Objective To investigate the efficacy and outcome in newly diagnosed multiple myeloma (MM) patients with renal insufficiency using bortezomib-or thalidomide-based regimens as front line treatment.Method Sixty-nine newly diagnosed MM patients with renal insufficiency were retrospectively analyzed from August 2006 to August 2014.Results ① Among thirty-nine patients with bortezomib based regimens (the bortezomib group),the overall response rate (ORR) was 89.7％ and complete response (CR) plus near CR(nCR) rate was 41.0％.By contrast,among thirty patients with thalidomide based regimens (the thalidomide group),the ORR was 83.3％ and CR + nCR rate was 26.7％.There was no significant difference of either ORR or CR + nCR rate between bortezomib and thalidomide groups.② The improvement rate of renal function in bortezomib group and thalidomide group were 87.2％ and 60.0％respectively (P =0.012).The median duration time of renal injury was 45 days in 52 patients with renal function improved,which was significantly shorter compared with 222 days in 17 patients without improvement (P ＜ 0.05).There was no difference of median serum creatinine and creatinine clearance rate between the two groups.③ The median progression-free survival (PFS) and the overall survival (OS) were 18 and 33.5 months,respectively in all patients.The three-year and five-year OS rates were 57％ and 17％,respectively.The median PFS was 19 months in bortezomib group,while it was only 12 months in thalidomide group (P =0.023).The median OS were 36.5 months and 25.5 months respectively,which was no difference (P =0.285).Conclusions The newly diagnosed MM patients with renal insufficiency could get higher ORR and the longer PFS using bortezomib-containing regimens as initial therapy.Meanwhile the improvement rate of renal function and the living quality in patients with bortezomib are better compared with those with thalidomide based treatment.

Objective:This study investigated the clinical characteristics of multiple myeloma with early death in the era of novel drugs. Methods:Medical records from 188 patients diagnosed from January 2009 to December 2015 were retrospectively reviewed, showing that early death occurred in 19 patients. Early death was defined as death by any cause within the first year after diagnosis. Results:(1) Early mortality was 10.1%, and the median age was 67 years old (range:40-84 years). Eight cases presented IgG type, and 11 cases were non-IgG type. All 19 patients were diagnosed to be at stageⅢin accordance with the Durie–Salmon staging system, and renal insufficiency occurred in 10 patients. In accordance with the International Staging System (ISS), four patients were diagnosed to be at stageⅡ, whereas 15 other patients were at stageⅢ. Extramedullary plasmacytoma (EMP) occurred in six cases, whereas 10 cases pre-sented high-risk patients with cytogenetic abnormalities. Elevated lactate dehydrogenase (LDH) was found in five cases, amyloidosis was detected in three patients, and secondary plasma cell leukemia was observed in two cases. The median score of performance sta-tus (KPS) was 70 (range: 20-80). A total of 16 patients were treated with bortezomib, and 3 patients were treated with CADT. (2) Among the 13 patients who were evaluated, the overall response rate was 46.2%(6/13), and the complete response (CR) and near-CR rate was 7.7%(1/13). (3) The median overall survival was 3 (1-11.5) months, although the two patients with secondary plasma cell leu-kemia survived for less than 2 months. (4) Eight patients died of disease progression (42.1%), eight patients died of severe infections (42.1%), and three patients died of thrombotic events. Conclusion:The important causes of early death include the following:high-risk cytogenetics, elevated LDH, EMP, amyloidosis, advanced age, poor performance status, and serious complications during treat-ment. In the era of novel drugs, we should improve early diagnosis rates and explore individualized treatment for high-risk multiple my-eloma for the benefit of a wide range of patients.

