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.

OBJECTIVETo explore therapeutic effect and action mechanism of regulating spleen-stomach needling on diabetic nephropathy (DN).

METHODSUsing multi-centric, randomized, controlled and blind principles, 144 cases of DN were divided into an observation group and a control group according to random digital tab, 72 cases in each one. Based on regular treatment of diabetes, the regulating spleen-stomach needling was applied at Zhongwan (CV 12), Quchi (LI 11), Hegu (LI 4) and Xuehai (SP 10), etc. in the observation group while Shenshu (BL 23), Taixi (KI 3), Sanyinjiao (SP 6), Yanglingquan (GB 34), etc. were selected in the control group by reference of Acupuncture and moxibustion. The treatment was given twice a day, six days as a treatment session with interval of one day between sessions. Totally six weeks were required. Changes of clinical symptoms and signs, fast blood glucose (FBG), urinary albumin excretion rate (UAER), beta2-microglobulin (beta2-MG), monocyte chemotactic protein-1 (MCP-1), lymphocyte membrane cholesterol, propanediol (MDA), PCO, 8-hydroxydeoxy guanosine (8-OHdG), superoxide dismutase (SOD), CD3+, CD4+, CD8+, and CD4+/CD8+ were observed before and after treatment in two groups.

RESULTSAs for improving clinical symptoms and signs, total effective rate was 84.29% (59/70) in the observation group and 55.56% (40/72) in the control group, which had statistical difference between two groups (P<0.01). As for regulating glycometabolism [(6.25 +/- 0.32) mmol/L vs (8.09 +/- 0.63) mmol/L], reducing UAER [(154.43 +/- 55.14) mg/24h vs (268.91 +/- 77.65) mg/24h], restraining over-expression of MCP-1 [(137.59 +/- 36.15) pg/mL vs (166.89 +/- 42.82) pg/mL], regulating level of oxidative stress, prohibiting oxidation of protein and adjusting quantity and activity of T lymphocyte subgroup, the observation group was superior to the control group (P< 0.05, P<0.01).

CONCLUSIONThe regulating spleen-stomach needling is an effective method for treatment of DN, which cold improve glycometabolism disturbance-induced progressive kidney injury, recover glomerular filtration, reduce urinary albumin excretion rate, restrain overexpression of MCP-1, adjust level of oxidative stress, prohibit oxidation of protein, increase protectiveness of membrane, adjust quantity and activity abnormity of T lymphocyte subgroup, leading to repairing lymphocyte damage and improving immune expression to delay kidney damage.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Diabetic Nephropathies ; immunology ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Spleen ; physiopathology ; Stomach ; physiopathology

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.

AIM: To compare intraocular pressure (IOP) fluctuations measured at home and in the clinic over a 24-hour period.METHODS: A prospective investigational study.A total of 120 Chinese participants were selected from five communities in the Chengdu area.Patients underwent a clinical interview and IOP was measured both at home and in the clinic.IOP were measured at 8 a.m., 10 a.m., 12 a.m., 2 p.m., 4 p.m., 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m.using the same pneumatonometer.Measurements were taken in the sitting position.RESULTS: The average 24-hour IOP measured in the clinic was slightly lower than that at home.The mean difference in 24-hour IOP measurements between home and clinic was 0.27 mmHg.The IOP fluctuation in the clinic was higher than at home (the mean difference was 0.01 mmHg).There was no statistically significant difference in the average 24-hour IOP measured at home vs in the clinic.The average IOP measured at 2 p.m.at home (16.04±5.95 mmHg) was significantly higher compared with the measurement in the clinic (15.43±5.16 mmHg) (P<0.05).The overall agreement between 24-hour IOP measurements made in the clinic and at home in diagnosis of primary open angle glaucoma was 85.0% (K coefficient: 0.68).CONCLUSION: The 24-hour IOP measured in the clinic was similar to that measured at home, and the method of measuring IOP in the clinic is acceptable in diagnosing primary open angle glaucoma.

Objective To measure the expression of activin receptor-like kinases 1(ALK1)in dermal fibroblasts from patients with systemic scleroderma(SSc)and to estimate its role in the production of fibronectin and plasminogen activator inhibitor-1(PAI-1).Methods Dermal fibroblasts were isolated from the lesions of 12 patients with SSc as well as the normal skin of 14 healthy controls,and subjected to a primary culture.The third-passage fibroblasts were used in the next experiment.Western blot and indirect immunofluorescence technique were utilized to quantify the expression of ALK1.A specific siRNA targeting ALK1 was designed,constructed,and transiently transfected into the control dermal fibroblasts,which were then classified into 2 groups to be cultured with or without the presence of transforming growth factor(TGF)-β1 for 72 hours followed by the detection of fibronectin and PAI-1 expression with Western blot.Results As Western blot and direct immunofluorescence technique showed,both control and SSc fibroblasts showed an expression of ALK1 in the cytoplasm and membrane,and the expression intensity of ALK1 in SSc fibroblasts was significantly higher than that in the control fibroblasts(1.97 ± 0.05 vs.1.12 ± 0.03,t =50.96,P ＜ 0.05).The expression of ALK1,fibronectin and PAI-1 was decreased by 90％,58％ and 31％ respectively in specific siRNA-transfected SSc fibroblasts compared with the control siRNA-transfected fibroblasts.TGFβ1 significantly increased the expression of ALK1,fibronectin and PAI-1 in the control siRNA-transfected fibroblasts,but the increase was markedly inhibited by the siRNA-targeting ALK1.Conlusion TGFβ1 can promote the production of fibronectin and PAI-1 via ALK1 in fibroblasts,and ALK1 may be involved in the development of sclerosis in SSc.

