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Background: Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID‐19 that is available only on the Chinese market. Despite being recommended for treating COVID‐19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID‐19 outcomes and its safety. Methods: We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID‐19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T‐FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS‐I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence. Results: The meta‐analysis included 24 retrospective studies involving a total of 11 830 patients. Low‐certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76–1.08) or LOHS (WMD = −0.24, 95% CI: −0.83 to 0.35) between FNC and Paxlovid in COVID‐19 patients. Low‐certainty evidence shows that the T‐FNANC was longer (WMD = 1.95, 95% CI: 0.36–3.53). Compared with the Paxlovid group, low‐certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63–0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46–0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID‐19 patients (OR = 0.61, 95% CI: 0.51–0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50–0.91), and very low certainty evidence shows significantly decreased the T‐FNANC (WMD = −4.62, 95% CI: −8.08 to −1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = −0.70, 95% CI: −3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48–8.17). Conclusions: FNC appears to be a safe and potentially effective treatment for COVID‐19 in China, but further research with larger, high‐quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are applicable worldwide. Trial Registration: PROSPERO number: CRD42024520565 [ABSTRACT FROM AUTHOR]

Aim: Intracoronary murmur results from turbulent flow due to coronary artery narrowing. This study evaluated the diagnostic performance of a method for acoustic analysis of turbulent murmur caused by coronary artery stenosis in coronary artery disease (CAD) in Chinese populations. Method: Patients admitted to the cardiovascular department of the Sixth Medical Center of the Chinese People's Liberation Army General Hospital between September 2021 and June 2022 for elective coronary angiography were prospectively enrolled. A digital electronic stethoscope was used to record heart sounds before angiography. Quantitative coronary angiography (QCA) served as the "gold standard" for CAD diagnosis to evaluate the diagnostic performance of the acoustic analysis method for CAD. Results: A total of 452 patients had complete QCA and heart sound data. The final interpretation results of the acoustic analysis method indicated 310 disease cases and 142 normal results. Increasing the cut-off values of coronary artery diameter stenosis from 30% to 50%, 70%, and 90% increased the sensitivity and NPV of the acoustic analysis method; the sensitivity was 75.6%, 81.9%, 83.3%, and 85.7%, respectively; the NPV was 33.1%, 57.0%, 69.7%, and 88.0%, respectively; the specificity and PPV decreased (specificity of 75.8%, 70.4%, 51.0%, and 37.5%, respectively; PPV of 95.2%, 89.0%, 69.4%, and 32.9%, respectively); and the AUC values were 0.757, 0.762, 0.672, and 0.616, respectively. The sensitivity of the acoustic analysis method for one-vessel disease was 86.6% when the cut-off value was 50%. The sensitivity for identifying left anterior descending coronary artery lesions was best, at 90.7%. The sensitivity for identifying isolated coronary artery branch lesions was 66.7%, whereas the sensitivity for identifying three-vessel disease in multi-vessel coronary artery lesions was better, at 82.9%. Conclusion: Acoustic analysis of turbulent murmur caused by coronary artery stenosis for diagnosis of CAD may have favorable performance in the Chinese population. This method has good performance in CAD diagnosis with a cut-off coronary artery diameter for stenosis of 50%. [ABSTRACT FROM AUTHOR]

Background: Single-balloon enteroscopy (SBE) is a valuable but difficult modality for the diagnosis and treatment of small-bowel disease. The water exchange method has the advantage of facilitating intubation during colonoscopy. Here, we evaluated the effects of water exchange on procedure-related variables related to SBE.Methods: This randomized controlled trial was conducted in a tertiary-care referral center in China. Patients due for attempted total enteroscopy were randomly allocated to undergo water exchange-assisted (water exchange group) or carbon dioxide-insufflated enteroscopy (CO2 group). All patients were planned to undergo both anterograde and retrograde procedures. The primary outcome was the total enteroscopy rate. Secondary outcomes included the maximal insertion depth, positive findings, procedural time, and adverse events.Results: In total, 110 patients were enrolled, with 55 in each group. Baseline characteristics between the two groups were comparable. Total enteroscopy was achieved in 58.2 % (32/55) of the water exchange group and 36.4 % (20/55) of the control group (P = 0.02). The mean (standard deviation) estimated intubation depth was 521.2 (101.4) cm in the water exchange group and 481.6 (95.2) cm in the CO2 group (P = 0.04). The insertion time was prolonged in the water exchange group compared with the CO2 group (178.9 [45.1] minutes vs. 154.2 [27.6] minutes; P < 0.001). Endoscopic findings and adverse events were comparable between the two groups.Conclusions: The water exchange method improved the total enteroscopy rate and increased the intubation depth during SBE. The use of water exchange did not increase the complications of enteroscopy. [ABSTRACT FROM AUTHOR]

