Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Objective To explore the effect of LIMK1 on the progression of cervical cancer(CC).Methods HeLa and C-33A human cervical cancer cells overexpressing LIMK1 were established and injected subcutaneously into nude mice.The tumor volume was measured and expression of NOX2,NOX4,p-Src,p-RUNX3,RUNX3,and MMP-9 proteins in tumor cells was detected by Western blot assays.LIMK1-overexpressing HeLa and C-33A cells were cultured in 5％O2 with antioxidants.The protein expression of LIMK1,NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 in the cells was detected by Western blot assays.Cell migration was assessed by a scratch assay.Transwell assays were used to assess cell migration and invasion.A monoclonal proliferation assay was used to assess cell proliferation.Results The tumor volume in nude mice injected with LIMK1-overexpressing HeLa cells was increased significantly,and NOX2,NOX4,p-Src,p-RUNX3 and MMP-9 protein levels were increased,while RUNX3 protein expression was decreased.In LIMK1-overexpressing HeLa and C-33A cells,the protein expression of LIMK1,NOX4,p-Src,p-RUNX3,and MMP-9 was increased,RUNX3 protein expression was decreased,and cell migration,invasion,and proliferation were increased.However,after adding antioxidants,the expression levels of NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 proteins,and cell migration,invasion,and proliferation were not different from those of control cells.Conclusions LIMK1 promotes the progression of cervical cancer by enhancing the ROS/Src pathway,thereby promoting the migration,invasion,and proliferation of cervical cancer cells.

Objective:To test the reliability and validity of the Chinese version of cyberbullying inventory for college students(CICS-CV)in the context of Chinese culture and make preliminary application.Methods:A total of 1 528 college students completed the CICS-CV, and 208 students completed CICS-CV after six months.Trait anger subscale of state-trait anger expression inventory-2, and Buss-Perry aggressive qusetionnaire were used as the criterion of cyberbullying aggression, and depression anxiety stress scales were used as the criterion for cyberbullying victimization to test its validity. Item analysis, exploratory factor analysis, reliability test, calibration validity test and corss-lag analysis were conducted by SPSS 24.0 software, and confirmatory factor analysis was conducted by Mplus 8.3.Results:The results of exploratory factor analysis showed that two factors were obtained named as cyberbullying aggression and cyberbullying victimization, and the factor loadings were 0.59-0.82, 0.59-0.80.Confirmatory factor analysis showed that the fitting index of the double factor model was fitting well ( χ2/ df=2.61, CFI=0.90, TLI=0.89, RMSEA=0.04, SRMR=0.05). The internal consistency coefficient of the two subscales were 0.88, 0.89, and test-retest reliability were both 0.97. There was a significant positive correlation between cyberbullying aggression(victimization) and the criterions( r=0.23-0.42, all P<0.05). Cross-lag analysis of moral disengagement and cyberbullying aggression showed that the first measurement of moral disengagement significantly predicted the second measurement of cyberbullying aggression( β=0.16, t=2.16, P<0.05). Conclusion:The CICS-CV has good reliability and validity, which can be used as an effective tool for evaluating college students' cyberbullying in China.

Objective:To explore the efficacy of rituximab combined with ABVD (epirubicin+ bleomycin+ vindesine +dacarbazine) regimen in treatment of Hodgkin lymphoma (HL) complicated with autoimmune hemolytic anemia (AIHA).Methods:The clinical data of 1 HL patient complicated with AIHA in November 2019 in Henan Cancer Hospital were retrospectively analyzed, and literatures were reviewed.Results:The patient received left cervical lymph node biopsy and bone marrow biopsy, and then lymphoma-related gene mutations and whole genetic genome detection were performed. The patient was diagnosed as HL (tuberous sclerosis in stage Ⅳ) complicated with AIHA. After 6 cycles of rituximab combined with ABVD regimen, the efficacy was evaluated. This patient's anemia was recovered, and HL also achieved complete remission.Conclusions:Rituximab combined with ABVD regimen is effective in treatment of HL patients complicated with AIHA.

Objective:To evaluate the immunological efficacy of a novel DNA vaccine against West Nile virus (WNV) in a mouse model.Methods:A DNA vaccine VRC-prME expressing the precursor membrane (prM) and envelope protein (E) of WNV Xinjiang strain (XJ11129-3) was constructed and its ability to express virus-like particles was verified in vitro. C57BL/6 mice were immunized twice with VRC-prME via intramuscular injection combined with electroporation with an interval of four weeks. Enzyme-linked immunoassay (ELISA) was used to detect serum antibodies after immunization. WNV (NY99 strain) single-round infectious particles were used to detect neutralizing antibodies. Cellular immune responses were analyzed by enzyme-linked immunoblot assay (ELISPOT) and intracellular cytokine staining (ICS). Results:VRC-prME induced a strong Th1-biased antibody response in mice that could cross-neutralize the WNV (NY99 strain) single-round infectious particles two weeks after the boost immunization. Moreover, the vaccine also elicited antigen-specific multifunctional CD8 + T cell responses (IFN-γ, IL-2, TNF-α). Conclusions:The novel DNA vaccine prepared in this study, expressing the prME protein of WNV XJ11129-3 strain, could induce stronger humoral and cellular immune responses in mice, which was worthy of further research and development for the prevention of WNV infection in China.

