Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Characteristic Evaluation of Gas Chromatography with Different Detectors for Accurate Determination of Sulfur Hexafluoride.

Sulfur hexafluoride (SF6), which survives in the atmosphere for an extremely long period of time, is the most potent greenhouse gas regulated under the Kyoto Protocol. So, the accurate monitoring of atmospheric SF6 plays an important role in the study of the control policies for reducing greenhouse gas emissions. The instruments for SF6 measurement are typically calibrated using certified reference materials. The concentrations of the commercially available SF6 reference materials usually have a broad range, from 1 µmol/mol to 6000 µmol/mol. Some characteristics including sensitivity, linear range, relative standard deviation, and accuracy are crucial for the determination of SF6 in such a broad concentration range. Therefore, the selection of a proper detector for the accurate determination of SF6 with such a broad range is extremely important to establish a gas chromatography (GC) method for developing SF6 reference materials. In this paper, several typical GC methods with different detectors, including a thermal conductivity detector (TCD), a pulsed discharge helium ionization detector (PDHID), and a flame photometric detector (FPD), were carefully established for the accurate determination of SF6 with different concentrations. The results show that an FPD detector has a relatively narrow linearity range, thus a quadratic equation should be established for building a calibration curve. The PDHID and TCD have good linearity with coefficients of 1.0000 in the concentration range of 10-100 µmol/mol (using a PDHID), and 100-1000 µmol/mol (using a TCD), respectively. Further considering the measurement errors of indication results, the PDHID is suitable for SF6 measurement when the concentrations are below 100 µmol/mol, whereas the TCD is suitable for SF6 measurement when the concentrations are over 100 µmol/mol. These results provide useful guidance in choosing an appropriate GC detector for the accurate determination of SF6, which are especially very helpful for developing SF6 reference materials.

End-to-End AUV Motion Planning Method Based on Soft Actor-Critic.

This study aims to solve the problems of poor exploration ability, single strategy, and high training cost in autonomous underwater vehicle (AUV) motion planning tasks and to overcome certain difficulties, such as multiple constraints and a sparse reward environment. In this research, an end-to-end motion planning system based on deep reinforcement learning is proposed to solve the motion planning problem of an underactuated AUV. The system directly maps the state information of the AUV and the environment into the control instructions of the AUV. The system is based on the soft actor-critic (SAC) algorithm, which enhances the exploration ability and robustness to the AUV environment. We also use the method of generative adversarial imitation learning (GAIL) to assist its training to overcome the problem that learning a policy for the first time is difficult and time-consuming in reinforcement learning. A comprehensive external reward function is then designed to help the AUV smoothly reach the target point, and the distance and time are optimized as much as possible. Finally, the end-to-end motion planning algorithm proposed in this research is tested and compared on the basis of the Unity simulation platform. Results show that the algorithm has an optimal decision-making ability during navigation, a shorter route, less time consumption, and a smoother trajectory. Moreover, GAIL can speed up the AUV training speed and minimize the training time without affecting the planning effect of the SAC algorithm.

Multibody System-Based Adaptive Formation Scheme for Multiple Under-Actuated AUVs.

Underwater vehicles' coordination and formation have attracted increasing attention since they have great potential for real-world applications. However, such vehicles are usually under-actuated and with very limited communication capabilities. On the basis of the multibody system concept, a multiple autonomous underwater vehicle formation and communication link framework has been established with an adaptive and radial basis function (RBF) strategy. For acoustic communication, a packets transmission scheme with topology and protocol has been investigated on the basis of an acoustic communication framework and transmission model. Moreover, the cooperative localization errors caused by packet loss are estimated through reinforcement learning radial basis function neural networks. Furthermore, in order to realize formation cruising, an adaptive RBF formation scheme with magnitude reduced multi-layered potential energy functions has been designed on the basis of a time-delayed network framework. Finally, simulations and experiments have been extensively performed to validate the effectiveness of the proposed methods.

