BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

ObjectiveBased on the adenosine 5'-monophosphate （AMP）-activated protein kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 （AMPK/Akt/Nrf2） pathway， this study aims to explore the mechanism by which modified Guishenwan improves glucose and lipid metabolism and oxidative stress in polycystic ovary syndrome （PCOS） rats. MethodsA PCOS rat model was established by continuous oral administration of letrozole （1 mg·kg^-1·d^-1） for 21 days. Successfully modeled rats were randomly divided into a model group， a metformin group （0.25 g·kg^-1）， and low-， medium-， and high-dose modified Guishenwan groups （4.01， 8.02， and 16.04 g·kg^-1·d^-1）， with 8 rats in each group. Ten normal rats were assigned to the normal group. The drug groups were given their respective doses， while the normal and model groups were given an equal volume of normal saline. Intervention lasted for 4 weeks. Testosterone （T）， estradiol （E₂）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Fasting blood glucose （FPG）， fasting insulin （FINS）， triglyceride （TG）， and total cholesterol （TC） levels were measured using an automatic biochemical analyzer， and the insulin resistance index （HOMA-IR） and insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. Malondialdehyde （MDA）， advanced glycation end products （AGEs）， and superoxide dismutase （SOD） levels in serum and ovarian tissue were measured using a chemical fluorescence method. Hematoxylin-eosin （HE） staining was used to assess ovarian tissue pathology. Real-time quantitative fluorescent polymerase chain reaction （Real-time PCR） and Western blot were used to measure the expression of AMPK/Akt/Nrf2 pathway-related genes and proteins in ovarian tissue. ResultsCompared with the normal group， the model group exhibited significantly increased levels of T， LH， LH/FSH， FPG， FINS， TG， TC， and HOMA-IR， while FSH， E₂， and HOMA-ISI were significantly decreased （P<0.05， P<0.01）. MDA and AGEs levels were significantly higher in both serum and ovarian tissue， and SOD levels were significantly reduced （P<0.05）. AMPK， Akt， and Nrf2 mRNA and protein expression in ovarian tissue was also significantly reduced （P<0.05）. The OGTT and ITT results showed significantly higher blood glucose levels at each time point （P<0.05， P<0.01）， with impaired glucose and insulin tolerance. Ovarian follicles showed polycystic changes， reduced corpus luteum， and sparse granulosa cell layers. Compared with the model group， the metformin group and the high-dose modified Guishenwan group showed significant decreases in T， LH， LH/FSH， FPG， FINS， TG， TC， and HOMA-IR， while FSH， E₂， and HOMA-ISI were significantly increased （P<0.05， P<0.01）. In the high-dose modified Guishenwan group， MDA and AGEs levels in serum and ovarian tissue were significantly reduced， and SOD levels were significantly increased （P<0.05）. The mRNA and protein expression of AMPK， Akt， and Nrf2 in ovarian tissue was significantly increased （P<0.05）. OGTT and ITT results showed that blood glucose levels in rats decreased significantly at each time point （P<0.05， P<0.01）. No obvious abnormalities were observed in ovarian tissue. Compared with the low-dose modified Guishenwan group， the high-dose group showed significant decreases in T， LH， LH/FSH， FPG， FINS， TG， TC， and HOMA-IR， while FSH， E₂， and HOMA-ISI were significantly increased （P<0.05）. OGTT and ITT results indicated that the high-dose modified Guishenwan group significantly improved glucose and insulin tolerance in rats. No significant abnormalities were observed in ovarian tissue. ConclusionModified Guishenwan effectively improves glucose and lipid metabolism abnormalities and inhibits oxidative stress in PCOS rats， potentially through regulation of the AMPK/Akt/Nrf2 pathway.

