Objective To observe the curative effects and toxicity of low-dose bortezomib plus thalidomide and chemotherapy in treatment of multiple myeloma. Methods 35 patients with initial, refractory or relapsed MM received at least two cycles of treatment with bortezomib at 1.1 mg/m2 intravenously on days 0,3, 7, and 10, and by daily oral thalidomide escalated from 50mg to 150 mg and chemotherapy. The chemotherapy regimens included MP, VAD and AD regimen which was chosen according to the status of patients. Results After a median follow-up of 20 months, the overall response rate was 82.8 %, complete remission (CR)48.6 %, very good partial remission (VEPR) 17.1%, and partial remission 17.1%. The 3-year PFS and OS were 60.92 % and 72.41% separately. ORR and OS were same in initial and refractory or relapsed MM patients. Grade 3 or 4 adverse events including debility (3/35), nausing and vomiting (8/35), constipation (4/35), peripheral sensory neuropathy (3/35), neutropenia (10/35) and thrombocytopenia (12 %) were observed.Conclusion The regimen of low-dose bortezomib plus thalidomide and chemotherapy is a highly effective and safety regimen for MM patients. The maintenane therapy with thalidomide may prolong PFS.

Tripterygium glycosides preparation which extracted from the traditional Chinese herb Tripterygium wilfordii (TWHY), was widely used to treat the autoimmune diseases. Previous works demonstrated that TWHF had potent anti-inflammatory and immunosuppressive properties. But the different quality and high incident rate of side effects of different manufactures inhibited its clinical application. Since TWHF had been generally known to play a therapeutical effect by synergism of multiple constituents, it was necessary to build the relationship between the HPLC fingerprint and bioactivity so as to ensure the quality safety and efficacy. The HPLC fingerprint showed that description and content of peaks from different manufactures were diverse. Only 11 common peaks were found. In this study, mice spleen cells stimulated by Con A were used to test the proliferation inhibition bioactivity of TWHF preparations, which were incubated with 30, 15, 7.5, 3.75, 1.88 and 0.94 mg x L(-1) TWHF preparations for 48 h. The results showed that mice spleen cells proliferation was inhibited by all TWHF preparations significantly compared with the control group, which suggested the TWHF preparations showed immune suppress activity. The TWHF preparations from 7 manufacture showed different IC50 value, which might belong to different contents which showed in the HPLC fingerprint. Moreover, a relationship between the HPLC fingerprint and the bioactivity were established to identify important constituents by grey relational analysis (GRA). The result showed that all the contents were relative with the IC50, especially No. 5 and 10 peaks, but No. 1 peak, which was proved to be triptolide, had few contribute to the inhibition of mice spleen cells proliferation. The study of relationship between the HPLC fingerprint and the IC50 by GRA could help to investigate mechanism of bioactive and provide an evidence for the quantification of multi-constituents.
Animals ; Anti-Inflammatory Agents ; analysis ; pharmacology ; Cell Proliferation ; drug effects ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Glycosides ; analysis ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Spleen ; cytology ; drug effects ; Tripterygium ; chemistry

