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Abstract Background Peripheral facial paralysis (PFP) results in functional disorder and social dysfunction, when it is under a severe condition at onset, long-term poor outcomes do occur. Different acupuncture methods have been reported to be potentially effective for shortening the disease course and reducing the occurrence of sequelae when they are applied at an early stage. Neuro edema is a common pathological feature in the acute phase, and many clinical studies have suggested its effect of reducing facial nerve edema. It is of value to estimate the effectiveness and safety of acupuncture treatment at the onset, and to assess the most suitable acupuncture method for the acute period. Methods and analysis All the RCTs and quasi-RCTs on acupuncture therapy for patients who is during acute stage of PFP will be included. The recovery rate of facial function, the time it takes to restore facial function and the odds of sequelae occurring will be the key parts we focus on. Psychological well-being and quality of life will also be evaluated. Literature searching will be conducted until December 31th, 2022 from eight databases systematically. Two reviewers will screen the literature and extract the data independently. RevMan software will be used for data analysis, and the version 2 of the Cochrane risk-of-bias tool (RoB 2) will be used to assess the certainty of evidence. Forest plots and summary findings will be generated. If data permits, a meta-analysis will be conducted. Ethics and dissemination Since this study will not involve clinical treatment of patients, ethics approval is not required. The result of this study will be submitted to a peer-reviewed journal for publication and as a proposal for clinical practice and further study on acupuncture treatment at the early stage of PFP. Discussion This review will summarize the evidence on the different type of acupuncture therapy for acute Bell’s palsy and Ramsay-Hunt syndrome. We anticipate that it would be safe and effective when applied to the acute phase of PFP, and some specific suitable acupuncture methods would be found resulting from this review. Systematic review registration International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020205127

Coronary artery ectasia (CAE) is a rare finding that is associated with poor clinical outcomes (Kawsara et al. 2018), and disorders in lipid metabolism have been reported in CAE. Lipids constitute one of the three metabolite types that regulate bodily functions and are also powerful signaling molecules (Han 2016; Zhu et al. 2021) that affect immunoregulation and inflammatory responses via a series of transcription factors and signaling pathways (Barrera et al. 2013). Although abnormal lipid metabolism and immunoinflammatory responses have been reported in CAE, their roles in the pathogenic mechanisms underlying CAE are currently unclear.

Abstract. In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder. There is evidence linking genetic polymorphisms and nonlinear metabolism to the Paroxetine’s pharmacokinetic (PK) variability. The purpose of the present study was to develop a population PK (PPK) model of paroxetine in Chinese patients, which was used to define the paroxetine’s PK parameters and quantify the effect of clinical and baseline demographic factors on these PK characteristics. The study included 184 inpatients with psychosis (103 females and 81 males), with a total of 372 serum concentrations of paroxetine for PPK analyses. The total daily dosage ranged from 20 to 75 mg. One compartment model could fit the PKs characterize of paroxetine. Covariate analysis revealed that dose, formulation, and sex had a significant effect on the PK parameters of paroxetine; however, there was no evident genetic influence of CYP2D6 enzymes on paroxetine concentrations in Chinese patients. The study determined that the population’s apparent distribution volume (V/F) and apparent clearance (CL/F), respectively, were 8850 and 21.2 L/h. The CL/F decreased 1-2-fold for each 10 mg dose increase, whereas the different formulations caused a decrease in V/F of 66.6%. Sex was found to affect bioavailability (F), which decreased F by 47.5%. Females had higher F values than males. This PPK model described data from patients with psychosis who received paroxetine immediate-release tablets (IR-T) and/or sustained-release tablets (SR-T). Paroxetine trough concentrations and relative bioavailability were different between formulations and sex. The altered serum concentrations of paroxetine resulting from individual variants and additive effects need to be considered, to optimize the dosage regimen for individual patients.

Backgroundcomputer-aided diagnosis of medical images is becoming more significant in intelligent medicine. Colposcopy-guided biopsy with pathological diagnosis is the gold standard in diagnosing CIN and invasive cervical cancer. However, it struggles with its low sensitivity in differentiating cancer/HSIL from LSIL/normal, particularly in areas with a lack of skilled colposcopists and access to adequate medical resources.Methodsthe model used the auto-segmented colposcopic images to extract color and texture features using the T-test method. It then augmented minority data using the SMOTE method to balance the skewed class distribution. Finally, it used an RBF-SVM to generate a preliminary output. The results, integrating the TCT, HPV tests, and age, were combined into a naïve Bayes classifier for cervical lesion diagnosis.Resultsthe multimodal machine learning model achieved physician-level performance (sensitivity: 51.2%, specificity: 86.9%, accuracy: 81.8%), and it could be interpreted by feature extraction and visualization. With the aid of the model, colposcopists improved the sensitivity from 53.7% to 70.7% with an acceptable specificity of 81.1% and accuracy of 79.6%.Conclusionusing a computer-aided diagnosis system, physicians could identify cancer/HSIL with greater sensitivity, which guided biopsy to take timely treatment.

