Ultrastable PLGA-Coated 177Lu-Microspheres for Radioembolization Therapy of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.

Long-term benefits of interferon-α therapy in children with HBeAg-positive immune-active chronic hepatitis B.

The long-term benefits of interferon-α (IFN-α) treatment in children with chronic hepatitis B (CHB) remain unclear. We conducted a retrospective and real-world study to evaluate the safety and long-term clearance rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in CHB children who received IFN-α monotherapy for 72 weeks and were with 13-year follow-up visit. Participants treated with IFN-α (n = 316) were more likely to become HBeAg negatve (39.87% vs. 27.37%; p < .05) and HBsAg negative (11.08% vs. 3.16%; p < .05) by the end of the treatment period than untreated participants (n = 95). Treated participants also had higher cumulative rates of HBeAg loss (74.13% vs. 59.27%; p < .05) and HBsAg loss (46.95 vs. 33.11%; p < 0.05) than untreated participants in parallel by the end of 13-year follow-up. In particular, the cumulative rate of HBsAg loss was higher in treated children aged 1-7 years than in those aged 8-17 years (71.40% vs. 39.0%; p < .01). Children who were HBeAg-negative at the end of IFN-α treatment or who had serum alanine aminotransferase levels of ≥80 IU/L at baseline were likely to have higher cumulative HBsAg loss rates. Accordingly, HBeAg loss at 72 weeks was positively associated with the cumulative HBsAg loss rate in untreated children. There were no serious adverse events of IFN-α therapy for the treated patients throughout the study period. Overall, IFN-α therapy was effective in obtaining higher long-term cumulative rates of HBeAg and HBsAg loss in children with HBeAg-positive immune-active CHB, especially among those aged 1-7 years.

Highly biocompatible thermosensitive nanocomposite gel for combined therapy of hepatocellular carcinoma via the enhancement of mitochondria related apoptosis.

Primary hepatocellular carcinoma (HCC) is a common malignant tumor. Surgery is the main treatment, but HCC patients have a potential risk of tumor recurrence. Besides, many limitations arise during the application of single first-line antitumor drugs. Here, we selected Pluronic F-127 and sodium alginate (SA) to prepare a thermosensitive gel (Gel). The optimal synergistic ratio of PTX and DOX on the SMMC-7721 cells was 1: 2 (w/w), calculated by the Chou-Talalay analysis. Then, PTX and DOX coloaded liposomes (PD-LPs) with such drugs ratios presented enhanced anticancer ability in vitro. Upon local injection, the PD-LPs Gel formed a nanoparticles reservoir at tumor via sol-gel transformation, while exhibiting a long-term effective anti-tumor ability in vivo. The relative tumor volume after the PD-LPs Gel treatment was reduced over 62%. Effective mitochondria related apoptosis induction was observed. Therefore, the local delivery of PD-LPs Gel can be a promising alternative method for the HCC therapy.

Predictive Significance of Radiographic Density of Sinus Opacity and Bone Thickness in Unilateral Maxillary Sinus Mycetoma.

OBJECTIVES: To identify the optimal cutoff value in Hounsfield units (HU) of maxillary sinus (MS) opacity and bone thickness (neo-osteogenesis) of MS as radiological predictors for mycetoma. METHODS: One hundred and sixty-four patients, including 59 patients with unilateral MS mycetoma, 31 with unilateral odontogenic maxillary sinusitis, 44 with chronic rhinosinusitis and 30 with rhinitis, who underwent sinus or turbinate surgery were recruited. The bone thickness, HU of the MS posterolateral wall and sinus opacity were evaluated using computed tomography scan. RESULTS: The bone thickness of the MS posterolateral wall in the mycetoma group was significantly higher than that in the odontogenic sinusitis and chronic rhinosinusitis (CRS) groups (p < 0.0001). The HU of the sinus opacity in the mycetoma group were significantly higher than those in the odontogenic and CRS groups (p < 0.0001). An optimal cutoff HU of sinus opacity >101.17 yielded a sensitivity of 96.6 and specificity of 100% for the diagnosis of MS mycetoma. An optimal cutoff of bone thickness >0.305 cm yielded a sensitivity of 84.7 and specificity of 60% for the diagnosis of MS mycetomas. CONCLUSIONS: The radiographic density measurement of MS opacification has a high predictive value for the diagnosis of MS mycetoma while radiographic neo-osteogenesis has not.