Underactuated AUV Nonlinear Finite-Time Tracking Control Based on Command Filter and Disturbance Observer.

The three-dimensional (3D) path following problem of an underactuated autonomous underwater vehicle with ocean currents disturbances is addressed in this paper. Firstly, the motion equation under the ocean currents disturbance is established, and the dynamic model of 3D tracking error is constructed based on virtual guidance method. Then, a finite-time control scheme based on super-twisting observer and command filtered backstepping technology is proposed. We adopt super-twisting observer based on finite-time theory to observe the ocean currents disturbances for improving the system robust. A command filtered backstepping is proposed to replace the differential process in the conventional backstepping method for avoiding the differential expansion problem. The filter compensation loop is designed to ensure the accuracy of the filtered signal, and the anti-integration saturation link is designed considering the influence of integral saturation. Lyapunov stability theory is used to prove the stability of the underactuated AUV. Simulation studies are conducted to show the effectiveness and robustness of the controller.

The Insertion Mechanism of a Living Cell Determined by the Stress Segmentation Effect of the Cell Membrane during the Tip-Cell Interaction.

Atomic force microscopy probes are proved to be powerful tools to measure and manipulate the individual cell, providing potential applications for the controlled drug/protein delivery. However, the measured insertion efficiency varies dramatically from 20 to 80%, in some cases, the nanotip can never penetrate the cell membrane no matter how much force is applied to it. Thus, the insertion mechanism of a living cell during the tip-cell interaction must be thoroughly investigated before this technology comes into practical applications. In this work, a multistructural cell model is established to study the tip-membrane interaction. The simulation results show that the stress of the cell membrane can be divided into two stages by the stress segmentation point S. After point S, the stress of the cell membrane increases slightly and most of the indentation force is allocated to the cytoskeleton. This phenomenon is called "stress segmentation effect of the cell membrane," which confirms the hypothesis based on the experimental studies. Moreover, according to the experimental and numerical studies, the hypothesis of the stress segmentation effect also explains the reason that modifying the cell membrane or using the manmade sharpened nanotip can increase the insertion efficiency.

Respiratory syncytial virus non-structural protein 1 facilitates virus replication through miR-29a-mediated inhibition of interferon-α receptor.

Human respiratory syncytial virus (RSV) non-structural protein 1 (NS1) has recently been suggested to inhibit type-I interferon (IFN)-dependent immune responses during RSV infection. However, the precise function of RSV NS1 protein in reducing the antiviral effects of IFNs against RSV is poorly understood. The roles of cellular miRNAs in the defence against RSV infection are not well characterized. In this study, qRT-PCR analysis revealed that miR-29a expression was upregulated in the recombinant wild-type RSV (rRSV-WT) group compared with the control group, but no changes were observed in the recombinant RSV mutant lacking NS1 (rRSV-ΔNS1) group. Using dual-luciferase reporter assay, we demonstrated that miR-29a could directly target IFNAR1 3'-UTR and downregulate IFNAR1 expression. In addition, RSV NS1 suppressed IFNAR1 expression at both RNA level and protein level in human lung adenocarcinoma cell line A549. RSV plaque assays showed that the number of RSV plaques in miR-29a mimics group was significantly higher than that in miR-29a inhibitor group or miRNA scramble control group. HA-NS1 overexpression increased the numbers of RSV plaque, but the promotive effect on virus replication was attenuated in cells transfected with miR-29a inhibitors. These results suggest that miR-29a, upregulated during RSV infection, is a negative regulator of IFNAR1 and is critical for RSV NS1-induced virus replication.

Survey on child leprosy patients and problems resulted from the disease in China.

