZ. We also thank the L & T Charitable Foundation, the Guangdong Science and Technology Department (2020B1212030004), and the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019BT02Y198) for their support.

A Simple Diagnosis-Related Groups-Based Reimbursement System Is Cost Ineffective for Elderly Patients With Displaced Femoral Neck Fracture Undergoing Hemiarthroplasty in Beijing.

Displaced femoral neck fractures (FNF) in the elderly are a major public health concern that necessitates hemiarthroplasty (HA) as the mainstay treatment option. Diagnosis-Related Groups (DRG) are a patient classification system that categorizes patients based on the resources expended on them. The first objective of this study was to evaluate if a simplified DRG-based reimbursement system in Beijing would lower total HA treatment costs for elderly patients with displaced FNF. In addition, we aimed to determine how age, gender, year of admission, length of in-hospital stay, and the Charlson index affected total treatment costs. This retrospective study included 513 patients from the Peking Union Medical College Hospital. The patients were diagnosed with unilateral displaced femoral neck fractures and had HA. Medical information was gathered, including baseline demographic and clinical data, as well as treatment costs. Patients were classified into two groups: those who spent more than the predetermined cut-off cost and those who did not. The cost did not include the use of a bipolar prosthesis. Data from the two groups were compared, and multiple regression analysis models were constructed. The median total cost of treatment was ¥49,626 ($7,316). The majority of the patients (89.7%; 460/513) were categorized as exceeding the cost cut-off. Multiple linear regression analysis revealed that total treatment cost was positively correlated with age (p < 0.01) and the duration of in-hospital stay (p < 0.01) but not with gender (p = 0.160) or the Charlson index (p = 0.548). On implementing the DRG-based reimbursement system, the overall treatment costs increased by ¥21,028 ($3,099) (p < 0.01). The implementation of simplified DRG-prospective payment systems did not result in a significant reduction in total treatment costs for elderly patients with FNF who underwent HA in Beijing. The overall cost of treatment was associated with several factors, including age, length of hospitalization, and year of admission.

Preparation of teamed boronate affinity magnetic nanoparticles for extraction of polyphenols from Flos Lonicerae Beverage under neutral pH prior to their determination by high-performance liquid chromatography-mass spectrometry.

Traditional boron affinity materials usually capture cis-diol-containing molecules under alkaline condition, but some cis-diol-containing molecules, such as polyphenols, are unstable and easy to be oxidized and degraded under alkaline condition. Teamed boronate affinity (TBA) can specifically capture cis-diol-containing molecules under neutral condition. However, the report about combination of TBA and magnetic nanoparticle for the extraction was rare. Here, we fabricated two kinds of teamed boronate affinity magnetic nanoparticles (TBAMP), including Fe3O4@TBAP and Fe3O4@SiO2@TBAP. Adsorption capacities of cis-diol-containing molecules on the latter were similar to these on the former, but the latter possessed more superior regeneration performance than the former. Therefore, the TBAMP with more superior regeneration performance was used as magnetic solid-phase extraction (MSPE) adsorbent for capturing polyphenols under neutral condition. The TBAMP MSPE was optimized in detail, and combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the simultaneous determination of 13 kinds of polyphenols from Flos Lonicerae Beverage. The proposed method showed low limit of detection between 0.01 and 0.20 ng mL-1. In blank Flos Lonicerae Beverage, 11 kinds of polyphenols ranged from 0.54 ng mL-1 to 52.99 ng mL-1 were detected. In the standard addition method, recoveries of cis-diol-containing polyphenols were between 85.7% and 102.1% with intra-day and inter-day relative standard deviation ranging from 3.2% to 5.1% and 5.3% to 7.3%, respectively.

Risk assessment and management of preoperative venous thromboembolism following femoral neck fracture.

