Objective To explore the effects of total flavonoids from portulaca against liver fibrosis in rats by detecting TGF-β1 gene and protein expressions. Methods A total of 48 SD rats were randomly divided into normal control, model control, glucyrrhizin aqueous,and total flavonoids groups,with 12 rats in each group. Except those in the normal control group, rats in other groups were intraperitoneally injected with 2 mL · kg-1 · d-1 carbon tetrachloride to induce liver fibrosis. Rats in glucyrrhizin aqueous group and total flavonoids ones were intragastrically administered with 15. 75 mg · kg-1 of glycyrrhizin aqueous solution or 35. 6 mg·kg-1 of total flavonoids aqueous solution,respectively. The normal and model control groups were administered with equal volume of aqueous solution. Thirty days later,rats were sacrificed by anesthesia. Livers were obtained to detect TGF-β1 gene and protein expressions by RT-PCR and Western-Blot. Results Relative gene expression of TGF-β1 in the normal control,model control,glucyrrhizin aqueous and flavonoids groups was 0. 725±0. 130,7. 493±1. 410,3. 016±1. 240,and 2. 668±1. 150,respectively. Total flavonoids from portulaca significantly reduced the gene (P<0. 01) and protein (P<0. 01) expressions of TGF-β1 . Conclusion Efficacy of total flavonoids from portulaca in treating hepatic fibrosis may be related to decreased TGF-β1 expression in rats.

[Objective] To investigate the value of HBV-M and HBV DNA of newborns born to HBsAg-positive mother, which were tested before combined immunization of hepatitis B. [Method] A total of 420 infants born to HBsAg-positive mothers delivered in Obstetric Department of the Third Affiliated Hospital of Sun Yat-Sen University from June 2006 to February 2008 were followed up at least 6 months and rechecked HBV-M to confirm the diagnosis of HBV intrauterine infection, which included 33 HBsAg or HBV DNA positive newborn babies and 6 newborns with both HBsAg seropositive and HBV DNA seropositive. [Result] HBV intrauterine infection rate was 0.95%. Using newborn both HBsAg positive and HBV DNA positive as diagnostic criterion to diagnose HBV intrauterine infection, the positive likelihood ratio was 208.3, while using newborn HBsAg positive or HBV DNA positive as diagnostic criterion, it was 14.3. [Conclusion] Newborn both HBsAg positive and HBV DNA positive obtained before combined immunization of hepatitis B may predict HBV intrauterine infection, and it may play as a clinical index of preliminary diagnosis of HBV intrauterine infection.

Objective: To investigate factors affecting X-ray structure of the spine in patients with ankylosing spondylitis (AS). Methods: A total of 206 AS patients were recruited. Clinical and laboratory parameters in AS patients were recorded in detail. Disease activity index [Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp)], X-ray structural damage index-modified stoke ankylosing spondylitis spine score (mSASSS) and grading results of radiographic examination of sacroiliac joint were calculated. Statistical analysis using Statistical Package form Soci-science(SPSS) 17.0 Chi-square test, rank test, Logistics regression analysis and other statistical methods were used. Differences of mSASSS levels, spine involvement (mSASSS>0) and rates of bone bridge formation were compared between different groups. Results: Incidences of spine involvement (100%) and bone bridge formation(65.2%) in AS patients ≥40 years old were significantly higher than those in AS patients <40 years old (90.6%、31.9%)(χ²=4.651, P=0.031; χ²=16.647, P<0.01), and the level of mSASSS was also higher (Z=5.575, P<0.01). In AS patients with BMI ≥24 kg/m², disease duration ≥5 years (49.2%, 50.4%), rates of bone bridge formation was significantly higher than those in AS with BMI <24 kg/m², but the disease duration (34.5%, 19.7%)(χ²=4.014, P=0.045; χ²=18.173, P=0.03), and mSASSS values were significantly higher (Z=2.281, P=0.023, Z=4.828, P<0.01). Bone bridge formation rate in smoking patients (50.6%) was significantly higher than that in non-smoking patients (31.0%) (χ²=7.346, P=0.007) and mSASSS value was significantly higher (Z=2.045, P=0.041). Bone bridge formation rates in AS with high-ESR and high-CRP(48.6%, 49.0%) were significantly higher than those in patients with normal-ESR and normal-CRP(25.6%, 28.9%)(χ²=10.784, P=0.001; χ²=8.102, P=0.004) and mSASSS value was clearly higher(Z=2.379, P<0.01; Z=3.112, P<0.01). Bone bridge formation rate in AS with BASDAI≥4 or ASDAScrp≥2.1 groups (52.8%, 46.4%) were significantly higher than that in AS with BASDAI<4 or ASDAScrp<2.1 groups (34.2%, 30.7%) (χ²=5.681, P=0.017; χ²=4.646, P=0.031) and mSASSS values were significantly higher (Z=3.887, P<0.01; Z=3.895, P=0.004). Rates of bone bridge formation among different X-ray grading of sacroiliac joint (10.8%, 35.6%, 60.3%) and MRI findings (33.3%, 50.0%, 15.4%) differed with each other (χ²=25.714, P<0.01; χ²=6.855, P=0.032). Logistics regression analysis showed that BMI [OR(95%CI)=1.145(1.037, 1.265), P<0.01], disease duration [OR(95%CI)=1.144(1.055, 1.239), P<0.01], smoking [OR(95%CI)=2.832(1.343, 5.969), P<0.01] and sacroiliac joint X-ray staging [OR(95%CI)=2.584(1.337, 4.997), P<0.01] were risk factors for the bone bridge formation in spine of AS. Conclusion Spinal involvement in AS is related to disease activity. Bone bridge formation correlateswith disease duration, BMI and disease-status, especially with smoking.