Nearly half of the tailings dams in China are in a state of high-security risks and overservice, and the safety of these tailings dams has always been a concern for relevant scholars. The seepage characteristics of tailings are one of the essential factors affecting the safety of tailings dam. Now, due to the improvement of mineral processing technology, there are many fine tailings dam; the study of the seepage characteristics of the tailings dam is no longer applicable. Fine-grained tailings form uneven deposition in these tailings dams, resulting in the permeability of tailings not conforming to the previous law. Therefore, it is of great significance to study the permeability of fine-grained tailings with uneven deposition. In this paper, the physical model of the simulated tailings dam is established to study the influence of the dry beach slope on the distribution and deposition law of fine tailings during discharge. The test results show that the average particle size of tailings decreases along the length of dry beach, showing the phenomenon of coarsening upstream and thinning downstream. Then, based on the data of fine tailings deposition, the variation characteristics of the permeability coefficient of layered tailings under stable and unstable seepage conditions are studied. The test results show that the variation process of tailings permeability coefficient can be divided into four stages: rapid compaction stage, slow compaction stage, failure stage, and stable stage. Under stable and unstable seepage conditions, the permeability coefficients of unstratified tailing sand are about 10% and 15% higher, respectively, than those in the initial state. The permeability coefficient of layered tailings formed by uneven settlement changes more obviously, which is about 12% and 20% higher than the initial state. [ABSTRACT FROM AUTHOR]

Background: A novel enveloped RNA beta coronavirus, Corona Virus Disease 2019 (COVID-19) caused severe and even fetal pneumonia in China and other countries from December 2019. Early detection of severe patients with COVID-19 is of great significance to shorten the disease course and reduce mortality. Methods: We assembled a retrospective cohort of 80 patients (including 56 mild and 24 severe) with COVID-19 infection treated at Beijing You'an Hospital. We used univariable and multivariable logistic regression analyses to select the risk factors of severe and even fetal pneumonia and build scoring system for prediction, which was validated later on in a group of 22 COVID-19 patients. Results: Age, white blood cell count, neutrophil, glomerular filtration rate, and myoglobin were selected by multivariate analysis as candidates of scoring system for prediction of disease severity in COVID-19. The scoring system was applied to calculate the predictive value and found that the percentage of ICU admission (20%, 6/30) and ventilation (16.7%, 5/30) in patients with high risk was much higher than those (2%, 1/50; 2%, 1/50) in patients with low risk (p = 0.009; p = 0.026). The AUC of scoring system was 0.906, sensitivity of prediction is 70.8%, and the specificity is 89.3%. According to scoring system, the probability of patients in high risk group developing severe disease was 20.24 times than that in low risk group. Conclusions: The possibility of severity in COVID-19 infection predicted by scoring system could help patients to receiving different therapy strategies at a very early stage. Topic: COVID-19, severe and fetal pneumonia, logistic regression, scoring system, prediction. [ABSTRACT FROM AUTHOR]

The interfacial bond between cement concrete base plate (CCBP) and asphalt concrete waterproofing layer (ACWL) is a weak portion in the newly developed Chinese high-speed railway ballastless track. The interface damage caused due to fluctuating temperature load and dynamic train load is one of the most critical problems in Northern China. This paper aims to investigate the interface damage evolution process under temperature load via experimental and simulation analysis. Full-scale transverse shear tests were performed to explore the interface bond-slip mode of the adjacent ACWL and CCBP. Then, a finite element model of a ballastless track structure was built and a cohesive zone model (CZM) was utilized to model the interface damage initiation, crack propagation, and delamination process under uniform/gradient temperature load. Furthermore, the dynamic response of the ballastless track where CCBP and ACWL were partly/totally debonded was investigated and compared with the perfectly bonded structure. The results demonstrate that bilinear CZM is capable of revealing the interface damage initiation, crack propagation, and delamination process under temperature load. The interface state between the adjacent CCBP and ACWL was greatly affected by temperature changes and the interface bonding state had a great impact on the dynamic response of ballastless track. [ABSTRACT FROM AUTHOR]

