1.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
2.Genetic analysis of a blood donor with combined FUT1 and ABO dual blood group gene variants resulting in para-Bombay and A 2 subtype blood types and a literature review
Ziyi HE ; Yingming HU ; Menghui BEI ; Xiaomei JIE ; Xianguo XU
Chinese Journal of Medical Genetics 2024;41(11):1379-1386
Objective:To investigate the serological and molecular genetic characteristics of a voluntary blood donor with combined FUT1 and ABO blood group gene variants causing para-Bombay and A2 subtype, and to review relevant literature on para-Bombay blood types carrying alleles such as FUT101W.37 and FUT101W.23. Methods:A blood donor with para-Bombay and A 2 subtype who participated in voluntary blood donation at the Dongguan Blood Center in August 2023 was selected as the study subject. Serological tests were performed to identify the ABO blood group, Lewis blood group antigens, and unexpected serum antibodies in the donor. Adsorption-elution test was conducted to detect trace antibodies in the blood donor′s plasma to trace the A, B and H antigens on the red blood cell surface. Sanger sequencing was carried out to analyze the sequences of the FUT1 and ABO genes. Using keywords such as " para-Bombay" " FUT1*01W.37" and " FUT1*01W.23" both in Chinese and English, relevant literature on para-Bombay blood type subjects carrying FUT1*01W.37 and FUT1*01W.23 alleles was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the retrieval time was set as from the establishment of database to December 2022. This study has been approved by the Ethics Committee of Dongguan Blood Center (No. 2022005), and informed consent of blood donation was obtained from the blood donor. Results:Serological testing of the blood donor revealed inconsistent results between forward and reverse ABO blood typing, negative H antigen on the red blood cell surface, Le(a-b+ ) secretor type for Lewis blood group, and unexpected anti-H antibodies in the plasma, indicating a suspected para-Bombay type. Absorption-elution test suggested the blood type of the blood donor to be para-Bombay and A subtype. Sanger sequencing showed that the donor has harbored homozygous FUT1*(c.35T+ c.803A)/(c.35T+ c.803A) variant, with the FUT1*(c.35T+ c.803A) allele containing a dual nucleotide variant unrecorded by the International Society of Blood Transfusion (ISBT) FUT1 gene variant database, which was similar to the weakly functional allele of FUT101W. 37(c.803G>A) as recorded by the ISBT database. The ABO genotype was heterozygous ABOA2.05/O.01.02. Combining the results of serological and genetic testing, the blood type of the blood donor was determined to be para-Bombay and A 2 subtypes. Literature review has identified a pregnant women from Qingdao carrying the FUT1*01W.37 allele and 2 individuals carrying a heterozygous FUT1*01W.23 allele. Conclusion:This study has discovered a blood donor with coexisting para-Bombay and ABO subtype blood groups. Based on the characteristics of red blood cell surface antigens, the FUT1*01W.37 as classified as an FUT1 null allele.
3.Homozygous variants of the new allele A4GALT result in rare p blood groups
Ziyi HE ; Yingming HU ; Guangping LUO ; Xiaomei JIE ; Menghui BEI ; Xianguo XU
Chinese Journal of Laboratory Medicine 2024;47(11):1345-1348
The proband was a 33-year-old pregnant woman (G4P1) who suffered spontaneous abortion in the first 3 months of pregnancy without a history of blood transfusion or transplantation. The fourth pregnancy was clinically diagnosed with threatened abortion, and a cesarean section was performed on June 28, 2023, at the Obstetrics and Gynecology Department of Dongguan Hospital of Traditional Chinese Medicine. During cross-matching tests, unexpected antibodies were detected in the proband′s plasma, which could not be specifically identified, and no suitable donor red blood cells could be found. The blood samples were sent to the Blood Transfusion Laboratory of Dongguan Blood Center. The laboratory used serology to identify the erythrocyte phenotype of the proband and confirmed the proband as having a rare p blood group. The unexpected antibody was identified as anti-PP1P K, and gene sequencing of the proband revealed that the new allele A4GALT* (c.100G>A+c.418_428delins) was homozygous, which is speculated to cause changes in the polypeptide chains p.Veral34ile and p.GERln140TRPFS *73, and inactivation of α1, 4-galactosyltransferase. At the same time, another new allele A4GALT*c.100G>A was found in family members, and it was predicted that the single change of p.Val34Ile caused by this mutation would not affect protein function or enzyme activity.
4.Application research of multiple intelligences theory combined with the ADDIE model in surgical clinical practice teaching
Yingming SONG ; Huiqing ZHANG ; Yanjun XU ; Liang WANG ; Chao HAN
Chinese Journal of Medical Education Research 2022;21(11):1553-1557
Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.