OBJECTIVES: To understand the situation of child leprosy patients in the low prevalence situation pertaining in China. METHOD: A retrospective survey by questionnaire was carried out in all 32 provinces of mainland of China in 2011. All data concerning child cases detected from January 2005 to December 2009 were collected by professional health workers working at county level. RESULTS: During the study, only 165 questionnaires were collected for analysis. Among 165 child cases, 96 were boys, 69 were girls with an average age of 11-7 years old. 80% of child cases were members of families with other leprosy affected people. 145 (85%) child cases took their MDT secretly (nobody outside the family knew the child suffered from leprosy), and three (1.8%) children died, one each from dapsone syndrome, suicide and severe pneumonia. During follow-up, four child cases developed new disability increasing the Grade 2 disability rate to 13.3% (22/165). At end of the study, 8.2% of children had discontinued their study at school, and 7.5% had moved to a remote place to do casual work, while 6.3% stayed at home. 31% of child patients thought that leprosy caused a negative impact on their daily life. Two children had a hostile attitude toward society due to the stigma caused by leprosy. CONCLUSIONS: In both high and low endemic areas, as long as there is an infectious source of leprosy in the family, there is a possibility for children to develop leprosy. Contact surveys should be done to detect early disease, especially when there are children in the household.

The role of functional traits and individual variation in the co-occurrence of Ficus species.

The processes that structure assemblages of species in hyper-diverse genera, such as Ficus (Moraceae), are not well understood. Functional diversity of co-occurring species can reveal evidence for assembly processes; however, intraspecific variation may weaken species-level patterns. We studied whether functional and phylogenetic diversity of Ficus species indicated the effects of spatial variation in filters associated with topography or niche partitioning related to resource use and biotic interactions. We also asked whether individual trait patterns supported species-level patterns. We studied six traits (leaf area, succulence, specific leaf area [SLA], maximum diameter breast high [dbh], fruit size, and latex exudation) for 22 Ficus species and 335 individuals > or = 10 cm dbh on a 20-ha forest plot in China. We found that higher elevation was correlated to changes in mean and reduced diversity of five traits, possibly due to frequent disturbances at higher elevations that favored fast-growing, poorly defended species with high SLA. Maximum dbh showed phylogenetic conservatism but high diversity among co-occurring species, suggesting adult stature is an important axis of within-quadrat niche partitioning. At the individual level, trait patterns were qualitatively consistent but were stronger than species-level patterns, especially for the leaf traits with the greatest intraspecific variation (SLA and succulence). Individual-level SLA exhibited the strongest evidence for both traits among and within-quadrat niche partitioning and indicated elevational filtering. Local niche partitioning and elevational filtering likely play an important role in maintaining species and functional diversity in the most speciose genus at our study site. Our results highlight the importance of individual variation, as it may reveal otherwise obscured niche effects.

Dental health and treatment needs in people with leprosy in China.

OBJECTIVES: To evaluate the dental health status and treatment needs of people affected by leprosy in China, and provide a basis for the development of national or regional dental health programmes to cover the treatment needs of this population. DESIGN: A cross-sectional study with 613 former leprosy patients was carried out in six leprosy villages, in three provinces in China (Nanjing, Taixing and Jiangyan in Jiangsu Province, Hanzhong and Shangluo in Shanxi Province and Yongzhou in Hunan Province). A questionnaire about demographic and clinical data was used. The World Health Organization's (WHO) basic methods were used to determine the tooth-based treatment needs. Periodontal status was determined by using the Community Periodontal Index of Treatment Needs (CPITN). In addition, prosthetic normative needs were assessed. RESULTS: Among the 613 people affected by leprosy, there were 472 people (77%) who had never visited a dentist and 172 people (28.1%) had never brushed their teeth; 302 (49.3%) brushed their teeth once a day. However, there were 267 people (43.6%) who thought their dental health was at an average level and 108 (17.6%) thought they had good dental health. 55.6% of the subjects required dental fillings, 32.7% required pulp care and restoration, and 71.1% required extraction. On CPITN, 23.2% of the subjects scored 2, 28.6% scored three and 48.0% scored four, showing that these people required systematic periodontal treatment. In addition, 84.5% of the subjects needed normative prosthetic treatment. CONCLUSIONS: Most of the subjects with leprosy in this study lacked self-care knowledge on dental health, and especially self-awareness of dental conditions. Normative treatment needs of people affected by leprosy were very high. This result calls for improved oral health education and oral health care in people with leprosy. Oral health education might preferably be integrated into already existing leprosy rehabilitation programs.

