1.ERK mediated C-Myc/PD-L1 synergy to investigate tumor suppression effect of Shenqi Yiliu decoction combined with cisplatin in combination with H22 hepatocellular carcinoma tumor bearing mice
Yuping YANG ; Yongqiang DUAN ; Min BAI ; Xin FENG ; Nan ZHOU ; Liren CAO ; Yarong LI ; Lan MA
Chinese Journal of Immunology 2024;40(3):586-591
Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.
2.Analysis of Helicobacter pylori infection in the natural population of Sanya City
Shi-Mei HUANG ; Lian-Guo LAN ; Da-Ya ZHANG ; Run-Xiang CHEN ; Xiao-Dong ZHANG ; Chen CHEN ; Fan ZENG ; Da LI ; Xian-Feng HUANG ; Qi WANG ; Shi-Ju CHEN ; Lei GAO ; Jun-Tao ZENG ; Fei-Hu BAI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(2):141-145
Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5%.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P<0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P>0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.
3.Construction of classification management model of medical equipment in public hospitals based on association rule algorithm and effect analysis
Lijuan BAI ; Xingguang ZHU ; Huaqing LAN ; Yongsheng TONG ; Feng WANG
China Medical Equipment 2024;21(10):135-140
Objective:To construct a classification management model of medical equipment in public hospitals based on association rules algorithm,and to analyze its application effect in hospital equipment management.Methods:Equipment classification management was performed based on Apriori algorithm(association rule analysis)and K-means algorithm(equipment abnormal information mining)in the association rules algorithm,the classification management model of medical equipment in public hospitals was constructed to mine the abnormal characteristics of equipment status.A total of 244 medical devices in clinical use in Beijing Huilongguan Hospital from 2022 to 2023 were selected.According to the application of the classification management model of medical equipment in public hospitals based on the association rule algorithm,the equipment use period from January to December 2022 was set before the application of the association rule algorithm model,and the equipment use period from January to December 2023 was set to the time after the application of the association rule algorithm model.The scores of equipment classification management,the failure rate of different types of equipment and equipment efficiency score before and after the application of association rule algorithm model were compared.Results:After the application of association rule algorithm model,the average scores of warehousing management,use management,maintenance management and scrap management were(89.65±4.65)points,(90.25±4.36)points,(87.69±3.12)points and(90.36±3.39)points,respectively,which were higher than before the application,the difference was statistically significant(t=17.866,14.671,18.128,19.479,P<0.05).After the application of association rule algorithm model,the number of medical image diagnostic and auxiliary equipment,health monitoring equipment,rehabilitation equipment and intervention and treatment equipment that failed was 2,3,2,and 3,and the failure rates were 3.33%,4.69%,2.86%and 6.00%,respectively,which were lower than those before the application,the difference was statistically significant(x2=5.925,6.117,7.937,5.316,P<0.05).After the application of association rule algorithm model,the average scores of overall utilization efficiency,quality stability efficiency and accurate diagnosis and treatment efficiency of the equipment were(96.39±3.69)points,(94.23±3.06)points and(95.47±4.36)points,respectively,which were higher than those before the application,and the difference was statistically significant(t=16.762,17.919,11.769,P<0.05).Conclusion:The application of the classification management model of medical equipment in public hospitals based on association rules algorithm can realize the classification management of medical equipment in hospitals,improve the operating efficiency and management level of equipment,and reduce the equipment failure rate.
4.Mechanism of Shenqi Yiliu Prescription Combined with Cisplatin on H22 Liver Cancer-bearing Mice Based on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway
Mengying YANG ; Yongqiang DUAN ; Yuxin JIA ; Min BAI ; Zhongbo ZHU ; Yarong LI ; Lan MA ; Mingyu ZHANG ; Xin FENG ; Lanlan HE ; Yuping YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):114-122
ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling, 40 surviving mice were randomly divided into model group, cisplatin group [2.5×10-3 g·kg-1·(3 d)-1], Shenqi Yiliu prescription group (27 g·kg-1·d-1), and a combination group (Shenqi Yiliu prescription group + cisplatin). The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention, the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry (IHC), immunofluorescence (IF), and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific protease-1 (Caspase-1), and gasdermin D (GSDMD) in tumor tissues. The levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA). ResultCompared with the mice in the blank group, those in the model group were in a poor mental state, sleepy, and lazy, and their fur color was dull, with increased levels of serum ALT and AST in liver function tests (P<0.01). Compared with the model group, the groups with drug intervention showed improved mental state, inhibited tumor growth to varying degrees, and decreased tumor weight, and the tumor inhibition rate in the combination group was the highest (P<0.01). HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant, while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test, the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased (P<0.01), and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased (P<0.05, P<0.01). Among them, the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant (P<0.01). TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention (P<0.05, P<0.01), especially the cisplatin group and Shenqi Yiliu prescription group (P<0.01). Western blot, IHC, and IF found that the protein expression levels of NLRP3, Caspase-1, and GSDMD in each group with drug intervention decreased (P<0.05, P<0.01). Compared with the mice in the cisplatin group, those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology, and the tumor weight of the mice in the combination group decreased (P<0.05). The levels of ALT and AST in the Shenqi Yiliu prescription group decreased (P<0.05), and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased (P<0.05, P<0.01), especially in the combination group (P<0.01). The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced (P<0.01). IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced (P<0.01). The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased (P<0.01), and the expression level of Caspase-1 protein in the combination group decreased (P<0.01). The decrease in GSDMD protein expression was not significant, and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect, which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis, and relieve the inflammatory response in mice with liver cancer.
5.Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation.