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.

Objective: To analyze the clinical features, treatment and outcomes of primary lymphoma of bone (PLB) . Methods: The clinical data of 11 PLB patients were retrospectively analyzed. Results: 11 patients were enrolled in our study including 7 females and 4 males. The median age of the patients was 45 years old. The main histologic type was diffuse large B cell lymphoma and anaplastic large cell lymphoma. Of the 11 PLB cases, 3 cases were at stage ⅠE, 2 at stage ⅡE, 6 at stage ⅣE respectively. 6 cases were treated with chemotherapy and radiotherapy, 2 cases with total joint arthroplasty and chemotherapy, and 3 cases chemotherapy alone respectively. 5 cases got complete remission, 4 cases partial remission and 2 cases stable disease respectively. The median progression free survival was 17 (5-58) months after a median follow up of 21 (6-58) months. Conclusions Most of PLB patients were clinically in late stage lacking of clinical and imagine features. The optimal treatment for PLB was radiotherapy combined with chemotherapy, and its prognosis was relatively good.

Objective To explore the value of real-time shear wave elastography in evaluating gastrocnemius muscle elasticity in patients with lumbar disc herniation.Methods One hundred patients with clinically diagnosed unilateral lumbar disc herniation were selected.Selective nerve root block combined with ozone ablation and pulsed radiofrequency therapy via the lateral crypt was performed.The real-time shear wave elastography was applied to detect the mean elastic modulus (Mean) and the maximum elastic modulus (Max) of bilateral tense gastrocnemius muslcs (kPa) before and after treatment.Statistical analysis was done.Results The EMean and EMax values of ipsilateral tension in gastrocnemius muscle before treatment were (11.28±2.60)kPa and (15.26±2.63)kPa,lower than those of contralateral (EMean:[16.284-5.25]kPa,EMax:[21.13±6.62]kPa;t=78.241,64.634,both P＜0.001).The EMean and EMax values of ipsilateral tension in gastrocnemius muscle after treatment were (13.18±2.38)kPa and (17.63± 2.73)kPa,higher than those before treatment (t=6.407,14.815,both P＜0.001).In different strength condition,EMean and EMax of gastrocnemius muscle before and after treatment were statistically significant (all P＜0.001).With the myodynamia increasing,EMean and EMax also increased before and after treatment.The differences between patients with any two different myodynamia were statistically different (all P＜0.05).Conclusion The muscle tissue recovery can be evaluated quantitatively by detecting EMean and EMax of tense gastrocnemius in patients with lumbar disc herniation using real-time shear wave elastography before and after treatment.

Objective To investigate the therapeutic effects and mechanisms of curcumin derivatives C66 treatment on hepatic fibrosis .Methods Thirty three C57BL/6J mice were randomly divided into 3 groups:normal control group ,model control group and curcumin derivatives C66 treatment group .Nine mice in normal control group were fed with water and food .Hepatic fibrosis model was induced in 24 mice by intraperitoneal injection of 40% carbon tetrachloride at a dose of 4 mL/kg for the first time ,followed by 2 mL/kg twice a week for 6 weeks . At week 6 ,6 mice were randomly selected to perform pathological examination to evaluate whether the hepatic fibrosis were successfully induced .Mice with hepatic fibrosis were randomized into model control group and curcumin derivatives C66 treatment group with 9 mice in each group .From week 6 on ,mice in the treatment group were lavaged with curcumin derivatives C66 at a dosage of 10 mg ·/(kg · d) .The rest mice were administered with equivalent dosage of 0 .5% carboxymethylcellulose sodium .Serum alanine aminotransferase (ALT) ,aspartate aminotransferase (AST ) and liver hydroxyproline ( Hyp ) contents were detected , and the semi‐quantitative analysis of liver fibrosis was performed by pathological examination in hepatic tissue by hematoxylin and eosin (HE) and Masson staining .The expressions of collagen Ⅰ ,α‐smooth muscle actin (α‐SMA) mRNA and collagen Ⅰ ,α‐SMA ,nuclear factor‐kappa B p65 (NF‐κB p65) ,inhibitor kappa B alpha (IκBα) protein in each group were detected by quantitative real‐time polymerase chain reaction (RT‐PCR) and Western blot .Data were analyzed with one‐way ANOVA analysis .Results The serum levels of ALT and AST in model control group ,C66 treatment group and normal control group were (202 .71 ± 19 .66 ) U/L , (233 .42 ± 23 .97 ) U/L ;(102 .00 ± 11 .04 ) U/L , (120 .87 ± 13 .83 ) U/L ;(36 .66 ± 6 .37) U/L and (43 .33 ± 8 .08)U/L ,respectively .The differences between model and normal control group were both significant (t=23 .96 and 22 .39 ,respectively ;both P<0 .05) .The C66 treatment group showed significantly lower levels of serum ALT and AST in contrast with model control group (t =11 .56 and 10 .52 ,respectively ;both P<0 .05) .Compared to the model control group ,hepatic Hyp contents in normal control group and C66 treatment group were significantly different (t= 17 .50 , P< 0 .05;t=11 .45 ,P<0 .05) .Collagen Ⅰand α‐SMA mRNA expressions in C66 treatment group were remarkably lower in contrast with that in model control group (t= 7 .23 and 7 .95 ,respectively ;both P< 0 .05) . Protein levels of Collagen Ⅰ ,α‐SMA and NF‐κB p65 decreased in C66 treatment group ,while IκBαincreased significantly (all P<0 .05) .Conclusion The application of C66 can contribute to the regression of liver fibrosis and the mechanism may rely on the regulation of NF‐κB expression .

