Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.

[Advances in Modeling of Multiple Myeloma in Mice].

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

[Progress in Chimeric Antigen Receptor-Modified Natural Killer Cells for Multiple Myeloma].

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Recurrent hematuria and painful necrotic purpura induced by acquired Protein S deficiency associated with monoclonal immunoglobulin.

Protein S deficiency is associated with an increased risk of thromboembolism, which may be caused by hereditary deficiency and several physiological and pathologic conditions, such as pregnancy, contraceptive use, liver diseases, inflammatory disease, and certain viruses infections. However, monoclonal immunoglobulin-mediated Protein S deficiency is rarely reported. Here we described a 49-year-old woman with a history of recurrent painful swelling in both lower extremities due to venous thrombosis for 7 years, accompanied by recurrent gross hematuria and multiple painful necrotic purpuras for 5 years, who was then diagnosed with acquired Protein S deficiency induced by the monoclonal immunoglobulin. Then she was successfully treated with rituximab combined with anticoagulation therapy. This case highlights the rare manifestations of Protein S deficiency and the influence of the monoclonal immunoglobulin produced by monoclonal B lymphocytes and monoclonal plasma cells on the activity of Protein S, which can be treated effectively with rituximab combined with anticoagulation therapy.

[Full-cycle Health Management of Multiple Myeloma].

Multiple myeloma is a hematologic tumor characterized by clonal proliferation of plasma cells.The development of novel agents and immunotherapy have substantially improved the prognosis of multiple myeloma,with an expectable median survival beyond ten years.Therefore,there is an urgent need to improve the management of this disease.Health management is effective in controlling chronic diseases and full-cycle management should be implemented from the early to the end stage of the disease.Implanting the full-cycle concept into the health management of multiple myeloma will guide and standardize the advances in this field.This review focuses on the full-cycle concept of multiple myeloma and the corresponding application of health management at each stage of the cycle.

[Receptor Activator of Nuclear Factor κB Ligand-Receptor Activator of Nuclear Factor κB Signaling Pathway in Myeloma Bone Disease].

Multiple myeloma is an incurable malignant disease characterized by proliferation of clonal plasma cells in the bone marrow.About 90% of the patients with multiple myeloma develop myeloma bone disease(MBD),which seriously affects the quality of life and prognosis of the patients.Traditional therapies for MBD include bisphosphonates,radiotherapy,and surgery.The recent studies have confirmed that the receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB(RANK) signaling pathway plays a key role in MBD,providing a new therapeutic target for MBD.This review summarized the role of RANKL-RANK signaling pathway in the pathogenesis of MBD and the advance in the targeted therapy.

The combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma.

The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Their response to treatment and survival was also analyzed. C-Myc and Mcl-1 expressions in bone marrow samples were analyzed by RT-PCR. The expression of Mcl-1 was evaluated in bone marrow sections by immunohistochemistry. MM cell lines were transfected with Mcl-1 siRNA. 1q21 gain was present in 55/153 (35.9%) patients and strongly associated with Myc rearrangement (31/153, 20.3%, P = 0.004). A positive correlation was observed between Myc and Mcl-1 mRNA levels in bone marrow cells from 47 patients (r = 0.57, P < 0.001). The combination of 1q21 gain and Myc rearrangement was associated with poorer overall survival than Myc rearrangement alone (16.8 vs. 27.9 months, P = 0.077) or 1q21 gain alone (16.8 vs. 60.7 months, P < 0.01). High Mcl-1 protein expression in bone marrow plasma cells was associated with Myc rearrangement. Mcl-1 silencing by siRNA inhibited Myc protein expression in three myeloma cell lines. Treatment with the small-molecule Mcl-1 inhibitor, UMI-77, produced similar results. Overall, the combination of Myc rearrangement and 1q21 gain was associated with particularly poor prognosis in patients with MM. Furthermore, our data are consistent with Mcl-1-dependent Myc protein activation.