Comprehensive fractal description of porosity of coal of different ranks.

We selected, as the objects of our research, lignite from the Beizao Mine, gas coal from the Caiyuan Mine, coking coal from the Xiqu Mine, and anthracite from the Guhanshan Mine. We used the mercury intrusion method and the low-temperature liquid nitrogen adsorption method to analyze the structure and shape of the coal pores and calculated the fractal dimensions of different aperture segments in the coal. The experimental results show that the fractal dimension of the aperture segment of lignite, gas coal, and coking coal with an aperture of greater than or equal to 10 nm, as well as the fractal dimension of the aperture segment of anthracite with an aperture of greater than or equal to 100 nm, can be calculated using the mercury intrusion method; the fractal dimension of the coal pore, with an aperture range between 2.03 nm and 361.14 nm, can be calculated using the liquid nitrogen adsorption method, of which the fractal dimensions bounded by apertures of 10 nm and 100 nm are different. Based on these findings, we defined and calculated the comprehensive fractal dimensions of the coal pores and achieved the unity of fractal dimensions for full apertures of coal pores, thereby facilitating, overall characterization for the heterogeneity of the coal pore structure.

Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis.

The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.

Serum proteomics identifies novel diagnostic biomarkers for asthma in preschool children.

Background: Asthma is characterized by airway hyperresponsiveness, reversible airway obstruction, and chronic airway inflammation. It is the most common chronic disease in childhood. However, the diagnosis of childhood asthma remains challenging, and there is an urgent need to develop new diagnostic methods. Methods: To identify biomarkers of asthma in children, we adopted the Orbitrap-based data-independent acquisition (DIA) mass spectrometry proteomics method to analyze the serum proteomic signatures of children with acute asthma and convalescent children. Results: We identified 747 proteins in 46 serum samples and 50 differentially expressed proteins (DEPs) that distinguished between asthmatic and healthy children. Next, functional enrichment analysis of the DEPs was conducted, it was indicated that the DEPs were significantly enriched in immune-related and function terms and pathways. Furthermore, we performed statistical analysis and identified MMP14, ABHD12B, PCYOX1, LTBP1, CFHR4, APOA1, IGHG4, ANG and IGFALS proteins as the diagnostic biomarker candidates. Ultimately, a promising asthma diagnostic model for preschool children based on IGFALS was built and evaluated. The area under the curve (AUC) of the IGFALS model was 0.959. Conclusions: In this study, the DIA proteome strategy was used and the largest number of proteins of asthmatic children serum proteomics was identified. The proteomics results showed that the DEPs play the central role of the inflammation-immune mechanism in asthma pathogenesis, suggesting that these proteins may be used in asthma diagnosis, prognosis, or therapy, and suggested biomarkers for asthma of preschool children. In conclusion, our results provide insight into the pathophysiology of asthma. We believe that the diagnostic model will facilitate clinical decision-making regarding asthma in preschool children.

Study of the Effect of Cell Prestress on the Cell Membrane Penetration Behavior by Atomic Force Microscopy.

In recent years, atomic force microscopes have been used for cell transfection because of their high-precision micro-indentation mode; however, the insertion efficiency of the tip of AFM into cells is extremely low. In this study, NIH3T3 mouse fibroblast cells cultured on a flexible dish with micro-groove patterns were subjected to various substrate strains at 5%, 10%, 15%, and 20%. It was found that the cell stiffness depends on the prestress of the cell membrane, and that the insertion rate of AFM tips into the cell membrane is proportional to the stiffness through the AFM indentation experiment. The finite element analysis proves that prestress increases the bending stiffness of the cytoskeleton, allowing it to better support the cell membrane, which realizes the stress concentration in the contact area between the AFM tip and the cell membrane. The results indicate that the prestress contributes to the mechanical properties of the cell and suggest that the insertion efficiency could be greatly improved with an increase of the prestress of the cell membrane.