5.Para-Bombay phenotype due to bi-allelic heterozygous base deletions of FUT1 gene.
Ziyi HE ; Yingming HU ; Xianguo XU ; Yuanjun WU ; Siping CUI
Chinese Journal of Medical Genetics 2022;39(11):1290-1293
OBJECTIVE:
To explore the genetic mechanism underlying a case with para-Bombay phenotype.
METHODS:
The ABO and Lewis phenotype were identified with serological methods. The coding regions of exons 6 and 7 of the ABO and FUT1 genes were amplified with PCR and directly sequenced. Haploid sequence analysis was carried out on the variant sites of the FUT1 gene.
RESULTS:
Serological analysis confirmed that the proband has a rare para-Bombay phenotype. Direct sequencing revealed that he was a B.01/O.01.02 heterozygote for the ABO gene, and had heterozygous deletion for the 768 and 881-882 sites of the FUT1 gene. Further haploid analysis showed that the c.881_882delTT deletion has occurred in one haploid while c.768delC was present in the other haploid. The proband was therefore determined as a FUT1*01N.13/01N.20 heterozygote, which have resulted in frameshift in polypeptide chain p.Phe294Cysfs*40 and p.Val257Phefs*23, respectively.
CONCLUSION
A rare bi-allelic heterozygous deletion of para-Bombay phenotype has been identified in a blood donor. The c.881_882delTT and c.768delC deletions may decrease the activity of α-1,2-fucosyltransferase.
Animals
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Male
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ABO Blood-Group System/genetics*
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Alleles
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Fucosyltransferases/genetics*
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Genotype
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Heterozygote
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Mutation
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Phenotype
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Humans
6.The role of XB130 gene in proliferation of hepatocellular carcinoma cells and its mechanism
Wenfang XU ; Yingming FEI ; Jiankang ZHOU ; Jiangnan CHEN ; Yadi ZHOU ; Qiuqiong L(U)
China Oncology 2018;28(2):117-122
Background and purpose: XB130 protein plays an important role in proliferation and invasiveness of tumor cells. However, there is little research on the role of XB130 protein in hepatocellular carcinoma (HCC) and the effect of XB130 is still unclear. This study investigated the role of XB130 gene in the proliferation of HCC cell and its potential mechanism. Methods: The protein expressions of XB130 in HCC cell lines, Huh7, HepG2 and SNU449, and liver cell line HL7702 were detected by Western blot. Huh7 cells were transfected with XB130-siRNA. Then cell viability was measured using cell counting kit-8 (CCK-8), and cell cycle was examined by flow cytometry. Protein expressions of p-AKT, p-GSK3β, cyclin D1 and p-Rb were detected by Western blot, while mRNA expression levels of E2F/DP1 target genes (cyclin E1, c-Myc and PCNA) were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results: The relative protein expressions of XB130 in Huh7, HepG2, SNU449 and HL7702 cells were 0.66±0.10, 0.78±0.11, 0.83±0.08 and 0.32±0.06, respectively. The difference between HCC cell lines and HL7702 cell line was statistically significant (P<0.01). The transfection efficacy of XB130-siRNA was confirmed to be highly effective in Huh7 cells, and the viability of XB130-siRNA transfected Huh7 cells declined 72 h after transfection (P<0.001). The ratio of Huh7 cells in G0/G1 phase was increased, while the ratio in S or G2/M was decreased 48 h after XB130-siRNA transfection (P<0.01). In addition, compared with negative control, protein expressions of p-AKT, p-GSK3β, cyclin D1 and p-Rb, and mRNA expression levels of cyclin E1, c-Myc and PCNA were all decreased in XB130-siRNA transfected Huh7 cells (P<0.001). Conclusion: XB130 promotes the proliferation of HCC cells by regulating cell cycle-related proteins and downstream transcription factors.