Case report: A novel variant (H49N) in Myelin Protein Zero gene is responsible for a patient with Charcot-Marie-Tooth disease.

This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.

Ultrasonography on the non-living. Current approaches.

The vast majority of clinicians associate diagnostic ultrasound with a tool that is designed for the living patient. However, it is of course possible to apply this imaging technology to evaluate the recently deceased patient for postmortem diagnosis, or even just examine postmortem tissue. We describe several cases in which ultrasound-enabled providers obtain answers in postmortem examinations and discuss potential future strategies and applications. In addition, we will also illustrate the use of sonography in minimally invasive post-mortem tissue sampling (MITS), an approach that can be used in post-mortem minimally invasive autopsies as well as for establishing ultrasound diagnostic parameters in new medical fields such as periodontal and dental implant specialties.

Research on Polycaprolactone-Gelatin Composite Scaffolds Carrying Nerve Growth Factor for the Repair of Spinal Cord Injury.

Objective: This study was to investigate the mechanism of action of polycaprolactone/gelatin (PCL/GE) composite fiber scaffold with nerve growth factor (NGF) in the recovery of spinal cord injury (SCI). Methods: Sixty female Sprague-Dawley (SD) rats were randomly assigned to the negative control group, the positive control group, the PCL/GE scaffold group, and the collagen-binding structural domain nerve growth factor (CBD-NGF)/PCL/GE scaffold group, with 15 rats in each group. Spinal cord transection was used to establish SCI models in rats. The negative control group received sham surgery, while the other three groups were given spinal cord transection at the tenth thoracic vertebra (T10) segment. The rats in the PCL/GE scaffold group were implanted with a 4 mm PCL/GE composite fiber scaffold, and those in the CBD-NGF/PCL/GE scaffold group were implanted with a CBD-NGF/PCL/GE composite fiber scaffold. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to evaluate the locomotor ability of the hind limbs of the rats, and the amplitude and latency of motor evoked potentials (MEP) were recorded by neurophysiological testing at 12 w postoperatively. The levels of growth-associated protein 43 (GAP43) and neurofilament protein 200 (NF200) in the spinal cord tissue of the injury site were determined using Western Blot at 12 w after surgery. Spinal cord tissues of 2 cm within the injury site, the thoracic segment above the injury site, and the lumbar segment below the injury site were collected from the measurement of axonal transport using fluorescent retrograde tracer fluorogold, and the integrated absorbance (IA) values of FC-positive cells were calculated. Results: After treatment, the negative control rats showed normal locomotion function of the hind limb with the highest BBB scores, while the positive control rats had the lowest BBB scores and showed paraplegia. The scaffold groups exhibited better locomotion function of the hind limb and higher BBB scores than the positive controls, with greater improvement observed in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Compared with the positive controls, the PCL/GE scaffold group and CBD-NGF/PCL/GE scaffold group exhibited significantly shorter latency and increased amplitude of MEP, with more significant changes observed in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Compared with the positive control group, the GAP43 and NF200 levels of spinal cord tissue were significantly elevated in both the PCL/GE scaffold group and the CBD-NGF/PCL/GE scaffold group, and the changes were more pronounced in the CBD-NGF/PCL/GE scaffold group (P < 0.05). The differences in the IA values of FC-positive cells in the spinal cord tissue of the lumbar segment below the injury site among the four groups did not come up to the statistical standard (P > 0.05). Compared with the positive control group, the FC-positive cell IA values of spinal cord tissue in the thoracic segment above the injury area were markedly increased in the PCL/GE scaffold group and the CBD-NGF/PCL/GE scaffold group, and the alterations were more significant in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Conclusion: PCL/GE composite fiber scaffold with NGF significantly improves motor and neurological functions in the hind limbs of SCI rats and promotes the recovery of axonal transport, and the mechanism may be associated with the upregulation of GAP43 and NF200 levels in spinal cord injury site tissues.

