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Background: China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government's systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the "Rare Diseases Cohort Study" (2016-2020), and publishing its first "Rare Disease Catalog" (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)-China's first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020.Results: The total 62,590 cases covered 166 disease/disease types, forming 183 disease cohorts. The data from nearly 22% of them (13,947 cases) is also linked to valuable biological samples. The average age of definitive diagnosis was 30.88 years; 36.07% of cases were under 18 years of age. Regional distribution analysis showed 60% of cases were from the more developed, wealthier East and North China, suggesting the local availability of quality care and patients' financial status were key access factors. Finally, 82.04% of cases were registered from the five clinical departments: Neurology, Endocrine, Hematology, Cardiovascular, and Nephrology, suggesting that either these are most affected by rare diseases, or that there were disease non-specific ascertainment factors.Conclusions: The preliminary analysis of the first 5-year's data provides unique and valuable insight on rare disease distribution in China, and higlights the directions for enhancing equity, scale and utility. [ABSTRACT FROM AUTHOR]

Background: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute.Methods: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters.Results: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients.Conclusion: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients. [ABSTRACT FROM AUTHOR]

Background: The malaria elimination plan of the Greater Mekong Subregion (GMS) is jeopardized by the increasing number of Plasmodium vivax infections and emergence of parasite strains with reduced susceptibility to the frontline drug treatment chloroquine/primaquine. This study aimed to determine the evolution of the P. vivax multidrug resistance 1 (Pvmdr1) gene in P. vivax parasites isolated from the China–Myanmar border area during the major phase of elimination. Methods: Clinical isolates were collected from 275 P. vivax patients in 2008, 2012–2013 and 2015 in the China–Myanmar border area and from 55 patients in central China. Comparison was made with parasites from three border regions of Thailand. Results: Overall, genetic diversity of the Pvmdr1 was relatively high in all border regions, and over the seven years in the China–Myanmar border, though slight temporal fluctuation was observed. Single nucleotide polymorphisms previously implicated in reduced chloroquine sensitivity were detected. In particular, M908L approached fixation in the China–Myanmar border area. The Y976F mutation sharply decreased from 18.5% in 2008 to 1.5% in 2012–2013 and disappeared in 2015, whereas F1076L steadily increased from 33.3% in 2008 to 77.8% in 2015. While neutrality tests suggested the action of purifying selection on the pvmdr1 gene, several likelihood-based algorithms detected positive as well as purifying selections operating on specific amino acids including M908L, T958M and F1076L. Fixation and selection of the nonsynonymous mutations are differently distributed across the three border regions and central China. Comparison with the global P. vivax populations clearly indicated clustering of haplotypes according to geographic locations. It is noteworthy that the temperate-zone parasites from central China were completely separated from the parasites from other parts of the GMS. Conclusions: This study showed that P. vivax populations in the China–Myanmar border has experienced major changes in the Pvmdr1 residues proposed to be associated with chloroquine resistance, suggesting that drug selection may play an important role in the evolution of this gene in the parasite populations. [ABSTRACT FROM AUTHOR]

Introduction: The health impact of retirement is controversial. Most previous studies have been based on self-reported health indicators or the endpoints of some chronic diseases (e.g., morbidity or mortality), but objective physiological indicators (e.g., blood pressure) have rarely been used. The objective of this study is to elucidate the health effects of retirement on blood pressure, thereby offering empirical evidence to facilitate the health of retirees and to optimize retirement policies., Methods: From 2012 to 2015, 84,696 participants of the Chinese Hypertension Survey (CHS) were included in this study. We applied the fuzzy regression discontinuity design (FRDD) to identify retirement's causal effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure. We also explored the heterogeneity in the effects of retirement across different sex and education level groups., Results: Based on the fully adjusted model, we estimated that retirement increased SBP by 5.047 mm Hg (95% CI: -2.628-12.723, P value: 0.197), DBP by 0.614 mm Hg (95% CI: -3.879-5.108, P value: 0.789) and pulse pressure by 4.433 mm Hg (95% CI: -0.985-9.851, P value: 0.109). We found that retirement led to a significant increase in male participants' SBP and pulse pressure as well as a possible decrease in female participants' blood pressure. Additionally, the blood pressure levels of low-educated participants were more vulnerable to the shock of retirement., Conclusion: Retirement is associated with an increase in blood pressure level. There is a causal relationship between the increase in blood pressure levels of men and retirement. Policy-makers should pay extra attention to the health status of men and less educated people when adjusting retirement policies in the future., (© 2024. The Author(s).)