BackgroundThere are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia.PurposeThis study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model.MethodsWe conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria.ResultsSerum RBP4 level had a highly significant association with hyperuricemia (P

Abstract Background The optimal timing to perform a total knee arthroplasty (TKA) after knee arthroscopy (KA) was controversial in the literature. We aimed to 1) explore the effect of prior KA on the subsequent TKA; 2) identify who were not suitable for TKA in patients with prior KA, and 3) determine the timing of TKA following prior KA. Methods We retrospectively reviewed 87 TKAs with prior KA and 174 controls using propensity score matching in our institution. The minimum follow-up was 2 years. Postoperative clinical outcomes were compared between groups. Kaplan-Meier curves were created with reoperation as an endpoint. Multivariate Cox proportional hazards regressions were performed to identify risk factors of severe complications in the KA group. The two-piecewise linear regression analysis was performed to examine the optimal timing of TKA following prior KA. Results The all-cause reoperation, revision, and complication rates of the KA group were significantly higher than those of the control group (p

Abstract Background Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. Methods A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs. Results During a median of 5.1 (interquartile range 3.9 to 5.9) years’ follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149–2.955), 1.828 (1.165–2.867), 2.212 (1.396–3.507), all p

Abstract Background Coronary artery ectasia (CAE) is an angiographic finding of abnormal coronary dilatation. Inflammation plays a major role in all phases of atherosclerosis. We investigated the relationship between CAE and serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels to test our hypothesis that patient age is associated with the efficacy of anti-inflammatory therapy for CAE. Methods We conducted a prospective analysis of 217 patients with CAE treated at the Department of Cardiology, Shanghai East Hospital, Ji’an Campus and the Baoshan People’s Hospital, from January 1, 2015 to July 30, 2019. Baseline data of patients, including sex; age; and history of hypertension, hyperlipidemia, and diabetes, were collected from patient medical records. Study participants were grouped by age as follows: CAE-A (n = 60, age ≤ 50 years), CAE-B (n = 83, 50 years 70). Additionally, there was a control (NC) group (n = 73) with normal coronary arteries. Results All patients received oral rosuvastatin therapy (10 mg, QN quaque nocte) when they were diagnosed with CAE and maintained good follow-up, with a loss rate of 0.0% at the end of the 6-month follow-up. The NC group received regular symptom-relieving treatments and rosuvastatin therapy. Of these four groups, the inflammatory markers, hs-CRP and IL-6, were significantly higher in patients with CAE than in the NCs (p

Abstract Background The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status. Methods Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p

Abstract Background Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM. Methods A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated. Results A total of 464 MACEs were documented. Both Kaplan–Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24–2.70, p

Abstract Background Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing. Conclusion These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities. Graphical abstract

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.

A high-performance liquid chromatographic method coupled with triple quadrupole mass spectrometry (LC-MS/MS) for the analysis of blonanserin and its active metabolite, N-desethyl blonanserin, in rat plasma has been developed and validated. The biological samples were treated by simple direct protein precipitation before separation on an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 3.5 μm) with a column temperature of 35°C at a flow rate of 0.5 mL/min. The mobile phase A is a mixture of methanol and water (75 : 25, v/v, 5 mM ammonium formate), and the mobile phase B is acetonitrile containing 0.1% formic acid. The ratio of mobile phase A to mobile phase B is 15 : 85. Electrospray ionization (ESI) multiple reaction monitoring modes are used for detection, which are m/z 368.10 ⟶ 296.90 (blonanserin), m/z 340.15 ⟶ 297.05(N-desethyl blonanserin), and m/z 348.15⟶ 302.05 (N-desethyl blonanserin-d8). The linear response range was 0.1–100.0 ng/mL for blonanserin and N-desethyl blonanserin. The lower limit of quantification (LLOQ), calibration curves, carryover, and matrix effects were sufficiently accurate and precise according to the National Medical Products Administration (NMPA) guidelines for bioanalytical method validation. This analytical method was successfully applied in a blonanserin-poloxamer thermosensitive gel pharmacokinetic study in rats.

An amendment to this paper has been published and can be accessed via the original article.