Highly stretchable, self-healable, and self-adhesive ionogels with efficient antibacterial performances for a highly sensitive wearable strain sensor.

Gel-based strain sensors with multi-functional outstanding properties have gained considerable attention. However, conventional gel sensors suffer from unsatisfactory mechanical properties and adhesion, and also a lack of self-healing and antibacterial ability. Herein, a multi-functional ionogel has been constructed based on Ag-Lignin nanoparticles (Ag-Lignin NPs), polyurethane (PU), and ionic liquids. The obtained ionogel exhibited excellent mechanical properties (tensile strength: 3.14 MPa, elongation at break: 1241%), and was conferred self-healing ability by introducing the disulfide bonds into the main chain (the best self-healing efficiency is 97.6%). The dynamic catechol redox system based on Ag-Lignin NPs endows the ionogel with repeatable and long-lasting adhesiveness. Besides, the obtained ionogel also presented favorable antibacterial and UV absorption properties. The sensor based on the ionogel possesses good and stable sensing performance. This study proposes a bright new strategy to fabricate multi-functional ionogel-based sensors exerting broad application prospects in the field of human movement and personalized physiological health monitoring.

Efficacy of Lauromacrogol Injection for Ablation of Benign Predominantly Cystic Thyroid Nodules and Related Factors: A Prospective Study.

OBJECTIVE: To prospectively evaluate the efficacy of lauromacrogol injection for ablation (LIA) of benign predominantly cystic thyroid nodules and its related factors. MATERIALS AND METHODS: A total of 142 benign predominantly cystic thyroid nodules (median volume, 12.5 mL; range, 0.4-156 mL) in 137 patients (male:female sex ratio, 36:101; mean age ± standard deviation [SD], 49 ± 13 years) were treated with LIA after being confirmed as benign via cytology. The volume reduction rate (VRR) of the nodules and cosmetic score were evaluated during follow-up at 1, 3, and 6 months after treatment and every 6 months thereafter. A VRR of ≥ 50% at the 12-month follow-up was considered to indicate effective treatment. The associations between the clinical factors and nodular ultrasound features, including the initial nodule volume, proportion of solid components, vascularity grade and ineffective treatment (VRR of < 50% at the 12-month follow-up), and regrowth were analyzed. RESULTS: All patients completed follow-up for at least 12 months. The average ± SD follow-up period was 32 ± 11 months (range, 12-54 months). The effective treatment rate was 73.2% (104/142), while the regrowth rate was 12.0% (17/142) at the last follow-up. Grade 2-3 intranodular vascularity in the solid components of the nodules was the only independent factor associated with ineffective treatment, with an odds ratio (reference category, grade 0-1) of 3.054 (95% confidence interval, 1.148-8.127) (p = 0.025). CONCLUSION: LIA is an effective treatment for predominantly cystic thyroid nodules. Grade 2-3 intranodular vascularity in the solid components of nodules is the only independent risk factor for ineffective LIA.

Overexpression of LpCPC from Lilium pumilum confers saline-alkali stress (NaHCO3) resistance.