Background: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function., Methods: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient., Results: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test., Conclusion: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH., (© 2024. The Author(s).)

Background: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss., Methods: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing., Results: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency., Conclusions: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2., (© 2024. The Author(s).)

Background and Objective: End-tidal PCO 2 (PetCO 2 ) patterns during exercise testing as well as ventilatory equivalents for CO 2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO 2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET)., Methods: 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls., Results: PetCO 2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO 2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO 2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO 2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO 2 at peak. PetCO 2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PeakVO 2 %pred correlated significantly with PetCO 2 at rest (r = 0.477, P < 0.001), AT (r = 0.609, P < 0.001) and peak exercise (r = 0.576, P < 0.001) in IPAH. N-terminal natriuretic peptide type-B (NT-proBNP) also correlated markedly with PetCO 2 , with a correlation coefficient of - 0.326 to - 0.427 (all P < 0.001). Additionally, PetCO 2 at rest, at AT and at peak correlated positively with peakVO 2 %pred and showed an inverse correlation with NT-proBNP in CTEPH patients (all P < 0.05)., Conclusions: PetCO 2 during exercise in IPAH and CTEPH patients was significantly different from normal subjects. Moreover, PetCO 2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PetCO 2 was progressively more abnormal with increasing disease severity according to peakVO 2 %pred and WHO-Fc., (© 2022. The Author(s).)

Background: Cardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aims to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively by these two methods. Moreover, the research assesses the predictive value of CPET and PFT parameters for severe CTEPH., Methods: We used data from 86 patients with CTEPH (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET data of CTEPH patients of different severity classified according to pulmonary artery pressure (PAP) (mm Hg) were collected and compared. Logistic regression analysis was performed to appraise the predictive value of each PFT and CPET parameter for severe CTEPH. The performance of CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves., Results: Data showed that minute ventilation at anaerobic threshold (VE @ AT) (L/min) and oxygen uptake at peak (VO 2 @ peak) (mL/kg/min) were independent predictors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of VE @ AT (L/min) and VO 2 @ peak (mL/kg/min) in identifying severe CTEPH was found to be moderate with the area under ROC curve (AUC) of 0.769 and 0.740, respectively. Furthermore, the combination of VE @ AT (L/min) and VO 2 @ peak (mL/kg/min) had a moderate utility value in identifying severe CTEPH with the AUC of 0.843., Conclusion: Our research suggests that CPET and PFT can noninvasively and effectively evaluate, monitor and predict the severity of CTEPH., (© 2021. The Author(s).)

Background: Kernel development and starch formation are the primary determinants of maize yield and quality, which are considerably influenced by drought stress. To clarify the response of maize kernel to drought stress, we established well-watered (WW) and water-stressed (WS) conditions at 1-30 days after pollination (dap) on waxy maize (Zea mays L. sinensis Kulesh)., Results: Kernel development, starch accumulation, and activities of starch biosynthetic enzymes were significantly reduced by drought stress. The morphology of starch granules changed, whereas the grain filling rate was accelerated. A comparative proteomics approach was applied to analyze the proteome change in kernels under two treatments at 10 dap and 25 dap. Under the WS conditions, 487 and 465 differentially accumulated proteins (DAPs) were identified at 10 dap and 25 dap, respectively. Drought induced the downregulation of proteins involved in the oxidation-reduction process and oxidoreductase, peroxidase, catalase, glutamine synthetase, abscisic acid stress ripening 1, and lipoxygenase, which might be an important reason for the effect of drought stress on kernel development. Notably, several proteins involved in waxy maize endosperm and starch biosynthesis were upregulated at early-kernel stage under WS conditions, which might have accelerated endosperm development and starch synthesis. Additionally, 17 and 11 common DAPs were sustained in the upregulated and downregulated DAP groups, respectively, at 10 dap and 25 dap. Among these 28 proteins, four maize homologs (i.e., A0A1D6H543, B4FTP0, B6SLJ0, and A0A1D6H5J5) were considered as candidate proteins that affected kernel development and drought stress response by comparing with the rice genome., Conclusions: The proteomic changes caused by drought were highly correlated with kernel development and starch accumulation, which were closely related to the final yield and quality of waxy maize. Our results provided a foundation for the enhanced understanding of kernel development and starch formation in response to drought stress in waxy maize., (© 2021. The Author(s).)