Short- and long-term outcomes with renin-angiotensin-aldosterone inhibitors in renal transplant recipients: A meta-analysis of randomized controlled trials.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) are often prescribed for renal transplant recipients (RTRs), but the outcomes of these medications in RTRs remain controversial. METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched. Randomized controlled trials investigating the outcomes of ACEI/ARBs in RTRs were included for meta-analysis. RESULTS: Twenty-two trials with 2242 patients were identified. After treatment for at least 12 months, ACEI/ARBs were associated with a decline in glomerular filtration rate (GFR) (weighed mean differences [WMD] -5.76 mL/min; 95% confidence intervals [CI]: -9.31 to -2.20) and a decrease in hemoglobin (WMD -9.81 g/L; 95% CI: -14.98 to -4.64). There were no significant differences in mortality between ACEI/ARB and non-ACEI/ARB groups (risk ratio [RR] 0.98, 95% CI: 0.58 to 1.76), nor in graft failure (RR 0.68, 95% CI: 0.38 to 1.32). After short-term treatment (less than 1 year), significant differences were found in changes of 24-hour proteinuria (WMD-0.57 g/d; 95% CI: -0.72 to -0.42) and serum potassium (WMD 0.25 mEq/L; 95% CI: 0.14 to 0.37) in ACEI/ARB groups compared to control arm, while these differences were not confirmed in the long run. CONCLUSION: This meta-analysis indicates ACEI/ARBs may be prescribed to RTRs with GFR and hemoglobin being carefully monitored.

[The value of chest computerized tomography in evaluation of bone disease and clinical prognosis of multiple myeloma].

OBJECTIVE: To assess the status and severity of bone disease in patients with multiple myeloma (MM) by using chest computerized tomography (CT) and the relationship between clinical prognostic parameters and bone disease. METHODS: All 46 newly diagnosed MM in-patients received both imaging tests of chest CT and plain X ray. An experienced radiologist reviewed all the imaging data. Clinical laboratory parameters, stages of Durie-Salmon (DS) and International Staging System (ISS) were evaluated. Five cytogenetic abnormalities of bone marrow myeloma cells were tested by fluorescence in situ hybridization (FISH). RESULTS: The sensitivity of CT and X ray to determine pathological fractures was comparable, the positive rates of which were 41.3% (19/46) and 30.4% (14/46) respectively (P = 0.29). Nevertheless, the positive rate of osteolytic lesions ascertained by CT was significantly higher than that by X ray (P < 0.001), 60.9% (28/46) vs 13.0% (6/46) with diameter 5-10 mm and 50.0% (23/46) vs 10.9% (5/46) with diameter more than 10 mm. Osteolytic lesion numbers found by CT were more than those by X ray [5(0-21) vs 0(0-4) lesions with diameter 5-10 mm (P < 0.001), 2(0-14) vs 0(0-2) lesions with diameter more than 10 mm (P < 0.001), respectively]. Patients with positive osteolytic lesions had higher percentage of RB1 gene deletion [46.7% (14/30) vs 18.8% (3/16), P < 0.001], D13s319 deletion [43.3% (13/30) vs 18.8% (3/16), P < 0.001] and high risk cytogenetic abnormalities [50.0% (15/30) vs 25.0% (4/16), P < 0.001]. CONCLUSIONS: Chest CT is more sensitive than plain X ray in detecting osteolytic myeloma bone disease. Osteolysis determined by CT is relevant to clinical DS stages and risk stratification of cytogenetic abnormalities.

[Clinical and cytogenetic characteristics of myeloma patients with overall survival less than 24 months].

