1.Clinical features of recompensation in autoimmune hepatitis-related decompensated cirrhosis and related predictive factors
Xiaolong LU ; Lin HAN ; Huan XIE ; Lilong YAN ; Xuemei MA ; Dongyan LIU ; Xun LI ; Qingsheng LIANG ; Zhengsheng ZOU ; Caizhe GU ; Ying SUN
Journal of Clinical Hepatology 2025;41(9):1808-1817
ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis (AIH)-related decompensated cirrhosis, to identify independent predictive factors, and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 (n=211). The primary endpoint was achievement of recompensation, and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up, the patients were divided into the recompensation group (n=16) and the persistent decompensation group(n=150).The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups; the Kaplan-Meier method was used for survival analysis; the Cox proportional-hazards regression model was used to identify independent predictive factors, and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled, with a median age of 55.0 years and a median follow-up time of 44.0 months, and female patients accounted for 87.2%. Among the 211 patients, 61 (with a cumulative proportion of 35.5%) achieved recompensation. Compared with the persistent decompensation group, the recompensation group had significantly higher white blood cell count, platelet count (PLT), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid, prothrombin time, international normalized ratio (INR), SMA positive rate, Model for End-Stage Liver Disease (MELD) score, Child-Pugh score, and rate of use of glucocorticoids (all P0.05), as well as significantly lower age at baseline, number of complications, and death/liver transplantation rate (all P0.05). At 3 and 12 months after treatment, the recompensation group had continuous improvements in AST, TBil, INR, IgG, MELD score, and Child-Pugh score, which were significantly lower than the values in the persistent decompensation group (all P0.05), alongside with continuous increases in PLT and albumin, which were significantly higher than the values in the persistent decompensation group (P0.05). The multivariate Cox regression analysis showed that baseline ALT (hazard ratio [HR]=1.067, 95% confidence interval [CI]: 1.010 — 1.127, P=0.021), IgG (HR=0.463,95%CI:0.258 — 0.833, P=0.010), SMA positivity (HR=3.122,95%CI:1.768 — 5.515, P0.001), and glucocorticoid therapy (HR=20.651,95%CI:8.744 — 48.770, P0.001) were independent predictive factors for recompensation, and the nomogram model based on these predictive factors showed excellent predictive performance (C-index=0.87,95%CI:0.84 — 0.90). ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity, a high level of ALT, a low level of IgG, and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.
2.Clinical comprehensive evaluation of Xiangju Capsules in treatment of rhinosinusitis.
Huan LIU ; Xin CUI ; Zhi-Fei WANG ; Qiang ZHANG ; Yuan-Yuan LI ; Lian-Xin WANG ; Jun-Yu XI ; Yan-Ming XIE ; Li-Xun LI ; Lei ZHANG
China Journal of Chinese Materia Medica 2023;48(15):4243-4252
The articles involving Xiangju Capsules were retrieved, and qualitative research and quantitative research methods were combined to evaluate the evidence of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) of this drug. Multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Xiangju Capsules in the treatment of rhinosinusitis and clarify the precise clinical positioning. The dimensions are graded A, B, C, or D. Multi-source safety evidence showed that the main adverse reactions were gastrointestinal reactions, rash, itching, dizziness, and headache. Based on the available studies, the risk is controllable and the safety is grade A. Meta-analysis showed that Xiangju Capsules + conventional western medicine could recover the Lund-Kennedy score, Lund-Mackay score, and CT score, relieve headache, nasal congestion, olfactory disturbance, and facial pain, with the effectiveness is grade B. The incremental cost-effectiveness ratio of Xiangju Capsules + conventional western medicine compared with conventional western medicine alone in the treatment of chronic rhinosinusitis was 263.71 yuan, about 0.82% of the per capita disposable income. The results of sensitivity analysis showed that the research results were relatively robust. Based on the assumption that the per capita disposable income in 2020 will be the threshold of patients' willingness to pay, it is more economical to use Xiangju Capsules + conventional western medicine. The drug belongs to grade A of the national medical insurance, with an average daily cost of 3.06 yuan, and the economy is grade B. This formula is modified from classic formulas and characteristic empirical formulas, be capable of improving immunity and preventing repeated attacks. It can be used for acute and chronic rhinitis-rhinosinusitis. It had a wide range of applicability, especially for the patients with head and face tenderness. Service innovation was reflected in the measures to guarantee supply, capacity, scalability, and coverage of grass-roots sales channels. The industrial innovation was improved through the management of medicinal resources, pharmaceutical industry, production technology, quality control, scientific research and development, and this formula won three national invention patents. Comprehensively, the innovation of Xiangju Capsules is grade B. According to the survey of 188 medical