1.XK gene deletion leading to McLeod syndrome and high-frequency antigen antibodies: identification and transfusion strategy
Jing LI ; Kewen YAO ; Yun DU ; Haiyan HU ; Hongli ZHANG
Chinese Journal of Blood Transfusion 2025;38(8):1107-1112
Objective: To investigate the hematological characteristics of the rare McLeod phenotype associated with X-linked chronic granulomatous disease, KEL and XK gene analysis, identification of unexpected antibodies, serological characteristics of high-frequency antigen antibodies, and transfusion strategies. Methods: Serological methods were employed to determine the ABO, Rh, and other blood group system antigen phenotypes of the child, along with screening and identification of unexpected antibodies. The titers of high-frequency antigen antibodies were measured using tube antihuman globulin and microcolumn gel card techniques. Kell blood group typing was performed using serological and genotyping methods, while XK gene sequencing was conducted via next-generation sequencing. Peripheral blood smears from the child's mother were examined for erythrocyte morphology. Results: The child's serological results were as follows: blood group O, ccDEE, MM, Le(a-b+), JK(a+b+), Fy(a+b-), and Kell phenotype K-k+, Kp(a-b+). Plasma analysis revealed alloantibodies anti-C、e, as well as a high-frequency antigen antibody anti-KL, with titers of 512 (tube method) and 2 048 (microcolumn gel method). Genotyping results showed KEL genotype K-k+, Kp(a-b+), Js(a-b+), while XK gene NGS identified a hemizygous deletion of exons 1-3 (XK
N. 01), consistent with XK: -1 or Kx-(McLeod). The mother's peripheral blood smear exhibited prominent acanthocytes. Conclusion: The hematological features of this rare McLeod phenotype with X-CGD include weakened Kell antigen expression and a complete exon deletion in the XK gene. Early clinical attention should be given to the symptoms and laboratory diagnosis of X-linked chronic granulomatous disease in pediatric patients. XK genotyping for McLeod phenotype should be prioritized to guide cautious transfusion strategies, preventing life-threatening complications due to incompatible blood products.
2.Population pharmacokinetics of Ainuovirine and exposure-response analysis in human immunodeficiency virus-infected individuals
Xiaoxu HAN ; Jin SUN ; Yihang ZHANG ; Taiyi JIANG ; Qingshan ZHENG ; Haiyan PENG ; Yao WANG ; Wei XIA ; Tong ZHANG ; Lijun SUN ; Xinming YUN ; Hong QIN ; Hao WU ; Bin SU
Chinese Medical Journal 2024;137(20):2473-2482
Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).
3.Association between the triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular diseases in people living with human immunodeficiency virus: Evidence from a retrospectively cohort study 2005-2022
Liqin SUN ; Yinsong LUO ; Xinyun JIA ; Hui WANG ; Fang ZHAO ; Lukun ZHANG ; Bin JU ; Haiyan WANG ; Duo SHAN ; Yun HE ; Hongzhou LU ; Jiaye LIU
Chinese Medical Journal 2024;137(22):2712-2719
Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.
4.Genome sequences of H7N9 avian influenza virus in poultry-related environment in Henan Province in 2023
Bicong WU ; Xue LUO ; Shidong LU ; Yun SONG ; Baifan ZHANG ; Haiyan WEI ; Yifei NIE ; Hui XIA ; Sijia WAN ; Ying YE ; Xueyong HUANG ; Wanshen GUO ; Hongxia MA
Chinese Journal of Microbiology and Immunology 2024;44(5):377-381
Objective:To analyze the genetic evolution and molecular characteristics of H7N9 avian influenza virus (AIV) isolated in a live poultry market.Methods:Samples such as poultry feces, sewage, and hair removal machine and chopping board swabs were collected. Real-time fluorescent quantitative PCR was used to detect influenza A virus and H7N9 AIV in the samples. The whole genome of H7N9 AIV was amplified with influenza A virus universal primers and sequenced. BLAST and MEGA X were used for sequence alignment, phylogenetic analysis and molecular characterization.Results:Seven poultry-related environment samples were collected in the live poultry market in Xuchang city in February 2023, and four were positive for H7N9 AIV. The whole genome sequences of three H7N9 AIV isolates were successfully obtained, and the isolates shared high nucleotide identity in different genes (98.37%-100.00%). BLAST analysis showed they were highly identical to H7N9 strains isolated from domestic poultry in China from 2020 to 2021. Genetic evolution analysis showed that the three isolates clustered in the same branch and were closer to the recent environmental isolates than to the recent strains isolated from human or avian. Through comparison with the sequences of the representative strains in different periods, it was found that the isolated strains in this study showed high avian pathogenicity with four amino acids KRAA inserted at the cleavage site; the hemagglutinin receptor-binding site was QSG, which was an avian binding receptor; there was a G186I mutation in hemagglutinin. Mammalian-adaptive mutation E627K was not detected in polymerase basic protein 2. Mutations (R292K and I38T) associated with drug resistance to neuraminidase inhibitor (oseltamivir) and polymerase acidic protein inhibitor (baloshavir) were not detected, suggesting that these isolates remained susceptible to these drugs. A S31N mutation was found in M2 protein, indicating they were resistant to alkamines.Conclusions:The three H7N9 AIV strains isolated in the live poultry market have high avian pathogenicity, but there are no significant increase in mutations related to the binding ability to human receptors, mammalian pathogenicity, viral transmissibility, or drug resistance as compared with previous representative strains causing human or avian infection.