OBJECTIVE: To explore the clinical characteristics of multiple myeloma (MM) patients with overall survival (OS) less than 24 months so as to stratify high-risk population. METHODS: A total of 177 newly diagnosed MM inpatients were recruited from July 2008 to July 2012. Clinical parameters at diagnosis of international staging system (ISS), lactic dehydrogenase (LDH), serum calcium, extramedullary involvement and amyloidosis were collected and cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH). Response and death were recorded as endpoints. Otherwise the follow-up period was over 24 months. RESULTS: And 73 patients dying within 24 months were classified into high-risk group while another 104 survivors for over 24 months into control group. Age and gender at baseline were comparable. However, OS of high-risk group was only 8 months while it was not attained during a median follow up of 38 months in control group (P < 0.001). The most common cause of death was progressive disease in both groups. The pre-treatment percentages of the following parameters were significantly higher in high-risk group, including ISS stage III (76.71% (56/73) vs 50.00% (52/104), P = 0.002), renal dysfunction (47.95% (35/73) vs 31.73% (33/104), P = 0.029), elevated LDH (20.55% (15/73) vs 7.69% (8/104), P = 0.015) and plasma cell leukemia (PCL, 5.48% (4/73) vs 0 (0/104), P = 0.016). Conversely, extramedullary involvement, plasmacytoma, amyloidosis and hypercalcemia were similar. Despite comparable chemotherapeutic regimens, the rate of deep response, including complete response (CR) and very good partial response (VGPR), was significant lower in high-risk group than that in control group (12.33% (9/73) vs 53.85% (56/104), P < 0.001). Overall response rates (ORR, i.e. CR+VGPR+ partial response (PR)) were markedly different (38.36% (28/73) vs 86.54% (90/104), P < 0.001). Univariate analysis of cytogenetic abnormalities indicated a higher proportion of 1q21 amplification in high-risk group (35.62% (26/73) vs 25.15% (22/104), P = 0.033). Multivariate Logistic regression revealed that ISS, LDH and primary response worse than PR independently affected early death (P = 0.046, 0.005, < 0.001). CONCLUSIONS: MM patients with OS less than 24 months have distinct clinical characteristics. And aggressive regimens are needed to improve the outcomes of high-risk population.

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review.

Background: Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy. Methods: The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software. Results: Nine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01). The median PFS of the daratumumab-based and RVD/RVD-lite groups were 52.6 months and 35.1 months respectively (HR 0.77, 95%CI, 0.66-0.90). The median OS of both groups was not reached, and there were no significant differences in OS between the two groups (HR 1.03, 95%CI, 0.86-1.23). The therapy discontinuation rate led by adverse events was significantly higher in the RVD/RVD-lite group than in the daratumumab-based regimen group for the TIE-NDMM (16% vs. 7%, P=0.03). Conclusion: This meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies.

Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma.

OBJECTIVE: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first-in-human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). METHODS: This is a multicenter phase I clinical trial consisting of the 3+3 dose-escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28-day cycle. RESULTS: Twenty-five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose-limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any-grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time-to-plasma peak concentration of 0.8-1.5 h. The mean half-life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response-evaluable patients, 63.7% achieved stable disease or better. CONCLUSIONS: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose-expansion phase.

Noncoding RNAs in the crosstalk between multiple myeloma cells and bone marrow microenvironment.

Multiple myeloma (MM) is the second most common hematological malignancy; however, it remains incurable, and the underlying pathogenesis and mechanisms of drug resistance remain unclear. It is widely recognized that the bone marrow microenvironment plays a crucial role in regulating the immune response, inducing drug resistance, and promoting tumor proliferation and invasion in MM, and thus serves as a potential therapeutic target. Among the various signaling loops between myeloma cells and components of the microenvironment, noncoding RNAs are emerging as crucial regulators of intercellular communication within the microenvironment. Noncoding RNAs, such as microRNAs, long noncoding RNAs, circular RNAs, and PIWI-interacting RNAs, have been associated with numerous biological processes involved in myeloma cell growth, survival, migration, invasion, and drug resistance. This review summarizes recent advances in the regulatory mechanisms of noncoding RNAs involved in the interaction between the MM bone marrow microenvironment and discusses the therapeutic potential of noncoding RNAs in MM.

Treatment attrition rates and relevant risk factors in multiple myeloma: A real-world study in China.