BACKGROUND: Limited studies are available to investigate the prevalence of preoperative venous thromboembolism (VTE) in elderly patients with femoral neck fractures. Our primary aim was to determine the incidences of VTE and its risk or protective factors in such patient population. The secondary objective was to evaluate the need of therapeutic anticoagulation for isolated calf muscular venous thrombosis (ICMVT) prior to femoral neck fracture surgery. METHODS: This is a retrospective case-control study, including 301 femoral neck fracture patients who were admitted to our institution between January 2014 and March 2017. Bilateral Doppler ultrasonography was performed in each of the patients as a preoperative VTE screening. The event rate of VTE was calculated, and significant risk or protective factors were determined by using a multivariate logistic regression model. Patients with ICMVT were divided into anticoagulation and no anticoagulation groups to assess the efficacy and safety of preoperative therapeutic anticoagulation. Intraoperative blood loss, drainage volume, blood transfusion, perioperative hemoglobin change, and rate of thrombosis extension were compared between the two groups. RESULTS: The overall preoperative incidence of VTE in patients with femoral neck fracture was 18.9% (57/301), in which deep vein thrombosis (DVT) was 18.9% and pulmonary embolism (PE) was 1%. Among the DVT cases, 77.2% (44/57) were ICMVTs. Multiple fractures (odds ratio [OR] = 9.418; 95% confidence interval [CI] = 2.537 to 34.96), coexisting movement disorder (OR = 3.862; 95% CI = 1.658 to 8.993), bed rest for more than 7 days (OR = 2.082; 95% CI = 1.011 to 4.284) as well as elevated levels of D-dimer (OR = 1.019; 95% CI = 1.002 to 1.037) and fibrinogen (OR = 1.345; 95% CI = 1.008 to 1.796) led to an increase in the risk of VTE, while the recent use of antiplatelet drug (OR = 0.424; 95% CI = 0.181 to 0.995) and prophylactic anticoagulation (OR = 0.503; 95% CI = 0.263 to 0.959) decreased the risk of VTE. For the 39 patients with ICMVT undergoing femoral neck fracture surgery, there were no significant differences in the rate of thrombosis extension between anticoagulation and no anticoagulation groups, but significantly decreased postoperative hemoglobin was observed in the anticoagulation group. CONCLUSION: Our findings showed a high prevalence of preoperative VTE in elderly patients with femoral neck fracture, with risk factors identified. We found that the most detected VTE were ICMVTs. Our study suggested that a direct surgery without preoperative use of therapeutic anticoagulation for ICMVT would not reduce the risk of thrombus extension, and the therapeutic use of anticoagulation may worsen postoperative anemia.

Immunotherapy Targeting Adenosine Synthase A Decreases Severity of Staphylococcus aureus Infection in Mouse Model.

Staphylococcusaureus is a severe pathogen found in the community and in hospitals. Most notably, methicillin-resistant S. aureus (MRSA) is resistant to almost all antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments such as immunotherapeutic approaches. Previous research showed that S. aureus exploit the immunomodulatory attributes of adenosine to escape host immunity. In this study, we investigated adenosine synthase A (AdsA), an S. aureus cell wall-anchored enzyme as possible targets for immunotherapy. Mice vaccinated with aluminum hydroxide-formulated recombinant AdsA (rAdsA) induced high-titer anti-AdsA antibodies, thereby providing consistent protection in 3 mouse infection models when challenged with 2 S. aureus strains. The importance of anti-AdsA antibody in protection was demonstrated by passive transfer experiments. Moreover, AdsA-specific antisera promote killing S. aureus by immune cells. Altogether, our data demonstrate that the AdsA is a promising target for vaccines and therapeutics development to alleviate severe S. aureus diseases.

Perioperative Period of a Hemophilia-related Osteoarthropathy Therapeutic Regimen and Analysis of Complications.

OBJECTIVE: To investigate the effectiveness of our department's therapeutic regimen and treatment of complications during the perioperative period of hemophilia-related osteoarthropathy. METHODS: In this retrospective study, data on 101 patients with hemophilia who had undergone operative treatment in our hospital from January 2000 to August 2014 were assessed. Ninety-one of the patients had hemophilia A and 10 hemophilia B. All patients were male. Changes in Hospital for Special Surgery (HSS), Harris and American Orthopedic Foot and Ankle Society (AOFAS) scores, occurrence of complications during the perioperative period and the clinical treatment and prognosis pre- and postoperatively and during follow-up were analyzed. Relevant clinical data were obtained through telephone calls, outpatient follow-up, and medical clinical record searches. RESULTS: The 101 patients who were followed up (for an average of 96 months) had 147 orthopedic operations, including joint replacement, hemophilia-related false tumor resections, and tendo-achillis lengthening. The HSS scores for knee surgeries increased from 52 points preoperatively to 86 postoperatively, Harris scores for hip joint surgery from 26 to 87 points, respectively, and AOFAS scores for foot and ankle surgeries from 39 to 81 points, respectively. Eight patients had wound complications, four intra-articular hematomas, two peroneal nerve injuries, one a proximal femur splitting fracture and one deep venous thrombosis. CONCLUSIONS: Surgical treatment is a safe and reliable choice for addressing complications including hemophilia-related osteoarthropathy given the implementation of effective measures for treatment during the perioperative period.

Obligate anaerobic Salmonella typhimurium strain YB1 treatment on xenograft tumor in immunocompetent mouse model.

