Multiple myeloma (MM) is a malignant plasma cell disease, accounting for about 1% of all malignant tumors, is still uncurable, minimal residual disease (MRD) is the reason, therefore, removal of minimal residual disease maybe possible to cure the disease. In a variety of treatment methods, immune gene therapy for multiple myeloma is a hot research topic in recent years, has achieved good results in vitro and in vivo experiments, in this review immune genes therapy in multiple myeloma research would be discussed.

Objective To investigate costimulatory molecules CD80 and CD86 expression in acute myelogenous leukemic cells and clinical implication.MethodsThe expression of CD80 and CD86 in the patients with acute myelogenous leukemia and HL-60 cells,U937 cells,NB4 cells,K567 cells was confirmed by Flow Cytometer.ResultsCD80 was very low or no expression in patients with acute myelogenous leukemia.CD86 expressed in acute myelogenous leukemia (27.86±19.65)%,which was much higher than that in control group[(1.21±0.13)%,t＝3.55,P＜0.01].No significant changes were observed in the expression of CD86 in M4 cells(48.65±21.92)%,M5 cells(39.25±18.67)% and control group(50.20±20.31)%(P＞0.05).After the cells were cultured for 24 h and 48 h,the expression of CD86 was (30.62±5.35)% and (29.43±4.67)% in HL-60 cells ,(24.12±5.23)% and (26.56±6.54)% in U937 cells,and,(21.25±3.78)% and (23.21±6.98)% in NB4 cells (all P＞0.05).The expression of CD80 and CD86 was very low in K562 cells.ConclusionsCostimulatory molecules CD86 expressed in acute myelogenous leukemic cells in the patients with acute myelogenous leukemia and HL-60 cells,U937 cells,NB4 cells.

Objective To evaluate the effect of applying emergency care simulator (ECS)on cardiopulmonary resuscitation skill training. Methods Clinical doctors and nurses(n=1 472)received the skill training of unarmed cardiopulmonary resuscitation (CPR),electric defibrillation and tracheal intubation by using simple CPR simulator (n=667)or ECS (n=805)respectively. After training,the examination was carried out and questionnaires were handed out. The completion time of operations, the scores and pass rates of examinations,the evaluations of training methods were compared between the two groups. The statistical data were analyzed by t(t')-test or Chi-square test with SPSS 19.0 and P <0.05 was considered as the criterion of significance. Results Compared with those of group using simple CPR simulator,the group using ECS showed obviously shortened completion time((309±125)s vs. (242±61)s,t'=12.65,P=0.00;(87±36)s vs. (55±31)s,t'=20.28,P=0.00;(239±87)s vs. (145±53),t'=24.4,P=0.00),significantly increased scores ((83.5±14.8)vs. (90.2±17.6), t'=7.93,P=0.00;(84.7±19.3)vs. (92.1±21.5),t'=6.95,P=0.00;(81.6±15.3)vs. (89.6±13.5), t'=10.53,P=0.00)and pass rates of examinations (84.1%(561/667)vs. 92.5%(745/805),χ2=25.96, P<0.01;82.2%(548/667)vs. 91.2%(734/805),χ2=26.41,P<0.01;80.8%(539/667)vs. 91.4%(736/805),χ2=35.48,P<0.01)as well as higher evaluation of training methods. Conclusions Application of ECS can obviously improve the training effect of CPR and it can be widely popularized in the edu-cation and training of emergency medicine skills.