7.Correlation Study between Resistin rs2161490 and rs1423096 and Type 2 Diabetes Mellitus
Yingming ZHU ; Xinqiang XU ; Qiang ZHOU ; Bo CHEN ; Tianxing JI
Journal of Modern Laboratory Medicine 2017;32(1):48-52
Objective To explore the correlation between resistins rs2161490and rs1423096 genotype with type 2 diabetes mellitus (T2DM)in Guangdong.Methods Collected 178 blood of newly diagnosed T2DM in the Second Affiliated Hospital of Guangzhou Medical University from January 2015 to November 2015 as the patient group and 192 blood of healthy physi-cal examination as the control group.Analysis of the two groups of gene distribution frequency was to reach the genetic equi-librium,comparative two gene loci frequencies of resistin rs2161490 and rs1423096 in case group and control group was sta-tistically significant,and compared the distribution frequency of rs2161490 locus T→C and rs1423096 locus A→G between the patient group and the control group.Then made a logistic regression analysis:analysing the risk two loci each genotype of resistin rs2161490 and rs1423096 to T2DM,adjust of the gender and age,and the changes of the risk of the two variables. Comparative blood lipids biochemical indexes between case group and the control group,mode the correlation analysis be-tween TG,CHOL,HDL-C and LDL-C levels of serum lipids in patients with rs2161490 and rs1423096 each genotypewere performed.Results The sample was consistent with Weinberg Hardy’s law of inheritance,which was representative of the population,comparing two gene loci frequency of resistin rs2161490 and rs1423096 of case group and control group:com-parinng CT,TT,CC of rs2161490 genotype,there was no statistically significant difference (P=0.834,>0.05),and com-parinng AA,AG,GG of rs2161490 genotype,there was no statistically significant difference (P=0.960,>0.05).Each gen-otypes with T2DM risk analysis,there was no statistically significant difference(P>0.05).Adjusting the risk change after the two variables,gender and age,there was no statistically significant difference (P>0.05);TG,CHOL,HDL-C and LDL-C in each of the genes expression levels correlation analysis,there was no statistically significant difference (P>0.05).Con-clusion Analysis results showed that the frequency of two loci all genotypes in the case group and control group were no statistical significance (P>0.05).The risk of two loci gene type of rs2161490 with rs1423096 and type 2 diabetes were be-fore and after the covariate adjustment had no statistical significance (P>0.05 ).Each genotype of rs2161490 with rs1423096 and lipid levels had no statistical significance (P>0.05).Thus infer that two genotypes is not risk for type 2 dia-betes genes in guangdong area.
8.The relationship between serum tumor markers and the severity of silicosis
Shencun FANG ; Haitao ZHANG ; Bin XU ; Chun WANG ; Yingming ZHANG
Chinese Journal of Laboratory Medicine 2017;40(7):515-519
Objective To investigate the relationship between serum tumor markers and the severity of silicosis.Methods Retrospective study.Total of 160 patients with silicosis were included in the study, and 160 healthy volunteers were recruited as the control group.Tumor marker levels in both bronchoalveolar lavage fluid(BALF)and serum were detected by the immunochemiluminecence methods.The pulmonary function parameters, blood gas analysis and lactate dehydrogenase(LDH)were also analyzed.Lung tissue obtained by a patient with silicosis was stained by neuron specific enolase(NSE), carbohydrate antigen125(CA125) and carbohydrate antigen19-9(CA19-9).Results Serum NSE, CA125 and CA19-9 levels were significantly higher in cases than those in controls[(34.47±13.30)μg/L vs(10.24±7.20)μg/L,t=20.27, P<0.000 1;(33.96±17.80)kU/L vs(12.23±15.30)kU/L, t=11.71, P<0.000 1;(4.68±5.67)kU/L vs(2.78±3.45)kU/L,t=3.67,P<0.002].Significant negative correlations were found between values of tumor markers(CA125 and CA19-9) and spirometric parameters,such as forced expiratory volume in one second %(FVE1%), forced expiratory volume in one second/forced vital capacity(FVE1/FVC), carbon monoxide diffusion capacity (Dlco) and total lung capacity(TLC) (r=-0.423,P=0.001;r=-0.323,P=0.011;r=-0.479,P=0.001;r=-0.285,P=0.043) and (r=-0.324,P=0.022;r=-0.256,P=0.023;r=-0.354,P=0.013;r=-0.356,P=0.012).Significant positive correlations were also observed between values of these tumor markers and LDH(r=0.378,P=0.001 and r=0.347,P=0.21).Significant negative correlations were found between NSE and Dlco and TLC(r=-0.374,P=0.004 and r=-0.368,P=0.002).Significant positive correlations were also observed between NSE and LDH(r=0.404,P=0.001).The NSE and CA19-9 levels in BALF were significantly higher than those in serum[(39.32±29.30)μg/L vs(25.7±12.12)μg/L,t=2.15,P=0.036;(21.36±12.11)kU/L vs(11.28±10.78)kU/L, t=2.64,P=0.012].Patients experienced a decrease in NSE and CA19-9 concentrations following whole lung lavage[(39.20±10.24)μg/L vs(15.32±8.35)μg/L,t=8.02,P<0.05;(26.24±12.23)kU/L vs(18.84±5.64)kU/L,t=2.46,P<0.05].Immunohistochemical studies showed positive NSE and CA19-9 staining in lung biopsy specimen.Conclusion Elevated serum tumor markers including NSE, CA125 and CA19-9 would provide valuable clinical information to assess disease severity in silicosis.
