Volume 102 ·  Issue 30 ·  2022

In order to ensure the continuous development of clinical practice guidelines rating and improve the rating efficiency, the Guidelines and Standards Research Center of the Journal of Chinese Medical Association and the Cooperation Center for Guidelines Implementation and Knowledge Transformation of the World Health Organization invited 106 experts from 42 specialties in 13 provinces or municipalities directly under the Central Government nationwide to comprehensively rate the Chinese guidelines and consensus published in medical journals in 2021 using the newly developed Rankings Tool for Scientificity, Transparency and Applicability of Guidelines (abbreviated as STAR), so as to help users select guidelines and consensus to guide clinical practice and promote the targeted improvement of the quality of guidelines and consensus.

In view of the shortcomings of existing evaluation methods and tools for clinical practice guidelines, this study developed a Rankings tool for Scientificity, Transparency and Applicability of clinical practice guidelines, abbreviated as STAR, and verified its reliability and validity and evaluated its ease of use. Establish a multi-disciplinary expert working group including guideline methodologists, statisticians, journal editors, medical staff, etc. to determine the rating field entries and corresponding scores based on profile evaluation, Delphi method and analytic hierarchy process, determine the list of tools through consensus meetings, and verify the reliability, validity and ease of use of the tools. Finally, a comprehensive evaluation tool with 39 entries and corresponding scores in 11 fields was formed. Intrinsic reliability analysis of the tool revealed that the average Cronbach's alpha coefficient value for each domain was 0.646; The reliability Cohen's kappa coefficients between methodological raters and clinical raters were 0.783 and 0.618, respectively; The overall content validity index of the entry was 0.905; Criterion validity analysis determination coefficient (R²) is 0.76; The average ease-of-use score of the items was 4.6, and the median time to evaluate 1 guide was 20 min. STAR has good reliability and rating efficiency, and can comprehensively rate the scientificity, transparency and applicability of Chinese guidelines.

With the widely usage of proteasome inhibitors, immunomodulating agents, monoclonal antibodies and autologous stem cell transplantation in the first line, most of multiple myeloma(MM) patients achieved high response rate and prolonged the survival period, but most of MM patients will relapse eventually. There are a lot of unmet needs for the management of relapse and refractory myeloma (RRMM). Although there are several guidelines for the diagnosis and treatment of RRMM, but doctors often find some controversies in clinical practice. The controversies will be discussed in this paper expected to guide the practice of younger doctors.

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO′s position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis.

The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients.

A total of 87 patients were retrospectively analyzed. The age[M(Q₁,Q₃)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS.

VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM).

Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software.

A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months (P<0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively (P=0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached (P=0.324 and P=0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months (P=0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months (P=0.001).

MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

To explorer Secretory mature B cell surface antigen (sBCMA) expression level, changes during treatment and clinical significance in newly diagnosed MM patients.

Clinical data of 158 MM patients admitted to the Department of Hematology, the First Affiliated Hospital of Soochow University from August 2018 to September 2020 were analyzed retrospectively. The concentration of sBCMA in the patients was determined by BCMA ELISA and compared with the normal range. The results were compared with clinical efficacy, age, type, R-ISS stage, renal impairment, and humoral immune function.

The median age of the patients was 57 (31-73 years old), 86 (54.5%) males and 72 (45.5%) females, mainly IgG type, 81 patients(51.2%). SBCMA value M(Q₁,Q₃) was 76.50 (55.50, 94.40) μg/L, 100% higher than the upper limit of normal value. According to the efficacy evaluation, the patients were divided into complete remission(CR) group, very good partial remission(VGPR) group, partial remission(PR) group and ineffiecacy group, the results showed the level of sBCMA in CR group[80.10 (58.05, 96.90) vs 15.70 (9.85, 28.65) μg/L] and VGPR group[74.60 (52.20, 93.00) vs 17.20 (13.30, 38.80) μg/L]was significantly higher than that before treatment(all P<0.001), and there was no significant difference in PR group and ineffective group before and after treatment (all P>0.05).The amount of serum intact protein M protein was positively correlated with the level of sBCMA expression in newly diagnosed patients (r=0.22, P=0.040), and there was no correlation between the proportion of bone marrow plasma cells and sBCMA expression (r=0.07, P=0.449).The correlation between sBCMA levels at initial diagnosis and MM type[IgG type, IgA type vs light chain type:(78.6±3.5), (72.4±5.4) vs (83.8±6.9)μg/L], age[≥65 vs<65 years: (73.6±5.5)vs (79.3±3.1)μg/L], R-ISS stage[stage Ⅰ, Ⅱ vs Ⅲ:(80.2±3.1) vs (69.4±6.1)μg/L], renal impairment [Creatinine clearance rate (Ccr) ≤30 vs>30 ml/min:(81.6±4.8) vs (76.5±3.4)μg/L], and high-risk karyotype[high-risk vs standard-risk:(73.6±5.7) vs (80.2±3.2)μg/L] were not associated (all P>0.05). Expression levels of sBCMA were negatively correlated with IgM levels in MM patients (r=-0.39, P=0.002) and after treatment (r=-0.25, P=0.015).