5.Anti-SARS-CoV-2 antibody levels in previously infected and re-infected populations in Henan Province, China
Yun SONG ; Shidong LU ; Bicong WU ; Haiyan WEI ; Wenhua WANG ; Yafei LI ; Xue LUO ; Jingjing PAN ; Hongxia MA ; Haifeng WANG ; Ying YE ; Wanshen GUO ; Xueyong HUANG
Chinese Journal of Microbiology and Immunology 2024;44(9):801-808
Objective:To analyze the reinfection rates in people previously infected with SARS-CoV-2 in Zhengzhou and Yuzhou cities (first infected with Delta/B.1.617.2 variant), and Anyang city (first infected with Omicron/BA.1.1 variant) in January 2022 and the population characteristics, and compare the differences in antibody levels among different populations.Methods:Serum samples were collected from 371 previously infected, 134 reinfected and 19 uninfected people for IgG antibody detection. Among them, serum samples from 45 previously infected, 44 reinfected and 19 uninfected people were tested with different novel coronavirus variants (early original strain, BA.5.2 variant, XBB.1.5 variant) for neutralizing antibody detection.Results:The rate of reinfection was 32.82% (85/259) in Zhengzhou and Yuzhou cities, and 19.92% (49/246) in Anyang city. The IgG antibody level in reinfected people was higher than that in previously infected and uninfected people ( P<0.05). The IgG antibody level in uninfected group was higher in people vaccinated within three months than in those vaccinated six months ago ( P<0.05). The IgG antibody level in the group receiving four doses of vaccine was higher than that in the group receiving three doses of vaccine ( P<0.05). The results of true virus neutralization antibody detection showed that in the Zhengzhou and Yuzhou cases, the level of neutralization antibody against the early original strain was higher than those against the BA.5.2 variant and the XBB.1.5 variant ( P<0.05), and the level of neutralizing antibody against BA.5.2 variant was higher than that against XBB.1.5 variant ( P<0.05). In Anyang city cases, the level of neutralizing antibody against the early original strain was higher than those against BA.5.2 variant and XBB.1.5 variant ( P<0.05); in the reinfected population, the level of neutralizing antibody against the early original strain was higher than that against the XBB.1.5 variant ( P<0.05). In addition, the levels of all neutralizing antibodies in both previously infected and reinfected people were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody in the infected population in Zhengzhou and Yuzhou cities was higher than that in the infected population in Anyang city and in uninfected population ( P<0.05). The levels of antibodies against BA.5.2 and anti-XBB.1.5 variants in infected people in Zhengzhou and Yuzhou cities were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody against BA.5.2 variants in the previously infected population in Anyang city was higher than that in the uninfected population ( P<0.05), and the level of neutralizing antibody against XBB.1.5 variants in the infected population in Anyang city was higher than that in the uninfected population ( P<0.05). Conclusions:After infection with SARS-CoV-2, the neutralizing antibodies produced in the human body have a certain cross-protection effect on other variants, but the antibody level will gradually decrease over time. Protection from a previous early SARS-CoV-2 variants infection against the current main circulating Omicron variants (such as XBB variants) is low, and the immunity conferred by pervious infection or booster vaccination may not be able to provide sufficient protection against new variants.