Neonicotinoid insecticides (NNIs) have attracted global concern due to its extensive use in agricultural activities and their potential risks to the animal and human health, however, there is limited knowledge on the regional traits and ecological risks of NNIs in the aquatic environments. We herein investigated the occurrence of NNIs within the midsection of Yangtze River in China, offering the inaugural comprehensive report on NNIs within this region. In this study, eleven NNIs were analyzed in 108 river water and sediment samples from three seasons (normal, dry and wet season). We detected a minimum of seven NNIs in the water and four NNIs in the sediment, with total concentrations ranging from 12.33 to 100.5 ng/L in water and 0.08–5.68 ng/g in sediment. The levels of NNIs in both river water and sediment were primarily influenced by the extent of agricultural activities. The estimated annual load of NNIs within the midsection of Yangtze River totaled 40.27 tons, April was a critical contamination period. Relative potency factor (RPF) analysis of the human exposure risk revealed that infants faced the greatest exposure risk, with an estimated daily intake of 11.27 ng kg−1∙bw∙d−1. We established the acute and chronic thresholds for aquatic organisms by employing the Species Sensitive Distribution (SSD) method (acute: 384.1 ng/L; chronic: 168.9 ng/L). Based on the findings from this study, 33% of the river water samples exceeded the chronic ecological risks thresholds, indicating the urgent need for intervention programs to guarantee the safety of the river for aquatic life in the Yangtze River Basin. [Display omitted] • The annual flux of NNIs was estimated to be 40.27 tons in the studied river. • The concentration of NNIs showed the trend of wet > normal > dry season. • Seasonal agricultural application was important source of NNIs in the area. • NNIs posed chronic risk to the aquatic organisms. [ABSTRACT FROM AUTHOR]

To explore contaminant concerns as a result of anthropogenic disturbance of the river system, this study provided the first extensive investigation of the contamination profiles, possible driving factors, and ecological risks of 40 target compounds including pharmaceuticals and personal care products (PPCPs), neonicotinoid pesticides (NNIs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) in sediments of the whole Yangtze River (the world's third longest river). Among these target compounds, PPCPs were the dominant contaminants with a total concentration (∑ 15 PPCPs) of 2.13–14.99 ng/g, followed by ∑ 7 PCBs (

T cell epitopes restricted by several protective HLA alleles, such as B*57, B*5801, B*27, B*51 and B*13, have been very well defined over the past two decades. We investigated 32 well-known T cell epitopes restricted by protective HLA molecules among 54 Chinese men who have sex with men (MSM) at the early stage of HIV-1 infection. Subjects in our cohort carrying protective HLA types did not exhibit slow CD4 T cell count decline (P = 0.489) or low viral load set points (P = 0.500). Variations occurred in 96.88% (31/32) of the known wild-type epitopes (rate 1.85–100%), and the variation rates of the strains of two CRF01_AE lineages were significantly higher than those of non-CRF01_AE strains (76.82% vs. 48.96%, P = 0.004; 71.27% vs. 8.96%, P = 0.025). Subjects infected with CRF01_AE exhibited relatively rapid disease progression (P = 0.035). Therefore, the lack of wild-type protective T cell epitopes restricted by classic protective HLA alleles in CRF01_AE HIV-1 strains may be one of the reasons why rapid disease progression is observed in Chinese MSM with HIV-1 infection. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the distribution of HLA-A genes and identify alleles related to cervical cancer.Materials and Methods: A total of 252 cervical cancer patients (56 Han ethnic and 196 Uyghur ethnic) and 213 controls (103 Han ethnic and 110 Uyghur ethnic) were recruited in this study. HLA-A alleles were examined by polymerase chain reaction with sequence-specific primers. The frequencies of different HLA-A alleles were compared between the two ethnic groups as well as patients and controls. The correlation of HLA-A frequencies with various clinical characteristics and short-term treatment efficacy was analyzed.Results: (1) Significantly higher frequencies of HLA-A*03:01 and HLA-A*03:02 and lower frequencies of HLA-A*11:01, HLA-A*24:02, and HLA-A*30:01 were observed in the Uyghur control groups than in Han control groups (P ≤ 0.05). (2) The frequency of HLA-A*01:01 in patients was significantly higher than controls. In contrast, the frequencies of HLA-A*30:01 and HLA-A*33:03 were lower in patients (P ≤ 0.05). (3) The frequency of HLA-A*30:01 in Han patients was lower than Han control group (P ≤ 0.05). However, there was no statistically significant in the frequency of HLA-A between Uyghur patients and controls (P > 0.05). (4) There was no significant association between HLA-A alleles and HPV16 or squamous cell carcinoma antigen levels (P > 0.05). (5) The frequency of HLA-A*30:01 allele in complete response + partial response group was higher than stable disease + progressive disease group (P ≤ 0.05).Conclusions: People from two ethnic groups displayed different HLA-A gene distribution. HLA-A*30:01 and HLA-A*33:03 alleles are the protective factors to cervical cancer patients from Xinjiang while HLA-A*01:01 serves as the susceptible gene. [ABSTRACT FROM AUTHOR]

