Sensory integration for neuroprostheses: from functional benefits to neural correlates.

In the field of sensory neuroprostheses, one ultimate goal is for individuals to perceive artificial somatosensory information and use the prosthesis with high complexity that resembles an intact system. To this end, research has shown that stimulation-elicited somatosensory information improves prosthesis perception and task performance. While studies strive to achieve sensory integration, a crucial phenomenon that entails naturalistic interaction with the environment, this topic has not been commensurately reviewed. Therefore, here we present a perspective for understanding sensory integration in neuroprostheses. First, we review the engineering aspects and functional outcomes in sensory neuroprosthesis studies. In this context, we summarize studies that have suggested sensory integration. We focus on how they have used stimulation-elicited percepts to maximize and improve the reliability of somatosensory information. Next, we review studies that have suggested multisensory integration. These works have demonstrated that congruent and simultaneous multisensory inputs provided cognitive benefits such that an individual experiences a greater sense of authority over prosthesis movements (i.e., agency) and perceives the prosthesis as part of their own (i.e., ownership). Thereafter, we present the theoretical and neuroscience framework of sensory integration. We investigate how behavioral models and neural recordings have been applied in the context of sensory integration. Sensory integration models developed from intact-limb individuals have led the way to sensory neuroprosthesis studies to demonstrate multisensory integration. Neural recordings have been used to show how multisensory inputs are processed across cortical areas. Lastly, we discuss some ongoing research and challenges in achieving and understanding sensory integration in sensory neuroprostheses. Resolving these challenges would help to develop future strategies to improve the sensory feedback of a neuroprosthetic system.

Upper limb intention tremor assessment: opportunities and challenges in wearable technology.

BACKGROUND: Tremors are involuntary rhythmic movements commonly present in neurological diseases such as Parkinson's disease, essential tremor, and multiple sclerosis. Intention tremor is a subtype associated with lesions in the cerebellum and its connected pathways, and it is a common symptom in diseases associated with cerebellar pathology. While clinicians traditionally use tests to identify tremor type and severity, recent advancements in wearable technology have provided quantifiable ways to measure movement and tremor using motion capture systems, app-based tasks and tools, and physiology-based measurements. However, quantifying intention tremor remains challenging due to its changing nature. METHODOLOGY & RESULTS: This review examines the current state of upper limb tremor assessment technology and discusses potential directions to further develop new and existing algorithms and sensors to better quantify tremor, specifically intention tremor. A comprehensive search using PubMed and Scopus was performed using keywords related to technologies for tremor assessment. Afterward, screened results were filtered for relevance and eligibility and further classified into technology type. A total of 243 publications were selected for this review and classified according to their type: body function level: movement-based, activity level: task and tool-based, and physiology-based. Furthermore, each publication's methods, purpose, and technology are summarized in the appendix table. CONCLUSIONS: Our survey suggests a need for more targeted tasks to evaluate intention tremors, including digitized tasks related to intentional movements, neurological and physiological measurements targeting the cerebellum and its pathways, and signal processing techniques that differentiate voluntary from involuntary movement in motion capture systems.

Perceptually Weighted Rate Distortion Optimization for Video-Based Point Cloud Compression.

