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Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

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ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”， and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4， 2022 to January 11， 2023. Data on demographic characteristics， clinical symptoms， medical history， and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics， and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study， of which 45 had reinfection， 605 （22.4%）were males， 608 （22.5%）were doctors， 1 275 （47.2%） were nurses， and 2 351 （86.9%） received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was （34.9±9.1） years old. The number of cases with mild/moderate illness， asymptomatic infection， fever， headache， dry cough， expectoration， and chest tightness were 2 704 （100.0%）， 92 （3.4%）， 2 385 （88.2%）， 2 066 （76.4%）， 1 642 （60.7%）， 1 807 （66.8%）， and 439 （16.2%）， respectively. Reinfection was a protective factor for fever （OR=0.161， P<0.001）， headache （OR=0.320， P<0.001）， and peak body temperature （β=-0.446， P<0.001）. ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease， healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations， with a lower proportion of being asymptomatic.

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PURPOSE: Pegylated liposomal doxorubicin (PLD) is highly effective for treating multiple myeloma (MM). Hand-foot syndrome (HFS) is a dose-limiting adverse event of PLD that may reduce a patient's quality of life or prevent certain patients from receiving PLD. Several researchers have discovered that pyridoxine, an activated form of vitamin B6, may prevent PLD-associated HFS. We designed a prospective randomized trial to examine whether prophylactic pyridoxine might prevent the incidence or delay the occurrence of PLD-induced HFS in patients with MM. METHODS: Patients who met the trial's eligibility requirements were randomized and then administered either pyridoxine 100 mg twice daily or no pyridoxine, in both cases accompanied by their PLD-containing chemotherapeutic agent. Follow-up of patients was performed until the completion of induction therapy, the development of HFS or disease progression. RESULTS: Between January 1, 2017, and January 1, 2019, 105 patients were randomly assigned to the pyridoxine group (n = 52) or the no pyridoxine group (n = 53). In the pyridoxine and no pyridoxine groups, HFS developed after a median of 4 (range, 1-8 cycles) and 3 (range, 1-7 cycles) chemotherapeutic cycles, respectively. There were no grade 3 incidents recorded. Overall, 13.3% of patients experienced HFS. A 11 of 53 (20.8%) patients in the no pyridoxine group experienced HFS, compared to 3 of 52 (5.8%) patients in the pyridoxine group (P = .042); there was no difference in HFS grades (P = .725). CONCLUSIONS: The findings of benefit from prophylactic pyridoxine in this open-label trial have suggested its promise as a treatment for reducing HFS in MM patients. Further research with a placebo-controlled design is recommended. CLINICAL TRIAL REGISTRATION: ChiCTR2100050294.

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Objective@#To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients.@*Methods@#200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018.@*Results@#The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response.@*Conclusions@#Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.

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Objective@#To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) .@*Methods@#Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively.@*Results@#①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3rd month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) .@*Conclusion@#HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.

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Objecitv e To investigate the effects of a recombinant protein osteoclast inhibitory lectin related protein 2( OCILRP2)-Fc on LPS-induced endotoxemia by blocking OCILRP 2 signaling pathway and to in-vestigate the roles of OCILRP2 during inflammation.Methods Real-time PCR was used to detect OCILRP2 ex-pression at mRNA level in RAW264.7cells before and after in vitro stimulation with LPS.A mouse model of en-dotoxemia was established by intraperitoneal injection of BALB /c mice with a median lethal dose of LPS .Two hours prior to LPS treatment, mice were intraperitoneally injected with OCILRP2-Fc, human IgG or PBS, re-spectively .Several parameters including the survival rate of BALB/c mice with and without LPS treatment , spleen weight for arterial hyperemia analyzing , histopathological changes of lung and liver by HE staining , serum levels of inflammatory cytokines (IL-6, IL-12, TNF-αand IFN-γ)by ELISA , NF-κB activity by Western blot, were analyzed .Results Real-time PCR showed that LPS elevated in vitro OCILRP2 expression at mRNA level in macrophages (P<0.05).Upon the treatment of OCILRP2-Fc, BALB/c mice suffered from endotoxemia showed obviously increased survival rate , decreased spleen hyperemia , attenuated pathological injury of lung and liver, reduced levels of IL-6, IL-12, TNF-αand IFN-γin serum samples (P <0.05) as compared with mice treated with human IgG and PBS .LPS induced NF-κB p65 phosphorylation and IκB degradation were inhibited by OCILRP2-Fc treatment.Conclusion OCILRP2-Fc protects mice from endotoxemia by blocking OCILRP 2 signaling, which suggests that OCILRP2 plays an important role in LPS induced inflammation.

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Objective To discuss current detection of food intolerance in health check-up populations and the influence of food intolerance on immune system and inflammation parameters.Methods Serum levels of 14 kinds of food-specific IgG antibodies were analyzed by using enzyme linked immunosorbent assay (ELISA) among 257 healthy check-up adults.White blood cell count,eosinophils,globulin,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),rheumatoid factor (RF),antinuclear antibodies (ANA) and T cell function were compared between the positive group and the negative group.Student's t test and Chi-square test were used for data analysis.Results Food-specific IgG antibodies were found in 134 participants (52.14％).The most common intolerant foods were egg,crab and milk.Moderate to severe food intolerance was caused by egg or milk.There was significant difference in eosinophils and serum globulin between the positive and the negative group (t =-0.07,x2 =8.91,both P ＜0.05).However,no difference was observed in white blood cell count,ESR,CRP,RF,ANA and T cell function between two groups (all P ＞ 0.05).Conclusion Eosinophils and serum globulin may significantly increased in people with food intolerance,although white blood cell count,ESR,CRP,RF,ANA and T cell function could be normal.