The expression of sBCMA in MM patients is a reliable indicator of the clinical efficacy of MM and is related to the occurrence of MM immune deficiency and recovery after treatment. sBCMA can be used as a new independent marker for monitoring and predicting the efficacy of MM patients.

To investigate the expression of miR-17-5p in the plasma of patients with multiple myeloma (MM) and its role in tumorigenesis and development.

Patients diagnosed with unidentified monoclonal gammopathy of undetermined significance (MGUS) or MM in Cancer Hospital of Zhengzhou University from April 2013 to April 2018 were enrolled, as well as 20 healthy volunteers. Reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-17-5p in plasma circulation and bone marrow mononuclear cells. There were 22 cases with newly diagnosed MM (NDMM), 11 cases with complete remission MM (CRMM) and 59 case with recurrent refractory MM (RRMM). The expression levels of miR-17-5p in each group were analyzed. The correlation analysis was used to evaluate the relationship between plasma miR-17-5p and the proportion of serum M protein and bone marrow plasma cells in patients with untreated multiple myeloma. Receiver operating characteristic (ROC) curve was used to evaluate the possibility of plasma miR-17-5p as a molecular marker related to MM diagnosis. After over expression or knockdown of miR-17-5p expression, CCK-8 method was used to detect the effect of miR-17-5p on the proliferation of MM cell line. The effect of miR-17-5p on the proliferation of MM cells was detected in nude mice subcutaneous tumorigenesis experiment.

The expression of miR-17-5p in bone marrow mononuclear cells in NDMM and RRMM group were higher than those in healthy volunteers [1.37 (0.47, 4.87), 2.68 (1.02, 5.02) vs 1.00 (1.00, 1.00), all P<0.05], and the expression levels of miR-17-5p in plasma were also higher than those in healthy control group [1.85 (0.92, 3.51), 2.79 (1.22, 5.04) vs 1.00 (1.00, 1.00), all P<0.05]. The expression of miR-17-5p in MM cell lines such as KMS-11, RPMI-8226, H929, MM-1R, U266B1 were higher than that in bone marrow mononuclear cells of healthy control group (3.96±0.68, 1.58±0.32, 3.51±0.55, 5.08±0.76, 3.22±0.75 vs 1.00±0, all P<0.05) ; Plasma miR-17-5p was positively correlated with the ratio of serum M protein and bone marrow plasma cells (r=0.50, P<0.05; r=0.60, P<0.01). ROC curve showed that the specificity was 0.591 and the sensitivity was 0.900 of plasma miR-17-5p as a molecular marker related to diagnosis (area under ROC curve=0.74, cut-off value: 0.491). CCK-8 results showed that over expression of miR-17-5p increased the proliferation of RPMI-8226 and NCI-H929 cell lines at 72 hours compared with the control group (1.37±0.11 vs 1.07±0.09, 2.14±0.09 vs 1.82±0.11, both P<0.05), and low expression of miR-17-5p reduced the proliferation of NCI-H929 and MM-1R cell lines at 72 hours compared with the control group (1.38±0.09 vs 1.83±0.11, 1.45±0.10 vs 1.73±0.09, both P<0.05). The subcutaneous tumorigenesis experiment in nude mice showed that the tumor volume of miR-17-5p over expression group was larger than that of the control group [(1 865±181) vs (1 389±227) mm³, P<0.05], and the tumor volume of miR-17-5p low expression group was smaller than that of the control group [ (1 006±171) vs (1 389±227) mm³, P<0.05].

miR-17-5p may play an oncogene role in MM cell lines as a plasma molecular marker related to the development of MM disease.

To investigate the clinical manifestations and prognosis of multiple myeloma (MM) patients with t(8;14)(q24;q32).