Dynamic point cloud is a volumetric visual data representing realistic 3D scenes for virtual reality and augmented reality applications. However, its large data volume has been the bottleneck of data processing, transmission, and storage, which requires effective compression. In this paper, we propose a Perceptually Weighted Rate-Distortion Optimization (PWRDO) scheme for Video-based Point Cloud Compression (V-PCC), which aims to minimize the perceptual distortion of reconstructed point cloud at the given bit rate. Firstly, we propose a general framework of perceptually optimized V-PCC to exploit visual redundancies in point clouds. Secondly, a multi-scale Projection based Point Cloud quality Metric (PPCM) is proposed to measure the perceptual quality of 3D point cloud. The PPCM model comprises 3D-to-2D patch projection, multi-scale structural distortion measurement, and fusion model. Approximations and simplifications of the proposed PPCM are also presented for both V-PCC integration and low complexity. Thirdly, based on the simplified PPCM model, we propose a PWRDO scheme with Lagrange multiplier adaptation, which is incorporated into the V-PCC to enhance the coding efficiency. Experimental results show that the proposed PPCM models can be used as standalone quality metrics, and they are able to achieve higher consistency with the human subjective scores than the state-of-the-art objective visual quality metrics. Also, compared with the latest V-PCC reference model, the proposed PWRDO-based V-PCC scheme achieves an average bit rate reduction of 13.52%, 8.16%, 10.56% and 9.54%, respectively, in terms of four objective visual quality metrics for point clouds. It is significantly superior to the state-of-the-art coding algorithms. The computational complexity of the proposed PWRDO increases by 1.71% and 0.05% on average to the V-PCC encoder and decoder, respectively, which is negligible. The source codes of the PPCM and PWRDO schemes are available at https://github.com/VVCodec/PPCM-PWRDO.

Sensory stimulation for upper limb amputations modulates adaptability of cortical large-scale systems and combination of somatosensory and visual inputs.

Touch-like phantom limb sensations can be elicited through targeted transcutaneous electrical nerve stimulation (tTENS) in individuals with upper limb amputation. The corresponding impact of sensory stimulation on cortical activity remains an open question. Brain network research shows that sensorimotor cortical activity is supported by dynamic changes in functional connections between relevant brain regions. These groups of interconnected regions are functional modules whose architecture enables specialized function and related neural processing supporting individual task needs. Using electroencephalographic (EEG) signals to analyze modular functional connectivity, we investigated changes in the modular architecture of cortical large-scale systems when participants with upper limb amputations performed phantom hand movements before, during, and after they received tTENS. We discovered that tTENS substantially decreased the flexibility of the default mode network (DMN). Furthermore, we found increased interconnectivity (measured by a graph theoretic integration metric) between the DMN, the somatomotor network (SMN) and the visual network (VN) in the individual with extensive tTENS experience. While for individuals with less tTENS experience, we found increased integration between DMN and the attention network. Our results provide insights into how sensory stimulation promotes cortical processing of combined somatosensory and visual inputs and help develop future tools to evaluate sensory combination for individuals with amputations.

The epidemiological characteristics and effectiveness of countermeasures to contain coronavirus disease 2019 in Ningbo City, Zhejiang Province, China.

A novel coronavirus (SARS-CoV-2) has spread worldwide and led to high disease burden around the world. This study aimed to explore the key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19). A susceptible-exposed-infectious-asymptomatic-recovered (SEIAR) model was developed for the assessment. The information of each confirmed case and asymptomatic infection was collected from Ningbo Center for Disease Control and Prevention (CDC) to calculate the key parameters of the model in Ningbo City, China. A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic infections had an increasing trend. The proportion of elder people in the asymptomatic infections was lower than younger people, and the difference was statistically significant (Fisher's Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic infections, accounting for 17.37%. We found that the secondary attack rate (SAR) of asymptomatic infections was almost the same as that of symptomatic cases, and no statistical significance was observed (χ2 = 0.052, P = 0.819) by Kruskal-Wallis test. The effective reproduction number (Reff) was 1.43, which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions had not been strengthened, the duration of the outbreak would have lasted about 16 months with a simulated attack rate of 44.15%. The total attack rate (TAR) and duration of the outbreak would increase along with the increasing delay of intervention. SARS-CoV-2 had moderate transmissibility in Ningbo City, China. The proportion of asymptomatic infections had an increase trend. Asymptomatic infections had the same transmissibility as symptomatic infections. The integrated interventions were implemented at different stages during the outbreak, which turned out to be exceedingly effective in China.

Texture Discrimination with a Soft Biomimetic Finger Using a Flexible Neuromorphic Tactile Sensor Array That Provides Sensory Feedback.