PurposeTo investigate a multi-parametric protocol for breast MRI examination and lesions assessment correlated to the American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) categorization, and to improve the management of the breast lesions.Materials and Methods 301 pathologically confirmed lesions on 278 patients were retrospectively included. The scan protocol used a dynamic contrast enhancement sequence (DCE) of 1 mm×1 mm×1 mm spatial resolution, 120 temporal resolution and a diffusion weighted imaging (DWI) of b=1000 s/mm2. The malignant morphological features on the early-enhanced images, type II or III time intensity curve and the apparent diffusion coefficient (ADC) value less than benign/malignant threshold was equally weighted. Each was given 1 point when present malignant features and treated different on mass and non-mass-like enhancement lesions. When the sum of score was ≥2 points, the lesion was categorized as BI-RADS 5. When the sum of score was 1 point, the lesion was categorized as BI-RADS 4. When the sum of score was <1 point, the lesion was categorized as BI-RADS 3. The other specific benign findings were categorized as BI-RADS 2. No abnormality on DWI, DCE, T2WI and T1WI was categorized as BI-RADS 1. The final categories were correlated to the pathological grades as benign (B), high risk (HR) and malignant (M).Results When grouped HR as malignant (M+HR), the area under curve (AUC) of the ROC was 0.860. When grouped HR as benign (B+HR), the AUC of the ROC was 0.876, and the optimized sensitivity, specificity and accuracy was 85.3%, 86.8% and 85.1%, respectively, which were better than the other grouping. If the management of HR lesions could be lumptoectomy or short-term follow-up, the positive predictive value (PPV) of BI-RADS 5 for excisable lesions (M+HR) was 93.2%, the PPV of BI-RADS 4 for excisable lesions (M+HR) was 46.9% and the biopsy was essential. The PPV of BI-RADS 3 and below for follow-up lesions (B+HR) was 90.4%.Conclusion A simple diagnosis algorithm was established, which equally weighted the DCE morphological feature, DCE-TIC and DWI-ADC. The diagnosis protocol was well consistent with BI-RADS categorization and could predict the benign, high risk and malignant lesions in pathology as well as the proper management.

Objective:Aldose reductase,involved in the pathogenesis of diabetic complications,was recombinated with an adeno associated virus vector pSNAV2.0,and it was transfected into human embryonic kidney 293(HEK 293)cells.The gene engineering produced AR would be used as a target protein to screen aldose reductase inhibitors.Restriction endonuclease digestion and ligation procedures were performed to construct the AR expression plasmid vector pSNAV-hAR.Methods:After confirmation the recombinant plasmid by PCR,restriction endonuclease digestion,and DNA sequencing,pSNAV-hAR was transfected into HEK293 cells.Western blot and immunofluorescence analysis were performed to detect the expression of AR and its enzyme activity.Results:The results of a series of analysis including AR activity assay,Western blot and immunofluorescence analysis shown the expressed protein mediated by the adeno associated virus vector transfecting HEK 293 cells,was functional AR.The traditional aldose reductase inhibitors,Sobinil and Zopolrestat,were used to test and verify the constructed cell model.Conclusion:The established AR expression model can be used in mechanismresearch of activation of polyol pathway on diabetic complications and screening potential aldose reductase inhibitors.

AIM: To investigate the clinical features of dry eye with type 2 diabetic patients,and to analyze the correlation between the clinical features of dry eye and the disease condition.METHODS: Retrospective case series study.Dry eye cases with type 2 diabetic were analyzed from March to December in 2016.And the clinical features of patients were summarized.Dry eye examination including tear break-up time (BUT) and Schirmer test (schirmer Ⅰ test,SⅠt).Patients were divided into <60 years and≥60 years group by the age.And patients were divided into <5 group,5-9 years group,≥10 years according to the duration of diabetes.According to the condition of blood glucose,patients were divided into glucose controlled group and the group blood glucose uncontrolled.The results were statistically analyzed with gender,age,duration of diabetes and blood glucose level.RESULTS: There were 178 cases collected.All cases were diagnosed as dry eye both eyes.The patient`s age ranged from 32 to 85 years,with an average 58.41±13.06 years.There were 110 (61.8%) male cases,and 68 (38.2%) female cases.In all cases,the mean value of BUT was 4.52±2.31s,and the mean value of SⅠt was 4.25±1.99mm/5min.The value of women were more than men,but the differences were not significant statistically.Patients of ≥60 group were less than the age group of <60 patients,and the difference was significant statistically (t=4.153,4.021;P<0.01).In different course,all groups were lower than the normal.The value of≥10 years group was the least,<5 years group was the highest,and 5-9 years group was middle one.The differences were statistically significant (F=68.884,60.204;P<0.01).The value of blood glucose controlled group was significantly higher than the group blood glucose uncontrolled,and the difference was statistically significant (t=-6.615,-5.918;P<0.01).CONCLUSION:There were two types dry eye in 2 diabetic patients: the instability of tear-film and the reduction of tear secretion.The clinic features of dry eye were related to age,the course of the disease,and the level of blood glucose.