Background: Primary hyperoxaluria(PH)is a rare autosomal recessive genetic disease that contains three subtypes (PH1, PH2 and PH3). Approximately 80% of PH patients has been reported as subtype PH1, this subtype of PH has been related to a higher risk of renal failure at any age. Several genetic studies indicate that the variants in gene AGXT are responsible for the occurrence of PH1. However, the population heterogeneity of the variants in AGXT makes the genetic diagnosis of PH1 more challenging as it is hard to locate each specific variant. It is valuable to have a complete spectrum of AGXT variants from different population for early diagnosis and clinical treatments of PH1., Case Presentation: In this study, We performed high-throughput sequencing and genetic analysis of a 6-year-old male PH1 patient from a Chinese family. Two variants (c.346G > A: p.Gly116Arg; c.864G > A: p.Trp288X) of the gene AGXT were identified. We found a nonsense variant (c.864G > A: p.Trp288X) that comes from the proband's mother and has never been reported previously. The other missense variant (c.346G > A: p.Gly116Arg) was inherited from his father and has been found previously in a domain of aminotransferase, which plays an important role in the function of AGT protein. Furthermore, we searched 110 pathogenic variants of AGXT that have been reported worldwide in healthy local Chinese population, none of these pathogenic variants was detected in the local genomes., Conclusions: Our research provides an important diagnosis basis for PH1 on the genetic level by updating the genotype of PH1 and also develops a better understanding of the variants in AGXT by broadening the variation database of AGXT according to the Chinese reference genome.

Background: Psychological distress is highly prevalent among migraineurs during public health emergencies. The coronavirus disease 2019 (nCOV-2019) has created mass panic in China due to its highly contagious by contact and aerosols and lack of effective treatment. However, the emotion status of migraineurs stayed unclear during the nCOV-2019 outbreak., Objective: To understand psychological distress of migraineurs by comparing with common population and identify potential high-risk factors of severe psychological distress among migraine patients., Method: We enrolled the migraineurs treated at the department of Neurology of West China Hospital and healthy controls with age- and sex-matched to migraineurs. Data on clinicodemographics and psychological distress in the month of February 2020 (during in the nCOV-2019 outbreak in China) were collected. We used the Kessler 6-item (K-6) scale to assess psychological distress. Potential risk factors of severe psychological distress were identified using univariate and multivariate logistic regression., Results: The 144 migraineurs and 150 controls were included in the study. Migraineurs showed significantly higher K-6 scores than controls (P < 0.001). Migraine attack frequency in previous 30 days and time spent paying attention to outbreak showed significant in multivariate logistic regression with respective odds ratios of 2.225 (95%CI 1.361-3.628, P = 0.001) and 1.589 (95% 1.117-2.26, P = 0.01)., Conclusion: During public health outbreaks, healthcare professionals should focus not only on controlling and reducing migraine attack but also on mental health of migraineurs, especially those with high frequency migraine attack.

Background: Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). HAP2/GCS1, a TBV candidate, is critical for fertilization in Plasmodium. Here, the genetic diversity of PvHAP2 was studied in Plasmodium vivax parasite populations from the Greater Mekong Subregion (GMS)., Methods: Plasmodium vivax clinical isolates were collected in clinics from the China-Myanmar border region (135 samples), western Thailand (41 samples) and western Myanmar (51 samples). Near full-length Pvhap2 (nucleotides 13-2574) was amplified and sequenced from these isolates. Molecular evolution studies were conducted to evaluate the genetic diversity, selection and population differentiation., Results: Sequencing of the pvhap2 gene for a total of 227 samples from the three P. vivax populations revealed limited genetic diversity of this gene in the GMS (π = 0.00036 ± 0.00003), with the highest π value observed in Myanmar (0.00053 ± 0.00009). Y133S was the dominant mutation in the China-Myanmar border (99.26%), Myanmar (100%) and Thailand (95.12%). Results of all neutrality tests were negative for all the three populations, suggesting the possible action of purifying selection. Codon-based tests identified specific codons which are under purifying or positive selections. Wright's fixation index showed low to moderate genetic differentiation of P. vivax populations in the GMS, with F ST ranging from 0.04077 to 0.24833, whereas high levels of genetic differentiation were detected between the China-Myanmar border and Iran populations (F ST = 0.60266), and between Thailand and Iran populations (F ST = 0.44161). A total of 20 haplotypes were identified, with H2 being the abundant haplotype in China-Myanmar border, Myanmar and Thailand populations. Epitope mapping prediction of Pvhap2 antigen showed that high-score B-cell epitopes are located in the S307-G324, L429-P453 and V623-D637 regions. The E317K and D637N mutations located within S307-G324 and V623-D637 epitopes slightly reduced the predicted score for potential epitopes., Conclusions: The present study showed a very low level of genetic diversity of pvhap2 gene among P. vivax populations in the Greater Mekong Subregion. The relative conservation of pvhap2 supports further evaluation of a Pvhap2-based TBV.

