1.Mechanism of Huayu Jiedu Decoction in Inhibiting Malignant Biological Characteristics of Multiple Myeloma
Zuo-Tao LI ; Hai-Liang LI ; Zhi-Min YAN ; Jie LIN ; Xiao-Yun CHEN ; Yan-Quan LIU ; Yi-Li WANG
Journal of Experimental Hematology 2024;32(5):1438-1443
Objective:To analyze and explore the effects of Huayu Jiedu Decoction on the malignant biological characteristics of multiple myeloma(MM)cells and its molecular mechanism,so as to provide experimental basis and theoretical basis for the alternative therapy of anti-MM in traditional Chinese medicine.Methods:Different concentrations of Huayu Jiedu Decoction were used to intervene myeloma U266 cells.The changes of cell proliferation activity were detected by CCK-8 assay,apoptosis was detected by Annexin V/PI double staining flow cytometry,and apoptosis and protein expression of related signaling pathways were detected by Western blot.Real-time quantitative PCR was used to detect mRNA expression changes of high mobility group protein B1(HMGB1),CXC chemokine receptor 4(CXCR4)and interleukin-6(IL-6).Results:Huayu Jiedu Decoction inhibited the proliferative activity of U266 cells and induced their apoptosis in a concentration and time dependent manner(r=-0.713,r=-0.827).After treatment with Huayu Jiedu Decoction for 48 h,the expressions of anti-apoptotic protein Bcl-2 and survivin were down-regulated,while the expression of pro-apoptotic protein Bax was up-regulated,and the phosphorylation level of TLR4/NF-κB signaling pathway was inhibited.After intervention of Huayu Jiedu decoction,the expressions of HMGB1 and IL-6 mRNA were significantly decreased,while the expression of CXCR4 was not significantly decreased.Conclusion:Huayu Jiedu Decoction can inhibit the proliferative activity of U266 cells and induce programmed death.Its molecular mechanism may be related to regulating the expression of apoptotic proteins,inhibiting the activation of TLR4/NF-κB pathway and down-regulating the expression of HMGB1 and IL-6 mRNA.
2.A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers.
Xiao Peng YU ; Jia Lu CHEN ; Yue TANG ; Chen CHEN ; Ying Hong QIU ; Hong WU ; Tian Qiang SONG ; Yu HE ; Xian Hai MAO ; Wen Long ZHAI ; Zhang Jun CHENG ; Xiao LIANG ; Jing Dong LI ; Chuan Dong SUN ; Kai MA ; Rui Xin LIN ; Zhi Min GENG ; Zhao Hui TANG ; Zhi Wei QUAN
Chinese Journal of Surgery 2023;61(4):321-329
Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.
3.Advances in applications of molecular dynamics simulation techniques to the research of self-assembled nano-drug delivery systems
Wei-feng ZHU ; Zhi-wei ZHOU ; Wen-liang KUANG ; Quan DING ; Ji-wen ZHANG ; Wen-ting WU
Acta Pharmaceutica Sinica 2023;58(1):118-126
Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.
4.Clinical Efficacy and Mechanism of Osteoking in Treatment of Knee Osteoarthritis Based on Real-world Data
Ruihan LI ; Jun ZHOU ; Zhi LIANG ; Shuai GAO ; Rui QUAN ; Xisheng WENG ; Yanqiong ZHANG ; Na LIN ; Weiheng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):63-71
ObjectiveTo investigate the clinical efficacy and mechanisms of Osteoking in the treatment of knee osteoarthritis (KOA) in real-world practice, so as to provide a basis for the rational clinical use of Osteoking. MethodFrom the Osteoking for knee osteoarthritis case registration system, 638 KOA cases treated with Osteoking were selected and analyzed in SPSS 26.0. The clinical data were collected from 20 hospitals in China from May 2020 to December 2021. Descriptive analyses of patient age, gender, body mass index, course of treatment and other parameters were performed. The Mann-Whitney U test was performed to compare the visual analogue scale (VAS) and Western Ontario and McMaster universities arthritis index (WOMAC) scores before and after treatment. The integrative pharmacology-based research platform of traditional Chinese medicine (TCMIP) v2.0 was used for network analysis of the core targets of Osteoking in treating knee osteoarthritis. Furthermore, 20 KOA patients treated with Osteoking in the Third Affiliated Hospital of Beijing University of Chinese Medicine from October to December in 2022 were enrolled in the treatment group, and 20 healthy volunteers in the control group. The enzyme-linked immunosorbent assay was employed to measure the serum levels of related indicators to verify the prediction results. ResultA total of 638 KOA patients were treated with Osteoking, including 429 (67.24%) receiving Osteoking alone and 209 (32.76%) receiving Osteoking combined with other therapies. The female patients (415, 65.05%) were more than the male patients (223, 34.95%). The patients showed the mean age of (63.48±13.51) years, mean body mass index of (24.09±2.98) kg·m-2, and mean course of treatment of (15.78±9.66) days. Most of the patients were rated as grades Ⅱ (46.24%) and Ⅲ (34.64%) in Kellgren-Lawrence (K-L) grading and in the relief stage (82.45%) in clinical staging. There was no significant correlation between clinical staging and K-L grading results. The cluster analysis identified three TCM syndromes: Qi stagnation and blood stasis, cold-dampness obstruction, and liver-kidney deficiency. The overall clinical efficacy evaluation showed that VAS score decreased from (6.01±0.85) scores before treatment to (2.54±1.73) scores after treatment (P<0.05), and the WOMAC score decreased from (93.25±25.91) scores before treatment to (50.73±25.14) scores after treatment (P<0.05). The network analysis predicted that Osteoking might regulate the transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) signaling pathways to exert the therapeutic effect. The clinical trial showed elevated TGF-β1 level (P<0.01) and lowered NF-κB subunit RELA and tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) levels (P<0.05) after treatment. The synergistic effects of these changes provide a multidimensional and comprehensive therapeutic efficacy for KOA, alleviating the joint pain and limited mobility in patients. ConclusionOsteoking showed significant therapeutic efficacy in treating KOA. Osteoking may act on multiple pathways involved in cartilage metabolism and inflammation. The findings provide experimental evidence and theoretical support for elucidating the multi-target mechanism of Osteoking in treating KOA.
5.A Real-World Clinical Study of Osteoking Combined with Intra-Articular Injection of Sodium Hyaluronate in Treatment of Knee Osteoarthritis
Rui QUAN ; Jun ZHOU ; Yan JIA ; Yan YAN ; Shuai GAO ; Zhi LIANG ; Ruihan LI ; Shuwen LI ; Yanqiong ZHANG ; Xisheng WENG ; Na LIN ; Baohong MI ; Weiheng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):72-79
ObjectiveTo investigate the improvement of the efficacy of Osteoking in patients with knee osteoarthritis in the onset and remission stage and to systematically explore its potential intervention mechanism, so as to provide a certain reference for improving the clinical application value of Osteoking and guiding its clinical rational drug use. MethodThrough the real-world study of the treatment of knee osteoarthritis with Osteoking, the data was obtained and entered into the "Osteoking for the treatment of knee osteoarthritis case registration system", and 105 patients with episodic and remission knee osteoarthritis from the outpatient or inpatient orthopedic department of 20 medical institutions, including the Third Affiliated Hospital of Beijing University of Chinese Medicine, Peking Union Medical College Hospital, Wangjing Hospital of the Chinese Academy of Chinese Medical Sciences and Hunan Aerospace Hospital, from May 1, 2020 to December 31, 2021, were selected in the system. It included 60 patients treated with Osteoking and joint injection, and 45 patients treated with joint injection alone. The WOMAC osteoarthritis index score, visual analogue (VAS) pain score, individual types of pain symptoms (cold pain, hot pain, tingling, dull pain, soreness) and other TCM symptoms were observed and compared between the two groups, and statistically analyzed. In order to further elucidate the potential molecular mechanism of Osteoking combined with joint injection in the treatment of knee osteoarthritis in the treatment of onset and remission, this study used the "Bone Injury Cross Database (
6.Clinical Study of Osteoking Combined with Non-Steroidal Anti-inflammatory Drugs in Treatment of Knee Osteoarthritis
Zhi LIANG ; Jun ZHOU ; Rui QUAN ; Shuai GAO ; Ruihan LI ; Shuwen LI ; Baohong MI ; Yanqiong ZHANG ; Na LIN ; Weiheng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):80-86