practitioners and 196 patients in 20 provinces, municipalities, and autonomous regions of China, the drug was characterized by easy preparation and administration, individualized medication, simple technology and management, convenient use, storage, and transport, and controllable adverse reactions, with the suitability is grade B. Xiangju Capsules showed the cost of 45.9 and 275.4 yuan for treatment of acute and chronic rhinitis-rhinosinusitis, respectively, being well affordable. It was sold in 35 000 medical institutions in China. The dosage form was suitable for transportation, storage, and grass-root application. With rich, sustainable, and available medicinal resources, the accessibility of Xiangju Capsules is grade A. This drug can be used for both acute and chronic rhinitis-rhinosinusitis, clearing heat and expelling pus, and strengthening the exterior to prevent relapse. After this drug was available on the market, over 4 000 cases were studied, with rich experience in human use accumulated, and characteristics of traditional Chinese medicine is grade B. Overall, the clinical value of Xiangju Capsules is class B. It is suggested that Xiangju Capsules should be used in accordance with the relevant policies of basic clinical drug administration to play its role.
Humans
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Rhinitis/drug therapy*
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Sinusitis/drug therapy*
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Medicine, Chinese Traditional
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Headache
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China
;
Capsules
3.Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis.
Yong-Yi ZHOU ; Hai-Jie CHEN ; Jia XUE ; Nan WU ; Jia-Huan YUAN ; Xun-Hong LIU ; Li-Si ZOU ; Cui-Hua CHEN ; Zhi-Chen CAI ; Wei YANG ; Jian-Ming CHENG
China Journal of Chinese Materia Medica 2023;48(17):4663-4674
A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods*
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Multivariate Analysis
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Chromatography, High Pressure Liquid/methods*
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Drugs, Chinese Herbal/chemistry*
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Amino Acids/analysis*
4.Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation.
Guang-Yang WENG ; Wei-Wen YOU ; Huan-Xun LIU ; Yun CAI ; Xin DU
Journal of Experimental Hematology 2023;31(5):1333-1339
OBJECTIVE:
To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients.
METHODS:
Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed.
RESULTS:
14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA.
CONCLUSION
VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.
Humans
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Nucleophosmin
;
Prognosis
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Leukemia, Myeloid, Acute/genetics*
;
Mutation
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Azacitidine/therapeutic use*
;
fms-Like Tyrosine Kinase 3/genetics*
5.Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum.
Jia XUE ; Hai-Jie CHEN ; Yong-Yi ZHOU ; Jia-Huan YUAN ; Zhi-Chen CAI ; Nan WU ; Cui-Hua CHEN ; Xun-Hong LIU ; Li-Si ZOU ; Sheng-Xin YIN ; Wei YANG ; Jian-Ming CHENG
China Journal of Chinese Materia Medica 2023;48(13):3448-3461
A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid
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Epimedium
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Tandem Mass Spectrometry
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Chromatography, Liquid
;
Multivariate Analysis
6.Simultaneous determination of multiple bioactive constituents in Abelmoschi Corolla by UFLC-QTRAP-MS/MS.
Sheng-Xin YIN ; Li-Fang WEI ; Yu-Qi MEI ; Xun-Hong LIU ; Li-Si ZOU ; Zhi-Chen CAI ; Jia-Huan YUAN ; Hai-Tao GE ; Dian-Guang WANG ; Dan-Dan WANG
China Journal of Chinese Materia Medica 2021;46(10):2527-2536
A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 38 active components in Abelmoschi Corolla, including flavonoids, organic acids, nucleosides and amino acids, so as to investigate the effects of different harvesting and processing methods on multi-active components in Abelmoschi Corolla. The chromatographic separation was performed on a XBridg®C_(18) column(4.6 mm×100 mm, 3.5 μm) with(0.1% formic acid water) methanol-acetonitrile(1∶1) as the mobile phase for gradient elution at 30 ℃. The flow rate was 0.5 mL·min~(-1). The components were detected in a multiple-reaction monitoring(MRM) mode. The gray relational analysis(GRA) was used to comprehensively evaluate the multiple active components of Abelmoschi Corolla at different harvesting times and drying temperatures. The results showed that 38 components had a good linearity with correlation coefficients all above 0.999 0. The method featured a good precision, repeatability and stability with the relative stan-dard deviations(RSDs) of less than 5.0%. Recoveries ranged from 98.06% to 104.4% with RSD between 0.22% and 4.9%. The results of GRA indicated that a better quality in the samples collected on September 9 th. Samples dried at 90 ℃ had a better quality. The established method is accurate and reliable, and can be used to assess the internal quality of Abelmoschi Corolla. This study can provide basic materials for determining appropriate harvesting time and processing method of Abelmoschi Corolla.
