Objective:To explore the efficacy of ixazomib combination treatment therapies for multiple myeloma (MM), and the influencing factors of prognosis.Methods:The clinical data of 80 MM patients admitted to Yancheng Third People's Hospital from January 2020 to January 2022 were retrospectively analyzed. All patients received 3 courses of ixazomib combination treatment therapies (28 d was 1 course). All combination treatment therapies included ID group (ixazomib + dexamethasone, 11 cases) and ID + immunomodulator group (ixazomib + dexamethasone + lenalidomide/thalidomide, 50 cases), ID + other chemotherapy drugs group (ixazzomib + dexamethasone + doxorubicin liposome/cyclophosphamide/bendamustine, 19 cases). The clinical efficacy of patients in different treatment regimens was compared, and the prognosis was followed up and recorded. The clinical characteristics between the survival and the dead patients were compared. Cox proportional risk model was used to make multivariate analysis of the overall survival of MM patients receiving ixazomib combination therapies.Results:The treatment was effective in 9 cases (81.82%) of the ID group, 32 cases (64.00%) of the ID + immunomodulator group, and 9 cases (47.37%) of the ID + other chemotherapy drugs group. There was no statistically significant difference in the effectiveness rate of 3 ixazomib combination regimens ( χ2 = 0.62, P = 0.432). All patients were followed up for 5 to 20 months, with an average follow-up time of (15±4) months. There were statistically significant differences in immunoglobulin type, Durie-Salmon stage, early treatment line and therapeutic efficacy between the survival group (49 cases) and the death group (31 cases) (all P < 0.05). Multivariate Cox regression analysis showed that the clinical effectiveness (effectiveness vs. ineffectiveness: OR = 0.242, 95% CI 0.103-0.567, P = 0.001) and the previous first-line treatment (the first-line vs. the other lines: OR = 0.577, 95% CI 0.452-0.736, P < 0.001) were independent protective factors for the overall survival of MM. Conclusions:The 3 ixazomib combination therapies have a certain efficacy in the treatment of MM; ID regimen has the best clinical efficacy and survival. The clinical effectiveness and the previous first-line treatment are independent protective factors for the survival of MM.

Objective:To prepare the resiquimod-loaded lipid microbubbles R848-MBs, evaluate their enhanced ultrasound imaging and high intensity focused ultrasound (HIFU) ablation effects, and explore their ability to improve tumor immune microenvironment synergize with HIFU.Methods:R848-MBs were prepared by the thin film hydration-mechanical shock method; The basic characteristics and safety of R848-MBs were detected, the HIFU controlled-release characteristics were verified in vitro and the drug metabolism and biological distribution were investigated in vivo. The ability of enhancing ultrasound imaging was observed in vitro and in vivo. To investigate the enhanced HIFU ablation effect of R848-MBs, six EMT6 tumor-bearing mice were randomly divided into HIFU group and R848-MBs+ HIFU group, three mice in each group, the changes in contrast average sound intensity before and after ablation in mouse tumor areas and the change of ultrasound image gray value in tumor area were evaluated, the tumor were resected to observe the coagulative necresis by TTC staining and HE staining. Forty-five tumor-bearing mice were randomly divided into control group, Free R848 group, HIFU group, Blank-MBs+ HIFU group and R848-MBs+ HIFU group, nine mice in each group. On the third day after treatment, 3 mice in each group were randomly selected and killed, to evaluate the ability of R848-MBs to improve tumor immune microenvironment synergize with HIFU. The expression level of CRT on the surface of tumor cells were detected by immunofluorescence staining, the proportion of mature DC in lymph nodes, spleen, and CD8 + T cells in spleen were detected by flow cytometry. The treatment effectiveness of each group( n=6) were evaluated by measuring tumor volume, observing and drawing survival curves. Results:The R848-MBs lipid microbubbles with good safety were successfully prepared, with a concentration of 2.58×10 9/ml, as spherical bubbles under optical microscope and laser confocal microscopy, in a particle size of (1.72±0.11)μm, at a surface potential of (-10.16±0.73)mV. The cumulative drug release was up to 83.44% after HIFU (90 W, 3 s) in vitro. The concentration of R848 in plasma decreased rapidly, and the drug concentration in tumor tissue of the R848-MBs+ HIFU group was higher than that of the R848 group 24 hours after treatment ( P<0.01). The ultrasound imaging of R848-MBs was significantly enhanced in contrast mode in vitro and in vivo; R848-MBs can significantly enhance the HIFU ablation effect, the contrast average sound intensity change in the tumor area before and after ablation in the R848MBs+ HIFU group was greater than that in the R848 group ( P<0.05), and the immediate ultrasound grayscale value change in the HIFU+ R848-MBs group was 46.34±3.21, which was significantly greater than that in the HIFU group (10.67±1.53), with statistical significance ( P<0.000 1). Coagulation necrosis was observed in tumor HE staining and TTC staining. The results of treatment efficacy in vivo showed that R848-MBs+ HIFU group had the strongest therapeutic effect, and R848-MBs combined with HIFU treatment could significantly prolong the survival period of mice compared with intravenous injection of free R848 ( P<0.01). Immunofluorescence staining and flow cytometry results showed an increase in the expression level of CRT on the surface of tumor tissue in the R848-MBs combined with HIFU group, and the percentage of mature DC in tumor draining lymph nodes (58.53±1.04)% were significantly higher than those in the HIFU group (37.56±2.13)% ( P<0.001), and the percentage of mature DC in the spleen (70.65±1.91)% were significantly higher than those in the HIFU group (36.46±3.89)% ( P<0.001), the percentage of CD8 + T cells in the spleen (27.46±3.04)% was significantly higher than that in the HIFU group (18.69±0.29)% ( P<0.01). Conclusions:The HIFU controlled-release lipid microbubbles R848-MBs can not only enhance the efficiency of HIFU ablation, but also improve the tumor immune microenvironment.