Objective To investigate the iodine nutritional status of school children, lactating women and infants in iodine deficient areas of Baicheng and Wushi Counties in Xinjiang Autonomous Region. Methods According to the geographic location of east, south, west and north of county, 10 primary schools of 8 townships were selected. In each school, 10 children among each gender and age group from 8 to 10 years old were selected. A total of 300 school children were chosen. One hundred and four infants aged 0-2 years old and their mother were selected in 8 townships. Iodine content in edible salt at household level, the urinary iodine in school children and lactating women, total goiter rate(TGR) and the status of the intelligence quotient (1Q) of school children, the status of psychological development of infants were observed. Direct titration assay for testing the salt iodine, colorimetric ceric-arsenic assay and vitriolic ammonium assimilation were used for testing urinary iodine. The size of thyroid gland was measured by palpation. The Combined Raven Test for Chinese Rural was used to test the IQ. The psychological development of infants was tested by Danver Development Screening Test (DDST). Results The coverage rate of iodized salt at household level was 73.1% (123/182), however, the proportion of households using adequately iodized salt was 64.1% (118/182). The medium of urinary iodine in school children was 103.7 μ/L, with 47.8%(75/157) less than 100 μg/L and 28.0% (44/157) less than 50 μg/L; it was 123.0 μg/L in Baieheng County, with 44.4%(28/63) less than 100 μg/L and 33.3%(21/63) less than 50 μg/L; it was 100.3 μg/L in Wushi County, 50.0%(47/94) less than 100 μg/L and 24.5%(23/94) less than 50 μg/L. The medium of urinary iodine in locating women was 143.3 μg/L, it was 119.7 μg/L and 184.6 μg/L in Baicheng and Wushi Counties, respectively. The total rate of goiter in school children was 14.3%(43/300), it was 10.8%(13/120) and 16.6%(30/180) in Baicheng and Wushi Counties, respectively. The average IQ in school children was 80.6±11.6, it was 83.0±11.6 and 79.0±11.7 in Baicheng and Wushi Counties, respectively. The proportion of mental retardation in school children (IQ≤69) was 13.0% (39/300), it was 6.7% (8/120) and 17.2%(31/180) in Baicheng and Wushi Counties, respectively. In addition, the proportion of psychological development in infants being normal, suspicious and abnormal was 78.8%(82/104), 12.5% (13/104) and 8.7%(9/104), respectively. Conclusion This study confirms the fact that there is also existence of mental retardation in children and infants, caused by iodine deficiency.

Animals ; Cisplatin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; metabolism ; Male ; Proteinuria ; etiology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