This study aimed to assess the feasibility and long-term outcome of laparoscopic total mesorectal excision for middle and lower rectal cancer. Retrospective assessment was performed on 612 patients with middle and low rectal cancer in the surgery department of our hospital. Three-hundred and three patients underwent laparoscopic total mesorectal excision (LTME), and 309 patients underwent open TME (OTME). All the data regarding patient details, operative variables and the short- and long-term outcomes were collected and compared. The sphincter-preserving rates of the two groups were similar. The conversion rate in LTME was 2.31% (seven cases). Fourteen cases (6.67%) of protective diverting stoma were fashioned in the LTME group compared with 57 cases (26.64%) in the OTME group. The postoperative morbidity was the same in these two groups, while the postoperative period until bowel movement and hospital discharge was shorter in the LTME group (P < 0.01). The median follow-up period was 34 (6-81) months for the LTME group and 36 (6-81) months for the OTME group. Local recurrence rates, the five-year disease-free survival rate and the five-year overall survival rate showed no difference between the two groups. Laparoscopic surgery is feasible and safe in patients with middle and lower rectal caner and can provide favorable short-term and long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined., Objective: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes., Design: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395)., Setting: University teaching hospitals in Hong Kong, China, and Australia., Patients: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy., Intervention: Standard hemostatic treatment ( n  = 97) or OTSC ( n  = 93)., Measurements: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization., Results: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P  = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points])., Limitation: Clinicians were not blinded to treatment and the option of crossover treatment., Conclusion: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement., Primary Funding Source: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

Since the COVID-19 outbreak was detected and reported at the end of 2019, the pandemic continues worldwide, with public health authorities and the general public in each country struggling to balance safety and normal travel activities. However, the complex public health environment and the complexity of human behaviors, as well as the constant mutation of the COVID-19 virus, requires the development of theoretical and simulation tools to accurately model all segments of society. In this paper, an agent-based model is proposed, the model constructs the real geographical environment of Shanghai Huangpu District based on the building statistics data of Shanghai Huangpu District, and the real population data of Shanghai Huangpu District based on the data of China's seventh Population census in 2020. After incorporating the detailed elements of COVID-19 transmission and the real data of WHO, the model forms various impact parameters. Finally, the model was validated according to the COVID-19 data reported by the official, and the model is applied to a hypothetical scenario. Shanghai is one of the places hardest hit by the current outbreak, Huangpu District is the "heart, window and name card" of Shanghai, and its importance to Shanghai is self-evident. so we used one-to-one population modeling to simulate the spread of COVID-19 in Huangpu District of Shanghai, In addition to the conventional functions of crowd movement, detection and treatment, the model also takes into account the burden of nucleic acid detection on the model caused by diseases similar to COVID-19, such as seasonal cold. The model validation results show that we have constructed a COVID-19 epidemic agent risk assessment system suitable for the individual epidemiological characteristics of COVID-19 in China, which can adjust and reflect on the existing COVID-19 epidemic intervention strategies and individual health behaviors. To provide scientific theoretical basis and information decision-making tools for effective prevention and control of COVID-19 and public health intervention in China.