Repeated inoculation of antimony resistant bacterium reduces antimony accumulation in rice plants.

Applying beneficial bacteria in rice rhizosphere to manage heavy metal behaviour in soil-plant system is a promising strategy. However, colonization/domination of exogenous bacteria in rhizosphere soils remains a challenge. In this study, a bacterium Ochrobactrum anthropi, which showed the potential of transforming soluble SbIII into Sb2O3 mineral, was repeatedly inoculated into the rice rhizosphere weekly throughout the rice growth period, and the colonization of this bacterium in rice rhizosphere soils and its effect on Sb accumulation in rice plants were investigated. Results showed that repeated inoculants changed the native bacterial community in rhizosphere soils in comparison with the control, but the inoculated O. anthropi was not identified as an abundant species. With weekly inoculation, the decrease in Sb in rice roots and straws was maintained throughout the rice growth period, with decrease percentages ranging from 36 to 49% and 33-35%. In addition, decrease percentages of Sb in husks and grains at the maturing stage obtained 34 and 37%, respectively. Furthermore, the XRD identified the formation of valentinite (Sb2O3) on rice root in inoculation treatment, and the decrease percentages in aqueous SbIII in rhizosphere were 53-100% through the growth period. It demonstrated that weekly inoculants performed their temporary activity of valentinite formation, and reduced Sb accumulation in rice plants efficiently. This study suggests that regardless of successful colonization, repeated inoculation of beneficial bacteria is an option to facilitate the positive effects of inoculated bacteria in the management of heavy metal behaviour.

High-performance vertical field-effect organic photovoltaics.

Limited by the inherent energy loss (Eloss) in carrier transport process, the device efficiency of organic solar cells shows inferior to traditional inorganic photovoltaic devices. Generally, molecular design, morphology optimization and interfacial engineering are usually required to alleviate Eloss. Here, vertical field-effect organic photovoltaic (VFEOPV) by integrating an bulk-heterojunction (BHJ) organic photovoltaic (OPV) with vertical field effect transistor (VFET) is invented, in which VFET generates a large, uneven, internal electric field, eliminating the requirement for driving force to dissociate excitons and prevents non-radiative recombination in OPV. In this way, the performance of solar cell can be well controlled by the gate voltage of VFET and the Eloss of VFEOPVs based on J71: ITIC system is dramatically reduced below 0.2 eV, significantly improving power conversion efficiency (PCE) from 10% to 18% under gate voltage of 0.9 V, which only causes negligible additional power consumption (~10-4mJ/cm2). Besides, the device also exhibits multi-functionality including transistor and phototransistors with excellent photodector performance. This work provides a new and general strategy to improve the OPV performance which is compatible with present optimization methods, and can be applied to improve PCE of other types of solar cells such as Perovskite and inorganic solar cells.

Ultrasound-mediated piezoelectric nanoparticle modulation of intrinsic cardiac autonomic nervous system for rate control in atrial fibrillation.

Rate control is a cornerstone of atrial fibrillation treatment. Barium titanate nanoparticles (BTNPs) are piezoelectric nanomaterials that can generate local electromagnetic fields under ultrasound activation, stimulating nearby neuronal tissue. This study aimed to modulate the inferior right ganglionated plexus (IRGP) of the heart and reduce the ventricular rate during rapid atrial pacing (RAP)-induced atrial fibrillation using ultrasound-mediated BTNPs. Adult male beagles were randomly divided into a phosphate-buffered saline (PBS) group (n = 6) and a BTNP group (n = 6). PBS or nanoparticles were injected into the IRGP of both groups before RAP. The biological safety of the material was evaluated according to electrophysiology recordings, thermal effects and level of inflammation. Compared to the PBS group, the BaTiO3 piezoelectric nanoparticle group had reduced ventricular rates in the sinus rhythm and atrial fibrillation models after stimulating the IRGP by applying ultrasound. In addition, transient stimulation by BTNPs did not lead to sustained neuronal excitation in the IRGP. The activation of the BTNPs did not induce inflammation or thermal damage effects in the IRGP. Ultrasound-mediated BTNP neuromodulation can significantly reduce the ventricular rate by stimulating the IRGP. Thus, ultrasound-mediated BTNP neuromodulation is a potential therapy for atrial fibrillation rate control.