The clinical data of MM patients with G-banding results from 2004 to 2009 in Hematology Department of People's Hospital of Peking University were retrospectively analyzed. The general data, M protein related examination, cytogenetics data, therapeutic regimen and response evaluation of MM patients with t(8;14)(q24;q32) were collected.

Of all newly diagnosed multiple myeloma patients, the number of patients who had G-banding results was 940, among which 265 had abnormal karyotype in G-banding, accounting for 28.19%. The incidence of t(8;14)(q24;q32) detected by G-banding in MM patients was 0.85%(8/940), t(8;14)(q24;q32) accounted for 3.02%(8/265) of all choromosome abnormalities detected by G-banding. Seven of eight patients were male with a median age of 63.5(56-76) and the immunoglobulin sub-types seven in eight patients were lambda. All eight patients had DS stage Ⅲ at the time of initial diagnosis. FISH detection of these eight patients showed six patients(75%) with 1q21 amplification, and five patients(62.5%) with G-banding results showed abnormal chromosome 1. Among the eight patients, the number of patients reached complete response ,very good response and partial response were separately four, one and two, and the overall response rate(ORR) was 87.5%. After the median follow-up 35 months(23-65months), 2 patients died, and the OS of the dead patients exceeded 5 years.

Patients with t(8;14)(q24;q32) accounted for 0.85% of the total who have the results of G banding in our hospital. Of our 8 patients, the light chain sub-type Lambda was more than Kappa, the patients were more common in males, accompanied by 1q21 amplification and chromosome 1 abnormality. The tumor load was high at the time of diagnosis, but the overall response to treatment was fair.

To analyze the related factors of worsening renal function (WRF) in patients with acute right ventricular myocardial infarction (RVMI) during hospitalization.

A total of 98 patients with acute RVMI admitted to the emergency comprehensive ward of Beijing Anzhen Hospital from August 2011 to January 2020 were enrolled in this cross-sectional study. According to the situation of WRF, the patients were divided into non-WRF group (76 cases) and WRF group (22 cases). WRF was defined as ≥0.3 mg/dL increase in serum creatinine level from baseline on day 6 of hospitalization (if hospital stay<6 days, it was at discharge). Baseline data, intravenous fluid infusion, diuretic and significant positive balance of patients′ intake and output volume [any 24 h intakes and outputs ≥1 000 ml or any consecutive 72 h intakes and outputs ≥2 000 ml within 6 d of hospitalization (if hospitalization<6 d, it was from admission to discharge)] were obtained, and the differences of above indicators between the two groups were analyzed. Multiple logistic regression model was used to analyze the related factors of WRF.

The ages of patients in WRF group and non-WRF group were 60 (50, 68) and 63 (52, 72) years, and the male proportions were 63.6% (14 cases) and 76.3% (58 cases), respectively, and there was no significant difference (all P>0.05). The proportion of positive balance was 31.8% (7 cases) in WRF group, which was higher than 14.5% (11 cases) in non-WRF group (P=0.034). The rate of loop diuretic use in WRF group was 4.5% (1 case), lower than that in non-WRF group 10.5% (8 cases) (P=0.027). After adjusting for age, sex, baseline estimated glomerular filtration rate (eGFR), preoperative isoproterenol/temporary pacemaker/atropine use, significant positive balance of intake and output volume, and loop diuretic use, it was found that eGFR≥60 ml·min^-1·1.73 m^-2 and significant positive balance were associated with WRF, the OR (95%CI) were 0.71 (0.62-0.86) and 1.21 (1.02-1.43) (both P<0.05); After eliminating the variable of significant positive balance in the above model, loop diuretic use was found to be a correlation factor for WRF, with an OR (95%CI) of 0.89 (0.72-0.97) (P<0.05).

Significant positive balance of intake and output volume during hospitalization in patients with acute RVMI is a risk factor for WRF on day 6 or at discharge. In the presence of a significant positive balance, loop diuretic use is a protective factor for WRF.

To investigate the safety and efficacy of fully covered self-expandable metal stents(FCSEMS) completely inserted into the common bile duct in the treatment of benign biliary stricture(BBS).

From December 2018 to December 2020, 22 cases of BBS treated by FCSEMS completely inserted into the common bile duct were analyzed retrospectively in the cholelithic center of Shanghai East Hospital Affiliated to Tongji University, including 12 males and 10 females, with average ages of (50.9±8.6) years.