Objective To study the effect of Sildenafil in the treatment of hypoxemia after operation of cyanotic congenital heart disease.Methods A total of 34 cases with hypoxemia after operation of cyanotic congenital heart disease were collected between January 2009 to January 2015.They took Sildenafil with the dosage of 0.3-0.5 mg/kg every 6 hour.The change of heart rate (HR),systolic blood pressure (SBP),central venous pressure (CVP),pulmonary artery pressure (PAP),arterial partial pressure of oxygen [pa (O2)],arterial partial pressure of carbon dioxide [Pa (CO2)],oxygenation index [pa (O2)/FiO2],peak airway pressure (Ppeak),positive inotropic drug score (PIDS) and the lower bound of liver were observed at 4 time points,including before taking the medicine,after taking the medicine for 1 hour,after taking the medicine 1 day and after the ventilator was removed.Based on the data,the therapeutic effects of Sildenafil were studied.Results All 34 cases were cured.At the time point of 1 hour after taking Sildenafil,PAP,CVP and Ppeak decreased significantly,but pa (O2) and pa (O2)/FiO2 increased significantly (P ＜ 0.05).At the time point of 1 day after taking Sildinafil,SBP increased steadily,but PAP and CVP continued to get lower,and PIDS decreased significantly,while the liver lower bound was significantly reduced (P ＜ 0.05).At the time point of removing the ventilator,pa (O2) reached to (144.12 ± 26.25) mmHg,and hypoxemia was corrected,but PAP was reduced to (37.47 ± 3.77) mmHg,PIDS decreased to (17.56-± 1.94) scores,and heart failure was corrected.Compared with the previous 3 time points,there were statistically significant differences (P ＜ 0.05).Conclusion Sildenafil can highly selectively decrease pulmonary vascular resistance and obviously promote the correction of hypoxemia after operation of cyanotic congenital heart disease.

AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease.METHODS:Male SD rats were randomly divided into normal control ( NC) group, high fat ( HF) group and HF+liraglutide ( Lira) group.The rats in HF group and HF+Lira group were given high-fat diet for 16 weeks.After 12 weeks of high-fat diet feeding in HF+Lira group, Lira (600μg? kg-1? d-1 ) was intraperitoneally injected for 4 weeks.At the end of the 16th week, the rats were killed.The pathologi-cal changes of the liver were observed under optical microscope.The serum levels of alanine aminotransferase ( ALT) , as-partate aminotransferase ( AST) , triglyceride ( TG) and total cholesterol ( TC) were detected by automatic biochemical an-alyzer.TG contents of liver were measured by GPO-PAP method.The fasting insulin ( FINS) was determined by ELISA, and insulin resistance index was assessed by homeostasis mode assessment ( HOMA-IR) .The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR.RESULTS:Compared with NC group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF group were obviously increased (P<0.01).Compared with HF group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF+Lira group were all obviously decreased (P<0.05 or P<0.01).The mRNA expression of SOCS-3 and SREBP-1c in HF group was signifi-cantly higher than that in NC group (P<0.01).The mRNA expression of SOCSV3 and SREBP-1c in HF+Lira group was significantly decreased as compared with HF group (P<0.05).CONCLUSION:Liraglutide may improve the IR and re-
duce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c, so as to play a therapeutic role in nonalcoholic fatty liver disease.

Objective:To investigate the related factors and prognosis of invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The in-patients diagnosed with Klebsiella pneumoniae liver abscess in the Department of Infectious Diseases, Huashan Hospital, Fudan University from January 2015 to February 2021 were retrospectively enrolled. The patients were divided into IKLAS group and non-IKLAS group according to whether they had IKLAS or not. The clinical data between the two groups were compared, including the prevalence of diabetes mellitus, the details of liver abscess, clinical symptoms such as fever and abdominal pain, as well as laboratory tests such as glycosylated hemoglobin and hemoglobin. Statistical analysis was performed using chi-square test or independent sample t test. Multivariate logistic regression analysis was used to analyze the factors influencing the occurrence of IKLAS. Results:A total of 75 patients with Klebsiella pneumoniae liver abscess were enrolled, including 55 patients (73.33%) in the IKLAS group and 20 patients (26.67%) in the non-IKLAS group. Fifty-two point seven three percent (29/55) of the patients had diabetes mellitus and 12.73%(7/55) of the patients had abdominal pain in the IKLAS group, which were 20.00%(4/20) and 45.00%(9/20) in the non-IKLAS group, respectively, and the differences were both statistically significant ( χ2=6.38 and 7.28, respectively, both P<0.05). Most of liver abscesses were single (50/75, 66.67%), and more likely to occur in the right liver (50/75, 66.67%). The maximum diameter of liver abscess in the IKLAS group was (4.58±2.04) cm, which was smaller than that in the non-IKLAS group ((6.49±3.11) cm), and the difference was statistically significant ( t=2.82, P=0.011). Compared with those in the non-IKLAS group, patients in the IKLAS group had higher glycosylated hemoglobin (8.69%±2.64% vs 6.18%±1.31%) and hemoglobin ((112.25±22.04) g/L vs (100.05±18.59) g/L), and the differences were both statistically significant ( t=-4.25 and -2.21, respectively, both P<0.05). The proportion of patients using antibiotics combined with abscess drainage in the IKLAS group was 38.18%(21/55), and that in the non-IKLAS group was 85.00%(17/20). The difference between the two groups was statistically significant ( χ2=12.86, P<0.001). A total of 16 patients (21 eyes) were diagnosed as endogenous Klebsiella pneumoniae endophthalmitis (EKPE), and all of them were IKLAS patients, and 14 patients underwent monocular/binocular eyeball injection and/or vitrectomy and silicone oil filling. The visual acuity of 13 patients decreased significantly. Multivariate logistic regression analysis showed that complicated with diabetes mellitus was an independent risk factor for IKLAS (odds ratio ( OR)=5.02, 95% confidence interval (95% CI) 1.01 to 25.03, P=0.049). The large diameter of liver abscess was a protective factor for IKLAS ( OR=0.64, 95% CI 0.47 to 0.86, P=0.003). Conclusions:The patients with IKLAS have less abdominal pain, and most of them complicate with diabetes mellitus. Diabetes mellitus is an independent risk factor for the occurrence of IKLAS, while the large diameter of liver abscess is a protective factor. EKPE is associated with poor visual prognosis.