Apple occupies a dominant position in fruit production globally, and has become the main income source of local smallholder farmers in Luochuan County in the Loess Plateau area, one of the largest apple production areas in China. However, the annual productivity of apple orchards in this region remains low and has gradually declined over the years. The distinction and correlation of production constraints can contribute to the promotion of apple orchard productivity and the development of a sustainable orchard system. In the present study, survey data from 71 smallholder farmers were analyzed using a yield gap model to distinguish the production constraints and determine their correlation with the yield gap based on the structural equation model (SEM). The results indicated that the average apple yield in Luochuan County was 29.9 t ha−1 yr−1, while the attainable yield (Yatt; the highest yield obtained from the on-farm surveys) was 58.1 t ha−1 yr−1. The average explained and unexplainable yield gaps were 26.3 and 1.87 t ha−1 yr−1. According to the boundary line analysis, crop load, number of sprayings and base fertilizer N were the top three constraints on apple production in 9.8, 7.8 and 7.8% of the plots, respectively. Among the production constraints, crop load and fruit weight affected apple yield through direct pathways, whereas other constraints influenced apple yield through an indirect pathway based on the SEM, explaining 51% of the yield variance by all the main production constraints. These results can improve the current understanding of production constraints and contribute to the development of management strategies and policies for improving apple yield.

Mango is an important cash crop in the tropics and subtropics. Determining the yield gap of mango and production constraints can potentially promote the sustainable development of the mango industry. In this study, boundary line analysis based on survey data from 103 smallholder farmers and a yield gap model were used to determine the yield gap and production constraints in mango plantations in the northern mountain, central valley and southern mountains regions of Tianyang County, Guangxi, China. The results indicated that the yield of mango in three representing regions of Tianyang County, Northern Mountains, Central Valley and Southern Mountains, was 18.3, 17.0 and 15.4 t ha−1 yr−1, with an explainable yield gap of 10.9, 6.1 and 14.8 t ha−1 yr−1, respectively. Fertilization management, including fertilizer N, P2O5 and K2O application rates, and planting density were the main limiting factors of mango yield in all three regions. In addition, tree age influenced mango yield in the Northern Mountains (11.1%) and Central Valley (11.7%) regions. Irrigation time influenced mango yield in the Northern Mountains (9.9%) and Southern Mountains (12.2%). Based on a scenario analysis, the predicted yield would increase by up to 50%, and fertilizer N use would be reduced by as much as approximately 20%. An improved understanding of production constraints will aid in the development of management strategy measures to increase mango yield.

Sustainable feeding of the growing population in China without ecological destabilization is a grand challenge. In this populous country where agriculture is dominated by smallholder farming, developing innovative technology and translating scientific knowledge into action for smallholder farmers is a crucial step in addressing this challenge. Here, we present a novel approach for technology innovation and dissemination to achieve sustainable intensification in the fields of smallholder farmers. The Science and Technology Backyard (STB) is a hub in a rural area that links knowledge with practices to promote technology innovation and exchange. In this study, the framework and functions of STB are introduced, and the key implications for sustainable intensification across millions of smallholder farmers are explicitly stated: (i) develop innovative technology based on stated demands of farmers; (ii) disseminate technology by innovative social service models though combined top-down approaches with bottom-up measures to enable smallholders in rural areas. This paper provides a perspective on transformation of small-scale agriculture toward sustainable intensification in China and useful knowledge applicable to other developing countries.

Smallholders in developing countries commonly use intercropping to produce crops with higher yield and value. Many intercropping studies have been conducted under experimental conditions, but few studies have been performed in farmers' fields. We conducted a 4-year study using data from real farms to examine the relationships between yield and yield components of intercropped maize in the North China Plain. Three field experiments were conducted to compare the suitability of different maize varieties in intercropping. In the farm study, the grain yield of maize intercropped with watermelon was reduced by more than one third as compared to maize in wheat-maize double cropping, mainly due to lower ear density and lower 100-grain weight. Under real farm conditions, the yield of intercropped maize increased with increasing ear density and 100-grain weight, while yield of sole maize increased with increasing grain number per ear and 100-grain weight. In the field experiments, the maize cultivars commonly used in double cropping gave similar yields when grown in the intercropping system and their yields were closely related to ear density and 100-grain weight. Our results demonstrated that ear density, rather cultivar, was a key factor affecting the productivity of intercropped maize. Therefore, maintaining high ear density is a practical way for promoting productivity of maize in farmers' intercropping practices.

Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.

We present the data corresponding to the ultrastructural characteristics of Paenibacillus polymyxa isolates and control efficacy of P. polymyxa ShX301 for controlling Verticillium wilt of cotton, isolated in experimental fields at the Sanyuan Agricultural Experiment Station of North-West Agriculture and Forestry University, Sanyuan county, Shaanxi province, China. Ultrastructural characteristics of P. polymyxa isolates made using technique of transmission electron microscopy. A strain ShX301 has a broad-spectrum antifungal activity against V. dahliae and other plant pathogens and has been used for in vitro experiments for controlling this disease in greenhouse, ''Biocontrol potential of Paenibacillus polymyxa against Verticillium dahliae infecting cotton plants'' [1].