All 22 cases of FCSEMS insertion were successful. The average indwelling time was (221.9±19.8) d. There were no complications of enterobiliary reflux such as liver abscess, acute cholangitis, and common bile duct obstruction. FSCEMS proximal displacement occurred in 2 cases (9.1%) with the removal time of 62 min and 115 min, respectively. There was no FCSEMS proximal displacement in 20 cases (90.9), with an average removal time of (29.7±6.3) min. All the 22 cases were followed up for 16.0 (8.0, 25.3) months, and there was no recurrence of stenosis.

FCSESM completely inserted into the common bile duct is an effective method for the treatment of BBS, which can avoid the occurrence of enterobiliary reflux.

This article reports a case of a 6-year-old 6-month-old boy with a history of growth retardation, accelerated growth and increased testicular volume nearly 6 months before admission, endocrine hormone measurement consistent with central precocious puberty, and cranial magnetic resonance revealed suprasellar cystic-solid mass occupation. The patient underwent complete tumor resection through transcranial approach, and the pathology was consistent with epithelial craniopharyngioma. Hypopituitarism and central diabetes insipidus occurred after surgery, and sex hormones were inhibited. Craniopharyngioma with central precocious puberty as the first manifestation is extremely rare and rarely reported in China. Most patients have a history of slower growth rate, but it is relatively hidden, and there is growth catch-up in the later stage, but the predicted height is still significantly impaired. Male patients with central precocious puberty with young onset age need MRI screening to be alert to organic lesions.

Hereditary methylmalonic acidemia (MMA) is a common organic acid metabolism disease in China, mainly seen in infants and young children, with nervous system damage as the first and main manifestation. This article reports an adolescent patient with MMA with interstitial lung disease and pulmonary hypertension as the first manifestation. Multi-system manifestations such as macrocytic anemia and peripheral neuropathy were found by examination. The genetic test and blood and urine organic acid determination confirmed the diagnosis of MMA with hyperhomocysteinemia (cblC) type. The primary disease of MMA such as parenteral supplementation of cobalamin and pulmonary hypertension were treated with good results. This case broadens the understanding of the heterogeneity of clinical manifestations of MMA. For adolescent patients with interstitial lung disease and pulmonary hypertension, attention should be paid to include this disease in the differential diagnosis. Early diagnosis and timely treatment can significantly improve the outcome of patients.

Pertussis can infect people of all ages. The description of pertussis manifestations in traditional textbooks is based on the observation and summary of primary infection in typical cases, especially children aged 1 to 10 years old, in the era before vaccine use. In the era of vaccine, the clinical manifestations of whooping cough are affected by factors such as age, immune history or infection history, mixed infection, etc., and the clinical manifestations are complex and diverse. Typical cases are only a small number of cases that can be identified clinically, and a large number of cases are mild symptoms without typical symptoms, especially adolescents and adults, which need to be diagnosed with the help of laboratory tests. This article systematically describes the clinical manifestations of pertussis in the vaccine era, so as to improve clinicians' understanding of the diversity of clinical manifestations of pertussis, and promote the timely diagnosis, treatment and management of pertussis cases.

In recent years, the incidence and prevalence of metabolic diseases related to lifestyle, such as obesity, type 2 diabetes, hyperlipidemia and other diseases, have increased rapidly, increasing the incidence and mortality of cardiovascular and cerebrovascular diseases. These diseases involve cardiovascular medicine, endocrinology, nutrition and sports medicine and other departments. It is difficult to comprehensively diagnose and treat them in only a single professional field, which reduces the efficiency and effect of disease treatment and increases the economic and time burden of patients. Therefore, the academic community has proposed "cardiovascular metabolic medicine", a new subspecialty of internal medicine, to carry out interdisciplinary intersection, integration and mutual cooperation, aiming to focus on patients, focus on disease prevention, carry out comprehensive management of multiple diseases, and reduce the risk of cardiovascular diseases. This article will introduce the history of cardiovascular metabolic medicine, analysis of current situation, future prospects and so on.

