Study on the kinetics of formation process of emulsion of heavy oil and its functional group components.

Enhanced oil recovery (EOR) by in situ formation of oil-in-water emulsion in heavy oil cold production technology has received growing interest from the petroleum industry. We present an experimental study of emulsification of model oils prepared by heavy oil and its functional group compositions dissolved into toluene brought into contact with a surfactant solution. The effects of functional group composition, emulsifier concentration, temperature, pH and stirring speed on the emulsification rate of heavy oil was investigated. A second-order kinetic model characterizing the temporal variation of conductivity during the emulsification has been established. The results show that acidic and amphoteric fractions exhibit higher interfacial activity, larger emulsification rate constant and faster emulsification rate. With the increase of emulsifier concentration, the emulsification rate constant increase to the maximum value at a concentration of 0.05 mol/L before decreasing. Temperature increase benefits the emulsification rate and the activation energy of the emulsification process is 40.28 kJ/mol. Higher pH and stirring speed indicate faster emulsification rate. The heterogeneity of emulsions limits the accuracy of dynamic characterization of the emulsification process and the determination method of emulsification rate has always been controversial. The conductivity method we proposed can effectively evaluates the emulsification kinetics. This paper provides theoretical guidance for an in-depth understanding of the mechanism and application of cold recovery technology for heavy oil.

Bisbenzylisoquinoline alkaloid fangchinoline derivative HY-2 inhibits breast cancer cells by suppressing BLM DNA helicase.

The high expression of BLM (Bloom syndrome) DNA helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to study the antitumor effect of fangchinoline derivative HY-2 by targeting BLM642-1290 DNA helicase, and then explore its inhibitory mechanism on proliferation of MDA-MB-435 breast cancer cells. We confirmed that the mRNA and protein levels of BLM DNA helicase in breast cancer were higher than those in normal tissues. HY-2 could inhibit the DNA binding, ATPase and DNA unwinding of BLM642-1290 DNA helicase with enzymatic assay. HY-2 could also inhibit the DNA unwinding of DNA helicase in cells. In addition, HY-2 showed an inhibiting the MDA-MB-435, MDA-MB-231, MDA-MB-436 breast cancer cells expansion. The mRNA and protein levels of BLM DNA helicase in MDA-MB-435 cells increased after HY-2 treatment, which might contribute to HY-2 inhibiting the DNA binding, ATPase and DNA unwinding of BLM DNA helicase. The mechanism of HY-2 inhibition on BLM DNA helicase was further confirmed with the effect of HY-2 on the ultraviolet spectrogram of BLM642-1290 DNA helicase and Molecular dynamics simulation of the interacting between HY-2 and BLM640-1291 DNA helicase. Our study provided some valuable clues for the exploration of HY-2 in the living body and developing it as an anticancer drug.

Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase.

BACKGROUND: The high expression of BLM (Bloom syndrome) helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to screen potential antiproliferative small molecules from 12 small molecules (the derivatives of bisbenzylisoquinoline alkaloids tetrandrine and fangchinoline) by targeting BLM642-1290 helicase. Then we explore the inhibitory mechanism of those small molecules on proliferation of MDA-MB-435 breast cancer cells. METHODS: Fluorescence polarization technique was used to screen small molecules which inhibited the DNA binding and unwinding of BLM642-1290 helicase. The effects of positive small molecules on the ATPase and conformation of BLM642-1290 helicase were studied by the malachite green-phosphate ammonium molybdate colorimetry and ultraviolet spectral scanning, respectively. The effects of positive small molecules on growth of MDA-MB-435 cells were studied by MTT method, colony formation and cell counting method. The mRNA and protein levels of BLM helicase in the MDA-MB-435 cells after positive small molecule treatments were examined by RT-PCR and ELISA, respectively. RESULTS: The compound HJNO (a tetrandrine derivative) was screened out which inhibited the DNA binding, unwinding and ATPase of BLM642-1290 helicase. That HJNO could bind BLM642-1290helicase to change its conformationcontribute to inhibiting the DNA binding, ATPase and DNA unwinding of BLM642-1290 helicase. In addition, HJNO showed its inhibiting the growth of MDA-MB-435 cells. The values of IC50 after drug treatments for 24 h, 48 h and 72 h were 19.9 µmol/L, 4.1 µmol/L and 10.9 µmol/L, respectively. The mRNA and protein levels of BLM helicase in MDA-MB-435 cells increased after HJNO treatment. Those showed a significant difference (P < 0.05) compared with negative control when the concentrations of HJNO were 5 µmol/L and 10 µmol/L, which might contribute to HJNO inhibiting the DNA binding, ATPase and DNA unwinding of BLM helicase. CONCLUSION: The small molecule HJNO was screened out by targeting BLM642-1290 helicase. And it showed an inhibition on MDA-MB-435 breast cancer cells expansion.