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AIM: To observe if there is a synergistical effect on induction of apoptosis when arsenic trioxide alone or combination with bortezomib in KM3 cells. METHODS: KM3 cells were treated with arsenic trioxide alone or combined with bortezomib, the numbers of viable cells were determined by trypan blue exclusion. Cell growth inhibition was examined by MTT method. The cells were simultaneously stained with annexin V-FITC and PI and apoptosis was determined by bivariate flow cytometry using a FACScan. Reverse trascriptional-PCR (RT-PCR) method was used to examine the change of p65 mRNA and Western blotting to measure the expression of protein p65, p-p65, caspase-3, -8, -9, and poly ADP-ribose polymerase (PARP). RESULTS: Arsenic trioxide inhibited the cell growth and induced apoptosis. The mechanism was responsible for the activation of caspase-mediated induction of apoptosis. A synergistic effect of combination with bortezomib on apoptosis was observed. CONCLUSION: Arsenic trioxide inhibits KM3 cell growth and induces apoptosis with a synergistical effect when cotreated with bortezomib.

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Objective To study the clinical features and risk factors of invasive fungal infection (IFI) in multiple myeloma ( MM) . Methods Three hundred and fifty-seven cases of MM were retrospectively analyzed for IFI, clinical features, complicating diseases, treatment of fungus and side effect of anti-fungal drugs. Results Forty-four cases ( 12. 3% ) of IFI were diagnosed. Three of them were diagnosed definitely, 8 clinically and 33 probably. Ten cases incurred IFI in (he induction therapy, 4 in platform, 27 in progress and 3 in the treatment with autologous stem cell transplantation. The lung was the commonest site of infection ( 50. 0% ) . The total effective rates of amphotericin B liposome, voriconazole, itraconazole, caspofungin and fluconazol were 83. 3% , 75. 0% , 78. 9% , 75. 0% and 57. 1% respectively (P= 0.493). In a multivariate analysis, independent factors significantly associated with IFI were diabetes (P=0.035, OR 2. 527, 95%CI 1.005-6.052), dialysis (P=0. 022,OR 2. 768, 95%CI 1. 161-6. 600), persistent agranulocytosis (P = 0.019, OR 3.215, 95% CI 1.200-7.407), broad-spectrum antibiotic therapy (P = 0.009,OR 3. 350,95% CI 1.353-8.295) and fludarabine treatment( P = 0. 001,0R 4. 669, 95% CI 1.813-12.023). Conclusions Patients with MM are in high risk of IFI. The lung is the commonest site of infection. The therapeutic effect was similar with itraconazole, voriconazole, caspofungin and amphotericin B liposome in MM patients with complicating IFI. The risk factors for IFI in MM were diabetes, dialysis, persistent agranulocytosis and the use of broad-spectrum antibiotics and fludarabine.

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Objective To compare effects and toxicities of DVd and VAdM regimen for newly diagnosed multiple myeloma.nethods 17 newly diagnosed active multiple myeloma received DVd treatment,dexamethasone(20 mg/d)on days 1～4 as an intravenous infusion.16 newly diagnosed active multiple myeloma on days 1～4 plus melphalan(12 mg/d)as an intravenous infusion.Results Objective response rates(DVd,76.5%;VAd,81.3%,P=0.737)were similar between the two treatment groups.In the DVd group,the mean time to max response was shorter than the VAdM group[(3.2±1.7)months vs.(4.6±1.0)months,P=0.039].DVd was associated with low Grade 3/4 neutropenia(23.5% vs.68.8%,P=0.015),less use of G-CSF(11.8% vs.62.5%,P=0.004),less use antibiotic(11.8% vs.37.5%,P=0.118),lower incidence of hospitalization for adverse events(37.5% vs.17.6%,P=0.259),but more hand-foot syndrome.Coilcinsion The DVd regimen demonstrated similar efficacy compared with VAdM,while with less toxicity and supportive care,which might be used as a modified VAd regimen for newly diagnosed myeloma.

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Objective To study whether bortezomib combined with dexamethasone can relieve bone pain of patients with multiple myeloma and to see whether bortezomib have effect on bone metabolism through determining the concentration of bone turnover marks.Methods 59 cases of patients with multiple myeloma treated with BD and 38 cases of patients treated with VADM were observed before and after chemotherapy to compare the alleviation of bone pain,the improvement of the ability to move and the occurrence of skeletal related events between the two groups.The plasma from 25 patients were collected before and after chemotherapy when they were in hospital each time and the concentrations of TRACP-5b,BALP and DKK1 in plasma were determined by ELISA.Results BD group was better than VADM group in the rate of alleviation of bone pain,the improvement of the ability to move and the incidence of skeletal related events(75.7% vs 50%,64.9% vs 20.8% and 13.8% vs 57.8%,all P