Background: Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by infection of the larval stage of tapeworm Echinococcus granulosus. In human CE, the parasites develop and form cysts in internal organs. The differentiated cysts can be classified into five types based on WHO-IWGE standard CE1-5 representing different developmental stages. Infection with E. granulosus triggers hosts' humoral and cellular response, displaying elevated serum antibodies and Th1 and Th2 cytokines, which are presumed to be in association with the disease outcome. Identification of immunological markers for evaluation of disease progression has been a growing concern. However, the distinctive profile of cytokines and antibodies associated with the cyst progression has not been ascertained., Methods: To better understand the interaction between host immune response and disease outcome, the present study followed-up four CE patients over three years by yearly measuring serum level of 27 cytokines, total IgG and isotypes, and ultrasound scanning, beginning in year 1 for all patients with CE1 and CE2 cysts before treatment and continued in year 2 with CE4 and in year 3 with CE3-CE5 post-treatment., Results: Nine cytokines including Th1-type IL-2, Th17-type IL-17A, and inflammatory cytokines IL-1β, IL-1Rα and TNF-α, chemokines IL-8, MIP-1α, MIP-1β, and growth factor G-CSF were significantly elevated in patients with cyst type CE1, compared to the normal controls, and then declined to a normal level at CE4 and CE5. Examining the antibody production, we found that serum specific IgG was significantly increased in patients with active and transitional cysts, specifically the total IgG at CE1/CE3/CE4-CE5, IgG4 at CE1 and IgG1 at CE1/CE3 cyst status, in comparison with the normal controls, but showed no significant changes between the cyst stages., Conclusions: Our findings provide new information on the profile of multiplex cytokines and serum antibodies associated with cyst stages in cystic echinococcosis patients through a three-year follow-up, implying that further studies using an approach combining cyst-associated immune parameters may aid in identifying immunological markers for differentiation of disease progression.

Background: Warfarin therapies not only are used to prevent stroke in patients with high risk of cardioembolism such as patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), but also was associated with lower stroke severity and more favorable functional outcomes in patients with acute ischemic stroke due to middle cerebral artery occlusion. It was speculated that pre-stroke warfarin may promote collateralization and result in reduced stroke severity. This study aimed to investigate the association between pre-stroke warfarin use and leptomeningeal collaterals in patients with acute ischemic stroke due to occlusion of the middle cerebral artery., Methods: We enrolled consecutive acute ischemic stroke patients (occlusion of the middle cerebral artery within 24 h) with known history of AF and/or RHD at the neurology department of the West China Hospital from May 2011 to April 2017. Computed tomography angiography (CTA) before treatment was used to detect the thrombus. Regional leptomeningeal collateral (rLMC) score based on CTA images was used to assess collateral circulation. Prior use of warfarin was recorded. Univariate and multivariate analyses were performed to detect the association of prior warfarin use with the collateral circulation., Results: A total of 120 patients were included; 29 (24.2%) were taking warfarin before stroke. The international normalized ratio (INR) in patients with prior warfarin use was 1.53 ± 1.00, compared with 1.02 ± 0.09 in patients without prior warfarin use (P < 0.001). Prior oral warfarin therapy was inversely associated with poor rLMC (OR = 0.07, 95%CI 0.01-0.44, P = 0.005). There were no associations between prior warfarin use and initial stroke severity or functional outcomes at 3 months., Conclusion: Warfarin use seems improve collateralization in patients with acute stroke. However, clinical controlled studies should be used to verify this claim.