9.Expression of TNF-α and IL-10 at various altitudes in rats with severe acute pancreatitis
Yanjun XU ; Liang MA ; Changhong LIAN ; Yingming SONG ; Xinmin WU ; Yamin GUO ; Zeping HUANG
Chinese Journal of Hepatobiliary Surgery 2014;20(1):56-59
Objective To observed the expression of serum TNF-α and IL-10 in rats with severe acute pancreatitis (SAP) at different altitudes,and to explore the relationships between TNF-α and IL-10,the pathological changes of the pancreas,and the experimental basis for clinical diagnosis and treatment of SAP.Methods 72 specific pathogen free (SPF) Wistar male rats were divided randomly into three groups:1 500 meters altitude (group L),3 300 meters altitude (group M),and 4 300 meters altitude (group H).These three groups were then each divided randomly into four subgroups:control (group n),6 hours after pancreatitis (group p 6 h),12 hours after pancreatitis (group p 12 h),and 24 hours after pancreatitis (group p 24 h).Pancreatitis was induced by intraductal administration of 5% sodium taurocholate hydrate (NaTc).The rats were killed at 6,12,and 24 hours after NaTc injection in groups p.The group n rats were killed after 6 hours of pancreas observation.Blood samples and pancreatic tissues were collected post mortem and enzyme-linked immunosorbent assay (ELISA) measured serum TNF-α and IL-10.Results Compared with the control (group n),histopathological scores,IL-10,and TNF-α in the same altitude had a significant difference (P < 0.05) in group p at each time point.In the same altitude of group p,histopathological scores and IL-10 were increased with time elapsed (P < 0.05),while TNF-α was decreased with time elapsed (P < 0.05).There was a significant difference between group Mp and Lp in histopathological scores,IL-10,and TNF-α (P < 0.05),and the same result between group Hp and Lp (P < 0.05),but there was no significant difference between group Hp and Mp (P < 0.05).Meanwhile,IL-10 had a positive relationship with histopathological score,but TNF-α had a negative relationship with histopathological score.Conclusions The level of TNF-α increased with increasing altitude but significantly reduced with elapsed time.The level of IL-10 increased with both increasing altitude elapsed time.These results suggested that TNF-o and IL-10 might play a important role at different times in severe acute pancreatitis.
10.Chondrogenic co-culture of allogenic decalcified bone matrix and bone marrow mesenchymal stem cells in the joint cavity:comparison of cartilage traits in the same joint cavity
Bin XU ; Liang ZHOU ; Yingming WANG ; Sanxiang QIAN
Chinese Journal of Tissue Engineering Research 2014;(8):1165-1171
BACKGROUND:Loose bodies in the knee are found to survive for a long term and maintain certain histophysiological properties of cartilage tissue. Therefore, a bold hypothesis is proposed that the joint cavity may be a preferred environment for chondrocyte growth and development, supporting the concept of “intracavitary culture and intracavitary transplantation”.
OBJECTIVE:To observe the trait difference of chondrogenic culture with alogenic decalcified bone matrix and bone marrow mesenchymal stem cels in the joint cavity orin vitro versus cartilage in the same cavity.
METHODS:There were three groups in this experiment: inin vitro culture group, bone marrow mesenchymal stem cels from newborn rabbits undergoing chondrogenic culture were co-cultured with decalcified bone matrix from adult rabbitsin vitro; in intracavitary culture group, bone marrow mesenchymal stem cels from newborn rabbits undergoing chondrogenic culture were co-cultured with decalcified bone matrix from adult rabbits in the joint cavity; normal cartilage in the same cavity served as control group.
RESULTS AND CONCLUSION: (1) After 12 weeks of culture, in the in vitro culture group, hematoxylin-eosin staining showed a smal amount of chondrocytes proliferated, with blue-stained nuclei; toluidine blue staining showed chondrocytes arranged disorderly, surrounded by a smal amount of matrix; Masson staining showed a smal positive area and irregular cellarrangement; type II colagen immunohistochemistry staining showed a few of yelow particles in the cytoplasm and extracelular matrix. (2) After 12 weeks of culture, in the intracavitary culture group, hematoxylin-eosin staining showed proliferation of chondrocytes with blue-stained nuclei; toluidine blue staining showed cluster-shaped arrangement of chondrocytes surrounded by the matrix with lacuna formation; Masson staining showed there were many positive cels with blue-stained matrix that arranged in a certain stress direction; immunohistochemical identification of type II colagen was positive, and brown-yelow stained particles could be discerned in the extracelular matrix. These findings indicate that tissue-engineered cartilage can be generated by co-culture of alogenic decalcified bone matrix and bone marrow mesenchymal stem cels in the joint cavity orin vitro, and the cartilage cultured in the joint cavity is more close to normal cartilage than that cultured in vitro.

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