Lilium Pumilum with wide distribution is highly tolerant to salinity. The blue copper protein LpCPC (Lilium pumilum Cucumber Peeling Cupredoxin) gene was cloned from Lilium pumilum, which has the conserved regions of type I copper protein. Moreover, LpCPC has the closest relation to CPC from Actinidia chinensis using DNAMAN software and MEGA7 software. qRT-PCR indicated that LpCPC expression was higher in root and bulb of Lilium pumilum, and the expression of the LpCPC gene increased and reached the highest level at 12 h in bulbs under 20 mM NaHCO3. The transgenic yeast was more tolerant compared with the control under NaHCO3 stress. Compared with the wild type, overexpressing plants indicated a relatively lower degree of wilting. In addition, the chlorophyll content, soluble phenol content, and lignin content of overexpressing lines were higher than that of wild-type, whereas the relative conductivity of overexpressing plants was significantly lower than that of wild-type plants. Expression of essential genes including NHX1 and SOS1 in salt stress response pathways are steadily higher in overexpression tobacco than that in wild-types. Transgenic lines had much higher levels of CCR1 and CAD, which are involved in lignin production, compared with wild-type lines. The yeast two-hybrid technique was applied to screen probable interacting proteins interacting with LpCPC. Eight proteins interacted with LpCPC were screened, and five of which were demonstrated to be associated with plant salinity resistance. Overall, the role of gene LpCPC is mediating molecule responses in increasing saline-alkali stress resistance, indicating that it is an essential gene to enhance salt tolerance in Lilium pumilum.

Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine.

Background: Candida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine's protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells. Materials and Methods: Hsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to "charge" the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice. Results: Nanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo. After immunization, the antibodies in mice could protect the mice infected by C. albicans. Conclusion: As an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo. This strategy can be adapted for the future design of vaccines.

[Changes of dental emergency cases in the first half from 2017 to 2020 in Shanghai Ninth People's Hospital].

PURPOSE: This study aimed to summarize and analyze dental emergence data and compare with the same period from 2017 to the first half of 2020, to provide a basis for improving the quality of dental emergency care and formulating rational allocation. METHODS: A total dental emergency cases from 2017 to the first half of 2020 were collected, statistical analysis was carried out according to patients' sex and age, chief complaints and diagnosis with SPSS 18.0 software package. RESULTS: The top three diseases in 2017 of dental emergency were maxillofacial trauma, facial infection and dental pulp disease. From 2018, most of the specialized patients were treated due to oral craniomaxillofacial injury , maxillofacial infection and tumors. The top three chief complaints for 3 consecutive years were facial swelling, toothache and dental trauma. The difference of emergency data within 4 years was statistically significant. CONCLUSIONS: There are a large number of patients which follow the regular pattern and a wide scope of disease types in dental emergency department. The total amount has a rising trend year by year. After divisions of dental emergency department are established, the patients' treatment is more timely, convenient and targeted, and the quality of medical service has been improving.

Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding.

Inherited macrothrombocytopenia (IMTP) is a rare disorder characterized by a reduced platelet count and abnormally large platelets. The main clinical symptom of IMTP is mild bleeding in some patients. At present, more than 30 genes have been identified in patients with syndromic and non-syndromic IMTP. In this study, a 3-year-old boy and his mother who presented with mild epistaxis and/or gingival bleeding were diagnosed as having IMTP. Wen then selected whole sequencing to explore the genetic lesion of the patients. After data filtering and mutation validation, a novel frameshift mutation (NM_001130004: c.398_399insTGCG, p.F134AfsX60) of α-actin 1 (ACTN1) was identified in the proband and his mother but absent in other unaffected individuals. Previous studies have proven that mutations in ACTN1 may lead to IMTP with mild to absent bleeding phenotype. The novel mutation, resulting in a truncated protein in exon 4 of the ACTN1 gene, was absent in the public database, such as 1000G and genomAD. Further Western blot revealed that the expression of α-actin 1 in the proband was decreased overtly, which indicated that the novel frameshift mutation may induce non-sense-mediated mRNA decay. In summary, this study not only broadened the variants spectrum of ACTN1 gene, which may contribute to the genetic counseling of IMTP, but also confirmed the diagnosis of IMTP, which may help the management and prognosis for the family members.

Incidence of malignancy in primary Sjogren's syndrome in a Chinese cohort.