Spinal and sacroiliac involvement in SAPHO syndrome: A single center study of a cohort of 354 patients.

OBJECTIVE: SAPHO syndrome is a highly heterogeneous disease with distinct treatment response. We report the largest cohort of SAPHO syndrome and explore its clinical classification with special interest in spinal and sacroiliac involvement. METHODS: A total of 354 patients with SAPHO syndrome were recruited in Peking Union Medical College Hospital. The demographic, clinical and imaging data were collected at baseline. Spinal and sacroiliac involvement was determined by the co-existence of related symptoms and imaging evidence of lesions in the spine or sacroiliac joints on either bone scintigraphy, CT or MRI. RESULTS: A total of 197 (55.6%) patients were identified to have spinal or sacroiliac involvement. Compared to those without spinal or sacroiliac lesions, these patients were significantly older at onset (38 ±â€¯12 vs 35 ±â€¯10 years old, p = 0.019) but had comparable duration of disease. Therapeutically, patients with spinal or sacroiliac involvement had been treated more aggressively with more frequently prescribed NSAIDs, glucocorticoids, DMARDs, TNF-α inhibitors, and bisphosphonates (all p ≤ 0.001). Nonetheless, greater disease activity was observed for these patients at baseline, supported by both inflammatory markers (ESR and hs-CRP) and visual analog scale (VAS) for pain (all p < 0.001). CONCLUSIONS: SAPHO patients with spinal or sacroiliac involvement are older at onset and have greater disease activity despite of more aggressive treatments compared to those without. Stratified management is in urgent need for this rare disease.

Genomic Characterization of a New HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Form in Guizhou in Southwest China.

A novel HIV-1 second-generation recombinant form (CRF01_AE/CRF07_BC) was isolated from an HIV-positive subject among men who have sex with men (MSM) in Guizhou province in Southwest China. Recombinant analyses of the near full-length genome suggested that the strain was composed of CRF01_AE and CRF07_BC with one region of CRF07-BC inserted into a CRF01-AE backbone. Further analysis indicated that the CRF01_AE regions of the recombinant were highly clustered together with a subcluster 4 lineage of CRF01_AE, which is exclusively circulating among MSM in China. The CRF07_BC region of the recombinant was clustered with the CRF07_BC cluster, which was identified among MSM. The emergence of the novel HIV-1 recombinant may be a harbinger of more novel intersubtypes recombinants occurring in Guizhou province in Southwest China, and was of great important in understanding the dynamics and complexity of the HIV-1 epidemic in this region.

Characterization of a Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Form in Guizhou, China.

We identified a novel CRF01_AE and 07_BC HIV-1 recombinant form in Guizhou province in southwest China. The phylogenetic analysis of the near full-length sequence reveals that it was divided into five segments by four breakpoints, and the CRF01_AE regions of the recombinant were clustered with subcluster 4 lineage of CRF01_AE, which mainly circulated among men who have sex with men (MSM) in China. The CRF07_BC regions of the recombinant were clustered with CRF07_BC lineage, which circulated among Chinese MSM. This is the first detection of a novel HIV-1 second-generation recombinant form (CRF07_BC/CRF01_AE) in Guizhou, which shows the increasing significance of heterosexual transmission contributing to the complexity of the HIV-1 epidemic in southwest China, and more effort measures should be taken to monitor the genetic evolution of HIV-1 strains and prevent HIV-1 transmissions.