Objective To investigate the association between Helicobacter pylori infection and nonalcoholic fatty liver disease(NAFLD).Methods This study was conducted acoording to the PRISMA guideline,with a PROSPERO registration number of CRD42023408932.Databases including PubMed,the Cochrane Library,Web of Science,Embase,CBM,Wanfang Data,CNKI,and VIP were searched for related articles published up to June 2023.This study was conducted for the case-control studies,cross-sectional studies,and cohort studies that included clear detection criteria for HP and evaluation criteria for NAFLD and performed the multivariate analysis to investigate the association between HP infection and NAFLD.Odds ratio(OR)and its 95%confidence interval(CI)were selected as the effect measures,and STATA 15.0 software was used to perform the Meta-analysis.Results A total of 33 primary studies were included,with 236 514 subjects in total.The Meta-analysis showed that HP was associated with the high prevalence rate of NAFLD(OR=1.25,95%CI:1.16—1.35,P<0.05,I2=93.7%).Subgroup analysis was conducted in terms of sample size,the diagnostic method for HP,the quality of primary study,the health status of subjects,and the type of primary study,but no clear source of heterogeneity was found.The Meta-regression analysis was conducted with the covariates of sample size,the diagnostic method for HP,the quality of primary study,the health status of subjects,and the type of primary study,and the results showed that the health status of subjects and the type of primary study might be the sources of heterogeneity.Sensitivity analysis showed that the overall results were stable,and funnel plots and the Egger test showed no significant publication bias.Conclusion HP is associated with the high prevalence rate of NAFLD in the general population,and large-scale prospective cohort studies are still needed to specifically and comprehensively evaluate the association between HP and NAFLD.

Background and objective Bone is a common site for metastasis in lung adenocarcinoma,but the mechanism behind lung adenocarcinoma bone metastasis is still unclear.And currently,there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models,which limits the research on the mechanism of lung adenocarcinoma bone metastasis.The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone,labeled with green fluorescent proteins(GFP)and fireflies luciferase(LUC),along with transcriptomic characterization,would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods.Methods The human lung ad-enocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model,and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3;cell counting kit-8(CCK-8),colony formation assay,scratch wound assays,Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells.A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing.Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established.Compared to parental cells,this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation,migration,and invasion abilities.Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells,with 1021 genes up-regulated and 1933 genes down-regulated.Gene Ontology(GO)functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery.The molecular functions identified as significantly enriched included signaling receptor activity,cal-cium ion binding,and extracellular matrix structural constituent.Additionally,the biological processes found to be enriched were cell adhesion and biological adhesion.The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiot-ics by cytochrome P450,retinol metabolism,drug metabolism-cytochrome P450,cell adhesion molecules,steroid hormone biosynthesis,and the nuclear factor kappa B(NF-κB)signaling pathway.Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established.The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.