Subthreshold splenic nerve stimulation prevents myocardial Ischemia-Reperfusion injury via neuroimmunomodulation of proinflammatory factor levels.

OBJECTIVES: Clinical outcomes following myocardial ischemia-reperfusion (I/R) injury are strongly related to the intensity and duration of inflammation. The splenic nerve (SpN) is indispensable for the anti-inflammatory reflex. This study aimed to investigate whether splenic nerve stimulation (SpNS) plays a cardioprotective role in myocardial I/R injury and the potential underlying mechanism. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham group, I/R group, SpNS group, and I/R plus SpNS group. The highest SpNS intensity that did not influence heart rate was identified, and SpNS at this intensity was used as the subthreshold stimulus. Continuous subthreshold SpNS was applied for 1 h before ligation of the left coronary artery for 45 min. After 72 h of reperfusion, samples were collected for analysis. RESULTS: SpN activity and splenic concentrations of cholinergic anti-inflammatory pathway (CAP)-related neurotransmitters were significantly increased by SpNS. The infarct size, oxidative stress, sympathetic tone, and the levels of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, were significantly reduced in rats subjected to subthreshold SpNS after myocardial I/R injury compared with those subjected to I/R injury alone. CONCLUSIONS: Subthreshold SpNS ameliorates myocardial damage, the inflammatory response, and cardiac remodelling induced by myocardial I/R injury via neuroimmunomodulation of proinflammatory factor levels. SpNS is a potential therapeutic strategy for the treatment of myocardial I/R injury.

The highly conserved 5' untranslated region as an effective target towards the inhibition of Enterovirus 71 replication by unmodified and appropriate 2'-modified siRNAs.

BACKGROUND: Enterovirus 71 (EV71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71. METHODS: Unmodified 21 nucleotide small interfering RNAs (siRNAs) and classic 2'-modified (2'-O-methylation or 2'-fluoro modification) siRNAs were designed to target highly conserved 5' untranslated region (UTR) of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs. RESULTS: Transfection of rhabdomyosarcoma (RD) cells with siRNAs targeting the EV71 genomic 5' UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2'-modified siRNAs exhibited similar RNA interference (RNAi) activity with dramatically increased serum stability in comparison with unmodified counterparts. CONCLUSION: Sequences were identified within the highly conserved 5' UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2'-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.

Dapsone hypersensitivity syndrome among leprosy patients in China.

OBJECTIVE: To Study the incidence and clinical characteristics of dapsone hypersensitivity syndrome (DHS) among MDT-treated leprosy patients from 2006 to 2009 in China. METHODS: A retrospective survey was carried out throughout China using a specially designed questionnaire. RESULTS: From 2006 to 2009, there were 63 new patients reported to have DHS with an incidence of 1.0%. Among these patients, 13 were complete types of DHS, the others were incomplete ones. The average age of patients with DHS was 38 years and the male to female ratio was 2.15. The average incubation period from taking dapsone to DHS onset was 32.8 days (2-6 weeks). There were 60 (95.2%) patients who presented with various skin lesions, 56 (88.9%) with fever, 40 (63.5%) with hepatic damage and 22 (34.9%) with lymphopathy. Seven patients died with a death rate of 11.1% among all patients with DHS. CONCLUSIONS: DHS is a serious adverse event resulted from dapsone. It can occur in a small number of new leprosy patients treated with dapsone containing regimen. Some patients may die of DHS if not taking timely and adequate management. Therefore local doctors should pay an attention to DHS among leprosy patients newly treated with the dapsone-containing MDT regimen.