A high-product superoxide dismutase(SOD)bacterial strain was first obtained from the soil around the warm spring of Changbai Mountain,which is alkaline-resistant.The nature analysis by the inhibition of H2O2 and chloroform-ethanol indicated that the SOD was Mn-SOD.It belongs to bacillus genus by the modal character,physiological and biochemical character.The phylogenetic analyses based on 16SrDNA sequence indicated that the strain 110-2 was closed to Bacillus sp.MO6 with 100% identity and 99% with Bacillus licheniformis.According to the sodA sequence of Bacillus licheniformis and conservative regions of many kinds of bacillus,which were published in GenBank,two pairs of primers were designed and the complete sequence of Mn-SOD(600bp)and the core fragment(430bp)were amplified by PCR techniques.The recombinant plasmid pMD18-SOD was built successfully.

In the current study, a total of nineteen triterpenoids (1-19) from 60% EtOH extracts of Stauntonia obovatifoliola Hayata subsp. intermedia stems were separated and purified by solvent extraction and chromatographic methods including silica gel, ODS as well as preparative HPLC. According to the results of chemical reactions and spectral data, compounds were identified as: lupeol (1), betulinonic acid (2), betulinic acid (3), 3-epi-betulinic acid (4), quinatic acid (5), 24-O-acetyl quinatic acid (6), 3-O-α- L-arabinopyranosyl-30-nor-hederagenin-28-O-α-L-rhamnopyranosyl-(1 --> 4) -β-D-glucopyranosyl-(1 --> 6) -β-D-glucopyranosyl ester (7), Stauntoside A (8), kalopanax saponin A (9), kalopanax saponin J (10), Kizuta saponin K10 (11), 3-O-α-L-rhamnopyranosyl (1--> 2) -α-L-arabinopyranosyl-hederagenin-28-O-β-D-xylopyranosyl-(1 --> 6) -β-D-glucopyranosyl ester (12), kalopanax saponin B (13), 3-O-α-L-rhamnopyranosyl-(1 --> 2) -α-L-arabinopyranosyl-hederagenin-28-O-β-D-glucopyranosyl-(1 --> 6) -β-D-glucopyranosyl ester (14), sieboldianoside A (15), septemoside A (16), kalopanax saponin K (17), septemloside I (18), and 3-O-α-L-arabinopyranosyl (1 --> 2)-β-D-glucuronopyranosyl- hederagenin (19). Among them, compounds 4, 6, 10, 12, 14, and 16-19 were isolated from the Stauntonia genus for the first time, and compound 6 was a new natural product.
Drugs, Chinese Herbal ; chemistry ; Magnetic Resonance Spectroscopy ; Magnoliopsida ; chemistry ; Molecular Structure ; Plant Stems ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; Triterpenes ; chemistry

OBJECTIVEThis study aims to determine the gene expression changes of iron transporters-divalent metal transporter 1 (DMT1) and ferroportin 1 (Fpn1) in the duodenal tissue of diet-induced obese mice.

METHODSC57BL/6J mice were randomly divided into normal control (NC) and obesity model (OM) group, 6 in each, and fed on conventional and high-fat diet respectively for 14 weeks by table of random number. Then the DMT1 and Fpn1 mRNA contents in duodenal tissues of the animals were measured by Real-time PCR method, and the protein expression levels were analyzed by Western blot test.

RESULTSThe Real-time PCR detection results showed that, compared with the NC group for which the mRNA expression level was defined as 1.0, the Fpn1 mRNA expression in OM group (0.58±0.11) was reduced significantly (t = 6.71, P = 0.014), whereas the relative expression level of DMT1 mRNA in OM group (0.89±0.26) showed no obvious alteration (t = 2.01, P = 0.122). Western blot results showed that the relative protein expression levels of Fpn1 in OM and NC group were 0.32±0.06 and 0.65±0.19, respectively, and the difference was statistically significant (t = 5.37, P = 0.026). The DMT1 protein relative abundance was 0.88±0.21 in OM group and 0.92±0.17 in NC group, and the difference has no statistical significance (t = 1.84, P = 0.185).

CONCLUSIONFpn1 gene expression is inhibited in the duodenum of diet-induced obesity mouse while DMT1 expression keeps unchanged, and this implies that decreased iron export from enterocytes into circulation might be responsible for the impaired iron absorption in obesity.

Animals ; Cation Transport Proteins ; Diet ; Diet, High-Fat ; Duodenum ; Gene Expression ; Iron ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; RNA, Messenger

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV).Therefore,we evaluated the factors related to the severity of adverse effects during HATT,especially those associated with liver failure.A retrospective study was carried out at Tongji Hospital from 2007 to 2012.Increases in serum transaminase levels of＞3,5,and 10 times the upper limit of normal (ULN) were used to define liver damage as mild,moderate,and severe,respectively.Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (＞171 μrnol/L) with or without decreased (＜40％) prothrombin activity (PTA) were diagnosed with liver failure.A cohort of 87 patients was analyzed.The incidence of liver damage and liver failure was 59.8％ (n=52) and 25.3％ (n=22),respectively.The following variables were correlated with the severity of hepatotoxicity:albumin (ALB) levels,PTA,platelet counts (PLT),and the use of antiretroviral therapies (P＜0.05).Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure,and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066.Judicious follow-up of clinical conditions,liver function tests,and coagulation function,especially in patients with high HBV loads and hypoalbuminemia is recommended.It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.