Objective To investigate the effects of continuous hemofihration on gastrointestinal dysfunction for treating patients with intra-abdominal hypertension.Methods A total of 37 patients were divided into two groups randomly (random number),namely control group (n =17) and continuous blood filtration (CBF) group (n =20).The patients of control group were treated with routine treatment,and the patients of CBF group were given CBF for 72 hours in addition to the routine treatment.The intra-abdominal pressure (IAP),gastrointestinal (GI) symptoms,and SOFA score were documented at 0 hour,24 hours,72 hours and 7 days after treatment.Results The MAP of patients in the CBF group was not significantly changed (P =0.218),while the IAP was decreased significantly (P =0.001) and the abdominal perfusion pressure (APP) increased significantly after CBF (P =0.036).Compared with the control group,there were more than 2 GI symptoms markedly relieved after CBF for 24 hours (P =0.049).The SOFA score of CBF group decreased significantly (P =0.037).There were no differences in 28-day and 60-day mortality between two groups.Conclusions The CBF can decrease IAP,increase APP,improve splanchnic blood circulation,and ameliorate gastrointestinal dysfunction.But CBF does not reduce the mortality in comparison with routine treatment.

Objective To investigate the value of 1q21 amplification in newly diagnosed myeloma patients.Methods Fifty-two cases of newly diagnosed multiple myeloma from June 2008 to June 2010 were enrolled.Fluorescence in situ hybridization (FISH) was used to detect the 1q21 amplification,and the clinical characteristics and treatment response were analyzed.Results 1q21 amplification was discovered in 30 of 52 patients (57.7 ％),Clinical characteristics such as gender,malignant pleural effusion,extramedullary plasmacytoma,bone destruction,β2 microglobulin,ALB,hemoglobin,blood calcium,plasma cell proportion,clinical stage seemed to have no correlation with 1q21 amplification.The 52 patients all received bortezomibbased regimens.The response rates were not significant difference between patients with and without 1q21 amplification,the OS was also not significant difference [26 months (6-30 months) vs 30 months (12-85 months),P =0.409],but the patients with presence of 1q21 gain resulted in significantly shorter PFS [8 months (1-30 months) vs 20 months (3--48 months),P=0.019].Multivariate analysis showed 1q21 with more than two additional genetic abnormalities was an independent prognostic predictor (P =0.031).Conclusion 1q21 amplification is one of the adverse prognostic predictors,the response rate is not significant difference between patients with and without 1q21 amplification in bortezomib-based group,but the 1q21 amplification could result in significantly shortened PFS.

Background Doxycycline is a broad spectrum antibiotic,and it is frequently used in the treatment of ocular surface diseases.Objective The purpose of the present study was to investigate the effect of doxycycline on the inhibition of cell proliferation in bovine corneal myofibroblasts in vitro and assess its contribution to ocular surface repairing mechanism.Methods Six fresh bovine corneas were collected.The corneal stromal layer was isolated by two-step method of 1.0 g/L and 2.0 g/L collegenase-1.Isolated cells were plated at mantaryay culture flask in 10％ FBS of RPMI-1640.Vimentin and alpha-smooth muscle actin (α-SMA) organization were evaluated by immunocytochemistry,and the cells with influoresccence staining for vimentin and α-SMA were identified as the corneal myofibroblasts.Doxycycline at the concentrations of 10,20,40,60,80 mg/L was added to the medium,respectively,in different concentrations of doxycycline groups.Dexamethasone (120 mg/L)was used in the same way in the positive control group,and no drug was used in the negative control group.Cell proliferation was evaluated by MTT and the cell cycle was analyzed by BD FACScan flow cytometer assay 24 hours and 48 hours after addition of any drug.Results The cells grew well and showed the positive response for vimentin and α-SMA.MTT assay showed that the A570values of bovine corneal myofibroblasts were gradually declined with the increase of the concentration of doxycycline and lapse of active time,showing statistically significant difference (Fconcentration =1233.778,P＜0.001 ; Ftime =227.564,P ＜ 0.001).And the difference between the two factors was also statistically significant (Ftime*concentration =51.656,P＜0.001).Flow cytometry cell cycle analysis showed that 24 hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.85％,84.36％,85.18％,87.12 ％ and 89.31％,showing significant increase in comparison with 63.89％ of the negative control group (all P＜0.05),and that of 40 mg/L doxycycline group was near the positive control group.Forty-eight hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.78％,86.15％,88.23％,89.57％,93.00％,with significant increase in comparison with 70.17％ of the negative control group (all P ＜ 0.01),and that of 40 mg/L doxycycline group was near the positive control group.Conclusions The growth of the bovine corneal myofibroblasts is inhibited by doxycycline in time-and dosedependent manner in the range from 10 mg/L to 80 mg/L,and 40 mg/L of doxycycline has an obviously inhibitory action as 120 mg/L dexamethasone.

Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.

OBJECTIVETo investigate the relationship between SREBP-1c and the risk of liver disease associated with the triacylglyceride lipase PNPLA3 I148M variant using a human hepatoma cell line model transfected with recombinant lentiviruses.

METHODSHuh7 cells were transfected with control lentivirus or lentivirus containing the PNPLA3 I148M variant (variant). The two cell groups were compared to assess differences in triglyceride content (using oil red O staining), levels of triglyceride and cholesterol (using automated biochemical analyzer), expression of SREBP-lc mRNA (using fluorescence quantitative PCR), and expression of SREBP-1c protein (using western blot.

RESULTSCells expressing the PNPLA3 I148M variant showed higher triglyceride content (0.54+/-0.03 mmol/L vs. control cells: 0.23+/-0.02 mmol/L; t=22.58, P<0.001), cholesterol level (0.28+/-0.03 mmol/L vs. control cells: 0.13+/-0.02 mmol/L; t =11.83, P<0.001), SREBP-1cmRNA expression (13.59+/-0.60 vs. 11.81+/-0.82; [The abstract and text in the paper say variant increases, but the data shown says the higher value is in the control cells. Please correct to properly express the data.] P=0.001), and SREBP-1c protein expression. The level of SREBP-1c was positively correlated with serum triglyceride in the cells expressing the PNPLA3 I148M variant (r=0.912, P<0.01).

CONCLUSIONThe risk of liver disease associated with the PNPLA3 I148M variant, which increases lipogenesis, may involve SREBP-1c and a pathway that increases triglycerides.

Cell Line, Tumor ; Humans ; Lipase ; Liver Diseases ; Membrane Proteins ; Risk Factors ; Sterol Regulatory Element Binding Protein 1 ; Triglycerides

OBJECTIVETo investigate the effects of long-term hormone replacement therapy (HRT) on the breasts of postmenopausal women using mammary ultrasonography.

METHODSAn open randomized clinical study was designed. The percutaneous estradiol gel was used in a cyclic regimen combined with micronized progesterone (MP) or medroxyprogesterone acetate (MPA). Sixty healthy women (natural menopause for 1 to 5 years) were recruited and divided into four groups according to the dosage of estrogen and two kinds of progestin. All were given for 25 days per month. Mammary ultrasonography was used to observe breast glandular section thickness, breast duct width, the morphology of lobular unit and the blood flow of color Doppler imaging at baseline and every year from the second to seventh year of HRT. The serum estradiol was also measured from the 15th to 25th day of the cycle. Breast pain was recorded by the subjects.

RESULTS(1) The breast glandular section thickness after HRT was larger than that of before HRT. The breast glandular section thickness became larger gradually over time while the breast duct width became smaller over time. The breast duct width of the fifth year of HRT was significantly different from that of the sixth year (P < 0.05). (2) Twenty-two persons had new breast structure changes after HRT, and the accumulated incidence was 41.5%. New solid lesions formation occurred in five subjects (8.3%) and new cyst formation occurred in one subject (1.7%). After the second year of HRT, the serum estradiol level of the subjects with breast structure changes was higher than that of without breast structure changes and in the sixth year of HRT, and the difference was significant (P < 0.05). After the second year of HRT, the breast glandular section thickness of the subjects with breast structure changes was larger than that of without breast structure changes and in the fifth and sixth year of HRT, the difference was significant (P < 0.05). (3) After HRT, the serum estradiol level of subjects with mastalgia was higher than that of without mastalgia and in the second and sixth follow-up year, the difference was significant (P < 0.05).