6.Ultrasound evaluation of respiratory muscle involvement in children with Duchenne muscular dystrophy
Xuan ZHANG ; Yun ZHANG ; Shuang CHEN ; Shiwen WU ; Yanfeng SUN ; Faqin LYU ; Haiyan KOU
Chinese Journal of Ultrasonography 2024;33(11):930-934
Objective:To study the ultrasonographic manifestations of intercostal muscle and diaphragm involvement in Duchenne muscular dystrophy (DMD) and their correlations with functional status, and to explore the pattern of muscle damage in patients with DMD and the potential role of ultrasonography in assessing disease progression.Methods:A total of 28 patients with DMD who received treatment in the Third Medical Centre of PLA General Hospital from May to December 2023 were prospectively collected as DMD group, and 28 healthy children matched in age and sex were included as controls for a prospective study.Diaphragm thickening fraction (DTF) and intercostal muscle thickening fraction (ICMTF) were measured by B-mode and M-mode ultrasonography, and the muscle gray values were recorded. The differences between groups were compared, and the values of DTF and ICMTF in evaluating the structural and functional changes of respiratory muscle were analyzed.Results:Compared with the control group, the gray value of respiratory muscle was significantly decreased in DMD group, the diaphragm and intercostal muscle were significantly thickened at the end of inspiratory and expiratory periods, DTF was significantly decreased, and ICMTF was significantly increased (all P<0.001). Conclusions:Ultrasound can evaluate the structural changes of respiratory muscle in DMD, so as to clarify the relationship between the structure and function of respiratory muscle in DMD patients.
7.Simultaneous detection of 34 emerging contaminants in tap water by HPLC-MS/MS and health risk assessment
Yixuan CAO ; Ziwei YUAN ; Xiaoxi MU ; Chenshan LV ; Haiyan CUI ; Tao WANG ; Zhiwen WEI ; Zhongbing CHEN ; Hongyan ZOU ; Keming YUN ; Meng HU
Chinese Journal of Forensic Medicine 2024;39(1):31-38
Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01~0.60 ng/L and the recoveries were between 60.7%and 119.8%.The intra-group precisions were between 0.05%~9.89%and the intra-day precisions were between 0.20%~14.40%for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84%),and the concentration range was ND~74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND~361.15 ng/L),where detection rate was 44%.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient<0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.
8.Correlation between diaphragmatic-rapid shallow breathing index and lung ultrasound score in elderly patients with mechanical ventilation and its predictive value for weaning results
Yun CHU ; Chuang GUO ; Haiyan FU
Chinese Critical Care Medicine 2024;36(2):152-155
Objective:To investigate the correlation between diaphragmatic-rapid shallow breathing index (D-RSBI) and lung ultrasound score (LUS) in elderly patients with mechanical ventilation and its predictive value for weaning results.Methods:A retrospective study was conducted. The clinical data of elderly patients (age > 60 years old) with invasive positive pressure ventilation (IPPV) admitted to the department of intensive care unit (ICU) of the First Affiliated Hospital of Jinzhou Medical University from January 2021 to June 2022 were enrolled. According to the outcome of withdrawal, the patients were divided into successful and failed groups. The differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), D-RSBI and LUS before weaning and extubation were compared between the two groups. Pearson correlation was used to analyze the correlation between D-RSBI and LUS. The predictive value of D-RSBI and LUS on weaning results of elderly patients with IPPV was analyzed by receiver operator characteristic curve (ROC curve).Results:A total of 398 elderly patients with IPPV were enrolled, including 300 successful weaning patients and 98 failed weaning patients. There were no significant differences in gender and age between the failed group and successful group [male: 55.1% (54/98) vs. 59.0% (177/300), age (years old): 67.02±5.03 vs. 66.96±4.99, both P > 0.05]. APACHEⅡ score in the failed group was significantly higher than that in the successful group (17.09±3.30 vs. 16.06±3.81, P < 0.05), and the D-RSBI and LUS score before extubation were significantly higher than those in the successful group [D-RSBI (time·min -1·mm -1): 2.19±0.33 vs. 1.60±0.22, LUS: 17.30±3.04 vs. 11.97±3.20, both P < 0.01]. All patients showed a significant positive correlation between D-RSBI and LUS score ( r = 0.406, P = 0.000). ROC curve analysis showed that the area under the curve (AUC) of D-RSBI for predicting weaning outcomes in elderly IPPV patients was 0.920, with a 95% confidence interval (95% CI) of 0.881-0.958 and P = 0.000. When the cut-off value was 1.85 times·min -1·mm -1, the sensitivity was 88.7% and the specificity was 86.7%. The AUC of LUS score for predicting weaning outcome in elderly IPPV patients was 0.875, with a 95% CI of 0.839-0.912 and P = 0.000. When the cut-off value was 14.50, the sensitivity was 75.7% and the specificity was 84.7%. Conclusion:There is a significant correlation between D-RSBI and LUS score in elderly mechanically ventilated patients, both of them can predict weaning outcome in elderly patients with mechanical ventilation.