Structural defect detection based on finite element model (FEM) updating is an optimization problem by minimizing the discrepancy of responses between model and measurement. Researchers have introduced many methods to perform the FEM updating for defect detection of the structures. A popular approach is to adopt the particle swarm optimization (PSO) algorithm. In this process, the fitness function is a critical factor in the success of the PSO-FEM approach. Our objective is to compare the performances of four fitness functions based on natural frequencies using the standard PSO-FEM approach for defect detection. In this paper, the definition of the standard PSO algorithm is first presented. After constructing the finite element benchmark model of the beam structure, four commonly used fitness functions based on natural frequencies are outlined. Their performance in defect detection of beam structures will be evaluated using the standard PSO-FEM approach. Finally, in the numerical simulations, the population diversity, success rate, mean iterations, and CPU time of the four fitness functions for the algorithm are calculated. The simulation results comprehensively evaluate their performances for single defect and multidefect scenario, and the effectiveness and superiority of the fitness function S4 will be demonstrated.

Abstract In this article, we investigate numerical solution of a class of multi-order fractional differential equations with error correction and convergence analysis. According to fractional differential definition in Caputo’s sense, fractional differential operator matrix is deduced. The problem is reduced to a set of algebraic equations, and we apply MATLAB to solve the equation. In order to improve the precision of numerical solution, the process of error correction for multi-order fractional differential equation is introduced. By constructing the multi-order fractional differential equation of the error function, the approximate error function is obtained so that the numerical solution is corrected. Then, we analyze the convergence of the shifted Chebyshev polynomials approximation function. Numerical experiments are given to demonstrate the applicability of the method and the validity of error correction.

Background: Previous studies have clearly demonstrated that XueZhiKang (XZK), an extract of cholestin, can decrease low-density lipoprotein cholesterol (LDL-C) and cardiovascular events. However, the mechanism of the effects of XZK on atherosclerosis (AS) in humans has been reported less frequently. In the present study, we investigated the impact of XZK on lipoprotein subfractions, oxidized LDL (oxLDL), and interleukin-6 (IL-6). Methods: From October 2015 to July 2016, 40 subjects were enrolled in this study. Of them, 20 subjects with dyslipidemia received XZK 1200 mg/day for 8 weeks (XZK group); 20 additional healthy subjects who did not receive therapy acted as controls. The plasma lipoprotein subfractions, oxLDL, and IL-6 were examined at baseline and again at 8 weeks. Results: Data showed that XZK could significantly decrease not only plasma LDL-C levels (87.26 ± 24.45 vs. 123.34 ± 23.99, P

Abstract Background Young ischemic stroke patients are common while classification and analysis based upon imaging characteristics are rarely reported. We intend to compare the clinical and MRI characteristics of cerebral stroke induced by intracranial atherosclerosis between young patients with branch occlusive disease (BOD) and those with non-branch occlusive disease (non-BOD) or small artery disease (SAD). Methods A total of 151 subjects with acute infarction within the middle cerebral artery (MCA) territory were included and patients with ipsilateral internal carotid artery stenosis or cardioembolism were excluded. Based on the distribution characteristics of infarction and the presence of ipsilateral MCA stenosis, the patients were divided into three groups: BOD-striatocapsular area infarction with ipsilateral MCA stenosis; non-BOD -infarction size exceeds the striatocapsular area and accompanied by ipsilateral MCA stenosis; SAD. The clinical and MCA stenosis characteristics of the three groups were compared. Results The number of BOD patients with hypertension was significantly higher than that of SAD (92.9% vs 53.7%, p = 0.000) and non-BOD (92.9% vs 57.1%, p = 0.001); subjects with smoking history significantly exceeded that of SAD (50% vs 26.9%, p = 0.03) and subjects with family history of cardiovascular disease was significantly less than that of non-BOD (14.3% vs 41.1%). Baseline NIHSS scores and mRS scores at discharge in patients with BOD were significantly lower than those with non-BOD (p = 0.000, p = 0.001). Majority of patients in non-BOD group displayed severe MCA stenosis (39 cases, 69.6%) while that in BOD group displayed mild stenosis (26 cases, 92.9%), and the difference was statistically significant (p = 0.000). Compared with non-BOD group, the stenosis in BOD group located at a relatively distal end in the M1 segment of MCA (S/M1, 58% vs 40%, p = 0.000) and was more localized (stenosis level/ (SL/M1), 1.86 (1.35–2.6) vs 2.9 (2.0–5.0), p = 0.002). Conclusion BOD in young patients with ischemic stroke induced by intracranial atherosclerosis is not rare (33.3%) and its clinical manifestations and prognosis are similar to those of SAD. This may be related to the mild localized stenosis at the distal end in the M1 segment of MCA. Control of hypertension might play a positive role in secondary prevention.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50–67%) for DLBCL patients and 46% (95% CI: 20–69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