The present authors have previously reported a novel approach to genetically engineer Salmonella typhimurium for the medically important therapeutic strategy of using bacterial agents to target malignant tumors in a breast cancer tumor-bearing nude mouse model. However, studying an immunocompromised mouse model for cancer therapy is insufficient, as certain crucial information about the influence of the immune system may be missing. In the present study, inoculation of the Salmonella strain, YB1, into a colon cancer tumor-bearing immunocompetent mouse model was investigated. The present study determined the tumor targeting efficiency, antitumor potential, the effects of multiple treatments and the systemic toxicity. Intravenous inoculation of YB1 in BALB/c mice exhibited high antitumor effects and also greatly increased the tumor targeting ability and safety compared with the previously-reported nude mouse model. In addition, repeated administration of YB1 further enhanced this effect. Furthermore, no marked toxicity was observed with YB1 treatment, while the VNP20009 and SL7207 strains demonstrated certain adverse effects. The findings of the present study indicate that the YB1 strain is effective and safe in targeting a colon cancer tumor in an immunocompetent mouse model.

Management of Humeral Shaft Fractures With Intramedullary Interlocking Nail Versus Locking Compression Plate.

Surgical fixation of humeral shaft fractures generally involves plating or nailing. It is unclear whether one method is more effective than the other. The aim of this study was to compare the results of the intramedullary nail and locking compression plate for the treatment of humeral shaft fractures. A total of 60 patients with humeral shaft fractures were randomized to undergo surgery with an intramedullary interlocking nail (n=30) or locking compression plate (n=30). The outcome was assessed in terms of intraoperative blood loss, operative time, hospital stay, union time, union rate, functional outcome, and incidence of complications. Functional outcome was assessed using the Constant score and the American Shoulder and Elbow Surgeons (ASES) score. Intraoperative blood loss, operative time, and hospital stay in group A (intramedullary interlocking nail) were significantly lower than those in group B (locking compression plate). No statistically significant difference was found regarding the union rate, mean Constant score, and mean ASES score between the groups. The average union time was found to be significantly lower for the intramedullary interlocking nail compared with the locking compression plate. The incidence of complications such as radial nerve palsy was found to be higher with the locking compression plate compared with the intramedullary interlocking nail. The intramedullary interlocking nail can be considered a better surgical option for the management of humeral shaft fractures because it offers decreased intraoperative blood loss; shorter operative times, hospital stays, and union times; and a lower incidence of serious complications such as radial nerve palsy.

MicroRNA-135b exerts oncogenic activity in glioblastoma via the inhibition of glycerol kinase 5 expression.

Glioblastoma is the most common primary malignancy of the adult central nervous system and is associated with a markedly poor prognosis. Elucidating the pathogenesis and molecular changes will assist in further understanding the pathogenesis and progression of the disease and offer novel targets for therapies. The present study demonstrated that the expression level of GK5 was lower in high-grade glioblastoma tissues compared with low-grade ones and it can promote proliferation in glioblastoma cells. The regulatory mechanism of GK5 in glioblastoma were also investigated. It was revealed that GK5 is a target of miR-135b in U87MG glioblastoma cells. Controry to GK5, the expression of miR-135b is upregulated in glioblastoma and its expression is positively associated with the grade of the disease. Finally, it was demonstrated that miR-135b promoted the proliferation of U87MG cells. Therefore, miR-135b may function as an oncogene by inhibiting GK5 in glioblastoma.

[Case-control study on influence of femoral neck fracture on deep venous thrombosis in patients undergoing prosthetic hip surgery].

OBJECTIVE: To investigate the association between femoral neck fracture and deep vein thrombosis (DVT) in patients undergoing prosthetic hip surgery. METHODS: The data of patients who underwent prosthetic hip surgery from January 2005 to July 2010 were collected, the cases were included into the study after exclusion of those could not be suitable for the study. The patients with diagnosis of deep-vein thrombosis (DVT) were identified together as the case group, and the patients without DVT were selected randomly and matched with frequency as the control group. The matching characteristics included age, gender and body weight. The patients with femoral neck fracture were counted in both case and control group. The odds ratio was calculated and the exposure rate of both group were compared. RESULTS: There were total 670 patients underwent prosthetic hip surgery during the period, and after exclusion,the data of 408 patients were collected into the study. There were 13 patients in the case group (4 males and 9 females, ranging in age fram 57 to 91 years), all of them suffering from femoral neck fracture and the exposure rate was 100.0% (13/13). There were 52 patients in the control group (18 males and 34 females, ranging in age from 57 to 91 years), 39 of them suffering from femoral neck fracture, the exposure rate was 75.0% (39/52); there was no statistically significant difference in exposure rate of two groups. CONCLUSION: The diagnosis of femoral neck fracture is not the independent risk factor for postoperative DVT of prosthetic hip surgery. The epidemiologic characteristics of femoral neck fracture indicate that the patients are in high risk of DVT, who meanwhile are the most of patients undergoing the prosthetic hip surgery. Though the surgery itself is a risk of DVT, it can reduce the risks for patients with femoral neck fracture through some therapeutic effects.