Objective: Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age., Methods: We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China., Results: A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients., Conclusion: In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.

Background: The C allele of the interferon-induced transmembrane protein-3 ( IFITM3 ) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections. Cohort and Method: A total 99 young healthy volunteers (18-20 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years) were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point. Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1) but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers. Conclusion: IFITM3 -rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the young cohort. This suggests that compensatory mechanisms exist which might contribute to viral control in patients carrying the rs12252-CC genotype who do not become sick after flu infection. However, such a potential compensatory effect appears to be lost overtime, as evidenced in the elderly cohort. If this compensatory mechanism is lost, it may make the CC carrying elderly more susceptible to severe influenza infection.

Background: Genetic susceptibility is one of the major etiological factors for nasopharyngeal carcinoma (NPC). Among the genetic predisposing factors, human leukocyte antigen (HLA) genes have been reported to be associated with NPC. This study aimed to investigate the associations of HLA-DRB1 alleles with NPC and the clinical significance of HLA-DRB1 alleles in NPC., Methods: From January 2009 to December 2013, 140 NPC patients (118 Han patients and 22 Uyghur patients) and 158 healthy controls (81 Han individuals and 77 Uyghur individuals) from Xinjiang Province were genotyped for HLA-DRB1 using the polymerase chain reaction-sequence specific primer technique. Chi-square analysis was used when comparing allele frequencies between groups. The clinical outcomes were evaluated by Kaplan-Meier method and Cox regression model., Results: Compared with healthy controls, the allele frequency of HLA-DRB1*0701 was increased in the Uyghur patients (P = 0.008) but not in the Han patients (P = 0.869). HLA-DRB1*0101 allele was presented with higher frequency in clinical Stage I + II group compared with clinical Stage III + IV group in the Han patients (P = 0.015) but not in the Uyghur patients (P = 1.000). Higher frequency of HLA-DRB1*1501 allele was observed in patients aged <45 years compared with those in patients aged ≥45 years (P = 0.002). Neither HLA-DRB1*0701 nor HLA-DRB1*0101 had a statistically significant association with 3-year survival., Conclusions: This study found HLA-DRB1*0701 in Uyghur population was associated with an increased risk of developing NPC. In Han population, we found HLA-DRB1*0101 was associated with protection from disease progression, and HLA-DRB1*1501 was associated with early age of onset. HLA-DRB1 could not be identified as a prognostic indicator for NPC in either Han or Uyghur patients.

Background: Most HLA association studies with NPC focus on Southern part of China. Thus, little is known about the genetic association of HLA with NPC in people from Northern China where the genetic background, environmental factors, and lifestyle are very different., Methods: 132 NPC patients and 168 normal controls of Han ethnic in Xinjiang Province were genotyped for HLA-A, -B, -C, -DRB1, and -DQB1 using the PCR-sequence specific primer technique., Results: Our results confirm previous findings that the HLA-B∗46 and HLA-A(∗)02B(∗)46 haplotypes are strongly associated with NPC, but we did not observe HLA-A(∗)11 and -B(∗)35 association with resistance to NPC. Instead, we found that HLA-B(∗)51 and -A(∗)30 are strongly associated with resistance to NPC. In addition, HLA-A(∗)24 was also strongly associated with susceptibility to NPC., Conclusion: A unique pattern of HLA association with NPC susceptibility and resistance was found in patients from Xinjiang Province compared to the published data based on patients from Southern China and Taiwan. HLA-B(∗)46 is most significantly associated with NPC, and its frequency in endemic areas such as Guangdong Province, Taiwan, and Thailand is much higher than in Xinjiang Province and other areas with much less NPC occurrence. Interestingly, HLA-A(∗)30 is in contrast with the resistant allele, whose frequency is much lower in endemic areas but higher in Xinjiang and other areas with little NPC., (Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

We looked at our HIV + slow progressors cohort to determine if there were any human leukocyte antigen (HLA) correlates for protection. No statistically significant allelic differences were found between the HIV + and control cohorts using regression analysis, though trends were noted. Data for Elite Controllers showed an increased frequency of B*57. Likewise, no correlation was inferred with the clinical data of the HIV + cohort. We hypothesize that the protective effect of HLA alleles may have been lost over time.

The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. Here we report that the CC genotype is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. Specifically, the CC genotype was estimated to confer a sixfold greater risk for severe infection than the CT and TT genotypes. More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent.