AIM: To study the genes responsible for retinitis pigmentosa. METHODS: A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer’s instructions. Data were aligned to UCSC Genome Browser build hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was performed with the Genome Analysis Toolkit (GATK v.3.3.0) IndelRealigner, and variants were called with the Genome Analysis Toolkit Haplotypecaller, without any use of imputation. Variants were filtered against a panel derived from 1000 Genomes Project, 1000G_ASN, ESP6500, ExAC and dbSNP138. In all members of Family ONE and Family TWO with available DNA samples, the genetic variant was validated using Sanger sequencing. RESULTS: A novel, pathogenic variant of retinitis pigmentosa, c.357_358delAA (p.Ser119SerfsX5) was identified in PRPF31 in 2 of 15 autosomal-dominant retinitis pigmentosa (ADRP) families, as well as in one, sporadic case. Sanger sequencing was performed upon probands, as well as upon other family members. This novel, pathogenic genotype co-segregated with retinitis pigmentosa phenotype in these two families. CONCLUSION: ADRP is a subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%-40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of PRPF31 mutations known to occur in ADRP, and provides further demonstration of the applicability of the BGISEQ500 sequencer for genomics research.

In the past few decades, vibration-based structural damage detection (SDD) has attracted widespread attention. Using the response data of engineering structures, the researchers have developed many methods for damage localization and quantification. Adopting meta-heuristic algorithms, in which particle swarm optimization (PSO) is the most widely used, is a popular approach. Various PSO variants have also been proposed for improving its performance in SDD, and they are generally based on the Global topology. However, in addition to the Global topology, other topologies are also developed in the related literature to enhance the performance of the PSO algorithm. The effects of PSO topologies depend significantly on the studied problems. Therefore, in this article, we conduct a performance investigation of eight PSO topologies in SDD. The success rate and mean iterations that are obtained from the numerical simulations are considered as the evaluation indexes. Furthermore, the average rank and Bonferroni-Dunn’s test are further utilized to perform the statistic analysis. From these analysis results, the Four Clusters are shown to be the more favorable PSO topologies in SDD.

Abstract We investigated simultaneously traditional and novel lipid indices, alone or in combination, in predicting coronary severity assessed by Gensini score (GS) in 1605 non-lipid-lowering-drug-treated patients undergoing coronary angiography. Firstly, levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), non high density lipoprotein cholesterol (non-HDL-C), apolipoprotein (apo) B, lipoprotein (a) [Lp(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC3, small dense LDL (sdLDL) and large HDL were increased, while HDL-C and apoA1 levels were decreased as GS status (all p for trend

Background: Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats. Methods: Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis. Results: Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks. Conclusions: Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling.

Background/Objective: The aim of this study was to examine the reliability and validity of the Chinese version of the School Function Assessment (SFA) for primary school students with cerebral palsy (CP) in Guangzhou, China. Methods: Ninety-three students with CP were recruited by convenience sampling from a special school. The Chinese version of the SFA was administered and an exploratory factor analysis with direct oblique rotation was used to extract the factor structure underlying the Activity Performance scales of the SFA. An intraclass correlation one-way random single measure was performed to study external reliability. Cronbach's alpha was used to study internal consistency. Results: The findings showed that the Chinese version of the SFA had high internal consistency with test–retest reliability [ICC (1, k) = 0.49–0.97]. Conclusion: This study has established the applicability of the SFA for both clinical and research purposes in the Chinese population, and presented evidence of satisfactory psychometric properties in use with primary school students with CP in special schools.

Objective To investigate the role of acromioclavicular joint morphology in the presence of subacromial erosion after hook plate fixation. Methods We retrospectively analyzed the clinical data of 36 patients (17 men, 19 women; mean age, 48.7 years; range, 21–76 years) treated with hook plate fixation for distal clavicular fractures (n = 20) or acromioclavicular joint dislocation (n = 16) from August 2011 to March 2013. The patients were divided into two groups: the subacromial erosion group (18 patients) and the normal group (18 patients). Differences in multiple anatomical parameters between the two groups were measured and compared. Results The distal clavicle–acromion angle was significantly larger in the subacromial erosion group (mean, 51.37° ± 5.59°) than in the normal group (mean, 44.20° ± 3.83°), as was the distal clavicle–coronal angle (mean, 25.44° ± 2.51° vs. 21.67° ± 4.06°, respectively). The thickness of the acromion was significantly different between men and women (9.72 ± 1.13 vs. 8.16 ± 1.89 mm, respectively). Conclusion The results of this study indicate that the distal clavicle–acromion angle and distal clavicle–coronal angle are closely correlated with the occurrence of subacromial erosion after hook plate fixation.