The compliant nature of soft fingers allows for safe and dexterous manipulation of objects by humans in an unstructured environment. A soft prosthetic finger design with tactile sensing capabilities for texture discrimination and subsequent sensory stimulation has the potential to create a more natural experience for an amputee. In this work, a pneumatically actuated soft biomimetic finger is integrated with a textile neuromorphic tactile sensor array for a texture discrimination task. The tactile sensor outputs were converted into neuromorphic spike trains, which emulate the firing pattern of biological mechanoreceptors. Spike-based features from each taxel compressed the information and were then used as inputs for the support vector machine classifier to differentiate the textures. Our soft biomimetic finger with neuromorphic encoding was able to achieve an average overall classification accuracy of 99.57% over 16 independent parameters when tested on 13 standardized textured surfaces. The 16 parameters were the combination of 4 angles of flexion of the soft finger and 4 speeds of palpation. To aid in the perception of more natural objects and their manipulation, subjects were provided with transcutaneous electrical nerve stimulation to convey a subset of four textures with varied textural information. Three able-bodied subjects successfully distinguished two or three textures with the applied stimuli. This work paves the way for a more human-like prosthesis through a soft biomimetic finger with texture discrimination capabilities using neuromorphic techniques that provide sensory feedback; furthermore, texture feedback has the potential to enhance user experience when interacting with their surroundings.

Recent Developments in Prosthesis Sensors, Texture Recognition, and Sensory Stimulation for Upper Limb Prostheses.

Current developments being made in upper limb prostheses are focused on replacing lost sensory information to the amputees. Providing sensory stimulation from the prosthesis can directly improve control over the prosthetic and provide a sense of body ownership. The focus of this review article is on recent developments while including foundational knowledge for some of the critical concepts in neural prostheses. Reported concepts follow the flow of information from sensors to signal processing, with emphasis on texture recognition, and then to sensory stimulation strategies that reestablish the lost sensory feedback loop. Prosthetic sensors are used to detect the physical environment, converting pressure, force, and position into electrical signals. The electrical signals can then be processed in an effort to identify the surrounding environment using distinctive characteristics such as stiffness and texture. In order for the amputee to use this information in a natural manner, there must be real-time sensory stimulation, perception, and motor control of the prosthesis. Although truly complete sensory replacement has not yet been realized, some basic percepts can be partially restored, allowing progress towards a more realistic prosthesis with natural sensations.

Sensory Feedback in Upper Limb Amputees Impacts Cortical Activity as Revealed by Multiscale Connectivity Analysis.

Sensory feedback in upper limb amputees is crucial for improving movement decoding and also to enhance embodiment of the prosthetic limb. Recently, an increasing number of invasive and noninvasive solutions for sensory stimulation have demonstrated the capability of providing a range of sensations to upper limb amputees. However, the cortical impact of restored sensation is not clearly understood. Particularly, understanding the cortical connectivity changes at multiple scales (nodal and modular) in response to sensory stimulation, can reveal crucial information on how amputees brain process the sensory stimuli. Using Electroencephalography (EEG) signals, we compared the cortical connectivity network in response to sensory feedback provided by targeted transcutaneous electrical nerve stimulation (tTENS) in an upper limb amputee during phantom upper limb movements. We focused our cortical connectivity analysis on four functional modules comprising of 20 brain regions that are primarily associated with a visually guided motor task (visual, motor, somatosensory and multisensory integration (MI)) used in this study. At the modular level, we observed that the hubness (a graph theoretic measure quantifying the importance of brain regions in integrating brain function) of the motor module decreases whereas that of the somatosensory module increases in presence of tTENS feedback. At the nodal level, similar observations were made for the visual and MI regions. This is the first work to reveal the impact of sensory feedback at multiple scales in the cortex of amputees in response to sensory stimulation.

Sensory stimulation enhances phantom limb perception and movement decoding.