Objective:To analyze the incidence of postoperative pulmonary complications and related factors in elderly patients after major abdominal surgery.Methods:Clinical data of elderly patients undergone major abdominal surgeries at Beijing Hospital were retrospectively analyzed.The incidence of postoperative pulmonary complications was studied, and related factors were analyzed using Logistic regression analysis.Results:A total of 96 cases were included.The incidence of postoperative pulmonary complications was 53.1%(51/96)in elderly patients after major abdominal surgery.Logistic regression analysis showed laparoscopy was a protective factor for postoperative pulmonary complications( OR=0.293, 95% CI: 0.100-0.865, P=0.026), while driving pressure > 18 cmH 2O(1 cmH 2O=0.098 kPa)( OR=3.300, 95% CI: 1.148-9.434, P=0.027)and intraoperative bleeding volume > 500 ml( OR=4.444, 95% CI: 1.091-18.180, P=0.037)were risk factors for postoperative pulmonary complications. Conclusions:Attention should be paid to the incidence of postoperative pulmonary complications in elderly patients after major abdominal surgery.Laparoscopy is a protective factor for postoperative pulmonary complications, while driving pressure more than 18 cmH 2O and intraoperative bleeding volume more than 500 ml can increase the risk of postoperative pulmonary complications.

Objective To explore the measurement accuracy of right coronary artery during coronary angiography (CAG)at 45Gdegree left oblique position.Methods The images of right coronary artery angiographic view of 45Gdegree left oblique position were divided into nine average areas.The images with marker segment of guiding wire located in the central area (n＝45)or subcentral area (n＝45)of CAG cases were collected retrospectively and randomly.The marker segment was measured by catheter calibration method,and the measure values were compared with the actual length (30 mm).Results A N OVA analysis suggested statistical differences among the three groups (F＝4.59,P＜0.05).By paired comparison,no significant differences were found in measured values between central areas (3 1.1 9± 4.12)mm or subcentral areas (29.55±2.75)mm and the actual length (P＞0.05).Significant differences were found in measured values between central areas and subcentral areas (P＜0.05).The measuring error of subcentral areas (－1.5%)was less than that of central areas (3.9%).Conclusion During CAG at 45Gdegree left oblique position,the values of subcentral area were more accurate than those of central area and the subcentral area was thus regarded as image area with less measurement error in interventional surgery.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective To explore the differences of aortic diameter measured by catheter calibration method and centimeter sizing catheter calibration method in endovascular graft exclusion for Stanford type B aortic dissection.Methods A total of 30 patients with Stanford B type aortic dissections treated with endovascular graft exclusion were measured with the two calibration methods to measure aortic diameters at left subclavicular artery position.The measurement parameters were compared with CTA measurement results.Results Statistical differences of measurement parameters were found among catheter calibration,centimeter sizing catheter calibration and CTA (F=3.15,P＜0.05),and paired comparison showed statistical differences between catheter calibration method and CTA result (P＜0.05),and between the results of catheter calibration method and centimeter sizing catheter calibration method (P＜0.05),while no statistical difference was found between centimeter sizing catheter calibration method and CTA result (P＞0.05).Taking CTA as golden standard method,Bland-Altman analysis indicated that the centimeter sizing catheter calibration method exerted better consistency with CTA.Conclusion The measurement value of centimeter sizing catheter calibration method is identical to the CTA measurement result,and superior to catheter calibration method for precise stent selection in Stanford type B aortic dissection.