Background: Guangxi is the province most seriously affected by rabies virus (RABV) in China. Those most affected by RABV each year are people in rural areas, where dogs are the main cause of human infection with the virus., Methods: In this study, we established a rabies vaccination demonstration program that included eradication, core, and peripheral areas. This program was implemented for 9 years and comprised three stages: 12 counties in the first stage (2008-2010), 21 counties in the second stage (2011-2013), and then extending to all counties of Guangxi Province in the third stage (2014-2016). The program included a dog vaccination campaign, surveillance of clinically healthy dogs who may be potential RABV carriers, monitoring anti-RABV antibody titers in vaccinated dogs, and compiling and reporting statistics of human rabies cases., Results: The target effectiveness was achieved in the eradication, core, and peripheral areas in all three stages. The vaccination demonstration program successfully promoted RABV vaccination of domestic dogs throughout Guangxi Province by drawing upon the experience gained at key points. Compared with a vaccination coverage rate of 39.42-46.85% in Guangxi Province overall during 2003-2007, this rate gradually increased to 48.98-52.67% in 2008-2010, 60.24-69.67% in 2011-2013, and 70.09-71.53% in 2014-2016, thereby meeting World Health Organization requirements. The total cases of human rabies in the province decreased from 602 in 2004 to 41 cases in 2017., Conclusions: The present pilot vaccination program obviously increased the rabies vaccination and seroconversion rates, and effectively reduced the spread of rabies from dogs to humans as well as the number of human rabies cases, thus successfully controlling rabies in Guangxi.

Background: Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis., Methods: By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis., Results: We identified MYO15A c.IVS25+3G>A and c.8375 T>C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls., Conclusions: Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A.

Background: Intestinal parasite infections (IPIs) are among the most significant causes of illness and disease of socially and economically disadvantaged populations in developing countries, including rural areas of the People's Republic of China. With the spread of the human immunodeficiency virus (HIV) among rural Chinese populations, there is ample scope for co-infections and there have been increasing fears about their effects. However, hardly any relevant epidemiological studies have been carried out in the country. The aim of the present survey was to assess the IPI infection status among a representative sample of HIV-positive Chinese in rural Anhui province, and compare the findings with those from a cohort of non-infected individuals., Methods: A case control study was carried out in a rural village of Fuyang, Anhui province, China. Stool samples of all participants were examined for the presence of intestinal parasites. Blood examination was performed for the HIV infection detection and anemia test. A questionnaire was administered to all study participants., Results: A total of 302 HIV positive and 303 HIV negative individuals provided one stool sample for examination. The overall IPI prevalence of intestinal helminth infections among HIV positives was 4.3% (13/302) while it was 5.6% (17/303) among HIV negatives, a non-significant difference. The prevalence of protozoa infections among HIV positives was 23.2% while the rate was 25.8% among HIV negatives. The species-specific prevalences among HIV positives were as follows: 3.6% for hookworm, 0.7% for Trichuris trichiura, zero for Ascaris lumbricoides, 0.3% for Clonorchis sinensis, 1.3% for Giardia intestinalis, 16.2% for Blastocystis hominis, 1.7% for Entamoeba spp. and 8.3% for Cryptosporidium spp.. Cryptosporidium spp. infections were significantly more prevalent among HIV positives (8.3%) compared to the HIV negative group (3.0%; P < 0.05). Among people infected with HIV, Cryptosporidium spp. was significantly more prevalent among males (12.6%) than females (4.4%; P < 0.05). According to multivariate logistic regression, the factors significantly associated with parasite infections of the people who were HIV positive included sex (male: OR = 6.70, 95% CI: 2.030, 22.114), younger age (less than 42 years old: OR = 4.148, 95% CI: 1.348, 12.761), and poor personal hygiene habits (OR = 0.324, 95% CI: 0.105, 0.994)., Conclusions: HIV positive individuals are more susceptible to co-infections with Cryptosporidium spp. than HIV negative people, particularly younger males with poor personal hygiene habits, indicating a need for targeted hygiene promotion, IPI surveillance and treatment.

Background: Rabies virus (RABV) can infect many different species of warm-blooded animals. Glycoprotein G plays a key role in viral pathogenicity and neurotropism, and includes antigenic domains that are responsible for membrane fusion and host cell receptor recognition., Case Presentation: A case of buffalo rabies in China was diagnosed by direct fluorescent antibody test, G gene reverse-transcriptase polymerase chain reaction, and RABV mouse inoculation test. Molecular characterization of the RABV was performed using DNA sequencing, phylogenetic analysis and amino acid sequence comparison based on the G gene from different species of animals., Conclusion: The results confirmed that the buffalo with suspected rabies was infected by RABV, which was genetically closely related to HNC (FJ602451) that was isolated from cattle in China in 2007. Comparison of the G gene among different species of animal showed that there were almost no amino acid changes among RABVs isolated from the same species of animals that distributed in a near region. However, there were many changes among RABVs that were isolated from different species of animal, or the same species from different geographic regions. This is believed to be the first case report of buffalo rabies in China, and the results may provide further information to understand the mechanism by which RABV breaks through the species barrier.