ObjectiveTo explore the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis based on real-world data and provide a basis for clinical medication. MethodFrom May 2020 to December 2021, the data of a total of 1 002 patients with knee osteoarthritis who did not undergo knee joint replacement surgery was collected through the registration method. 952 patients were ultimately included, including 133 cases orally taking Osteoking combined with non-steroidal anti-inflammatory drugs as the observation group and 73 cases orally taking non-steroidal anti-inflammatory drugs alone as the control group. Statistical analysis was conducted on the baseline data, VAS scores, WOMAC scores, and other items. The visit point is the 4th and 8th weeks after registration. In order to further elucidate the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis, the effective components of Osteoking and the relevant gene sets of non-steroidal anti-inflammatory drugs and knee osteoarthritis were obtained through network pharmacology methods and retrieval in bone injury cross database, TCMSP, and other databases. Venn analysis was performed on the relevant gene sets, and a PPI network diagram was constructed. Then key core targets were screened out, and enrichment GO and KEGG enrichment analyses were conducted. ResultThe VAS score of the observation group decreases by an average of (-2.79±1.206) scores in the 4th week, which is better than the control group [(-2.73±1.575) scores, P<0.05]. The VAS score of the observation group decreases by an average of (-3.97±1.308) scores in the 8th week, which is better than the control group [(-3.89±1.822) scores, P<0.05]. The total WOMAC score of the observation group decreases by an average of (-52.07±21.677) scores points in the 8th week, which is significantly better than the control group [(-46.75±25.368) scores, P<0.05]. The observation group has an average decrease of (-10.99±4.229) scores in WOMAC (pain) score in the 8th week, which is better than the control group [(-10.03±5.535) scores, P<0.05]. The observation group has an average decrease of (-1.49±2.901) in WOMAC (stiffness) score in the 4th week, which is better than the control group [(-0.92±1.998) scores, P<0.05], and the observation group has an average decrease of (-1.90±3.200) scores in WOMAC (stiffness) score in the 8th week, which is better than the control group [(-1.26±2.230) scores, P<0.05]. The observation group shows an average decrease of (-39.17±16.562) scores in WOMAC (joint function) score in the 8th week, which is significantly better than the control group [(-35.47±20.098) scores, P<0.05]. According to network pharmacology analysis, the core network target of Osteoking in treating knee osteoarthritis is manifested as regulating signal pathways such as signal transduction transcription activator 3(STAT3), vascular endothelial growth factor A(VEGFA), tumor necrosis factor (TNF) to regulate cell signaling, angiogenesis, chondrocyte proliferation and migration, and inflammatory cells, thereby inhibiting inflammatory reactions, reducing damage, and delaying the development of the disease. ConclusionAfter a 4-week and 8-week course of treatment for knee osteoarthritis with Osteoking combined with non-steroidal anti-inflammatory drugs, there is a significant therapeutic effect on relieving pain and joint stiffness and improving joint function. In network pharmacology, Osteoking is involved in regulating inflammatory factors, metabolic response-related biological processes, the proliferation and apoptosis of chondrocytes, etc. in the treatment of knee osteoarthritis, resulting in anti-inflammatory and analgesic effects and improving joint mobility and joint stiffness. Therefore, it is worthy of clinical promotion and application.
7.Masquelet technique with transfer of free iliac inguinal flap in reconstruction of infectious bone and soft tissue defect after metacarpal fracture surgery: a report of 16 cases
Junwen DONG ; Gaofeng LIANG ; Chao ZHANG ; Feng ZHI ; Xiaobo QUAN ; Zonghai JIA ; Yongtao CHENG ; Chaopeng DUAN ; Yunsheng TENG ; Yongming GUO
Chinese Journal of Microsurgery 2023;46(4):383-390
Objective:To investigate the clinical effects of Masquelet technique with the transfer of free iliac inguinal flap in reconstruction of infectious bone and soft tissue defect after metacarpal fracture surgery.Methods:From January 2014 to January 2020, 16 patients suffered from infectious bone and soft tissue defect after surgery of metacarpal fracture were treated in Department of Hand Surgery, Institute for Hygiene of Ordnance Industry (Weapon Industry 521 Hospital). Debridement and vacuume sealing drainage (VSD) coverage of wound were carried out in emergency surgery, and Masquelet technique combined with free iliac inguinal flap for reconstruction of infected metacarpal bone defect were performed in sub-emergency surgery. The patients were 14 males and 2 females with an average age of 38 (20-50) years old. Plates were removed in 10 patients and retained in 6 patients. Defects of metacarpal bone ranged from 0.8 cm×0.8 cm×2.0 cm to 1.5 cm×2.0 cm× 5.1 cm in size. Soft tissue defects ranged from 3.6 cm×6.8 cm to 7.8 cm×11.6 cm. Tendon defects were found in all 16 patients. After the