Background: The currently available polysomnography (PSG) equipments and operating personnel are facing increasing pressure, such situation may result in the problem that a large number of obstructive sleep apnea (OSA) patients cannot receive timely diagnosis and treatment, we sought to develop a nomogram quantifying the risk of OSA for a better decision of using PSG, based on the clinical syndromes and the demographic and anthropometric characteristics. Methods: The nomogram was constructed through an ordinal logistic regression procedure. Predictive accuracy and performance characteristics were assessed with the area under the curve (AUC) of the receiver operating characteristics and calibration plots, respectively. Decision curve analyses were applied to assess the net benefit of the nomogram. Results: Among the 401 patients, 73 (18.2%) were diagnosed and grouped as the none OSA (apnea-hypopnea index [AHI]

Background: The Wenchuan earthquake in China caused shock and grief worldwide. Sudden bereavement caused by the earthquake led to physical disorders as well as psychological disturbances in the bereaved individuals. The bereaved had a high risk for complicated grief (CG), which may have led to significant distress and impairment in their health. However, there was few available studies on CG among disaster-bereaved individuals in China after the disaster. The aim of this study was to identify factors (demographic characteristics and disaster-related variables) associated with symptoms of CG among the bereaved 18 months after the Wenchuan earthquake. Methods: This study was conducted with a cross-sectional design and a convenience sample of 271 bereaved individuals from three of the hardest hit areas. Data were collected by questionnaires and the instruments used in the study were: General questionnaire and Inventory of CG (ICG). Multivariate linear regression analysis was used to identify factors associated with symptoms of CG. Results: The mean score on ICG was 52.77 (standard deviation: 10.00). Being female and loss of a child were related to higher level of CG while having another child after the disaster and receiving psychological counseling experience were associated with lower level of CG. Forty-nine percent of the variance of CG was explained by these identified factors. Conclusions: Eighteen months after the Wenchuan earthquake, the symptoms of CG among the bereaved were higher than the previous studies with bereaved individuals. This study uncovers a vulnerable population of the bereaved at high risk for CG. Early assessments, targeted interventions, and policy support tailored for the disaster-bereaved individuals are necessary to identify and alleviate symptoms of CG and to improve their well-being.

Near-infrared fluorescence probes (NIFPs) have been widely used in immunoassay, bio-imaging and medical diagnosis. We review the basic principles of near-infrared fluorescence and near-infrared detection technology, and summarize structures, properties and characteristics of NIFPs (i.e., cyanines, xanthenes fluorescent dyes, phthalocyanines, porphyrin derivates, single-walled carbon nanotubes (SWCNTs), quantum dots and rare earth compounds). We next analyze applications of NIFPs in immunoassays, and prospect the application potential of lateral flow assay (LFA) in rapid detection of pathogens. At present, our team intends to establish a new platform that has highly sensitive NIFPs combined with portable and simple immunochromatographic test strips (ICTSs) for rapid detection of food-borne viruses. This will provide technical support for rapid detection on the port.

Vortex shedding from a moving obstacle potential in a two-component Bose–Einstein condensate is investigated numerically. For a miscible two-component condensate composed of ^23 Na and ^87 Rb atoms, in the wake of obstacle, the Kármán vortex street is discovered in one component, while the Kármán-like vortex street named ‘half-quantum vortex street’ is formed in another component. The other patterns of vortex shedding, such as the vortex dipoles, V-shaped vortex pairs and corresponding ‘half-quantum vortex shedding’, can also be found. The drag force acting on obstacle potential is calculated and discussed. The parameter region for various vortex patterns and critical velocity for vortex emission are presented. In addition, a ^85 Rb– ^87 Rb mixture is also considered, where the Kármán vortex street and other typical patterns exist in both components. Finally, we provide an experimental protocol for the above realization and observation.

Purpose To compare the analgesic effect of preoperative ropivacaine with or without tramadol for femoral nerve block in total knee arthroplasty (TKA). Methods 14 men and 46 women aged 59 to 80 years who were American Society of Anesthesiologists (ASA) grade I or II and were scheduled for TKA were randomised to receive preoperative femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 0 mg (n=15), 50 mg (n=15), or 100 mg (n=15), or no preoperative femoral nerve block (control) [n=15]. Femoral nerve block was performed by a single anaesthesiologist before the standardised combined spinal epidural anaesthesia. Postoperatively, patient-controlled analgesia was given. The visual analogue score (VAS) for pain at rest and on movement was recorded at 8, 12, 24, 48, and 72 hours. Passive knee range of motion (ROM) was measured at 24, 48, and 72 hours. Results The 4 groups were comparable in terms of age, gender, weight, ASA grade, and operating time. Compared with patients who received no femoral nerve block or ropivacaine alone, those who received femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 50 mg or 100 mg recorded a lower VAS for pain at rest and on movement at 8 to 72 hours, longer sensory and motor block time, and lower demand, delivery, and total amount of patient-controlled analgesia. The passive knee ROM at 24 to 72 hours was greater in patients with femoral nerve block than in those without. Conclusion Preoperative femoral nerve block with 20 ml of 0.375% ropivacaine and 100 mg tramadol resulted in the best analgesic effect.