Rationale: T-cell responses have been implicated in control and exacerbation of lung injury during influenza A virus (IAV) infection., Objectives: To examine the breadth and magnitude of influenza-specific CD4(+) and CD8(+) T-cell responses during acute phase of infection., Methods: Influenza-specific T-cell response to the entire pandemic H1N1/09 IAV proteome and T cell-related cytokine levels were measured in blood from previously healthy individuals with mild (n = 32) and severe (n = 16) IAV infection during the 2009 influenza pandemic. Virus-specific T-cell response in lung and blood was also performed in two acutely infected, severely ill patients using fluorescent-conjugated pdmH1N1/09 Matrix-MHC-I tetrameric complexes., Measurements and Main Results: Strong and broad CD4(+) but not CD8(+) T-cell responses were observed in the blood, and were higher in those with severe disease. Antigen-specific CD8(+) T cells in the lungs were on average 45-fold higher compared with blood in severely ill patients. Paradoxically, in patients with severe disease, IL-17, IL-2, IL-4, and IFN-γ levels were significantly decreased., Conclusions: High levels of circulating virus-specific CD4(+) T cells to two viral internal proteins (nucleoprotein and matrix) in the first phase of infection are associated with subsequent development of severe IAV infection. This finding could be an early and specific marker for ensuing clinical deterioration. Contrasting levels of antigen-specific CD8(+) T cells in lungs and blood have implications on design and analysis of clinical trials for T-cell vaccines because measurements of T cells in the periphery may not reflect events in the lungs.

Delayed HIV-1 disease progression is associated with a single nucleotide polymorphism upstream of the HLA-C gene that correlates with differential expression of the HLA-C Ag. This polymorphism was recently shown to be a marker for a protective variant in the 3'UTR of HLA-C that disrupts a microRNA binding site, resulting in enhanced HLA-C expression at the cell surface. Whether individuals with "high" HLA-C expression show a stronger HLA-C-restricted immune response exerting better viral control than that of their counterparts has not been established. We hypothesized that the magnitude of the HLA-C-restricted immune pressure on HIV would be greater in subjects with highly expressed HLA-C alleles. Using a cohort derived from a unique narrow source epidemic in China, we identified mutations in HIV proviral DNA exclusively associated with HLA-C, which were used as markers for the intensity of the immune pressure exerted on the virus. We found an increased frequency of mutations in individuals with highly expressed HLA-C alleles, which also correlated with IFN-γ production by HLA-C-restricted CD8(+) T cells. These findings show that immune pressure on HIV is stronger in subjects with the protective genotype and highlight the potential role of HLA-C-restricted responses in HIV control. This is, to our knowledge, the first in vivo evidence supporting the protective role of HLA-C-restricted responses in nonwhites during HIV infection.

Obstacles to developing an HIV-1 vaccine include extensive viral diversity and lack of correlates of protective immunity. High mutation rates allow HIV-1 to adapt rapidly to selective forces such as antiretroviral therapy and immune pressure, including HIV-1-specific CTLs that select viral variants which escape T-cell recognition. Multiple factors contribute to HIV-1 diversity, making it difficult to disentangle the contribution of CTL selection without using complex analytical approaches. We describe an HIV-1 outbreak in 231 former plasma donors in China, where a narrow-source virus that had contaminated the donation system was apparently transmitted to many persons contemporaneously. The genetic divergence now evident in these subjects should uniquely reveal how much viral diversity at the population level is solely attributable to host factors. We found significant correlations between pair-wise divergence of viral sequences and HLA class I genotypes across epitope-length windows in HIV-1 Gag, reverse transcriptase, integrase, and Nef, corresponding to sites of 140 HLA class I allele-associated viral polymorphisms. Of all polymorphic sites across these 4 proteins, 24%-56% were sites of HLA-associated selection. These data confirm that CTL pressure has a major effect on inter-host HIV-1 viral diversity and probably represents a key element of viral control.