Amino Acids
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Chromatography, High Pressure Liquid
;
Chromatography, Liquid
;
Nucleosides
;
Tandem Mass Spectrometry
7.Association between total cholesterol and type 2 diabetes: a prospective cohort study
Yuan LU ; Huan-le LIU ; Yun-tao MA ; Xiao-yu DAI ; Zhi-heng WANG ; Yan-xun LIU
Chinese Journal of Disease Control & Prevention 2020;24(4):380-383,479
Objective To explore the association between total cholesterol and type 2 diabetes ( T2DM) . Methods Non-diabetic people who aged 20 to 90 years at the baseline and who had physical examination more than 2 times were screened. Comparisons of the baseline characteristics were conducted with Student-t test or Pearson chi-square test. Generalized estimating equation ( GEE) was used to analyze the effect of total cholesterol of quantiles groups ( 2.10- mmol /L,4.16- mmol /L,4.76- mmol /L and 5.42 -13.29 mmol /L) to type 2 diabetes. Results The cohort with an average age of 3.53 years per person in- cluded 12 928 subjects and 45 626 person-years. During the follow-up,447 cases of new-onset diabetes occurred and the incidence density was 9. 80‰. The high incidence of type 2 diabetes increased with the increase of total cholesterol. After adjusting the factors including age,high density lipoprotein,hypertension and obesity,based on the 2. 10- mmol /L group,the relative risk ( RR) of the 4. 16- mmol /L,4. 76- mmol/L and 5. 42-13. 29 mmol /L group were 1. 24( 95% CI: 0. 83-1. 86) ,1. 75 ( 95% CI: 1. 19-2. 56) and 3. 60( 95% CI: 2. 51-5. 17) ,respectively. Conclusions Total cholesterol is associated with type 2 diabetes,and as the total cholesterol increases,the risk of developing type 2 diabetes increases.
8.Research progress in molecular biology of Lonicerae Japonicae Flos.
Zhi-Chen CAI ; Xun-Hong LIU ; Cheng-Cheng WANG ; Meng-Xia TAN ; Jia-Li CHEN ; Yu-Qi MEI ; Li-Fang WEI ; Huan CHEN ; Rong YANG ; Jia-Jia CHEN
China Journal of Chinese Materia Medica 2020;45(6):1272-1278
Molecular biology is a new subject that clarifies the phenomena and nature of life at the molecular level. Its development provides new biotechnology and methods for the study of traditional pharmacognosy. The formation of molecular biology has brought the development of pharmacognosy into a new era of gene research. Lonicerae Japonicae Flos is a classical Chinese medicine. Many scholars of home and abroad have carried out relevant studies on its molecular biology on the basis of the in-depth study with traditional methods, and have achieved certain results. In order to provide references on the method, technical for promoting the modernization of Lonicerae Japonicae Flos, and the development, protection, and utilization of other traditional Chinese medicine resources. This article summarized the application status of molecular biology methods and techniques on the identification, biosynthesis of active constituents, and molecular mechanism of secondary metabolite under stress conditions of Lonicerae Japonicae Flos in recent years. In hybridization technology of tag(RFLP), molecular markers based on PCR(RAPD, AFLP, SSR and ISSR), based on DNA sequence analysis of SNP and DNA barcode for the variety identification, diagnosis, identification of Lonicerae Japonicae Flos, and so forth in detail. At the same time, it is proposed that multi-omics technology can be used to build systems biology technology and platforms, and establish related models of secondary metabolite biosynthesis, so as to deepen acknowledge the molecular mechanism of the active component biosynthesis of Lonicerae Japonicae Flos and the accumulation of metabolites, life activities of other medicinal plants under adverse environment, then to regulate them.