9.Current Situation and Consideration of Refinement of Hospital Team Service based on Value-based Medicine
Jun DUAN ; Li YI ; Hanjie CHEN ; Chang LIU ; Yuhan DIAO ; Haiyan LIU ; Guixiang HE ; Jing MEI ; Yan LIU ; Yun CHEN
Chinese Hospital Management 2024;44(2):63-66
Objective To describe and analyze the current situation of the four same type of departments in an hospital in order to provide a reference for the construction of"the most cost-effective medical care".Methods The CN-DRG were used to automatically group and compare the medical capacity and inpatient service efficiency of the hospital department groups,and in the refined analysis,one DRG disease group of in situ cancer and non-malignant disease loss uterine surgery and single species uterine fibroid was included,and the Kruskal-Wallis H test was used to further compare the differences in length of stay and various costs.Results It included a total of 22630 patients,whose weights varied from a maximum of 3948.62 in diagnostic group 1 to a minimum of 133.55 in diagnostic group 11.The cost consumption indexes ranged from a minimum of 0.89 in diagnostic group 5 to a maximum of 1.04 in diagnostic group 2,while the time consumption indexes ranged from a minimum of 0.48 in diagnostic group 11 to a maximum of 0.81 in diagnostic group 5.When comparing the diagnostic groups,there were statistically significant differences(P<0.05)in hospitalization days,total cost,diagnostic cost,therapeutic cost,and cost of supplies.Specifically,when comparing the diagnostic and treatment groups within departments,the differences in hospitalization days and all costs were statistically significant(P<0.05)in departments 1 and 2,the differences in diagnostic cost,therapeutic cost,and cost of supplies were statistically significant(P<0.05)in department 3.Conclusion There exists a notable disparity in the extent to which each diagnostic and treatment group contributes to the hospital's service capacity and cost variability.Consequently,it is necessary to reasonably evaluate the length of hospital stay and medical cost of patients to achieve the highest cost-effective medical treatment.
10.Serological analysis of severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G antibodies level in Henan Province
Yujiao MU ; Haiyan WEI ; Yafei LI ; Yun SONG ; Shidong LU ; Bicong WU ; Ying YE ; Xueyong HUANG ; Hongxia MA
Chinese Journal of Infectious Diseases 2024;42(2):98-102
Objective:To analyze the specific immunoglobulin G (IgG) antibodies level in the population after the coronavirus disease 2019 (COVID-19) pandemic in Henan Province.Methods:A total of 5 178 peripheral venous blood samples were collected from 10 districts (counties) in Henan Province according to the national seroepidemiological survey program for COVID-19, and the method of cluster random sampling was adopted from March 6 to 15, 2023. Descriptive analysis was used for the basic data, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, SARS-CoV-2 infection of the respondents. The specific IgG antibody of SARS-CoV-2 was detected using chemiluminescence method. Statistical analysis was performed by using rank sum test, Kruskal Wallis test, and Dunn′s test.Results:The overall positive rate of SARS-CoV-2-specific IgG antibody was 83.35%(4 316/5 178). There were statistically significant differences in the specific IgG antibodies against SARS-CoV-2 produced by people of different sexes, different ages, infected or not, vaccinated or not, and vaccinated with different doses of SARS-CoV-2 vaccine ( Z=3.60, H=195.32, Z=6.10, 18.08, H=382.70, respectively, all P<0.001). The specific IgG antibodies produced by unvaccinated+ uninfected group, unvaccinated+ infected group, vaccinated+ uninfected group, and vaccinated+ infected group were 3.54(0.98, 11.00), 60.65(2.33, 84.80), 133.00(59.80, 173.00), and 142.00(98.30, 176.00), respectively. And the difference was statistically significant( H=354.62, P<0.001). The specific IgG antibodies of uninfected people increased with the increase of inoculum times( H=287.00 and 98.48, both P<0.001). The specific IgG antibodies of people who were not infected with SARS-CoV-2 in the groups of whose interval from the last inoculation of SARS-CoV-2 vaccine to blood collection was less than three months, three to six months and more than six months were 171.86(156.04, 196.57), 71.71(17.08, 110.38) and 132.14(57.59, 172.25), respectively, and the difference was statistically significant ( H=19.93, P<0.001). Among them, the absolute difference between the less than three months group and the three to six months group was statistically significant ( Z=3.67, P<0.001), and the absolute difference between the less than three months group and the more than six months group was statistically significant ( Z=3.47, P<0.001). The specific IgG antibodies level in the less than three months group was the highest. Conclusions:There is a certain correlation between the number of SARS-CoV-2 vaccine doses and the specific IgG antibodies level in uninfected people. The specific IgG antibodies could maintain a high level for three months after immunization.

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