AIM:To evaluate the optic nerve and axon impairment of relapsing - remitting multiple sclerosis ( RRMS) and neuromyelitis optica spectrum disorders ( NMOSD ) via detecting the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell complex( GCC) thickness by optic coherence tomography(OCT).
METHODS: Retrospective case control study. Two hundred three cases were collected from August 2014 to January 2016 in Beijing Tian Tan Hospital. They were divided into four groups, including the normal group (n=60), the RRMS group ( n = 60 ), the NMOSD anti -aquaporin- 4 autoantibody seropositive( NMOSD- AQP4 -Ab seropositive) group (n= 48), and the NMOSD-AQP4-Abseronegative group (n = 35). All people were detected for the average and four quadrants ( superior, inferior, nasal, temporal) of pRNFL thickness and the average and two quadrants (superior, inferior) of GCC thickness with OCT. One way analysis of variance or nonparametric tests was used to compare the differences of pRNFL and GCC thickness between groups.
RESULTS: Comparing with the normal group, the average and all quadrants of pRNFL and GCC thickness in the RRMS, the NMOSD - AQP4 - Ab seropositive and the NMOSD-AQP4-Ab seronegative group were thinner (P<0. 01). Among them, the pRNFL and GCC thickness in the NMOSD- AQP4 - Ab seropositive group was the thinnest. Differences between groups in the pRNFL thickness:compared with the RRMS group, all quadrants of pRNFL and GCC thickness in the NMOSD-AQP4-Ab seropositive group were significantly thinner(P<0. 01); compared with the NMOSD- AQP4- Ab seronegative group, the inferior, nasal and temporal pRNFL thickness in the NMOSD-AQP4-Ab seropositive group were significantly thinner(P<0. 05), while the superior quadrant did not show significant differences( P > 0. 05); compared with the RRMS group, the superior pRNFL thickness in the NMOSD - AQP4 - Ab seronegative group was significantly thinner ( P < 0. 05), while the inferior, nasal and temporal quadrants did not show significant differences ( P > 0. 05 ). Differences between groups in the GCC thickness: compared with both the RRMS and the NMOSD- AQP4- Ab seronegative group, all quadrants of GCC thickness in the NMOSD -AQP4-Ab seropositive group were significantly thinner (P<0. 05); compared with the RRMS group, the superior GCC thickness in the NMOSD - AQP4 - Ab seronegative group was significantly thinner(P<0. 01), while the inferior quadrant did not show significant difference(P>0.05).
CONCLUSION: The optic nerve and axon impairment in NMOSD - AQP4 - Ab seropositive group was the most severe and the impairment in RRMS group was the least severe. The impairment in NMOSD - AQP4 - Ab seronegative group was between the former two, and could be more similar to that of RMMS.

Objective To explore the sero-prevalence and risk factors for herpes simplex virus 2 (HSV-2) infection and unprotected sexual behavior in an ethnically diverse population of HIVinfected subjects in a county of Yunnan province. Methods HIV-infected individuals attending for routine follow-up by local Center for Disease Control and Prevention (CDC) were recruited to participate in the study under 'informed consent'. A face-to-face questionnaire interview was administered to each participant. Blood was drawn for HSV-2 testing by HerpeSelect HSV-2 ELISA (Focus Diagnostics) and CD4+ T counting. Results A total of 300 HIV-infected individuals participated in the study. The mean age of the subjects was 37.6 years with 76.7% as males. Ethnically, Han, Dai and Jingpo accounted for 44.3%, 37.3% and 16.0% of the sample, respectively. Half of the subjects reported HIV acquisition through injection drug use. The sero-prevalence of HSV-2 was 35.0%. Results from multiple logistic regression analysis indicated that individuals who acquired HIV through heterosexual contact were more likely to be HSV-2 positive than those who acquired HIV through injection drug use (OR=4.244,95%CI: 1.924-9.364),whereas Dai (OR=0.300,95% CI: 0.152-0.593) and Jingpo (OR=0.376, 95% CI: 0.167-0.850) were less likely to be HSV-2 positive than the Hans. Among 105 people who were co-infected with HIV/HSV-2, 60 had sexual intercourses in the past 3 months and 41.7% of them reported no or inconsistent use of condoms. Most unprotected sexual contacts occurred within married couples. Conclusion HSV-2 infection was highly prevalent among HIV-infected individuals in this county, and a significant proportion of HIV/HSV-2 co-infected subjects engaged in unprotected sex. HSV-2 testing, behavioral and biomedical interventions among HIV-infected individuals and their sexual partners should be involved in the local HIV prevention and control programs.

Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer (mPEG-PLA) as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index (PDI) was 0. 030, average drug loading of (11.5 ± 0.045) % (n = 3), and the encapsulation efficiency of (86.34 ± 0.11) % (n = 3). X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics (R² = 0.981 9). mPEG-PLA drug-loading nanoparticles release only 54%, with slow release effect, in line with Riger-Peppas model (R² = 0.967 9, n = 0.630 2), for non-fick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.
Administration, Intranasal ; Anisoles ; chemistry ; Calorimetry, Differential Scanning ; Nanoparticles ; chemistry ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Solubility ; X-Ray Diffraction