Lipophilic recombinant-protein insertion endows lymphocytes with enhanced targeting-infiltration ability in EGFR positive cancer.

Adoptive T cell transfer is one of the most promising ways to combat solid tumors. However, the weak infiltration of T cells into tumor sites has restricted their antitumor efficacy. To overcome this obstacle, we used the lipophilic protein painting strategy to improve tumor targeting and penetrating capacity of lymphocytes for the first time. We synthesized the lipid anchor consisting of a bispecific recombinant protein iRGD-antiEGFR and DSPE-PEG derivates, then successfully inserted it into the membranes of T cells. This surface modification was non-invasive and could efficiently improve the infiltration ability of T cells into multicellular spheroids and tumor masses. The surface modified T cells also displayed superior antitumor activities in EGFR-positive tumor xenografts via systematic infusion. Moreover, the permeability and antitumor efficacy of these surface painted T cells could be remarkably enhanced when used in combination with local low-dose irradiation.

[Effect of enzymolysis after acid and alkali pretreatment on extraction of tanshinones from Salviae Miltiorrhizae Radix et Rhizoma residues].

Salviae Miltiorrhizae Radix et Rhizoma residues were pre-treated with acid and alkali, degraded by using cellulose, and the effects of different processing methods on the extraction rate of tanshinones were compared to provide scientific basis for development and utilization of tanshinones from Salviae Miltiorrhizae Radix et Rhizoma residues. The results showed that in the Salviae Miltiorrhizae Radix et Rhizoma residues without pre-treatment, enzymatic hydrolysis time of 4.5 d could make most of the cellulose degraded when the concentration of substrate enzyme concentration was 6 U•mL-1, and the highest glucose concentration was 59.74 mg•g⁻¹. It was found that the best effect was achieved after alkali pre-treatment-cellulose C degradation among the different pre-treatment methods, and the glucose content reached 119.50 mg•g⁻¹, followed by the same concentration of acid pre-treatment-cellulose C degradation. The extraction amount of tanshinone ⅡA was increased by 82.54% after enzyme degradation, with a mass fraction of 2.451 mg•g⁻¹; extraction amount of tanshinone I was increased by 81.82% after enzyme degradation, with a mass fraction of 2.373 mg•g⁻¹; extraction amount of cryptotanshinone was increased by 64.4% after enzyme degradation, with a mass fraction of 1.080 mg•g⁻¹; extraction amount of dihydrotanshinone I was increased by 61.3% after enzyme degradation, with a mass fraction of 0.601 2 mg•g⁻¹. Acid and alkali pre-treatment combined with cellulose degradation could effectively improve the extraction rate of tanshinones from Salviae Miltiorrhizae Radix et Rhizoma residues. This method is operable and practical, and it is beneficial for improving the utilization efficiency of tanshinones (resource based chemicals) from Salviae Miltiorrhizae Radix et Rhizoma residues.

State-to-state dynamics of the H(*)(n) + HD → D(*)(n') + H2 reactive scattering.

The state-to-state dynamics of the H(*)(n) + HD → D(*)(n(')) + H2 reactive scattering at the collision energy of 0.5 eV have been carried out for the first time by using H-atom Rydberg tagging time-of-flight technique. Experimental results show that the angular distribution of the total H2 products presents clearly forward-backward asymmetric, which considerably differs from that of the corresponding H(+) + HD → D(+) + H2 reaction predicted by previously theoretical calculations. Such disagreement between these two processes suggests that the Fermi independent-collider model is also not valid in describing the dynamics of isotopic variants of the H(*) + H2 reaction. The rotational state distribution of the H2 products demonstrates a saw-toothed distribution with odd-j(') > even-j('). This interesting observation is strongly influenced by nuclear spin statistics.

Radiological analysis of maxillary artery relationships to key bony landmarks in maxillofacial surgery.

The maxillary artery (MA) is a key structure at risk of injury in numerous oral and maxillofacial surgical (OMS) procedures. Knowledge of safe distances from this vessel to surgically familiar bony landmarks could improve patient safety and prevent catastrophic haemorrhage. Distances between the MA and bony landmarks on the maxilla and mandible were measured using CT angiograms on 100 patients (200 facial halves). The vertical height of the pterygomaxillary junction (PMJ) was mean (SD) measurement of 16 (3) mm. The MA enters the pterygomaxillary fissure (PMF) a mean (SD) distance of 29 (3) mm from the most inferior point of the PMJ. The mean (SD) shortest distance between the MA and medial surface of the mandible was 2 (2) mm (with the vessel directly contacting the mandible in 17% of cases). The branchpoint (bifurcation of the superficial temporal artery (STA) and MA) was directly in contact with the mandible in 5% of cases. The mean (SD) distances between this bifurcation point and the medial pole of the condyle were 20 (5) mm and 22 (5) mm, respectively. A horizontal plane through the sigmoid notch perpendicular to the posterior border of the mandible is a good approximation of the trajectory of the MA. The branchpoint is usually within 5 mm of this line and inferior in 70% of cases. Surgeons should take note that both the branchpoint and the MA contact the surface of the mandible in a significant number of cases.

Angelica dahurica Extracts Attenuate CFA-Induced Inflammatory Pain via TRPV1 in Mice.