ObjectiveTo explore the mechanism by which modified Guishenwan alleviates inflammation in the rat model of polycystic ovary syndrome （PCOS） by regulating the mitogen-activated protein kinase （MAPK）/nuclear factor kappa B （NF-κB） pathway. MethodsAccording to the random number table method， 60 SPF female SD rats were randomized into a normal group （n=10） and a modeling group （n=50）. The normal group received routine feeding， while the modeling group was administrated with letrozole （1 mg·kg^-1·d^-1） by gavage for 21 days for the modeling of PCOS. The successfully modeled rats were randomized into model， diane-35 （0.2 g·kg^-1·d^-1）， high- （16.04 g·kg^-1·d^-1）， medium- （8.02 g·kg^-1·d^-1）， low- （4.01 g·kg^-1·d^-1） dose modified Guishenwan groups. The drug intervention groups were administrated with modified Guishenwan at corresponding doses by gavage， and the normal group and model group were given equal volumes of normal saline. All the groups were continuously treated for 28 days. After treatment， Gram staining of vaginal smears was employed to observe the estrous cycle in each group. Enzyme-linked immunosorbent assay was employed to determine the levels of follicle-stimulating hormone （FSH）， estradiol （E₂）， luteinizing hormone （LH）， testosterone （T）， and progesterone （PROG） in the plasma， as well as interleukin-1 beta （IL-1β）， tumor necrosis factor-alpha （TNF-α）， and interleukin-10 （IL-10） in the plasma and ovarian tissue. The LH/FSH ratio was calculated. The morphological changes in the ovarian tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the protein levels of extracellular-regulated protein kinase （ERK）， c-Jun N-terminal kinase （JNK）， p38 MAPK， NF-κB p65， IκBα， p-JNK， p-ERK， p-p38 MAPK， p-NF-κB p65， and p-IκBα in the ovarian tissue. Real-time quantitative polymerase chain reaction was used to determine the mRNA levels of ERK， JNK， p38 MAPK， NF-κB p65， and IκBα in the ovarian tissue. ResultsCompared with the normal group， the model group was in the estrus phase， with an increase in the number of ovarian vesicles and decreases in granulosa cells and corpus luteum formation （P<0.05）， and lowered levels of FSH and E₂ and elevated levels of LH， T， and LH/FSH in the plasma （P<0.05）. Compared with the model group， high-， medium-， and low-dose modified Guishenwan recovered the estrous cycle， increased the generation of granulosa cells and corpus luteum， reduced the number of vesicles， elevated the levels of FSH and E₂， and lowered the levels LH， T， and LH/FSH （P<0.05， P<0.01） in a dose-dependent manner. High-dose modified Guishenwan demonstrated the best therapeutic effect. Therefore， subsequent experiments for exploring the treatment mechanism were conducted in the normal group， model group， and high-dose modified Guishenwan group. The results showed that compared with the model group， high-dose modified Guishenwan lowered the levels of IL-1β， TNF-α， and IL-10 and elevated the level of IL-10 in the plasma and ovarian tissue （P<0.05， P<0.01）， down-regulated the protein levels of p-ERK， p-JNK， p-p38 MAPK， p-NF-κB p65， and p-IκBα， while up-regulating the protein level of IκBα （P<0.01）. At the same time， the mRNA levels of ERK， JNK， p38 MAPK， and NF-κB p65 in the high-dose modified Guishenwan group were down-regulated （P<0.05， P<0.01）. ConclusionModified Guishenwan can improve the ovarian function in rat model of PCOS induced by letrozole and has anti-inflammatory effects， which may be related to inhibition of the MAPK/NF-κB pathway.

OBJECTIVE To investigate the mechanism by which salvianolic acid A (Sal A) reduces the inflammatory response and oxidative stress of BV2 cells injured by oxygen and glucose deprivation/reperfusion (OGD/R).METHODS An OGD/R injury model of BV2 cells was established with sugar free Earle solution containing Na2S2O410 mmol·L-1.Na2S2O4 sugar free Earle solution was added and cultured in an incubator (37 ℃,5％CO2) for 1.5 h (oxygen glucose deprivation) before a normal medium was used for 24 h (reperfusion).Then,the cells were divided into the cell control group,OGD/R group,OGD/R+Sal A 1,5 and 10 μmol·L-1 group,OGD/R+ML385 group,OGD/R+ML385+Sal A 1,5 and 10μmol·L-1 group and OGD/R+edaravone (Eda,50μmol·L-1) group.After twenty-four hours of culture,the cell survival rate was measured by CCK8 kit.The contents of Interleukin-1β (IL-1β),IL-6,tumor necrosis factor-α(TNF-α),IL-10,IL-4 and transforming growth factor-β(TGF-β) in the