Amplified Fragment Length Polymorphism Analysis
;
Chromatography, High Pressure Liquid
;
DNA Barcoding, Taxonomic
;
Drugs, Chinese Herbal/pharmacology*
;
Lonicera/chemistry*
;
Medicine, Chinese Traditional
;
Microsatellite Repeats
;
Plants, Medicinal/chemistry*
;
Polymorphism, Restriction Fragment Length
;
Polymorphism, Single Nucleotide
;
Random Amplified Polymorphic DNA Technique
;
Secondary Metabolism
9.Advantages of cryopreservation technology for rare human sperm.
Ding-Ming LI ; Bo LIU ; Yang XIAN ; Li-Juan YING ; Yan ZHENG ; Min JIANG ; Fu-Ping LI ; Huan-Xun YUE
National Journal of Andrology 2018;24(8):705-707
ObjectiveTo search for an effective method for cryopreservation of rare human sperm (RHS) by comparing the effect of RHS cryopreservation technology with that of conventional cryopreservation technology on post-thaw sperm from patients with severe oligozoospermia.
METHODSSemen samples obtained from 82 patients with severe oligozoospermia were preserved by RHS cryopreservation technology, and another 24 samples cryopreserved by conventional technology, the former divided into groups A (sperm concentration < 1×10⁶/ml, n = 54) and B (1×10⁶/ml ≤ sperm concentration < 5×10⁶/ml, n = 28), and the latter included in group C (sperm concentration < 15×106 /ml, n = 24). The survival rate of post-thaw sperm and recovery rate of progressively motile sperm (PMS) were compared among the three groups.
RESULTSThe survival rate of post-thaw sperm was significantly higher in groups A and B than in C ([62.8 ± 18.7]% and [61.9 ± 17.2]% vs [50.7 ± 13.5]%, P < 0.05), and so was the recovery rate of PMS ([68.7 ± 18.4]% and [70.7 ± 15.5]% vs [29.2 ± 12.4]% , P < 0.05), but there were no statistically significant differences between groups A and B in either of the two parameters (P > 0.05).
CONCLUSIONSThe cryopreservation technology for rare human sperm may yield relatively stable post-thaw results and deserves a wide clinical application in preserving male fertility.
10.Effect of allogeneic blood transfusion and preoperative autologous blood donation on perioperative immune function in patients with gastrointestinal tumor
Xun ZHOU ; Huan WANG ; Xiaoqian LIU ; Nana ZHU ; Rong XIA ; Jianrong GUO
The Journal of Clinical Anesthesiology 2018;34(2):144-148
Objective To investigate the effect of allogeneic transfusion and preoperative autologous blood donation on perioperative cellular immunity and humoral immunity in patients with gastrointestinal neoplasms.Methods Sixty gastrointestinal cancer patients undergoing radical surgery,33 males and 27 females,aged 53 69 years,weighing 47-70 kg,ASA physical status Ⅰ or Ⅱ,were included in this study.Blood transfusion was started when the blood loss was more than 200~400 ml,Hb<70 g/L,and the patients were randomly divided into the preoperative autologous blood donation group (group P,n =30):intraoperative blood transfusion using the stored autologous blood transfusion;allogeneic blood transfusion group (group A,n =30):allogeneic blood transfusion.The levels of T lymphocyte subsets,NK cells and IL-2,IL-10,TNF-α,perforin (PF) concentration and plasma immunoglobulin IgG,IgA and IgM levels.Results The percentage of CD3+,CD4+,NK cells and the ratio of CD4+/CD8+ in group A at the end of surgery to 7 d after operation were significantly lower than those at the time of admission (P<0.05).The percentage of CD3+,CD4+ (P< 0.05).The level of IL-2 in group A was significantly lower than that in group P (P<0.05) 1-7 d after operation,and the level of IL-10 in group A was significantly higher than that in group P (P< 0.05).The levels of IgG and IgA 3 d after operation in group A were significantly lower than those in group P (P<0.05).The levels of IgG and IgA in group P were significantly decreased at the end of operation and recovered to preoperative levels 1-3 d after operation (P < 0.05).Conclusion Allogeneic blood transfusion can reduce the percentage of T-cell subsets and NK cells in cancer patients and delay their recovery,and also can transiently reduce the content of immunoglobulin IgG and IgA in plasma and thus affect the immune function of patients.However,the preoperative autologous blood donation has a slight effect on postoperative immune function in cancer patients.

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