Objective:To investigate whether endogenous hydrogen sulfide (H2 S)was involved in the pathogenesis of osteoarthritis (OA)and its underlying mechanism,to detect H2 S and its synthases ex-pression in knee cartilage in patients diagnosed with different severity of OA,and to explore the transcrip-tion and expression of gene MMP-13 in chondrocytes treated with IL-1βor H2S.Methods:Synovial fluids of the in-patients with different severity of OA hospitalized in Peking University First Hospital were collected for measurement of H2 S content using methylene blue assay.Articular cartilages of the patients who underwent knee arthroplasty were collected for the cell culture of relatively normal chondrocytes.The chondrocytes were cultured to the P3 generation and H2 S molecular probes were used for detection of endogenous H2 S generation in the chondrocytes.Immunocytochemistry was used to detect the localization of H2 S synthases including cystathionine β-synthase (CBS),cystathionine-γ-lyase (CSE),and mercap-topyruvate sulfurtransferase (MPST)in OA chondrocytes.Western blot was used to quantify the protein expressions of CSE,MPST,and CBS in cartilage tissues of the patients who were diagnosed with OA and underwent knee arthroplasty.The relatively normal human chondrocytes were cultured to passage 3 and then divided into 4 groups for different treatments:(1 )the normal control group,no reagent was added;(2)the IL-1βgroup,5 μg/L of IL-1βwas added;(3)the IL-1β+H2S group,200 μmol/L of NaHS was added 30 min before adding 5 μg/L of IL-1β;(4)the H2 S group,200 μmol/L of NaHS was added. The transcription and expression of gene MMP-13 in chondrocytes of each group were determined with Real-time PCR and Western blot,respectively.And the total NF-κB p65 and phosphorylated NF-κB p65 in chondrocytes were detected with Western blot.Results:The content of H2 S in the synovial fluid of degenerative knee was (14.3 ±3.3)μmol/L.Expressions of endogenous H2 S and its synthases including CBS,CSE and MPST were present in the cytoplasm of chondrocytes.CSE protein expression in Grade 3 (defined by outerbridge grading)cartilage tissues was significantly increased as compared with that of Grade 1 cartilage tissues (1.67 ±0.09 vs.1.26 ±0.11,P<0.05).However,no significant difference of CBS or MPST expression among the different groups was observed.The expression of MMP-13 protein in the IL-1βgroup was significantly higher than that in the normal chondrocytes (1 .87 ±0.67 vs.0.22 ± 0.10,P<0.05 ),and that in the IL-1β+H2 S group was significantly decreased than that in the IL-1βgroup (0.55 ±0.11 vs.1.87 ±0.67,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.The transcription of MMP-13 protein in the IL-1βgroup was significantly higher than that in the normal chondrocytes (31.40 ±0.31 vs.1.00 ±0.00,P<0.05), and that in the IL-1β+H2 S group was significantly decreased than that in the IL-1βgroup (24.41 ± 1.28 vs.31.40 ±0.31,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.The total NF-κB p65 in the IL-1βgroup was significantly higher than that in the normal chondrocytes (2.13 ±0.08 vs.0.73 ±0.08,P<0.05),and that in the IL-1β+H2S group was significantly decreased than that in the IL-1βgroup (1 .24 ±0.13 vs.2.13 ±0.08,P<0.05 ),and that in the H2 S group had no significant difference compared with that in the normal control group.The phosphorylated NF-κB p65 in IL-1βgroup was significantly higher than that in the normal chondrocytes (1.30 ±0.13 vs.0.19 ±0.04,P<0.05),and that in IL-1β+H2S group was significantly decreased than that in the IL-1βgroup (0.92 ±0.26 vs.1.30 ±0.13,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.Conclusion:H2 S affected the cartilage degeneration by partly inhibiting the degradation of extracellular matrix.