Exploring the R-ISS stage-specific regular networks in the progression of multiple myeloma at single-cell resolution

The Revised International Staging System(R-ISS)is a simple and powerful prognostic tool for multiple myeloma(MM).However,heterogeneity in R-ISS stage is still poorly characterised,hampering improvement of treatments.We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS.Plasma cells were clustered into nine groups(P1–P9)based on gene expression,where P1–P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1was enriched in P1,and they were validated to be upregulated in the MM cell line and in 22 other patients’myeloma cells.Furthermore,in progression,PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation,while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway.Finally,a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3.A few ligand-receptor pairs(CCL3/CCL5/CCL3L1-CCR1)were obviously active in monocyte-plasma communications in stage III.Herein,this study identified novel molecules,networks and crosstalk pairs in different R-ISS stages of MM,providing significant insight for its prognosis and treatment.

Analysis of the Predictive Factors for the Recurrence of Deep Infiltrating Endometriosis:A 2-Year Prospective Study

Objective:To investigate factors that may be associated with the recurrence of deep infiltrating endometriosis(DIE)and DIE-related symptoms.Methods:Starting in September 2014,women with a confirmed diagnosis of DIE based on surgical and histological findings were included in the prospective study with a 2-year follow-up in our hospital.A total of 84 consecutive patients were included,all of whom underwent laparoscopic surgery.The data were obtained from the medical records of the patients.Follow-up data,including presence of pain as assessed using the visual analog scale(VAS)score and ultrasonography/magnetic resonance imaging findings,were obtained at 3,6,9,12,and 24 months postoperatively.Variables,such as age,body mass index,severity and duration of symptoms,size and location of the lesion,and pre-and postoperative medical treatment,were evaluated using univariate and multivariate analyses to identify factors correlated to recurrence.Results:A total of 11(13.1%)patients presented with recurrence,with a mean time to recurrence of 14.2 months.The univariate analysis showed that the longer duration of menstruation(7.4 vs.6.0,P=0.010),the more advanced revised American Fertility Society(rAFS)stage(Stages I and II vs.III and IV,χ^(2)=9.964,P=0.001),the higher VAS score for dysmenorrhea(9.4 vs.5.2,P=0.001),and the more severe pain during defecation(7.8 vs.4.8,P=0.016)were positively correlated to DIE recurrence.However,the multivariate analysis also revealed that a more severe dysmenorrhea and advanced rAFS stage were the independent factors associated with the recurrence of DIE,with an odds ratio of 1.895(confidence interval[CI]:1.061-3.385,P=0.031)and 4.310(CI:1.091-17.028,P=0.037),respectively.Conclusions:More than 10%of patients presented with recurrence of DIE 2 years after surgery.Recurrence of DIE was more common in patients who complained of more severe dysmenorrhea and had an advanced rAFS stage.