cell supernatant were detected by ELISA.Reactive oxygen species (ROS) in cells was detected using the chemical fluo-rescence method.The contents of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD),glutathione peroxidase (GSH-PX) and chloramphenicol acetyltransferase (CAT) in cells were determined with the colorimetric method.Protein expressions of Kelch like ECH-associated protein 1 (Keap1),nuclear factor erythroid-2 related factor 2 (Nrf2),Heme oxygenase-1 (HO-1),NADPH:quinone oxidoreductase-1 (NQO1) and p-nuclear factor kappa-B p65 (p-NF-κB p65) were detected by Western blotting.RESULTS ①Compared with the cell control group,the cell survival rate of the OGD/R group was significantly decreased (P＜0.01).Compared with the OGD/R group,the survival rates of OGD/R+Sal A 1,5 and 10μmol·L-1 groups were significantly increased (P＜0.05,P＜0.01).②Compared with the cell control group,the contents of IL-1β,IL-6 and TNF-α were significantly increased,the contents of IL-10,IL-4 and TGF-β were significantly decreased,the contents of ROS and MDA were significantly increased,and the activities of SOD,CAT and GSH-Px were significantly decreased in the OGD/R group (P＜0.01).Compared with the OGD/R group,the content of IL-6 was significantly decreased,the contents of IL-10,IL-4 and TGF-β were significantly increased,the contents of ROS and MDA were significantly decreased,and the activities of SOD,CAT and GSH-Px were significantly increased in OGD/R+Sal A 1,5 and 10μmol·L-1 and OGD/R+Eda groups (P＜0.05,P＜0.01).③Compared with the cell control group,the protein expression of p-NF-κB P65 in the OGD/R group was significantly increased (P＜0.01).Compared with the OGD/R group,the protein expressions of Keap1 and cytoplasmic Nrf2 were significantly decreased,the expressions of nuclear Nrf2,HO-1 and NQO1 proteins were significantly increased,and the expression of p-NF-κB p65 protein was significantly decreased in OGD/R+Sal A 5 and 10 μmol·L-1 and OGD/R+Eda groups (P＜0.05,P＜0.01).In OGD/R+ML385,OGD/R+ML385+Sal A 1,5 and 10μmol·L-1 groups,the protein expression of Keap1 was significantly increased,the protein expressions of cytoplasmic Nrf2,nuclear Nrf2,HO-1 and NQO1 protein were significantly decreased,and the protein expression of p-NF-κB P65 was significantly increased (P＜0.01).CONCLU-SION Sal A reduces the inflammatory response and oxidative stress of OGD/R injured BV2 cells possi-bly by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB pathway.

Objective:To investigate the clinical characteristics and survival prognosis of patients with triple/quad-class exposed relapsed or refractory multiple myeloma(RRMM).Methods:The clinical data of patients with triple/quad-class exposed RRMM from eight centers in Shanxi Province between May 2017 and May 2024 were retrospectively analyzed.Overall survival(OS)and progression-free survival(PFS)were analyzed using the Kaplan-Meier method,and factors affecting survival were examined by the Cox proportional hazards model and Log-rank test.Results:Among the 112 patients with triple-class exposure,16 were quadruple-class exposed.The detection rates of high-risk cytogenetic abnormalities and extramedullary lesions in patients with triple-class exposure were 57.1%and 36.6%,respectively,while those in patients with quadruple-class exposure were 87.5%and 62.5%,respectively.The median PFS and OS of patients with triple-class expos-ure were 5.6 months and 12.2 months,respectively,while those of patients with quadruple-class exposure were 9.4 months and 16.9 months,respectively.Cox model analysis showed that extramedullary lesions and multi-line treatment(≥3 lines)were independent risk factors for the survival of patients with triple-class exposed RRMM(P<0.05).Previous autologous stem cell transplantation,subsequent con-ventional drug treatment,and B-cell maturation antigen(BCMA)chimeric antigen receptor T-cell(CAR-T)treatment were protective factors(P<0.05).After triple-class drug resistance,the Log-rank test verified that BCMA CAR-T treatment significantly prolonged the median PFS of patients compared to conventional drug treatment(9.4 months vs.5.2 months,P=0.026 9),whereas the difference in OS was not statistic-ally significant(16.9 months vs.7.9 months,P=0.263 4).Conclusions:Patients with triple/quad-class exposed RRMM have a poor prognosis,and BCMA CAR-T cell therapy can improve survival in patients with triple-class drug-resistant RRMM.