OBJECTIVES: To evaluate the incidence of malignancies in a cohort of Chinese patients with primary Sjögren's syndrome (pSS) and to identify the risk factors of malignancy in pSS patients. METHODS: A retrospective analysis was carried out in 1320 pSS patients who were recruited in Peking Union Medical College Hospital from 1990 to 2005 and were followed up for an average of 4.4 years. Among them, 29 patients developed malignancies. Standardized incidence ratios (SIRs) were calculated along with 95% CIs. Clinical characteristics were compared between patients with and without malignancies, as well as patients with haematological and non-haematological tumours. RESULTS: Of the pSS patients, 2.2% developed malignancies during follow-up. Total SIR and SIR for lymphoma were 3.25 and 48.1, respectively. Different types of malignancy were observed including eight lymphomas, two myeloid myelomas and 19 solid tumours, which consisted of invasive thymoma, breast cancer, lung cancer, gastrointestinal adenocarcinoma, hepatoma, squamous cell carcinoma of tongue, uterine cervix cancer, renal carcinoma, thyroid carcinoma and mucoepidermoid carcinoma of parotid gland. Risk factor analysis showed that lymphadenopathy, enlargement of parotid glands, monoclonal immunoglobulin and absence of hypergammaglobulinaemia were correlated with malignancies. CONCLUSIONS: The current study confirms the increased incidence of lymphoma in Chinese patients with pSS, with the majority of B-cell non-Hodgkin's lymphoma. Associations between pSS and other malignant tumours such as myeloid myeloma, mouth cancer, breast cancer and thymoma need to be further observed.

Robust and nanostructured chitosan-silica hybrids for bone repair application.

In this study, chitosan-silica hybrids (CSHs) with superior mechanical strength and homogeneous dispersion of nano-sized silica particles were synthesized via a facile sol-gel method aiming for bone regeneration. The effects of varied acidic conditions of sol-gel reaction and inorganic/organic ratios on the performance of the hybrid were investigated. CSHs synthesized under weak acidic conditions (acetic acid, pH 4.0) showed a homogeneous nanostructure and robust strength (maximum compressive strength: 42.6 ± 3.3 MPa and 271 ± 31 MPa in wet and dry forms, respectively). However, those developed under the strong acidic condition (HCl, pH 4.0) and the strong acid condition plus lower pH (HCl, pH 2.8) tended to aggregate and exhibited inferior mechanical properties (compressive strength: 6.3 ± 0.3 MPa in wet form at pH 2.8). Under the latter conditions, the interactions between silica and chitosan were weak. Moreover, the mechanical properties of the CSHs could be tuned in a wide range by conveniently varying the inorganic/organic composition ratio between 50% and 70%. In vitro cytocompatibility study indicated that CSHs were non-cytotoxic. These results suggested that the weak acidic sol-gel process were essential for fabricating chitosan-silica hybrids with high mechanical strength, which had potential to be applied as a bone substitute.

A cephalometric study in patients with Wilson's disease.

It was previously noticed that patients with Wilson's disease (WD) might have distinct dento-maxillo-facial structures. We performed a case-control study to investigate the characteristics of facial structure between patients with WD and healthy controls. We recruited 44 adult patients with WD and 67 healthy controls and took their lateral cephalometric films. Thirteen angular parameters were used to describe the craniofacial features and evaluated blindly. Our date showed that higher SNA angle, ANB angle, angle of convexity and lower AB angle were detected in both male and female WD group. The average SNA angle in male patient group was 84.23 ±â€¯3.55, larger than the control group (81.52 ±â€¯3.53, p = 0.006) and lower facial proportion was 60.87 ±â€¯12.92%, higher than the control group (56.58 ±â€¯2.51%, p = 0.048). The average SNA angle in female patient group was 83.20 ±â€¯3.75, larger than that in control group (81.06 ±â€¯3.37, p = 0.039). Female neurologically early-onset WD patients (<20 years) had larger SNtoGoGn angle (37.53 ±â€¯5.29 vs 28.46 ±â€¯7.10, p = 0.004), higher lower facial proportion (57.42 ±â€¯1.65% vs 55.53 ±â€¯1.83%, p = 0.03), larger Y-axis (65.12 ±â€¯4.84 vs 58.47 ±â€¯2.72, p = 0.004), larger mandibular plane angle (32.24 ±â€¯5.32 vs 20.90 ±â€¯5.75, p < 0.001) and lower facial angle (85.76 ±â€¯4.36 vs 91.04 ±â€¯2.46, p = 0.009) than the late-onset female patients. In conclusion, we found both male and female WD patients tend to bear some craniofacial features of maxillary protrusion and vertical mandibular growths pattern. Female patients with early onset age of neurological symptoms were more inclined to have vertical mandible growth and mandibular retrusion.