Objective:To explore the change of B cell numbers in active MRL/lpr lupus mice , and their regulation mechanisms.Methods:B cell cycle and the percent of B cells in spleen lymphocytes of active MRL /lpr lupus mice and normal C 57/B6 mice were analyzed by using flow cytometry .The apoptotic B cells and their subclass were analyzed by Annexin V and PI staining.Further more ,B cells were purified by magnetic sorting , and real-time quantitative PCR was carried out to detect apoptosis-related gene.Results:Compared with the C57/B6 mice,the percent of B cells in active MRL/lpr lupus mice were significantly reduced (P<0.01),while the percent of apoptotic cells were significantly increased (P<0.01).The percent of early apoptotic B cells were sig-nificantly increased ( P <0.01 ) which including the immature and mature B cells , while the late apoptotic B cells were unchanged.Further more,we found that the anti-apoptotic protein BIRC3 was significantly reduced in active lupus B cells (P<0.01), while the pro-apoptotic protein BCL2L1 and BBC3(PUMA) were significantly increased(P<0.01).Conclusion: B cells in active lupus mice were significantly reduced while early apoptotic B cells were increased , which may be attributed to the changed balance between the anti-apoptotic and pro-apoptotic proteins , suggesting the reduction of B cells in SLE patients may be related to their increased early apoptosis .

Objective To establish and evaluate the CaV1?1?R528H gene knock?in mouse model of thyrotoxic hy?pokalemic periodic paralysis. Methods Thirty?six 8?week?old male CaV1?1?R528H gene knock?in mice and thirty?six 8?week?old wild?type male C57BL/6J mice were used in this study. Using three?factor two?level 2 × 2 × 2 factorial design ( the three factors including mutation, thyroxine and insulin, and two levels were with or without) , the mice were divided into 8 groups. The thyroxine groups were intraperitoneally injected with levothyroxine in a dose of 350 μg/kg once per day for 12 consecutive days to produce thyrotoxicosis. The insulin groups were intraperitoneally injected with short?acting insulin in a dose of 0?8 U/kg after the last administration of levothyroxine, and the potassium levels of different groups were meas?ured and recorded before (0 min) and after insulin injection (30 min, 60 min). Results (1) Compared with the control group, the following phenomena including irritability, dull coat, increased diet and water intake, and slow body weight gain, were observed in the thyrotoxic mice. Thyroid function tests showed that the levels of T3 and T4 in the thyrotoxic mice were significantly higher than those in the corresponding control mice (P<0?05), and the TSH level was significantly low?er than that of the corresponding control mice (P<0?05 ). (2) After administration of insulin or thyroxine alone, the po?tassium levels in the mutant and wild?type mice were not significantly different. However, after combined administration of thyroxine and insulin, the potassium levels in the mutant group were significantly lower than those in the wild?type mice at 30 min and 60 min ( P<0?05 for both). (3) The main effects and interactions:Mutation factor or thyroxine factor alone did not influence on the potassium level, only insulin showed hypokalemic effect (P<0?05). There were interactions be?tween thyroxine and mutation, and between insulin and mutation (P<0?05), but no interaction between thyroxine and in?sulin. Conclusions (1) A thyrotoxicosis state in mice is successfully developed in this study. (2) An CaV1?1?R528H gene knock?in mouse model of thyrotoxic hypokalemic periodic paralysis is successfully established.

Objective:To explore the effect of histone demethylase JMJD3 on B cell activation and apoptosis.Methods:B cells were sorted and purified from the peripheral blood of healthy people and SLE patients by using magnetic bead.After B cells were treated with IFN-αor R848 or IFN-α+R848,the percentages of CD86+B cells,CD69+B cells,CD86+Annexin V+B cells and CD69+Annexin V+B cells were detected by flow cytometry.The expression of JMJD3 was detected by Real Time PCR and Western blot.Results:The purity of sorted B cells was up to 95%.IFN-αenhanced both the activation and apoptosis and the JMJD3 expression of TLR7-activated B cells.The expression of JMJD3 was dependent on MAPK signal pathway,but not the NF-κB signaling pathway.Moreover,JMJD3 was highly expressed in B cells of peripheral blood from SLE patients compared to those from healthy people.Furthermore,JMJD3 inhibitors could inhibit the activation and apoptosis of IFN-αand R848 activated B cells.Conclusion:JMJD3 participated in the activation and apoptosis of IFN-αand TLR7-induced B cells, suggesting JMJD3 inhibitors may possess therapeutic effect for alleviating symptom of SLE.

Objective To explore the effect of transitional care model (TCM) on the prevention of complications in patients with severe cerebral infarction. Methods Sixty patients with severe cerebral infarction were randomly divided into the experiment group and the control group, 30 cases in each group. The control group was given conventional nursing and the observation group received TCM. The two groups were compared in terms of the incidence of complications and re-admission rate. Result The incidence of complications and the rate of re-admissions in the experiment group were significantly lower than those of the control group (P<0.05). Conclusion TCM can reduce the incidence of complications in patients with severe cerebral infarction, lower the incidence of hospital admission, relieve the pain of patients and improve the quality of life of patients.