Objective:To investigate the current situation and influence factors of prehospital thrombolysis treatment for ST segment elevation myocardial infarction (STEMI) in China, to analyze the main factors affecting prehospital thrombolysis implementation, and optimize the pre-hospital thrombolysis strategy for STEMI to reduce mortality.Methods:A multicenter cross-sectional survey was conducted. 21 cities from six major geographical regions in China were selected by using convenient sampling method. An anonymous online electronic questionnaire was used to investigate the current situation and influence factors of prehospital emergency physicians and grassroots physicians implementing prehospital thrombolysis treatment for STEMI patients. Chi-square test was used to analyze the differences in count data between groups, and multivariate logistic regression was used to analyze the factors affecting prehospital thrombolysis in STEMI.Results:A total of 5 163 prehospital emergency physicians and physicians from grassroots township health centers/community health service centers or village clinics participated in this survey. Among them, 3208 (62.13%) have never implemtent thrombolysis, and 1 955 (37.87%) have did it before. The results of the multivariate logistic regression analysis indicated that physicians with 5-10 years of experience ( OR=1.41, 95% CI: 1.18-1.69, P<0.01), 11-20 years of experience ( OR=1.25, 95% CI: 1.03-1.52, P=0.02), those working in village clinics ( OR=1.30, 95% CI: 1.05-1.61, P=0.02), those in pre-hospital emergency medical institutions/departments ( OR=3.19, 95% CI: 2.80-3.64, P<0.01), those whose units are equipped with remote ECG transmission capabilities ( OR=1.72, 95% CI: 1.50-1.96, P<0.01), or ECG AI-assisted diagnostic tools ( OR=1.31, 95% CI: 1.15-1.49, P<0.01), and those who believe that thrombolysis is highly effective and should be widely adopted ( OR=2.55, 95% CI: 2.09-3.12, P<0.01) or consider it somewhat effective but warranting caution ( OR=2.11, 95% CI: 1.73-2.59, P<0.001), were more likely to make pre-hospital thrombolysis decisions for STEMI patients. To improve the current situation of pre-hospital thrombolysis for STEMI, the top four measures prioritized by pre-hospital emergency and grassroots physicians were enhancing the rescue capabilities of primary care doctors (92.22%), strengthening guidance from higherlevel hospitals (84.99%), increasing support for information technology (83.37%), and improving public health education (74.75%). Conclusions:The implementation rate of prehospital thrombolysis for STEMI in China still needs to be improved. Optimizing the prehospital thrombolysis strategy for STEMI, strengthening the allocation of basic medical resources and information technology support, and improving the referral mechanism are conducive to the implementation of prehospital thrombolysis for STEMI.

Objective To explore the biological function and downstream mechanism of ETS1 in glioma.Methods Bioinformatics and immunohistochemistry were used to analyze the differential expression characteristics of ETS1 in gliomas;qRT-PCR was employed to detect the expression level of ETS1 mRNA and lncRNA X-inactive specific transcript(XIST).CCK-8 and 5-ethyl-2′-deoxyuridine experiments were conducted to detect cell growth.Western blot was used to detect the expression of apoptosis-related proteins(Bax,Bak,Bcl-2).PROMO database was utilized to predict the binding sites between ETS1 and XIST promoter.Dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction assays were performed to verify the binding relationship between ETS1 and the XIST promoter region.cBioPortal database was used to analyze the correlation between the expression of ETS1 mRNA and XIST in glioma tissues.Results The expression levels of ETS1 mRNA and protein were significantly upregulated in glioma(P<0.05).The depletion of ETS1 significantly inhibited the proliferation of glioma cells and promoted cell apoptosis(P<0.05).ETS1 could target and bind with the XIST promoter and promote the expression of XIST(P<0.05).The overexpression of XIST reversed the effects of ETS1 on the proliferation of glioma cells and the promotion of cell apoptosis(P<0.05).Conclusion ETS1 is highly expressed in glioma tissues.It could promote the expression of lncRNA XIST,boost the proliferation of glioma cells,and inhibit cell apoptosis.