OBJECTIVE: A major challenge for controlling a prosthetic arm is communication between the device and the user's phantom limb. We show the ability to enhance phantom limb perception and improve movement decoding through targeted transcutaneous electrical nerve stimulation in individuals with an arm amputation. APPROACH: Transcutaneous nerve stimulation experiments were performed with four participants with arm amputation to map phantom limb perception. We measured myoelectric signals during phantom hand movements before and after participants received sensory stimulation. Using electroencephalogram (EEG) monitoring, we measured the neural activity in sensorimotor regions during phantom movements and stimulation. In one participant, we also tracked sensory mapping over 2 years and movement decoding performance over 1 year. MAIN RESULTS: Results show improvements in the participants' ability to perceive and move the phantom hand as a result of sensory stimulation, which leads to improved movement decoding. In the extended study with one participant, we found that sensory mapping remains stable over 2 years. Sensory stimulation improves within-day movement decoding while performance remains stable over 1 year. From the EEG, we observed cortical correlates of sensorimotor integration and increased motor-related neural activity as a result of enhanced phantom limb perception. SIGNIFICANCE: This work demonstrates that phantom limb perception influences prosthesis control and can benefit from targeted nerve stimulation. These findings have implications for improving prosthesis usability and function due to a heightened sense of the phantom hand.

Towards machine to brain interfaces: sensory stimulation enhances sensorimotor dynamic functional connectivity in upper limb amputees.

OBJECTIVE: Recent development of sensory stimulation techniques demonstrates the ability to elicit touch-like phantom sensations in upper limb amputees. The cortical processing of this phantom sensation and the corresponding influences on sensorimotor functional connectivity have not been studied. We hypothesize that sensory stimulation has a profound impact on the sensorimotor cortical functional interactions, which will be uncovered by dynamic functional connectivity (dFC) analysis of amputees' electroencephalogram (EEG) recordings. APPROACH: We investigated dFC between cortical areas associated with somatosensory, motor, visual, and multisensory processing functions using EEG signals. We applied dFC to the EEG of two amputees performing hand movements with and without sensory stimulation and compared the results with those from three able-bodied subjects. We quantified the changes due to sensory stimulation using dFC metrics, namely temporal distance, number of connection paths, temporal global and local efficiencies, and clustering coefficient. MAIN RESULTS: We show a significant effect of sensory stimulation on functional connectivity in the amputee brains, with notable facilitation on multisensory processing among the cortical systems involved in sensorimotor processing. The dFC metrics reveal that sensory stimulation enhances the speed of information transfer (shown by decreases in temporal distance) and the number of connection paths between the brain systems involved in sensorimotor processing, including primary somatosensory and motor, and higher order processing regions. SIGNIFICANCE: This is the first work to reveal dynamic communication between somatosensory, motor, and higher order processing regions in the cortex of amputees in response to sensory stimulation. We believe that our work provides crucial insights into the cortical impact of sensory stimulation in amputees, which may lead to the design of personalized brain-informed sensory feedback paradigms. This in turn may lead to building novel Machine to Brain Interfaces involving sensory feedback and the resultant enhanced motor performance.

Investigation on a family cluster of COVID-19 in Ningbo / 预防医学

Objective@#To report an investigation of a family cluster of coronavirus disease 2019 ( COVID-19 ) in Ningbo, so as to provide reference for the prevention and control measures.@*Methods@#According to the COVID-19 Prevention and Control Program ( fourth version ) , an epidemiological investigation was conducted to collect the demographic information, clinical features and exposure history, to find the close contacts, and to figure out the source and route of infection. @*Results@#Twelve confirmed cases and one asymptomatic case were reported. The attack rate was 16.05%. Among them, five were males and eight were females; the age ranged from 11 to 85 years old, with a median of 39 years old; most had mild symptoms. The incubation period was 2-13 days, with a median of 6.5 days. The first case ( Case 1 ) developed the symptoms on January 22, and had close contact with Zhang, an asymptomatic case, on January 20. Zhang was related to a cluster in the Buddhist assembly on January 19. Case 1, who caused the spread of the epidemic among family members, participated in several family visits and dinners from January 22 to 27 with other 24 families, resulting in six secondary cases and six third-generation cases. There were 54 close contacts except the family members, no infection was found. @*Conclusion@#This family cluster may result from the close contact with an asymptomatic case, and then spread within families through having dinners and living together.