CONCLUSIONSThere is an increasing trend of the percentage of glandular tissues of the breast after HRT. There is an increasing trend of the serum estradiol level and the breast glandular section thickness among the subjects with the breast structure changes; there is an increasing trend of the serum estradiol level among the subjects with mastalgia. Mammary ultrasonography can be used to monitor breast structure changes and breast lesions during HRT.

Aged ; Breast ; pathology ; Estradiol ; therapeutic use ; Estrogen Replacement Therapy ; adverse effects ; Female ; Humans ; Medroxyprogesterone Acetate ; therapeutic use ; Menopause ; Middle Aged ; Time Factors ; Ultrasonography, Mammary

OBJECTIVETo discuss the avail of balloon and stent-assisted Guglielmi detachable coil (GDC) placement in treatment of wide-necked cerebral aneurysm.

METHODSEighty-seven patients with 92 wide-necked aneurysms undergone endovascular procedures using the balloon and stent-assisted remodeling technique. Respectively, appropriate Neuroform stents delivered with a 5 mm landing zone on either side of the aneurysm neck, the microcatheter entered through the interstice, aneurysms were embolized at one or several times. Two catheters were used in balloon-remodeling technique, balloon were inflated across the neck of the aneurysms after the microcatheter entering the aneurysms, then the GDC were used to embolize the aneurysms.

RESULTSThirty-one aneurysms were completely occluded, 3 subtotally (> 90%) and 1 incompletely (70% - 90%) occluded using stent-assisted technique, all carry arteries were unblocked, 3 patients with mild neurological dysfunction and no mortality. Fifty aneurysms were completely occluded and 4 incompletely occluded using balloon-assisted technique, 1 patients with mild neurological dysfunction and no mortality. Two aneurysms were completely occluded and 1 incompletely occluded using stent-assisted and balloon-assisted technique. The mean period of follow-up was 5.8 months. Rates of recanalization were 16.7% for stent-remodeling group and 12.5% for balloon-remodeling group.

CONCLUSIONSThe stent and balloon-assisted remodeling technique are safe and effective in treating wide-necked aneurysms. Balloon-remodeling technique has more security comparing with stents.

Angioplasty, Balloon ; Embolization, Therapeutic ; methods ; Female ; Follow-Up Studies ; Humans ; Intracranial Aneurysm ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Treatment Outcome

Objective: To understand the level of health behaviors related to prevention and control of Corona Virus Disease 2019, COVID-19 among primary school students in Wuhan during the epidemic, and to provide a basis for further targeted health education and promotion. Methods: Stratified random sampling was used to select 12 primary schools in Wuhan. Relying on the "questionnaire star", the head teacher of the selected school sent the questionnaire link to students through the QQ or WeChat group, and all students participated in the survey voluntarily. Results: A total of 8 569 valid questionnaires were collected. The rate of prevention and control of COVID-19 among primary school students in Wuhan was 39.3%. Among them, wearing masks, hand hygiene and other healthy behavior accounted for 53.4%, 42.0% and 75.2%, respectively. Multivariate logistic regression analysis showed that girl, grade 3-4 and 5-6, higher maternal education (>graduate degree) were more likely to have overall health behaviors in the prevention and control of COVID-19, and the OR values were 1.13(95%CI=1.04-1.24), 1.18(95%CI=1.06-1.31) 1.58(95%CI=1.41-1.75) and 1.62(95%CI=1.00-2.62)(P<0.05), respectively. Compared with fathers whose occupations were state agencies, managers of enterprises and institutions, students whose fathers’ occupations were professional technicians and ordinary employees were less likely to have level of overall health behaviors in the prevention and control of COVID-19, and the OR values were 0.78(95%CI=0.61-0.99) and 0.72(95%CI=0.58-0.90)(P<0.05), respectively. Conclusion The level of health behaviors of primary school children in Wuhan against COVID-19 was not high and targeted health education and promotion should be provided.