Efficacy of bisphosphonates in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a prospective open study.

OBJECTIVES: To evaluate the clinical efficacy of bisphosphonates treatment for spinal bone marrow oedema (BME) in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: SAPHO syndrome patients presenting to Peking Union Medical College Hospital from 2015 to 2016 were recruited. Patients were administered pamidronate disodium 1 mg/kg/d intravenously, for 3 days, at baseline and 3 months later. The symptoms were evaluated using the Visual Analog Score (VAS) for pain, and other clinical measures including, spinal BME scores, ß-crosslaps, osteocalcin, and inflammatory factors, were collected. RESULTS: A total of 30 patients (20 women and 10 men) with a median age of 47.2 (interquartile range 8.8) years were recruited. In a short time, the patients showed a significant decrease in VAS (before vs. after; first treatment: 5.70±1.62 vs. 2.30±1.29 cm, second treatment: 4.03±1.88 vs. 2.17±1.23 cm) and ß-crosslaps (first treatment: 0.4441±0.1923 vs. 0.0859±0.0374 pg/ml, second treatment: 0.2891±0.1983 vs. 0.0962±0.0324 pg/ml) (all p<0.05). At 12-month follow-up, compared with the baseline, we noticed a significant drop in the VAS (5.70±1.62 vs. 2.43±1.25 cm), erythrocyte sedimentation rate (28.87±25.26 vs. 18.00±18.65 mm/h), high-sensitivity C-reactive protein level (11.76±10.19 vs. 5.84±5.88 mg/L), osteocalcin (2.30±1.27 vs. 1.65±0.80 ng/ml), and BME (30.50±24.09 vs. 22.13±27.79) (all p<0.05). No one had serious adverse events. CONCLUSIONS: Bisphosphonates can significantly and rapidly relieve symptoms in patients with SAPHO syndrome and have a long-term effect on inflammation and spinal BME. We suggest that bisphosphonates could be used as the first-line therapeutic drug for SAPHO syndrome, especially in patients with spinal BME.

Three patterns of osteoarticular involvement in SAPHO syndrome: a cluster analysis based on whole body bone scintigraphy of 157 patients.

OBJECTIVES: To explore the patterns of osteoarticular involvement in SAPHO syndrome. METHODS: Baseline clinical characteristics and imaging data of 99mTc-MDP whole-body bone scintigraphy (WBBS) were collected from 157 out of 164 patients diagnosed with SAPHO syndrome. The twelve most frequently involved osteoarticular sites were analysed by hierarchical cluster analysis with the Ward minimum-variance method. RESULTS: Three distinctive patterns of osteoarticular involvement were identified: the spinal type (70 patients, 44.6%), with predominantly thoracic, lumbar or sacral vertebral lesions; the costal type (52 patients, 33.1%), with lesions of anterior ribs, particularly the first ribs; and the sternoclavicular type (35 patients, 22.3%), with predominantly sternal and bilateral sternoclavicular lesions, characterized by the typical bullhead sign. Notably, a total of 77 (49%) patients exhibited lesions of ribs on WBBS, of which 61.3% involved the first ribs. Interestingly, patients of spinal type were older at onset of cutaneous manifestations than those of sternoclavicular type (P = 0.036) and costal type (P = 0.035). The disease course was remarkably longer in sternoclavicular type than costal type (P = 0.001) and spinal type (P < 0.001). CONCLUSION: The osteoarticular involvement in SAPHO syndrome can be categorized as three distinct patterns with different corresponding clinical features. The costal involvement in SAPHO syndrome, which was under-recognized previously, may define a distinct sub-type of the disease.