The coronary artery calcification (CAC) is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1) plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC.A total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS). The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5 ± 0.4 vs. 0.2 ± 0.2, P0 and the highest tertile of big ET-1 (P

BACKGROUND: Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with DM. METHODS AND FINDINGS: Three hundred and seventy-three diabetic patients who were scheduled for coronary angiography due to typical stable angina pectoris were enrolled in this study. They were classified into the three groups according to tertiles of Gensini score (GS, low group 28, n=121). The relationship between the leukocyte and its subsets counts with the severity of CAD were evaluated. The data indicated that there were significant correlations between leukocyte and neutrophil counts with GS (r=0.154 and 0.156, respectively, all P28 points) was 5.0 × 10(9) cells/L in diabetic patients.

The association of B7-1/CD28 between antigen presenting cells (APCs) and T-cells provides a second signal to proliferate and activate T-cell immunity at the induction phase. Many reports indicate that tumor cells transfected with B7-1 induced augmented antitumor immunity at the induction phase by mimicking APC function; however, the function of B7-1 on antitumor immunity at the effector phase is unknown. Here, we report direct evidence of enhanced T-cell antitumor immunity at the effector phase by the B7-1 molecule. Our experiments in vivo and in vitro indicated that reactivity of antigen-specific monoclonal and polyclonal T-cell effectors against a Lass5 epitope presented by RMA-S cells is increased when the cells expressed B7-1. Use of either anti-B7-1 or anti-CD28 antibodies to block the B7-1/CD28 association reduced reactivity of the T effectors against B7-1 positive RMA-S cells. Transfection of Lass5 cDNA into or pulse of Lass5 peptide onto B7-1 positive RMA-S cells overcomes the requirement of the B7-1/CD28 signal for T effector response. To our knowledge, the data offers, for the first time, strong evidence that supports the requirement of B7-1/CD28 secondary signal at the effector phase of antitumor T-cell immunity being dependent on the density of an antigenic peptide.

BACKGROUND: Glycated hemoglobin (HbA1c) predicts clinical cardiovascular disease or cardiovascular mortality. However, the relationship between HbA1c and myocardial injury following elective percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (DM) has not been investigated. OBJECTIVES: The study sought to assess the relationship between HbA1c and myocardial injury following elective PCI in patients with type 2 DM. METHODS: We studied a cohort of consecutive 994 diabetic patients with coronary artery disease (CAD) undergoing elective PCI. Periprocedural myocardial injury was evaluated by analysis of troponin I (cTnI). The association between preprocedural HbA1c levels and the peak values of cTnI within 24 hours after PCI was evaluated. RESULTS: Peak postprocedural cTnI > 1×upper limit of normal (ULN), >3×ULN and >5×ULN were detected in 543 (54.6%), 337 (33.9%) and 245 (24.6%) respectively. In the multivariate model, higher HbA1c levels were associated with less risk of postprocedural cTnI >1×ULN (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.76-0.95; P = 0.005). There was a trend that higher HbA1c levels were associated with less risk of postprocedural cTnI >3×ULN (OR, 0.90; 95% CI, 0.81-1.02; P = 0.088). HbA1c was not associated with the risk of postprocedural cTnI elevation above 5×ULN (OR, 0.95; 95% CI, 0.84-1.08; P = 0.411). CONCLUSIONS: The present study provided the first line of evidence that higher preprocedural HbA1c levels were associated with less risk of myocardial injury following elective PCI in diabetic patients.

The hydrothermal reaction of Zn(CH3COO)2, NaOH and l-cysteic acid produced the title compound, [Na2Zn(C3H5NO5S)2]n. The ZnII cation is situated on an inversion centre and is in a distorted octahedral environment, being chelated by two deprotoned l-cysteic acid ligands through two amino N atoms and two carboxylic O atoms, with the two axial positions occupied by two carboxylic O atoms from two other l-cysteic acid ligands. Each l-cysteic acid ligand bridges five NaI ions via its sulfonate group and two ZnII ions via its carboxyl group, forming a three-dimensional framework. Weak N—H...O hydrogen bonding is observed in the crystal structure.

Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs) with prostate specific membrane antigen (PSMA) have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells). To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ). Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy.