Strategy to prevent cardiac toxicity induced by polyacrylic acid decorated iron MRI contrast agent and investigation of its mechanism.

Polyelectrolyte modified iron oxide nanoparticles have great potential applications for clinical magnetic resonance imaging (MRI) and anemia treatments, however, possible associated heart toxicity is rarely reported. Here, polyacrylic acid (PAA)-coated Fe3O4 nanoparticles (PION) were synthesized and lethal reactions appeared when it was applied in vivo. The investigation of underlying mechanism showed that PION could break electrolyte balance and further resulted in serious heart failure, which was observed under color doppler ultrasound and dynamic vector blood flow technique. The results demonstrated that PION had a strong absorption tendency for divalent ions and the maximum tolerated dose (MTD) was lower than 100 mg/kg. From electrocardiography (ECG), PION presented an obvious impact on CaV1.2 ion channel, which leading to fatal arrhythmia. An appropriate solution for preventing this deadly effect was pre-chelation Ca2+ (n (Ca): n (COOH) = 3: 8) to PION (PION-Ca), which displayed much higher cardiac and electrophysiological safety when sealing the binding point of divalent cation ions with PAA. The injection in Beagle dogs further confirmed the safety of PION-Ca. This study explored the mechanism and offered a solution for cardiac toxicity induced by PAA-coated nanoparticles, which guides for enhancing the safety of such polyelectrolyte decorated nanoparticles and provides assurance for clinical applications.

Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy.

T cell therapies require the removal and culture of T cells ex vivo to expand several thousand-fold. However, these cells often lose the phenotype and cytotoxic functionality for mediating effective therapeutic responses. The extracellular matrix (ECM) has been used to preserve and augment cell phenotype; however, it has not been applied to cellular immunotherapies. Here, a hyaluronic acid (HA)-based hydrogel is engineered to present the two stimulatory signals required for T-cell activation-termed an artificial T-cell stimulating matrix (aTM). It is found that biophysical properties of the aTM-stimulatory ligand density, stiffness, and ECM proteins-potentiate T cell signaling and skew phenotype of both murine and human T cells. Importantly, the combination of the ECM environment and mechanically sensitive TCR signaling from the aTM results in a rapid and robust expansion of rare, antigen-specific CD8+ T cells. Adoptive transfer of these tumor-specific cells significantly suppresses tumor growth and improves animal survival compared with T cells stimulated by traditional methods. Beyond immediate immunotherapeutic applications, demonstrating the environment influences the cellular therapeutic product delineates the importance of the ECM and provides a case study of how to engineer ECM-mimetic materials for therapeutic immune stimulation in the future.

[A clinical analysis of primary Sjögren's syndrome with anticentromere antibodies].