primary procedure of Masquelet technique combined with free iliac inguinal flap, routine anti-infection, anticoagulant, antispasmodic and other treatments were offered to all patients. Then all patients were observed by fortnightly reviews. After infection was cleared, the second phase of Masquelet treatment began. The defects of metacarpal bone were reconstructed with autologous cancellous bone grafts, and measures to prevent from infection together with other therapies were offered after the surgery. Follow-up of the second phase surgery was carried out once per 1-2 weeks and then per 2-4 months after bone union. The follow-up review items included: wound infection and necrosis, appearance, shape, texture and sensory recovery of flap. Bone union of infectious metacarpal defect was evaluated, recurrence of infection was closely observed as well as the resorption or nonunion of bone by X-rays. Hand function was assessed according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Donor sites healing and functional recovery were also included in the postoperative observation.Results:The follow-up time ranged from 1.5-3.0 (average 2.4) years. There was no necrosis of iliac inguinal flap, no recurrence of infection, and the flaps all healed well. The appearance, shape and texture of flaps were found close to the adjacent skin in all patients. Two-point discriminations (TPD) of the transferred iliac inguinal flaps were at 8-10 mm. X-ray reviews showed that bone union achieved in all patients. The time of bone union were 2.1-3.4 months (2.9 months in average) after bone grafting. There was no bone resorption, infection or nonunion. According to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 13 patients were excellent and 3 patients were good. All donor sites had primary healing with the motion of donor hips unaffected.Conclusion:Masquelet technique combined with free iliac inguinal flap is an effective, safe and feasible surgical procedure in reconstruction of infectious bone and soft tissue defect after metacarpal fracture surgery. It offers a satisfactory outcome with relatively less damage to the donor site.
8.Experimental study of proteasome inhibitor MG132 up-regulates Wnt/β-catenin signaling pathway to improve osteoporosis.
Rong-Xue SHAO ; Liang ZHANG ; He-Jie YANG ; Zhi-Jing ZHANG ; Jun YUE ; Hao PAN ; Hui ZHOU ; Ren-Fu QUAN
China Journal of Orthopaedics and Traumatology 2022;35(1):59-64
OBJECTIVE:
To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis.
METHODS:
Total of 32 female SD rats, weighing 220 to 250 g and 8 weeks old, were selected. They were randomly divided into 4 groups(n=8). Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis, and then they were given proteasome inhibitors MG132 and dimethyl sufoxide (DMSO) respectively. Group C was a sham group and rats were given MG132. Group D was a normal group and rats were given MG132 too. The rats were killed in batches at 6 and 12 weeks after administration, and the femoral neck tissues were obtained. Relevant data were analyzed, such as pathomorphological observation, micro-CT analysis, detection of 20S proteasome activity in tissues, and expression of Wnt and β-catenin.
RESULTS:
Morphological observation showed that the trabecular were slightly thinner, reticulated, and occasionally interrupted in group A, while the trabecular were obviously thinner and discontinuous in group B. And the trabecular were intact and arranged reticulated in group C and D. The analysis results of bone mineral density(BMD), bone surface(BS), bone volume/total volume(BV/TV) and trabecular thickness(Tb.Th) showed that group B was worse than other groups in all parameters at different time points(P<0.05), and group A was worse than group C and group D in BS(P<0.05), there was no significant difference in all parameters between group C and group D. RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05). According to the results of Western blot, the gray values of Wnt protein and β-catenin protein in group A were significantly higher than those in other groups (P<0.05).
CONCLUSION
MG-132, a ubiquitin proteasome inhibitor, can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation of β-catenin protein, and delaying the occurrence and development of osteoporosis.
Animals
;
Bone Density
;
Female
;
Leupeptins
;
Osteoporosis/drug therapy*
;
Proteasome Inhibitors/pharmacology*
;
Rats
;
Rats, Sprague-Dawley
;
Wnt Signaling Pathway
;
beta Catenin/metabolism*
9.Epidemiological characteristics of hand, foot and mouth disease among people aged 6 and over in Beijing, 2011-2020.