OBJECTIVE To investigate the mechanism by which salvianolic acid A (Sal A) reduces the inflammatory response and oxidative stress of BV2 cells injured by oxygen and glucose deprivation/reperfusion (OGD/R).METHODS An OGD/R injury model of BV2 cells was established with sugar free Earle solution containing Na2S2O410 mmol·L-1.Na2S2O4 sugar free Earle solution was added and cultured in an incubator (37 ℃,5％CO2) for 1.5 h (oxygen glucose deprivation) before a normal medium was used for 24 h (reperfusion).Then,the cells were divided into the cell control group,OGD/R group,OGD/R+Sal A 1,5 and 10 μmol·L-1 group,OGD/R+ML385 group,OGD/R+ML385+Sal A 1,5 and 10μmol·L-1 group and OGD/R+edaravone (Eda,50μmol·L-1) group.After twenty-four hours of culture,the cell survival rate was measured by CCK8 kit.The contents of Interleukin-1β (IL-1β),IL-6,tumor necrosis factor-α(TNF-α),IL-10,IL-4 and transforming growth factor-β(TGF-β) in the cell supernatant were detected by ELISA.Reactive oxygen species (ROS) in cells was detected using the chemical fluo-rescence method.The contents of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD),glutathione peroxidase (GSH-PX) and chloramphenicol acetyltransferase (CAT) in cells were determined with the colorimetric method.Protein expressions of Kelch like ECH-associated protein 1 (Keap1),nuclear factor erythroid-2 related factor 2 (Nrf2),Heme oxygenase-1 (HO-1),NADPH:quinone oxidoreductase-1 (NQO1) and p-nuclear factor kappa-B p65 (p-NF-κB p65) were detected by Western blotting.RESULTS ①Compared with the cell control group,the cell survival rate of the OGD/R group was significantly decreased (P＜0.01).Compared with the OGD/R group,the survival rates of OGD/R+Sal A 1,5 and 10μmol·L-1 groups were significantly increased (P＜0.05,P＜0.01).②Compared with the cell control group,the contents of IL-1β,IL-6 and TNF-α were significantly increased,the contents of IL-10,IL-4 and TGF-β were significantly decreased,the contents of ROS and MDA were significantly increased,and the activities of SOD,CAT and GSH-Px were significantly decreased in the OGD/R group (P＜0.01).Compared with the OGD/R group,the content of IL-6 was significantly decreased,the contents of IL-10,IL-4 and TGF-β were significantly increased,the contents of ROS and MDA were significantly decreased,and the activities of SOD,CAT and GSH-Px were significantly increased in OGD/R+Sal A 1,5 and 10μmol·L-1 and OGD/R+Eda groups (P＜0.05,P＜0.01).③Compared with the cell control group,the protein expression of p-NF-κB P65 in the OGD/R group was significantly increased (P＜0.01).Compared with the OGD/R group,the protein expressions of Keap1 and cytoplasmic Nrf2 were significantly decreased,the expressions of nuclear Nrf2,HO-1 and NQO1 proteins were significantly increased,and the expression of p-NF-κB p65 protein was significantly decreased in OGD/R+Sal A 5 and 10 μmol·L-1 and OGD/R+Eda groups (P＜0.05,P＜0.01).In OGD/R+ML385,OGD/R+ML385+Sal A 1,5 and 10μmol·L-1 groups,the protein expression of Keap1 was significantly increased,the protein expressions of cytoplasmic Nrf2,nuclear Nrf2,HO-1 and NQO1 protein were significantly decreased,and the protein expression of p-NF-κB P65 was significantly increased (P＜0.01).CONCLU-SION Sal A reduces the inflammatory response and oxidative stress of OGD/R injured BV2 cells possi-bly by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB pathway.

Objective:To investigate the clinical characteristics and survival prognosis of patients with triple/quad-class exposed relapsed or refractory multiple myeloma(RRMM).Methods:The clinical data of patients with triple/quad-class exposed RRMM from eight centers in Shanxi Province between May 2017 and May 2024 were retrospectively analyzed.Overall survival(OS)and progression-free survival(PFS)were analyzed using the Kaplan-Meier method,and factors affecting survival were examined by the Cox proportional hazards model and Log-rank test.Results:Among the 112 patients with triple-class exposure,16 were quadruple-class exposed.The detection rates of high-risk cytogenetic abnormalities and extramedullary lesions in patients with triple-class exposure were 57.1%and 36.6%,respectively,while those in patients with quadruple-class exposure were 87.5%and 62.5%,respectively.The median PFS and OS of patients with triple-class expos-ure were 5.6 months and 12.2 months,respectively,while those of patients with quadruple-class exposure were 9.4 months and 16.9 months,respectively.Cox model analysis showed that extramedullary lesions and multi-line treatment(≥3 lines)were independent risk factors for the survival of patients with triple-class exposed RRMM(P<0.05).Previous autologous stem cell transplantation,subsequent con-ventional drug treatment,and B-cell maturation antigen(BCMA)chimeric antigen receptor T-cell(CAR-T)treatment were protective factors(P<0.05).After triple-class drug resistance,the Log-rank test verified that BCMA CAR-T treatment significantly prolonged the median PFS of patients compared to conventional drug treatment(9.4 months vs.5.2 months,P=0.026 9),whereas the difference in OS was not statistic-ally significant(16.9 months vs.7.9 months,P=0.263 4).Conclusions:Patients with triple/quad-class exposed RRMM have a poor prognosis,and BCMA CAR-T cell therapy can improve survival in patients with triple-class drug-resistant RRMM.