OBJECTIVE: To investigate the clinical manifestations, immunological features and prognosis of primary Sjögren's syndrome (pSS) with anticentromere antibodies (ACA). METHODS: Sixty pSS patients with ACA in our hospital between 1985 and 2006 were screened retrospectively and compared with those without ACA. RESULTS: The mean age at the onset of pSS with ACA was higher than that of those without ACA [(48 +/- 11) yr vs (41 +/- 12) yr, P =0.000]. There was no difference in sex ratio, dry mouth, dry eyes and positive salivary gland biopsy between the two groups (P > 0.05). Compared with those without ACA, patients with ACA presented a higher prevalence of liver involvement (68.3% vs 37.0%, P = 0.000), while a lower prevalence of renal involvement (13.3% vs 30.9%, P = 0.009), neuropathy (1.7% vs 11.5%, P = 0.025) and hypergammaglobulinemia (20.8% vs 45.7%, P = 0.002). The difference was not significant between the two groups in Raynaud's phenomenon, articular involvement, myositis, hematologic involvement, lung involvement, and thyroiditis. While both groups showed the same prevalence of antinuclear antibody (ANA), the patterns of ANA-IF were different and the discrete speckled pattern was the most frequent in patients with ACA and occurred in 61.7%. Different from those without ACA, patients with ACA presented a lower prevalence of anti-SSA, anti-SSB, rheumatoid factor, and anti-U1RNP, while showed a higher prevalence of antimitochondrial antibodies (AMA) and AMA-M2. The most frequent cause of death was the complications associated with cirrhosis, notably bleeding varices (3/5 cases). CONCLUSION: Patients with ACA present a high risk of liver involvement. Because of the remarkable difference in the mean age of disease onset and also differences in systemic damage, immunological and antibody features, pSS with ACA may be a special subtype of pSS.

[Lung involvement of primary Sjögren's syndrome].

OBJECTIVE: To evaluate the incidence, clinical manifestations and immunological features of lung involvement in patients of primary Sjögren's syndrome (pSS). METHODS: Five hundred twenty-two patients with pSS in Peking Union Medical College Hospital between 1985 and 2005 were screened retrospectively for lung involvement by either the abnormalities of chest imaging, lung function or the pulmonary artery systolic pressure estimated by ultrasonic echocardiogram > or = 40 mm Hg (1 mm Hg = 0.133 kPa), excluding infections, chronic obstructive pulmonary disease, asthma, congenital heart disease, rheumatic heart disease and other diseases. The difference was compared between patients with and without lung involvement. All patients fulfilled the 2002 international classification (criteria) for pSS. RESULTS: (1) The incidence of lung involvement in pSS was 42.3% (221/522) and occurred from 0 to 384 months (median, 48 months) after onset, while 25.2% occurred before the diagnosis of pSS. Only 47.1% of the patients showed respiratory symptoms. The average age of onset was older in patients with lung involvement than in those without lung involvement [(43 +/- 13) yr vs (37 +/- 14) yr, t = -5.445, P = 0.000]. Incidences of dry mouth (89.6% vs 81.1%, chi2 = 7.145, P = 0.008), dry eyes (78.7% vs 66.4%, chi2 = 9.472, P = 0.002) and rampant caries (55.2% vs 42.2%, chi2 = 8.647, P = 0.003) were higher in patients with lung involvement than those without. There was no significant difference in sex ratio between the two groups. (2) Interstitial lung disease was the most common lung involvement and occurred in 23.2% of the patients. Pulmonary artery hypertension in 12.5%, multiple pulmonary bullae in 9.2%, pleural effusion in 6.0% and multiple pulmonary nodules in 5.6%. (3) The major histopathological patterns were nonspecific interstitial pneumonia (5/11 cases), lymphocytic interstitial pneumonia (3/11 cases). (4) Incidences of Ranaud' s phenomenon (26.7% vs 13.0%, chi2 = 15.77, P = 0.000 ), low-grade fever (20.4% vs 13.0%, chi2 = 5.175, P = 0.023), arthrosis (29.4% vs 21.6%, chi2 = 4.164, P = 0.041), anti-U1RNP (18.2% vs 11.2%, 2 = 5.069, P = 0.024) and hypergammaglobulinemia (51.6% vs 39.5%, chi2 = 6.597, P = 0.01) were higher in patients with lung involvement than in those without. The incidence of renal tubule acidosis was lower in patients with lung involvement than in those without (5.4% vs 12.6% chi2 = 7.616, P = 0.006). (5) The death incidence in pSS with pulmonary involvement was 5.5 times higher than in those without. The most frequent cause of death was infection (64.3%), especially pulmonary infection. CONCLUSION: Lung involvement in pSS is common. As it is an important factor related to the prognosis of this disease, chest X-ray, HRCT, lung function and ultrasonic echocardiogram after the diagnosis are suggested.