Cytotoxic effect of in vitro expanded NK cell-carrying oncolytic reovirus on colorectal cancer cells / 中国肿瘤生物治疗杂志

@# Objective: To evaluate whether human NK cells expanded in vitro can be used as carrier cells of reovirus and to investigate its clinical application value. Methods: Expansion of human NK cells in vitro, and flow cytometry was used to analyse the purity of CD3-CD56+ cells. Expanded NK cells were loaded with reovirus and observed by confocal microscopy, to determining the location of reovirus on NK cells. CCK-8 assay was used to detect reovirus-induced oncolysis of expanded NK cells carrying reovirus (Reo-NK) to tumor cells in the presence of neutralizing antibodies; Real-time fluorescence quantitative PCR was used to assess the relative expression of viral RNA in tumor cells. Cytotoxicity assay were performed to detect Reo-NK cells against KRAS mutant (DLD-1) and KRAS wild type (CaCo-2, HT29) colorectal cancer cell lines, ELISA matched paired antibodies assay was performed to measure the perforin level released by NK cells. Results: Confocal microscopy demonstrated that NK cells retained reovirus on the surface. Expanded NK cells could delivery reovirus to tumor cells in the presence of neutralizing antibodies, and the reovirus after delivery still had significant oncolytic activity (P<0.01); Corresponding qPCR result displayed that the expression of viral RNA in tumor cells significantly increased over time (P<0.01). Compared with NK group, Reo-NK group evidently enhanced the cytotoxicity on colorectal cancer cell lines with both KRAS gene mutant and wild (all P<0.05), and significantly increased the release of perforin (all P<0.05). Conclusion: In vitro expanded NK cells provide a convincing cell carrier for reovirus, while reovirus enhances the cytotoxicity of NK cells, and the combination of the two show a stronger killing effect on colorectal cancer cells，that has important clinical application value.

[Clinical Observation of Chaihu Guizhi Decoction in Treating SAPHO Syndrome].

Objective To evaluate the clinical efficacy and safety of Modified Chaihu Guizhi De- coction on SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Methods Totally 40 patients with SAPHO syndrome were randomized to the treatment group(20 cases) and control group(20 cases). The treatment group was treated with Modified Chaihu Guizhi Decoction, and the control group with alendronate sodium 70 mg each week. The therapeutic course for all was 12 weeks. The Visual Analogue Scale (VAS) pain scores, bath ankylosing spondylitis activity index (BASDAI) , bath ankylosing spondylitis functional index(BASFI) , erythrocyte sedimentation rate(ESR) and hypersensitivity C reactive protein (hs-CRP) were measured before and after treatment. Adverse events were observed. Results The VAS, BASDAI, and BASFI score significantly improved compared with baseline in the treatment group (P <0. 01 , P <0. 05). The VAS and BASDAI score of the treatment group improved compared with the control group after treatment (P <0. 05). Three patients in the control group reported adverse events with digestive tract symptoms, while there was no obvious adverse drug reactions in the treatment group. Conclusions Modified Chaihu Guizhi Decoction was superior to alendronate sodium in the treat- ment of SAPHO syndrome without obvious adverse drug reactions.

Health-related quality of life and psychological status of women with primary Sjögren's syndrome: A cross-sectional study of 304 Chinese patients.

Patients with primary Sjögren syndrome (pSS) always suffer from dryness, pain, and fatigue caused by the involvement of multiple different systems or organs. The uncomfortable disease symptoms, the consequent disability, and the side effects of therapeutic drugs decrease the quality of life and lead to emotional problems. We investigated the health-related quality of life and psychological status of a large cohort of women patients with pSS and associated factors.A total of 304 women with pSS referred to Peking Union Medical College Hospital during 2011 and 2014 were included. The internationally recognized Short Form (36) Health Survey (SF-36) was used to assess patients' quality of life; a higher score indicated a better quality of life. Patients' psychological status was assessed by the Hospital Anxiety and Depression Scale (HADS), and higher scores predicted more anxiety or depression.Patients with pSS had remarkably lower SF-36 scores. The Hospital Anxiety Scale (HAS) and Hospital Depression Scale (HDS) scores of the pSS patients (7 [4,10] and 6 [3,10], respectively) were significantly higher than that of patients with other internal diseases (3.37 ± 2.81 and 3.83 ±â€Š3.14; both P < .001). Negative predictors of quality of life were: pain (physical condition, ß = -0.225; P < .001); fatigue (physical condition, ß = -0.298; P < .001; and mental condition, ß = -0.319; P < .001). Risk factors for anxiety were: young age (ß = -0.059; P = .035); pain (ß = 0.025; P = .028); or fatigue (ß = 0.029; P = .004). Risk factors for depression were: xeroderma (ß = 0.030; P = .003); pain (ß = 0.022; P = .047); or fatigue (ß = 0.033; P = .001).Patients with pSS have a low quality of life with anxiety and depression. Pain and fatigue are primary factors for lower quality of life, which cause more anxiety and depression.

Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients.

OBJECTIVE: The aim was to assess the clinical, laboratory and radiological features of SAPHO syndrome. METHODS: We recruited all patients presenting to Peking Union Medical College Hospital from 2004 to 2015 diagnosed with SAPHO syndrome. The medical data, laboratory test results and imaging were collected for all patients. RESULTS: One hundred and sixty-four patients (111 women and 53 men) were recruited to our cohort. The mean age of the patients was 40.71 years. Nine patients had osteoarticular symptoms without skin involvement. One hundred and forty-three and 25 patients had palmoplantar pustulosis and severe acne, respectively. Psoriasis vulgaris was accompanied by palmoplantar pustulosis or severe acne in 24 patients. One hundred and sixty-four patients suffered from pain in the anterior chest wall, followed by spine (12 in the cervical region, 36 in the thoracic region and 111 in the lumbosacral region) and peripheral joint (136 patients) involvement. None of the patients had IBD. The hs-CRP level was increased in 70.8% patients. Only 2.4% were HLA-B27 positive. CT scan indicated osteolysis, sclerosis and hyperostosis in the anterior chest wall and spine in SAPHO syndrome patients. The bull-horn sign was the typical characteristic of SAPHO syndrome seen in bone scintigraphy images. One hundred and thirty-one (79.9%), 85 (51.8%), 100 (61%) and 54 (32.9%) patients took NSAIDs, CSs, DMARDs and oral bisphosphonates, respectively. CONCLUSION: SAPHO syndrome is predominant in middle-age women, characterized by dermatological and osteoarticular manifestations with unknown aetiology. CT scan and bone scintigraphy are useful for diagnosis. There is still no standard treatment to control the disease.

Engineered nanomedicine for myeloma and bone microenvironment targeting.

Bone is a favorable microenvironment for tumor growth and a frequent destination for metastatic cancer cells. Targeting cancers within the bone marrow remains a crucial oncologic challenge due to issues of drug availability and microenvironment-induced resistance. Herein, we engineered bone-homing polymeric nanoparticles (NPs) for spatiotemporally controlled delivery of therapeutics to bone, which diminish off-target effects and increase local drug concentrations. The NPs consist of poly(D,L-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and bisphosphonate (or alendronate, a targeting ligand). The engineered NPs were formulated by blending varying ratios of the synthesized polymers: PLGA-b-PEG and alendronate-conjugated polymer PLGA-b-PEG-Ald, which ensured long circulation and targeting capabilities, respectively. The bone-binding ability of Ald-PEG-PLGA NPs was investigated by hydroxyapatite binding assays and ex vivo imaging of adherence to bone fragments. In vivo biodistribution of fluorescently labeled NPs showed higher retention, accumulation, and bone homing of targeted Ald-PEG-PLGA NPs, compared with nontargeted PEG-PLGA NPs. A library of bortezomib-loaded NPs (bone-targeted Ald-Bort-NPs and nontargeted Bort-NPs) were developed and screened for optimal physiochemical properties, drug loading, and release profiles. Ald-Bort-NPs were tested for efficacy in mouse models of multiple myeloma (MM). Results demonstrated significantly enhanced survival and decreased tumor burden in mice pretreated with Ald-Bort-NPs versus Ald-Empty-NPs (no drug) or the free drug. We also observed that bortezomib, as a pretreatment regimen, modified the bone microenvironment and enhanced bone strength and volume. Our findings suggest that NP-based anticancer therapies with bone-targeting specificity comprise a clinically relevant method of drug delivery that can inhibit tumor progression in MM.