Angelica dahurica, belonging to the family Apiaceae, is a well-known herbal medicine. The roots of Angelica dahurica are commonly used for the treatment of headache, toothache, abscess, furunculosis, and acne. However, little is known about their analgesic molecular mechanism underlying pain relief. In this study, we used behavioral tests to assess the analgesic effect of the ADE (Angelica dahurica extracts) on CFA (complete Freund's adjuvant)-induced inflammatory pain mice models. TRPV1 (Transient Receptor Potential Cation Channel Subfamily V Member 1) protein activity in dorsal root ganglion (DRG) was assessed with a calcium imaging assay. TRPV1 expression was detected with western blot and immunohistochemistry. Then, we examined the constituents of ADE using combined ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC/Q-TOF-MS). Our results showed that ADE effectively attenuated mechanical and thermal hypersensitivities in CFA-induced inflammatory pain model in mice. ADE also significantly reduced the activity and the protein expression of TRPV1 in DRG from CFA mice. Therefore, ADE might be an attractive and suitable analgesic agent for the management of chronic inflammatory pain.

iRGD synergizes with PD-1 knockout immunotherapy by enhancing lymphocyte infiltration in gastric cancer.

Poor infiltration of activated lymphocytes into tumors represents a fundamental factor limiting the therapeutic effect of adoptive cell immunotherapy. A tumor-penetrating peptide, iRGD, has been widely used to deliver drugs into tumor tissues. In this study, we demonstrate for the first time that iRGD could also facilitate the infiltration of lymphocytes in both 3D tumor spheroids and several xenograft mouse models. In addition, combining iRGD modification with PD-1 knockout lymphocytes reveals a superior anti-tumor efficiency. Mechanistic studies demonstrate that the binding of iRGD to neuropilin-1 results in tyrosine phosphorylation of the endothelial barrier regulator VE-cadherin, which plays a role in the opening of endothelial cell contacts and the promotion of transendothelial lymphocyte migration. In summary, these results demonstrate that iRGD modification could promote tumor-specific lymphocyte infiltration, and thereby overcome the bottleneck associated with adoptive immune cell therapy in solid tumors.

Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer.

Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic-co-glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI) was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% (P=0.002). Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization.

A comparison of effectiveness between oral rapid testing and routine serum-based testing for HIV in an outpatient dental clinic in Yuxi Prefecture, China: a case-control study.

OBJECTIVE: To compare the outcomes of routine provider-initiated HIV testing and counselling (PITC) and oral rapid HIV testing for dental clinic outpatients in a hospital. DESIGN: We employed a case-control study design and recruited dental outpatients into routine serum-based and oral rapid testing groups. We compared the acceptance, completion and result notification rate between groups. SETTING: A dental outpatient clinic in the Yuxi People's Hospital, Yunnan. PARTICIPANTS: A total of 758 and 816 dental outpatients were enrolled for routine and oral rapid testing, respectively. RESULTS: The percentage of participants willing to receive routine HIV testing was 28.1% (95% CI 24.9% to 31.3%) and 96.1% (95% CI 94.8% to 97.4%, χ2=186.4, p<0.001) for the rapid testing. Among accepted participants, the percentage of participants who received HIV testing was 26.8% (95% CI 20.9% to 32.7%) in the routine testing group and 100.0% in the oral rapid HIV testing group (χ2=77.5, p<0.001). About 93.0% of routine testers returned for the test results on the next day, whereas all rapid testers received their test results on the same day (χ2=34.6, p<0.001). These correspond to an overall completion rate of 7.0% (95% CI 5.2% to 8.8%) and 96.1% (95% CI 94.8% to 97.4%, p<0.001), respectively. Among the 545 patients who declined routine serum-based HIV testing, the main reasons included, an unnecessary hassle (254/545, 46.6%), having been previously tested (124/545, 22.8%) and self-perceived low risk of HIV infection (103/545, 18.9%). In contrast, only 32 individuals declined oral rapid testing, and having received a previous test was the primary reason. Three patients in the rapid testing group were later confirmed HIV-positive, yielding an HIV prevalence of 0.38%. CONCLUSION: Oral rapid HIV testing is a feasible and efficient approach in a clinical setting.

Nutrition and Health Survey of Taiwan Elementary School Children 2001-2002: research design, methods and scope.

The "Nutrition and Health Survey of Taiwan's Elementary School Children (2001-2002)" was to investigate the nutritional status, influential dietary and non-dietary factors, health and development, and school performance, as well as the inter-relationships among these factors. The survey adopted a two-staged stratified, clustered probability sampling scheme. Towns and districts in Taiwan with particular ethnic and geographical characteristics were designated into 13 strata including Hakka areas, mountain areas, eastern Taiwan, the Penghu Islands, 3 northern regions, 3 central regions and 3 southern regions. Eight schools were selected from each stratum using the probabilities proportional to sizes method. Twenty-four pupils were randomly selected within each school. The survey included face-to-face interviews and health examinations. Taking seasonal effects into consideration, the face-to-face interviews were evenly allocated into each of the two semesters. A total of 2,419 face-to-face interviews and 2,475 health examinations were completed. Interview data included household information, socio-demographics, 24-hour dietary recall, food frequency, dietary and nutritional knowledge, attitudes and behaviors, physical activity, medical history, oral health, pubertal development, and bone health. Health exam data included anthropometry, blood pressure, physical fitness, bone density, dental health, and blood and urine collection. SUDAAN was used to adjust sampling design effect. There were no significant differences in sibling rank and parental characteristics between respondents and non-respondents, which indicates that our survey is representative and unbiased. The results of this survey will increase our understanding on the nutrition and health status of schoolchildren and can be used to shape public health policy in Taiwan.