Epidemiological characteristics of coronavirus disease 2019 in Ningbo / 预防医学

Objective@#To analyze the epidemiological characteristics of coronavirus disease 2019 （COVID-19） cases reported in Ningbo from January 22 to February 22, 2020, so as to provide guidance for the prevention and control of the COVID-19 epidemic.@*Methods@#The confirmed cases of COVID-19 reported by Ningbo were selected from National Diseases Prevention and Control Information System to analyze the epidemiological characteristics by descriptive epidemiological method, including time, spatial and population distribution, clinical symptoms and exposure history.@*Results@#A total of 157 confirmed cases of COVID-19 were reported and there was no death. The first confirmed case was reported on January 22. On the incidence curve, the peak was from January 22 to February 4, with a maximum of 15 cases in a single day. The incidence curve presented sustained human-to-human transmission. The number of the cases showed a declining trend from February 5. The confirmed cases were reported in all 10 counties（cities or districts）,among which 69（43.95%）cases were reported in Haishu District. The confirmed cases were mainly 30-69 years old,accounting for 78.34%;were mainly farmers,household workers and retired people,accounting for 59.87%;and were mainly clinically mild,accounting for 87.90%.There were 51 imported cases, accounting for 32.48%. The initial confirmed case was a local case. In the early stage of the epidemic, local cases and imported cases prevalent together,which was due to the outbreak caused by the large-scale buddhist activity on January 19.This event resulted in 67 confirmed cases and 15 asymptomatic cases. There totally reported 22 clusters with 138 （87.90%）confirmed cases. @*Conclusions@# In the early stage of the COVID-19 epidemic in Ningbo, the imported cases and local cases prevalent at the same time. Most of the cases were female, aged from 30 to 69 years, and their occupation were farmers, household workers and retired people. With comprehensive measures taken, the epidemic of COVID-19 in Ningbo have been under control.

Incidence dynamics and investigation of key interventions in a dengue outbreak in Ningbo City, China.

BACKGROUND: The reported incidence of dengue fever increased dramatically in recent years in China. This study aimed to investigate and to assess the effectiveness of intervention implemented in a dengue outbreak in Ningbo City, Zhejiang Province, China. METHODS: Data of a dengue outbreak were collected in Ningbo City in China by a field epidemiological survey according to a strict protocol and case definition. Serum specimens of all cases were collected for diagnosis and the virological characteristics were detected by using polymerase chain reaction (PCR) and gene sequencing. Vector surveillance was implemented during the outbreak to collect the larva and adult mosquito densities to calculate the Breteau Index (BI) and human biting rate (HBR), respectively. Data of monthly BI and light-trap density in 2018 were built to calculate the seasonality of the vector. A transmission mathematical model was developed to dynamic the incidence of the disease. The parameters of the model were estimated by the data of the outbreak and vector surveillance data in 2018. The effectiveness of the interventions implemented during the outbreak was assessed by the data and the modelling. RESULTS: From 11 August to 8 September, 2018, a dengue outbreak was reported with 27 confirmed cases in a population of 5536-people community (community A) of Ningbo City. Whole E gene sequences were obtained from 24 cases and were confirmed as dengue virus type 1 (DENV-1). The transmission source of the outbreak was origin from community B where a dengue case having the same E gene sequence was onset on 30 July. Aedes albopictus was the only vector species in the area. The value of BI and HBR was 57.5 and 12 per person per hour respectively on 18 August, 2018 and decreased dramatically after interventions. The transmission model fitted well (χ2 = 6.324, P = 0.388) with the reported cases data. With no intervention, the total simulated number of the cases would be 1728 with a total attack rate (TAR) of 31.21% (95%CI: 29.99%- 32.43%). Case isolation and larva control (LC) have almost the same TAR and duration of outbreak (DO) as no intervention. Different levels of reducing HBR (rHBR) had different effectiveness with TARs ranging from 1.05% to 31.21% and DOs ranging from 27 days to 102 days. Adult vector control (AVC) had a very low TAR and DO. "LC+AVC" had a similar TAR and DO as that of AVC. "rHBR100%+LC", "rHBR100%+AVC", "rHBR100%+LC+AVC" and "rHBR100%+LC+AVC+Iso" had the same effectiveness. CONCLUSIONS: Without intervention, DENV-1 could be transmitted rapidly within a short period of time and leads to high attack rate in community in China. AVC or rHBR should be recommended as primary interventions to control rapid transmission of the dengue virus at the early stage of an outbreak.