The acute phase of novel coronavirus pneumonia (COVID-19) is often complicated by acute kidney injury (AKI), which aggravates the disease and is an independent risk factor for death, while the long-term outcome of its kidney is unclear. Studies have shown that people with COVID-19 combined with AKI have a significantly increased risk of progression to chronic kidney disease (CKD); Compared with AKI people of other causes, COVID-19 patients have a higher risk of developing CKD; Even in mild patients without AKI, the risk of renal impairment remains increased after the acute phase. The indirect and direct effects of SARS-CoV-2 on kidney are important reasons for the outcome of AKI to long-term CKD in the acute phase of COVID-19, especially the latest basic research confirms that renal cells after SARS-CoV-2 infection can upregulate the pro-fibrotic signaling pathway, and lipid mediator storm also increases the possibility of transition from AKI to CKD. This article reviews the long-term renal outcome after the acute phase of COVID-19, in order to remind clinicians to pay attention to the chronic trend of renal injury after SARS-CoV-2 infection, and carry out more targeted and long-term follow-up and intervention.

Daratumumab is a human IgG kappa monoclonal antibody targeting CD38, which has direct antitumor and immunomodulatory effects. MAIA (NCT02252172) is a randomized, open-label Phase 3 clinical trial. In a preliminary analysis of the MAIA Phase 3 study (median follow-up of 28.0 months) in patients with newly diagnosed multiple myeloma (NDMM) who were not eligible for transplant, daratumumab + lenalidomide/dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and induced deeper responses, including improvement in complete response (CR) and negative minimal residual disease (MRD), compared with lenalidomide/dexamethasone (Rd). After a median follow-up of 36.4 months, the D-Rd regimen continued to show PFS benefit and deeper remission, even in patients over 73 years of age. However, health levels vary greatly in older patients, and subgroup analyses based on frailty will be richer than analyses based on age alone. Therefore, the study used age, per-patient medical history review (CCI), and baseline ECOG PS score to divide patients into three subgroups: healthy, moderate, and frail, which was further simplified to non-frail [396 healthy and moderate subgroup combinations: 196 (53.3%) in the D-Rd group and 200 (54.2%) in the Rd group; 341 in the frailty subgroup, 172 (46.7%) in the D-Rd group, and 169 (45.8%) in the Rd group].

Teclistamab is a T cell redirecting bispecific antibody that targets CD3 expressed on the surface of T cells and B cell maturation antigen (BCMA) expressed on the surface of myeloma cells. In the Phase 1 dose determination part of the study, terituzumab showed good efficacy in patients with relapsed or refractory multiple myeloma.

Multiple myeloma (MM) is a common malignant plasma cell disease that has hitherto been incurable. Malignant plasma cells highly express B cell maturation antigen (BCMA). Based on this, the therapeutic technology of chimeric antigen receptor T cell (CAR-T) targeting BCMA has gradually developed and become more mature. In March 2021, the world's first CAR-T product targeting BCMA was approved for marketing in the United States. The phase II clinical trial of this product achieved an overall response rate (ORR) of up to 73%, of which complete response and above (CR + sCR) accounted for 33%, but the median progression-free survival (mPFS) was only 8.8 months, which hindered the clinical application of BCMA CAR-T. BCMA CAR-T treatment could not effectively eliminate tumor stem cells, which may be one of the main causes of disease recurrence.

The immunomodulator lenalidomide is the main drug in the treatment of multiple myeloma (MM), and the combination with other drugs such as proteasome inhibitors and corticosteroids can induce remission in most patients, however almost all patients will relapse due to acquired drug resistance of multiple myeloma cells. To explore the non-genetic mechanisms of drug resistance, the study included 5 patients with longitudinal bone marrow samples, 4 who progressed during lenalidomide treatment, and 1 who progressed after lenalidomide treatment. Bone marrow samples from 5 patients were collected before treatment and at the time of relapse for tandem mass spectrometry (TMT) -based proteomic and phosphorylated proteomic analysis and RNA sequencing. Through proteomics analysis, the study found that the top 6 upregulated proteins in the relapsed group were TRIP13, RRM1, NCAPD2, NCAPH, MORF4L1, and CKD6 compared with the pre-treatment sample. Phosphorylated proteomics analysis showed that only 15 of 134 significantly changed phosphorylated peptides had protein expression changes, indicating that most of the sites with changed phosphorylation levels did not change their protein expression levels. Through RNA sequencing of 5 pairs of samples, it was found that among the highest upregulated proteins, the mitotic regulatory proteins TRIP13 and NCAPH had the highest Pearson correlation coefficient of RNA/protein expression of 0.84, followed by NCAPD2 (0.67), RRM1 (0.6) and CDK6 (0.39). In MM, the low correlation of protein and RNA implies a high degree of transcriptional and post-translational regulation.