Objective Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment in patients with Carbapenem-resistant Klebsiella pneumoniae bloodstream infections(CRKP-BSI).Methods Retrospective analysis of the clinical characteristics of 81 CRKP-BSI patients in our intensive care unit from July 2016 to June 2020,to indentify the risk factors of death and treatment effects of different antibiotic regimens.Results In 81 CRKP-BSI cases,the majority source were from abdominal and respiratory,accounting for 56.79%(46 cases)and 22.22%(18 cases),respectively.The 28-day mortality and hospitalization mortality of CRKP-BSI were 54.32%(44 cases)and 65.43%(53 cases).Multivariate regression analysis suggested that biliary tract disease before admission(P=0.026)and increased SOFA score at the onset of BSI(P=0.006)were independent risk factors for 28-day mortality.There was no statistically significant difference in 28-day mortality between the groups of antibiotic treatment based on tigecycline(44 cases)and polymyxin B(26 cases)[56.82%(25/44)vs.57.69%(15/26),P=0.943].Patients were evaluated based on their age(≤65 years vs.>65 years),gender,body mass index(≤25 kg/m2 vs.>25 kg/m2),and APACHEⅡ score(≤20 vs.>20),the use of renal replacement therapy and mechanical ventilation,there was no difference in the mortality among each subgroup.Conclusions Biliary tract disease before admission and SOFA score were independent risk factors for 28-day mortality.There was no significant difference outcomes between tigecycline-and polymyxin B-based therapy.

Objective: To investigate the effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease. Methods: A total of 30 male Sprague-Dawley rats were equally divided into normal control group, model group, and curcumin intervention group. The rats in the model group and the curcumin intervention group were given high-fat feed for 16 weeks, and those in the curcumin intervention group were given curcumin 200 mg/kg/day by gavage once a day after 8 weeks of high-fat feeding. The rats were sacrificed at the end of week 16. A light microscope was used to observe pathological changes in the liver, an electron microscope was used to observe the tight junction of the intestinal mucosa, an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), chromogenic substrate Limulus amebocyte lysate assay was used to measure plasma lipopolysaccharide (LPS) level, spectrophotometric method was used to measure the activity of serum diamine oxidase, ELISA was used to measure the serum level of tumor necrosis factor-α (TNFα), and immunohistochemistry was used to measure the expression of the tight junction protein occludin. One-way ANOVA test and SNK-q test were used for statistical analysis. Results: Under the light microscope, the control group had no hepatocyte steatosis, the model group had significant hepatocyte steatosis and inflammatory cell infiltration, and the curcumin intervention group had reduced hepatocyte steatosis and inflammatory cell infiltration. Under the electron microscope, the control group had a clear and complete structure of the tight junction of the intestinal mucosa and normal structures of mitochondria and endoplasmic reticulum; in the model group, the structure of the tight junction of the intestinal mucosa was destroyed, the intercellular space was widened, the desmosomes had a loose structure, there was edema in some mitochondria, and the endoplasmic reticulum was dilated; the curcumin intervention group had improvements in the structure of tight junction of the intestinal mucosa, intercellular space, edema in the mitochondria, and dilation of the endoplasmic reticulum. Compared with the control group, the model group had significant increases in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = -15.918, -14.402, -33.700, -8.944, and -10.832, P < 0.05); compared with the model group, the curcumin intervention group had significant reductions in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = 10.457, 7.752, 18.802, 5.202, and 4.279, P < 0.05). In the control group, occludin showed a linear distribution along the top of small intestinal mucosal epithelial cells. The model group had a significant reduction in positive staining compared with the control group, and the curcumin intervention group had a significant increase in positive staining compared with the model group. The relative expression of occludin was 0.29±0.03 in the control group, 0.12±0.02 in the model group, and 0.21±0.02 in the curcumin intervention group (P < 0.05). Conclusion Intestinal mucosal mechanical barrier is impaired in rats with NAFLD. Curcumin can reduce such damage, and its mechanism of action may be related to up-regulating the expression of occludin in the intestinal mucosa and reducing the levels of TNFα and LPS.