Rui MA ; Yun HE ; Hui Fang WANG ; Lu BAI ; Wei HAN ; Yi Fei CHENG ; Kai Yan LIU ; Lan Ping XU ; Xiao Hui ZHANG ; Yu WANG ; Yuan Yuan ZHANG ; Feng Rong WANG ; Xiao Dong MO ; Chen Hua YAN ; Xiao Jun HUANG ; Yu Qian SUN
Chinese Journal of Internal Medicine 2023;62(7):826-832
Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
Humans
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Cytomegalovirus
;
Retrospective Studies
;
Cohort Studies
;
Prospective Studies
;
Cytomegalovirus Infections/prevention & control*
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Graft vs Host Disease/prevention & control*
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Recurrence
;
Antiviral Agents/therapeutic use*
6.Effect of Shenqi Yiliu Prescription Combined with Cisplatin on Tumor in Hepatoma H22-bearing Mice Based on PTEN/PI3K/Akt Signaling Pathway
Xin FENG ; Yongqiang DUAN ; Min BAI ; Yuping YANG ; Liren CAO ; Junrui HU ; Yanhua SI ; Jing CHEN ; Zihan GONG ; Lan MA
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):96-103
ObjectiveTo investigate the tumor-suppressing effect of Shenqi Yiliu prescription combined with cisplatin in hepatoma H22-bearing mice based on the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. MethodH22-bearing mice were prepared and randomized into model group, cisplatin group, and cisplatin combined with high-, medium-, and low-dose Shenqi Yiliu prescription groups, with 10 mice in each group. Another 10 healthy mice were randomly selected as normal group. Shenqi Yiliu prescription was given by gavage with the high, medium, low dose of 54.06, 27.03, 13.515 g·kg-1·d-1, respectively, and cisplatin (2.5 mg·kg-1) was administered by intraperitoneal injection, twice a week. Normal group and model group received normal saline. After 13 days of treatment, mice were killed and the tumor inhibition rate was calculated. The pathomorphological changes of tumor were observed based on hematoxylin-eosin (HE) staining, and enzyme-linked immunosorbent assay (ELISA) and immunofluorescence method were used to detect the content of cyclin-dependent kinase inhibitor 1A (p21) and cyclin-dependent kinase inhibitor 1B (p27) in tumor tissue of mice. The levels of PTEN, PI3K and phosphorylated protein kinase B (p-Akt) in tumor tissue were measured by Western blot. ResultCompared with the model group, cisplatin alone and cisplatin in combination with the high-, medium-, and low-dose Shenqi Yiliu prescription decreased tumor mass (P<0.05), particularly the cisplatin in combination with the high-dose Shenqi Yiliu prescription. Necrosis of the tumor tissue was observed in each group, especially the cisplatin combined with high-dose Shenqi Yiliu prescription group. As compared with the model group, cisplatin alone and cisplatin in combination with the high-, medium-, and low-dose Shenqi Yiliu prescription raised the expression of p21, p27, and PTEN (P<0.05) and lowered the expression of PI3K and p-Akt (P<0.05), particularly the cisplatin in combination with high-dose Shenqi Yiliu prescription. ConclusionShenqi Yiliu prescription may regulate the expression of key molecules in PTEN/PI3K/Akt signaling pathway, thereby upregulating the expression of downstream proliferation inhibitors p21 and p27, further suppressing the tumor in H22-bearing mice, and enhancing the effect of chemotherapy.
8.SENP1 induced protein deSUMO modification increased the chemotherapy sensitivity of endometrial cancer side population cells.
Meng Lan YUAN ; Jie BAI ; Cheng Yao LI ; Na XUE ; Xu Hong CHEN ; Feng SHENG ; Xiao Zhi LIU ; Pu LI
Chinese Journal of Oncology 2022;44(12):1362-1368
Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.
Animals
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Female
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Humans
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Mice
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Apoptosis
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Cell Line, Tumor
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Cisplatin/pharmacology*
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Cysteine Endopeptidases/metabolism*
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Endometrial Neoplasms/genetics*
;
Side-Population Cells/pathology*
;
Sumoylation
9.Evaluation of inactivated COVID-19 vaccine on semen parameters in reproductive-age males: a retrospective cohort study.
Hong ZHU ; Xiao WANG ; Feng ZHANG ; Yong ZHU ; Mei-Rong DU ; Zhi-Wen TAO ; Can SUN ; Hai-Tao MA ; Ya-Dong LI ; Guo-Qing LIANG ; Jie REN ; Bai-Lan FENG ; Feng JIANG
Asian Journal of Andrology 2022;24(5):441-444
During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
COVID-19
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COVID-19 Vaccines
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Female
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Humans
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Male
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Pregnancy
;
Retrospective Studies
;
Semen
;
Semen Analysis
;
Sperm Count
;
Sperm Motility
;
Spermatozoa
;
Vaccination
;
Vaccines, Inactivated
10.Clinical Characteristics and Prognosis of Systemic Anaplastic Large Cell Lymphoma.
Juan FENG ; Hai-Long TANG ; Rui-Feng YUAN ; Li XU ; Yan-Hua ZHENG ; Rong LIANG ; Qing-Xian BAI ; Tao ZHANG ; Lan YANG ; Hong-Tao GU ; Guang-Xun GAO
Journal of Experimental Hematology 2022;30(4):1109-1115
OBJECTIVE:
To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL).
METHODS:
The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated.
RESULTS:
There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK+ patients while 53(15-73) years of the 30 ALK- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS.
CONCLUSION
sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Child
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Disease-Free Survival
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Female
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Humans
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Lymphoma, Large-Cell, Anaplastic/diagnosis*
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Male
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Middle Aged
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Prognosis
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Receptor Protein-Tyrosine Kinases
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Retrospective Studies
;
Young Adult

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