Crack Identification in CFRP Laminated Beams Using Multi-Resolution Modal Teager-Kaiser Energy under Noisy Environments.

Carbon fiber reinforced polymer laminates are increasingly used in the aerospace and civil engineering fields. Identifying cracks in carbon fiber reinforced polymer laminated beam components is of considerable significance for ensuring the integrity and safety of the whole structures. With the development of high-resolution measurement technologies, mode-shape-based crack identification in such laminated beam components has become an active research focus. Despite its sensitivity to cracks, however, this method is susceptible to noise. To address this deficiency, this study proposes a new concept of multi-resolution modal Teager-Kaiser energy, which is the Teager-Kaiser energy of a mode shape represented in multi-resolution, for identifying cracks in carbon fiber reinforced polymer laminated beams. The efficacy of this concept is analytically demonstrated by identifying cracks in Timoshenko beams with general boundary conditions; and its applicability is validated by diagnosing cracks in a carbon fiber reinforced polymer laminated beam, whose mode shapes are precisely acquired via non-contact measurement using a scanning laser vibrometer. The analytical and experimental results show that multi-resolution modal Teager-Kaiser energy is capable of designating the presence and location of cracks in these beams under noisy environments. This proposed method holds promise for developing crack identification systems for carbon fiber reinforced polymer laminates.

Geographical information systems-based spatial analysis and implications for syphilis interventions in Jiangsu province, People's Republic of China.

Spatial distribution rules and risk factors for syphilis were studied in Jiangsu province, People's Republic of China during 2005 and 2009. Trend surface analysis, spatial autocorrelation analysis and spatio-temporal clustering were applied with the incidence rates of the various counties in the province to determine spatial distribution rules and risk factors. Syphilis was found to be most severe in the southern region of the province where many counties could be shown to be hotspots with positive autocorrelation. Clusters were detected in the south-western region of Jiangsu with the county-level city of Yixing as the centre. Temperature, distance from railways and highways, and the normalised difference vegetation index were determined as supporting variables with regard to the transmission of the disease by both univariate and multivariate spatial correlation analyses. Interventions, including health education and awareness campaigns, should be strengthened throughout the province targeting the south-western areas, especially the clusters and hotspots detected in order to improve the situation.

The naturally occurring YMDD mutation among patients chronically infected HBV and untreated with lamivudine: a systematic review and meta-analysis.

BACKGROUND: Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B. METHODOLOGY/PRINCIPAL FINDINGS: Chinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21% (95% CI: 9.69%-14.95%). China had an incidence of 13.38% (95% CI: 10.90%-16.07%) and seven other countries had an incidence of 9.90% (95% CI: 3.28%-19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients' ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C. CONCLUSIONS: The YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patients untreated with lamivudine. These mutations might be the consequence of accumulated base mismatch due to the nature of viral polymerase. More fundamental and clinical studies are needed to clarify the influence of YMDD mutations in hepatitis B progression and antiviral treatment.

Genetic variation in IL28RA is associated with the outcomes of HCV infection in a high-risk Chinese population.

Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the association of single-nucleotide polymorphisms (SNPs) of IFNAR2, IL10RB, and IL28RA genes with susceptibility to HCV infection and resolution. Genotyping of IFNAR2, IL10RB, and IL28RA gene polymorphisms were performed using TaqMan® method from 552 patients with sero-positive anti-HCV and 421 uninfected controls. The distribution of IFNAR2 and IL10RB genotypes among the control, persistent infection, and spontaneous clearance groups did not differ. However, IL28RA-rs10903035 A allele was over-represented in persistent infection group when compared with uninfected controls and spontaneous clearance group, respectively (OR=1.54, 95%CI=1.23-1.92, P=0.004; OR=1.42, 95%CI=1.12-1.81, P=0.016), and AA genotype had a significant increased risk of persistent infection in different strata except for the females subgroup (P<0.05). IL28RA-rs11249006 GG genotype showed reduced susceptibility to persistent HCV infection (OR=0.53, 95%CI=0.31-0.91, P=0.044), and the protective effect was significantly different among subgroups stratified by age and likely source of infection (P<0.05). Besides, AG genotype had a significant negative effect on spontaneous clearance of HCV among young subjects (aged ⩽40) and patients infected with viral genotype-1 (P<0.05). Stratified analysis also showed that IL10RB-rs2834167 AG genotype was associated with an increased risk of persistent HCV infection in females, and GG genotype was associated with an increased risk of persistent HCV infection in females and patients with viral genotype non-1 (P<0.05). Haplotype analysis showed that IL28RA rs10903035-rs11249006 haplotype GG played a protective effect for HCV infection (OR=0.21, 95%CI=0.13-0.36, P<0.001; OR=0.20, 95%CI=0.12-0.34, P<0.001). This study indicates that two SNPs in IL28RA are correlated with susceptibility to HCV infection and spontaneous viral clearance, which implicates a primary role of IL28RA in the outcomes of HCV infection.

Spatial distribution of HIV/AIDS in Yunnan province, People's Republic of China.

Risk maps for the geographical distribution of human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) are needed for the direction of HIV prevention interventions. Our study, based on county-level data on the numbers of HIV/AIDS patients in the Yunnan province, People's Republic of China, applied trend surface analysis and spatial autocorrelation analysis to demonstrate the geographical distribution of HIV-positive patients in the province. The case load of HIV was found to be most severe in the central-west region of the province. While Kunming county was shown to be negatively correlated with its surrounding counties, many high-burden counties are surrounded by other counties with similar case numbers. We conclude that intervention efforts in Yunnan province should concentrate on the western and northeast regions, targeting the hotspots of infection.

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis.

BACKGROUND: Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research. METHODS: A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction. RESULTS: Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% vs 7.9%). CONCLUSIONS: The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.

The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users.

OBJECTIVE: To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus (HCV) infection, and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users. METHODS: Genomic DNAs of 362 anti-HCV sero-positive drug users and 225 control drug users were extracted from the peripheral blood leukocytes. The sero-positive patients were divided into those who had persistent infection and those who had spontaneously cleared the infection. Polymorphisms of LMP genes were determined by PCR combined with restriction fragment length polymorphism (RFLP). RESULTS: The distribution of LMP2 genotypes among the control, persistent infection and spontaneous clearance groups were not different. However, the LMP7 codon 145 Gln/Lys, Lys/Lys, and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in control group (OR=1.75, 95%CI=1.06∼2.90; OR=3.16, 95%CI=1.23-8.12; OR = 1.94, 95%CI=1.21-3.12, respectively). Similarly, the frequencies of the codon 145 Gln/Lys, Lys/Lys, and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in the spontaneous clearance group (OR=1.64, 95%CI=1.04-2.57; OR=2.40, 95%CI=1.09-5.28; OR=1.76, 95%CI=1.15-2.69, respectively). Stratified analysis indicated that combined genotype Gln/Lys + Lys/Lys of the LMP7 gene was related to an increasing susceptibility to HCV infection (OR=1.91, 95%CI=1.02-3.55; OR=2.19, 95%CI=1.24-3.89; OR=1.91, 95%CI=1.05-3.48, OR=2.86, 95%CI=1.41-5.78, respectively) and the risk of persistent HCV infection (OR=1.94, 95%CI=1.12-3.34; OR=2.02, 95%CI=1.21-3.38; OR=1.78, 95%CI=1.12-2.85, OR=2.23, 95%CI=1.09-4.58, respectively) among > 30-year-old, males, the injection drug user (IDU) subjects and/or the shorter duration drug users (≤5 y). CONCLUSION: These results suggest that polymorphism of the LMP7 gene may have an influence on the outcomes of HCV infection, and is one of the factors accounting for the genetic susceptibility to HCV infection among drug users.