BACKGROUND:Osteoporosis is defined as a chronic metabolic bone disease,and a large amount of evidence has shown that gut microbiota is involved in osteoporosis.However,the causal relationship between gut microbiota and osteoporosis is yet unclear.OBJECTIVE:To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.METHODS:Pooled statistics from the MiBioGen Consortium's Genome-Wide Association Analysis(GWAS)of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used.Inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis.Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.RESULTS AND CONCLUSION:The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis.Among them,the R7 genus of Christensenaceae(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028),Coprococus 3(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)and Trichospirillum(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003)may be protective factors for osteoporosis,while Hotella(MR Egger:β=0.006;IVW:β=0.002,P=0.033)and Eubacterium oxyoxide(MR Egger:β=0.001;IVW:β=0.003,P=0.046)may be potential risk factors for osteoporosis.Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis,while R7 of Christensenaceae,Coprococcus 3 and Spirillum can reduce the risk of osteoporosis.Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups.

BACKGROUND:Osteoporosis is defined as a chronic metabolic bone disease,and a large amount of evidence has shown that gut microbiota is involved in osteoporosis.However,the causal relationship between gut microbiota and osteoporosis is yet unclear.OBJECTIVE:To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.METHODS:Pooled statistics from the MiBioGen Consortium's Genome-Wide Association Analysis(GWAS)of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used.Inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis.Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.RESULTS AND CONCLUSION:The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis.Among them,the R7 genus of Christensenaceae(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028),Coprococus 3(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)and Trichospirillum(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003)may be protective factors for osteoporosis,while Hotella(MR Egger:β=0.006;IVW:β=0.002,P=0.033)and Eubacterium oxyoxide(MR Egger:β=0.001;IVW:β=0.003,P=0.046)may be potential risk factors for osteoporosis.Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis,while R7 of Christensenaceae,Coprococcus 3 and Spirillum can reduce the risk of osteoporosis.Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups.

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 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.

Background: Domestic yaks are the most important livestock species on the Qinghai-Tibetan Plateau. Adult female yaks normally breed in the warm season (July to September) and enter anestrous in the cold season (November to April). Nevertheless, it is unclear how ovarian activity is regulated at the molecular level. Objectives: The peculiarities of yak reproduction were assessed to explore the molecular mechanism of postpartum anestrus ovaries in yaks after pregnancy and parturition. Methods: Sixty female yaks with calves were observed under natural grazing in Haiyan County, Qinghai Province. Three yak ovaries in pregnancy and postpartum anestrus were collected. RNA sequencing and quantitative proteomics were employed to analyze the pregnancy and postpartum ovaries after hypothermia to identify the genes and proteins related to the postpartum ovarian cycle. Results: The results revealed 841 differentially expressed genes during the postpartum hypoestrus cycle; 347 were up-regulated and 494 genes were down-regulated. Fifty-seven differential proteins were screened: 38 were up-regulated and 19 were down-regulated. The differential genes and proteins were related to the yak reproduction process, rhythm process, progesterone-mediated oocyte maturation, PI3K/AKT signaling pathway, and MAPK signaling pathway categories. Conclusions Transcriptome and proteomic sequencing approaches were used to investigate postpartum anestrus and pregnancy ovaries in yaks. The results confirmed that BHLHE40, SF1IX1, FBPX1, HSPCA, LHCGR, BMP15, and ET-1R could affect postpartum hypoestrus and control the state of estrus.

Objective To study the expression characteristics of serum antinuclear antibodies (ANA) in lymphoma patients as well as their target antigens in cells, and to explore the possible relationship between lymphoma and ANA. Methods Indirect immunofluorescence was used to detect the ANA expression level in 100 cases of lymphoma and 200 population-based controls. Then the relationship between lymphoma and ANA was investigated by means of 1:2 matched with logistic regression models. Results The positive rate of ANA in lymphoma patients was higher than that in the control group [28 % (28/100) vs. 7 % (14/200)], with a statistical difference (OR= 13.66, 95 %CI 4.10-45.57, P< 0.01). The positive rate of ANA in females was higher than that in males, and the positive rate of ANA became higher with age. Lymphoma group had more complex fluorescence pattern and wider target antigen spectrum compared with the control group. Conclusions Detection of ANA in lymphoma may help in the early diagnosis,prognosis and treatment. ANA target antigen spectra of lymphoma patients are different from those in healthy people as well as patients with autoimmune disease. Further efforts should be made to identify the target antigens as well as their biological roles and clinical significances.