Shuai Bing DONG ; Xiao Li WANG ; Da HUO ; Ren Qing LI ; Yang YANG ; Zhi Chao LIANG ; Quan Yi WANG ; Lei JIA
Chinese Journal of Epidemiology 2022;43(2):207-212
Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) among people ≥6 years old in Beijing from 2011 to 2020. Methods: The incidence data of HFMD cases from 2011 to 2020 were collected from the National Notifiable Infectious Disease Reporting System of China Information for Disease Control and Prevention and the etiological surveillance of HFMD in 29 sentinel hospitals from 16 districts of Beijing. Descriptive epidemiological methods were used to analyze the distributions, pathogen constituents, and changes of HFMD cases in Beijing people ≥6 years old. Results: From 2011 to 2020, a total of 38 183 cases of HFMD were reported among people ≥6 years old in Beijing, of which 46 (0.12%) cases were severe. The average annual reported incidence was 19.04/100 000. The ratio of males to females were 1.37∶1(22 064∶16 119). The proportion of HFMD in people ≥6 years old increased from 7.56%(2 606/34 488) in 2011 to 24.54% (546/2 225) in 2020. The average incidence of HFMD was higher in Shunyi district, Yanqing district, and Tongzhou district than in other districts in Beijing. The positive rate of enterovirus in sentinel surveillance was 66.78% (1 976/2 959), the proportion of enterovirus group A 71 (EV-A71) was 45.29% (101/223) in 2014, no EV-A71 positive was detected in 2020, and the proportion of Coxsackievirus A 6 (CV-A6) increased from 15.11% (34/225) in 2016 to 81.08% (60/74) in 2020. Conclusions: From 2011 to 2020, the proportion of cases with HFMD in people ≥6 years old in Beijing increased yearly, and the proportion of EV-A71 positive patients decreased basically. Since 2016, CV-A6 has gradually become the dominant pathogen. More attention should be paid to the epidemic situation and dynamic pathogen changes of hand foot mouth disease in people ≥6 years old.
Child
;
China/epidemiology*
;
Enterovirus
;
Enterovirus A, Human
;
Enterovirus Infections/epidemiology*
;
Female
;
Hand, Foot and Mouth Disease/epidemiology*
;
Humans
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Infant
;
Male
10.The Value of T Cell subsets and Cytokine Levels Changes in the Clinical Diagnosis, Treatment and Prognosis Evaluation of Multiple Myeloma.
Zhi-Min YAN ; Yan-Quan LIU ; Zou-Fang HUANG ; Yan LIANG ; Jie LIN ; Jian-Zhen SHEN ; Xin-Ji CHEN
Journal of Experimental Hematology 2022;30(6):1791-1796
OBJECTIVE:
To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with MM and immune function status, biochemical indicators, and their relationships with clinical stage and prognosis, which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of MM patients.
METHODS:
The clinical data of 89 MM patients in two hospitals were collected, and 36 healthy people without tumor or infectious diseases were selected as the control group. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels, respectively. At the same time, automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum β2-microglobulin (β2-MG), lactate dehydrogenase (LDH), albumin (ALB), creatinine (CRE) and hemoglobin (HGB) levels, and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed.
RESULTS:
The proportions of NK cells and CD8+T lymphocytes in the peripheral blood of MM patients were significantly higher than that of the control group (P<0.01), the proportion of CD4+T and the ratio of CD4+/CD8+ were lower than those of the control group (P<0.05); however, there was no significant difference in the numbers CD3+T cells compared with the control group (P>0.05). The proportion of CD4+T and ratios of CD4+/CD8+ in MM patients were lower than those of normal controls, and were negatively correlated with MM staging (r=-0.964, r=-0.653), that is, the later the MM staging, the more obvious their levels were reduced, while CD8+T and NK cells were positively correlated with MM staging (r=0.891, r=0.728), that is, the later the MM staging, the more significant their levels increased. The levels of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) of MM patients in the disease stage Ⅰ, Ⅱ and Ⅲ were (5.87±0.92)%, (7.97±1.32)%, (11.52±4.71)% respectively, the difference was statistically significant compared with control group (P<0.05), and the level of Treg cells in MM patients with stage III was significantly higher than that in controls and patients with other disease stages (P<0.01). The proportion of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) in MM patients was positively correlated with the concentration of β2-MG and LDH (r=0.793, r=0.536), but had no significant correlation with HGB, ALB and CRE. The serum levels of IL-6, IL-10 and TNF-α in MM patients were significantly higher than those in the control group (P<0.05), which were closely related to MM staging(r=0.839, r=0.917, r=0.746), that is, the later the MM staging, the higher the levels; The serum IFN-γ level was negatively correlated with the stage of MM (r=-0.689), and its level gradually decreased with the increase of the disease stage and degree (P<0.01). There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage, but they were all up-regulated compared with the control group (P<0.05).
CONCLUSION
The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of MM patients, which is an effective indicator for the disease monitoring of MM patients.
Humans
;
Multiple Myeloma/therapy*
;
Cytokines
;
L-Lactate Dehydrogenase
;
T-Lymphocyte Subsets

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