Common pathogenic mechanisms may be involved in the prevalence of ischemic stroke and coronary heart disease. Recently, genome-wide association (GWA) studies identified a chromosome region (9p21) that confers the risk of coronary heart disease. In a hospital-based case-control study conducted in Chinese Hans, we tested the hypothesis that the methylthioadenosine phosphorylase (MTAP) gene on chromosome region 9p21 is involved in the aetiology of ischemic stroke using a tagging single nucleotide polymorphism (tSNP) strategy. We observed significant association of rs10118757 in the MTAP gene with ischemic stroke. The G allele of rs10118757 was associated with an increased risk of stroke, with a per-allele OR of 1.31(95% CI, 1.04-1.65, p=0.025). The association remains after controlling for confounding factors including age, gender, body mass index, smoking, alcohol drinking, hypertension, diabetes, and hyperlipidaemia (OR=1.38, 95 CI, 1.02-1.88, p=0.039). In addition, the GA+GG genotype of rs10118757 was associated with the increased risk of an undetermined subtype of ischemic stroke (OR=2.14, 95 CI, 1.35-3.38, p=0.001). Further, we also observed the combined effects of rs10118757 with alcohol drinking and hypertension, which increased the risk of ischemic stroke. Our observations support the hypothesis that the MTAP gene may be involved in the prevalence of ischemic stroke in Chinese Hans.

Background: To control HIV globally, a comprehensive understanding of host immunity to HIV in different human populations is needed. Relatively, little is known on the quantity and quality of HIV-specific T-cell responses in Chinese patients., Methods: We quantified HIV Gag-specific CD8+ and CD4+ T cells that are capable of producing interferon (IFN)-gamma and interleukin 2 and assessed their proliferative capacity in a cohort of 53 antiretroviral-naive chronically HIV-1-infected Chinese patients., Results: The proliferation of Gag-specific CD8+ T cells, but not their IFN-gamma or interleukin 2 production, was inversely proportional to HIV viral load and directly proportional to CD4+ T-cell counts. Gag-specific CD8+ T-cell proliferation was proportionate to the frequency of IFN-gamma-secreting CD8+ T cells. Such correlations, however, did not exist for Gag-specific CD4 T cells., Conclusions: These results suggest that good quality and large quantities of HIV Gag-specific T-cell responses are associated with virologic control in HIV-1-infected Chinese patients. We infer that protective T-cell vaccines tested in other populations should also provide benefit to the Chinese population.

In a hospital based case control study, we investigated the association of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and two genetic variants (rs10757274 and rs2383206) on chromosome region 9p21 with ischemic stroke in Chinese Hans. Two polymorphisms in the CDKN2A gene (rs3088440 and rs3731245) and two polymorphisms in the CDKN2B gene (rs3217992 and rs1063192) were selected by using a strategy of tagging single nucleotide polymorphisms (tSNP). We observed significant association of rs2383206 with ischemic stroke. Subjects with the GG/GA genotype of rs2383206 had a 1.51-fold (95%CI 1.11-2.05, p=0.009) increased risk of stroke, compared with those with the AA genotype. In addition, the GG/GA genotypes of rs2383206 and rs3731245 was associated with an increased risk of large vessel subtype and small vessel subtype of ischemic stroke, respectively, with ORs of 2.09 (95%CI 1.30-3.37, p=0.002) and 1.63 (95%CI 1.06-2.51, p=0.026), respectively. In gene-environmental interaction analysis, elevation of ischemic stroke risk was observed among AG+GG genotype carriers who consume alcohol, smoke cigarette, and have hypertension, with adjusted combined ORs of 2.86(1.51-5.41), 4.30(2.38-7.77), and 13.97(7.78-25.07), respectively, compared with low-risk individuals for rs2383206 (GG carriers who did not consume alcohol, smoke cigarette, and without hypertension). We provide evidence that genetic variants on chromosome region 9p21 may implicated in the prevalence of ischemic stroke in Chinese.

Background: To investigate epidemiology and HLA typing of highly exposed to HIV but persistently seronegative subjects (HEPS) in commercial blood donors in China., Methods: This was a cohort study for epidemiologic characteristics of highly exposed but persistently seronegative subjects. PCR with sequence-specific primer and PCR-SSP for HLA typing were applied., Results: Eight HEPS were identified. Compared HLA typing with seropositive couple, high frequency of HLA-a24, HLA-B40 genotyping was observed., Conclusion: Highly exposed to HIV but persistently seronegative subjects in commercial blood donors in China had high frequency of HLA-A24 and HLA-B40 genotype.