Background: For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China. Methods: MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the "HemaTank" Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition. Results: A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%-56.8%) than MM without ASCT (range 49.1%-64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, p < .001), elevated LDH (HR 1.47, p = .006), and comorbidities such as amyloidosis (HR 1.63, p = 0 .01), hepatic disease (HR 1.36, p = .022), pulmonary disease (HR 1.38, p = .022), and cardiac disease (HR 1.62, p = .004) were independent risk factors for MM patients attritted from the frontline treatment. Conclusion: In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.

A stratified therapeutic model incorporated with studies on regulatory B cells for elderly patients with newly diagnosed multiple myeloma.

OBJECTIVE: Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence-based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). METHODS: In this open-label, non-interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. RESULTS: Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) (n = 80), lenalidomide/dexamethasone (Rd) (n = 27), Bd with a third agent X (Bd + X) (n = 27), and other regimens (n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression-free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised-International Staging System (R-ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs <10% (p = 0.036) and SUVmax of PET-CT scan >4.2 (p = 0.000) were closely correlated with OS in the elderly MM. CONCLUSIONS: For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment.

A systematic review on performance analysis of critical time points in multiple myeloma treated by CAR-T cell immunotherapy.

BACKGROUND: Multiple myeloma (MM) is the second most common hematological malignancy without cure, and Chimeric Antigen Receptor T Cell (CAR-T) therapy has been shown great promising in MM. Unlike previous published studies mainly focusing on efficacy and safety, this study aims to summarize time points in the process of CAR-T therapy in MM and establish a standardized time-related CAR-T therapy platform to provide a reference for CAR-T treatment in MM. METHODS: All the literatures were retrieved from PubMed, Web of Science, Embase, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA). Relevant median detection time of efficacy and safety-related indicators of CAR-T therapy in MM were extracted from included literatures, and median values were applied to represent detection time points of indicators. Notably, the median values were not the certain and optimal detection time points, while the significance is that indicators could be detected more frequently around the median values to obtain the ideal results. RESULTS: This review presented the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM according to the chronological order. For short-term effects on inflammation status within 1 month after CAR-T initiation, the median time points of cytokine release syndrome onset, immune effector cell-associated neurotoxicity syndrome onset, neutrophils recovery and CAR-T expansion peak were 4.5, 8, 10 and 12 days, respectively. For medium-term effects on clinical response in MM beyond 1 month and up to 3 months following CAR-T infusion, the median time points of minimal residual disease negativity, the reduction of serum light chain to minimum, platelet recovery and the reduction of M protein to minimum were 30, 30, 44 and 90 days, respectively. CONCLUSIONS: This systematic review summarized the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM and constructed the time-related CAR-T therapy platform, providing an evidence-based standard for establishment of CAR-T treatment regimen in MM.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

An investigation on bloom dynamics of Alexandrium catenella and A. pacificum and toxin accumulation in shellfish along the coast of Qinhuangdao, China.

The dinoflagellate genus Alexandrium comprises most of the toxic bloom-forming species producing paralytic shellfish toxins (PSTs) in the sea. Recently, repeated paralytic shellfish poisoning episodes have been recorded in Qinhuangdao located at the west coast of the Bohai Sea. To elucidate the relationship between toxic Alexandrium blooms and the poisoning episodes, a year-round investigation was carried out in this region from July 2020 to July 2021. Two qPCR assays were used to detect A. catenella and A. pacificum, and LC-MS/MS was applied to analyze PSTs in phytoplankton and shellfish samples. The blooms of A. catenella and A. pacificum were found in April and July, respectively, and PST content in three bivalves exhibited notable increase following the bloom of A. catenella. The results revealed bloom dynamics of the two toxic Alexandrium species in the Bohai Sea for the first time, and further confirmed A. catenella as the causative agent of poisoning episodes.

Erratum: Real-world data combined with studies on Regulatory B Cells for newly diagnosed Multiple Myeloma from a tertiary referral Hospital in South-Western China: Erratum.

[This corrects the article DOI: 10.7150/jca.53209.].