OBJECTIVE: The G-403A polymorphism in RANTES gene may be involved in the development of coronary artery disease (CAD) through increasing RANTES-mediated leukocyte trafficking and activation. However, studies investigating the relationship between G-403A polymorphism and CAD yielded contradictory and inconclusive results. In order to shed some light on these inconsistent findings, a meta analysis was performed to clarify the role of G-403A polymorphism of RANTES gene in the susceptibility of CAD. METHODS: A systemic literature search of PubMed and EMBASE was conducted from their inception to March 23, 2012, to retrieve related studies. In addition, Conference Proceedings Citation Index-Science was searched, authors of relevant studies were contacted, and reference lists of the included studies and their related citations in PubMed were reviewed for additional pertinent studies. RESULTS: A total of 8 eligible studies were identified, with a total of 4252 CAD cases and 2150 controls. There was no evidence of significant association between G-403A polymorphism and CAD risk in any genetic model or pairwise comparisons (additive model: OR = 1.046, 95% CI = 0.883-1.239, I(2) = 65.9%; recessive model: OR = 1.140, 95% CI = 0.774-1.678, I(2) = 53.1%; dominant model: OR = 1.000, 95% CI = 0.820-1.21), I(2) = 62.6%; AA vs GG: OR = 1.141, 95% CI = 0.734-1.773, I(2) = 61.2%; GA vs GG: OR = 0.993, 95% CI = 0.800-1.232, I(2) = 64.6%). Subgroup analysis and meta regression indicated that ethnicity and genotyping method accounted for the significant heterogeneity among studies. In the stratified analysis by ethnic group, G-403A polymorphism was found to be associated with increased CAD risk in Caucasian population whereas its protective role was observed in Asian population in some but not all comparisons. CONCLUSION: Data from the current meta-analysis do not support the existence of a relationship between G-403A polymorphism and the development of CAD, and large sample size study employing unified genotyping method is needed to further evaluate the influence of G-403A polymorphism on susceptibility of CAD.

The title compound, [CoK(C2H6NO3S)3]n, is isotypic with its NiII analogue. The CoII atom is chelated by the three taurinate ligands in a distorted octahedral geometry and in a facial manner. Each taurinate ligand bridges two K+ ions via its sulfonate group, forming a three-dimensional framework. Weak N—H...O hydrogen bonding is observed in the crystal structure.

Tumors deficient in expression of the transporter associated with antigen processing (TAP) usually fail to induce T-cell-mediated immunity and are resistant to T-cell lysis. However, we have found that introduction of the B7.1 gene into TAP-negative (TAP(-)) or TAP1-transfected (TAP1(+)) murine lung carcinoma CMT.64 cells can augment the capacity of the cells to induce a protective immune response against wild-type tumor cells. Differences in the strength of the protective immune responses were observed between TAP(-) and TAP1(+) B7.1 expressing CMT.64 cells depending on the doses of gamma-irradiated cell immunization. While mice immunized with either high or low dose of B7.1-expressing TAP1(+) cells rejected TAP(-) tumors, only high dose immunization with B7.1-expressing TAP(-) cells resulted in tumor rejection. The induced protective immunity was T-cell dependent as demonstrated by dramatically reduced antitumor immunity in mice depleted of CD8 or CD4 cells. Augmentation of T-cell mediated immune response against TAP(-) tumor cells was also observed in a virally infected tumor cell system. When mice were immunized with a high dose of gamma-irradiated CMT.64 cells infected with vaccinia viruses carrying B7.1 and/or TAP1 genes, we found that the cells co-expressing B7.1 and TAP1, but not those expressing B7.1 alone, induced protective immunity against CMT.64 cells. In addition, inoculation with live tumor cells transfected with several different gene(s) revealed that only B7.1- and TAP1-coexpressing tumor cells significantly decreased tumorigenicity. These results indicate that B7.1-provoked antitumor immunity against TAP(-) cancer is facilitated by TAP1-expression, and thus both genes should be considered for cancer therapy in the future.

The transporter associated with antigen processing (TAP) and the major histocompatibility complex class I (MHC-I), two important components of the MHC-I antigen presentation pathway, are often deficient in tumor cells. The restoration of their expression has been shown to restore the antigenicity and immunogenicity of tumor cells. However, it is unclear whether TAP and MHC-I expression in tumor cells can affect the induction phase of the T cell response. To address this issue, we expressed viral antigens in tumors that are either deficient or proficient in TAP and MHC-I expression. The relative efficiency of direct immunization or immunization through cross-presentation in promoting adaptive T cell responses was compared. The results demonstrated that stimulation of animals with TAP and MHC-I proficient tumor cells generated antigen specific T cells with greater killing activities than those of TAP and MHC-I deficient tumor cells. This discrepancy was traced to differences in the ability of dendritic cells (DCs) to access and sample different antigen reservoirs in TAP and MHC-I proficient versus deficient cells and thereby stimulate adaptive immune responses through the process of cross-presentation. In addition, our data suggest that the increased activity of T cells is caused by the enhanced DC uptake and utilization of MHC-I/peptide complexes from the proficient cells as an additional source of processed antigen. Furthermore, we demonstrate that immune-escape and metastasis are promoted in the absence of this DC 'arming' mechanism. Physiologically, this novel form of DC antigen sampling resembles trogocytosis, and acts to enhance T cell priming and increase the efficacy of adaptive immune responses against tumors and infectious pathogens.