Calculated respiratory exposure to indoor size-fractioned polycyclic aromatic hydrocarbons in an urban environment.

Polycyclic aromatic hydrocarbons (PAHs) associated with inhalable particles are harmful to human health, especially to people in urban indoor environments. To evaluate human respiratory exposure to indoor PAHs properly, respiratory deposition fluxes of size-fractioned PAHs were estimated based on size-segregated distribution of PAHs in indoor air of an urban community of Guangzhou, China. The concentrations of ∑(16)PAH (sum of the 16 priority PAHs designated by the United States Environmental Protection Agency) were 28.9±10.0 ng/m(3), with the mean benzo(a)pyrene equivalent (BaPE) concentration at 4.1±1.6 ng/m(3). Particle size distributions of both ∑(16)PAH and BaPE concentrations peaked in the 1.0-1.8 µm fraction. The mean respiratory deposition flux of ∑(16)PAH was 5.9 ng/h, and accumulation mode particles contributed 20.5-83.8% of the respiratory deposition fluxes for individual PAHs. In addition, 8.6-10.2% of inhaled ∑(16)PAH were calculated to be deposited in the alveoli region, with accumulation particles as the largest contributor. In particular, ultrafine particles contributed 0.4-21.7% of individual PAHs deposited in the alveoli region, more than twice the fraction of the PAHs in the ultrafine particles (0.2-8.5%). Finally, lifetime cancer risk via inhalation of indoor particulate PAHs may be greater than the cancer risk guideline value (10(-6)), depending on specific assumptions used in this risk assessment.

Input pathways of organochlorine pesticides to typical freshwater cultured fish ponds of South China: hints for pollution control.

Air, rain, pond water, bank soil, pond sediment, fish feed, and fish were sampled from four freshwater cultured fish ponds (FWCFPs) in rural areas within the Pearl River Delta (PRD) of South China. Compositional analyses indicated that historical residues were the main sources of DDXs (defined as the sum of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDD), and dichlorodiphenyldichloroethylene (DDE) and 1-chloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDMU)), and hexachlorocyclohexanes (HCHs) in the FWCFPs. The input fluxes to the FWCFPs were estimated at 4.0, 1.6, 15, and -0.92 µg/m(2) ·year for DDXs and 3.8, 0.92, 2.9, and -1.4 µg/m(2) ·year for HCHs for dry deposition, wet deposition, feeding, and net air-water exchange in Dongguan, and 3.8, 1.2, 137, and -1.2 µg/m(2) ·year for DDXs and 3.6, 0.66, 5.0, and -1.0 µg/m(2) ·year for HCHs in Shunde, respectively. These results indicated that fish feed was the dominant input source of DDXs to the FWCFPs. As for HCHs, fluxes via dry deposition and feeding were similar and slightly higher than those via wet deposition. Biological effects due to the occurrence of DDXs in the FWCFPs were minimal, and consumption of freshwater fish from the PRD appeared to pose insignificant risk to human health based on some existing regulations and guidelines.

Tuning the non-equilibrium state of a drug-encapsulated poly(ethylene glycol) hydrogel for stem and progenitor cell mobilization.

Injectable and biodegradable hydrogels have been increasingly studied for sustained drug delivery in various molecular therapies. However, it remains a challenge to attain desired delivery rate at injection sites due to local tissue pressures exerted on the soft hydrogels. Furthermore, there is often limited controllability of stiffness and degradation rates, which are key factors required for achieving desired drug release rate and therapeutic efficacy. This study presents a stiff and metastable poly(ethylene glycol) diacrylate (PEGDA)-poly(ethylene imine) (PEI) hydrogel which exhibits an elastic modulus equivalent to bulk plastic materials, and controllable degradation rate independent of its initial elastic modulus. Such unique stiffness was attained from the highly branched architecture of PEI, and the decoupled controllability of degradation rate was achieved by tuning the non-equilibrium swelling of the hydrogel. Furthermore, a single intramuscular administration of granulocyte colony stimulating factor (GCSF)-encapsulated PEGDA-PEI hydrogel extended the mobilization of mononuclear cells to four days. A larger yield of expanded CD34+ and CD31+ endothelial progenitor cells (EPCs) was also obtained as compared to the daily bolus administration. Overall, the hydrogel created in this study will be useful for the controlled and sustained delivery of a wide array of drug molecules.