Objective To explore the prevalence and reference value of disease features of patients with spondyloarthritis. Methods Spondyioarthritis features and laboratory indexes and radiographic indexes of 505 patients with spondyloarthritis (SpA) including 353 patients with ankylosing spondylitis (AS), 62 patients with non-radiographic axial spondyloarthritis (nr-axSpA) and 90 patients with peripheral spondyloarthritis (pSpA) were recorded. One-way analysis of variance, Kruskal-Wallis test, x2-test, Logistic regression were used for statistical analysis. Results Sex ratio ( x2=20.673, P<0.01), age ( x2=22.258, P<0.01), disease duration ( x2=76.052, P<0.01) were different among AS, nr-axSpA and pSpA. Besides, Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp), erythrocyte sedimentation rate (ESR), C-reactionprotein (CRP) and Bath ankylosing spondylitis functional index (BASFI)were different among SpA subgroups ( x2/F=13.196-40.028, P<0.01). Prevalence of inflammatory back pain, peripheral arthritis, preceding infection, positive human lymphocyte antigen (HLA)-B27 and elevated CRP were different among SpA subgroups ( x2=11.416, 32.657, P<0.01). Prevalence of dactylitis in SpA with positive HLA-B27 was lower than that in SpA with negative HLA-B27 ( x2=5.414, P=0.02). Prevalence of enthesitis and dactylitis in SpA patients with peripheral arthritis was higher than that in SpA without peripheral arthritis involvement ( x2=7.177, 14.428, P<0.01). Prevalence of good response to Non-steroid anti-inflammatory drugs. (NSAIDs) in patients with anterior uveitis involvement was higher than SpA without anterior uveitis involvement ( x2=4.578, P=0.032). SpA patients were stratified by total number of SpA features into 4 subgroups (n≤1, n=2, n=3, n≥4). Prevalence of inflammatory back pain, positive HLA-B27, good response to NSAIDs were the top three in all subgroups. Inflammatory back pain and HLA-B27 (+) were risk factors for axSpA (OR=3.254, 3.323, P<0.01). Peripheral arthritis, dactylitis, and preceding infection were risk factors for pSpA (OR=3.759, 4.134, 17.044, P<0.01). Conclusion Inflammatory back pain, HLA-B27 (+) and good response to NSAIDs should be emphasized for the diagnosis of SpA. Inflammatory back pain and HLA-B27(+) always means axSpA. Peripheral arthritis, dactylitis and preceding infection always indicates pSpA.

Objective To explore the influence of collateral circulation on the cognition of persons with severe unilateral carotid artery stenosis or occlusion using transcranial Doppler (TCD) imaging combined with P300.Methods A total of 185 patients with stenosis or occlusion of the carotid artery were enrolled and randomly divided into a monocollateral group (n=83),a multicollateral group (n=79) and a noncollateral group (n=23).The monocollateral group was further divided into an anterior communicating artery (AcoA) group,an ophthalmic artery (OA)group and a post communicating artery (PcoA) group according to their collateral circulation.All patients and 40 normal controls (NC) were tested using the Montreal cognitive assessment (MoCA) and P300,and the correlation between the MoCA and P300 scores was analyzed.Results Compared with the NC group,all the other three groups had significantly lower average MoCA scores and P300 amplitudes.They also had significantly longer average P300 latency periods.Compared with the multicollateral group,both the monocollateral and noncollateral groups had significantly lower average MoCA scores and P300 amplitudes and longer P300 latencies.Comparing the monocollateral group with the noncoilateral group revealed the same trends.Among the monocollateral patients the average MoCA score of the AcoA group was significantly higher than the PcoA and OA group averages,while their average P300 latency period was significantly shorter and the amplitude significantly greater than the PcoA group's average.Correlation analyses showed that the MoCA score was negatively correlated with the P300 latency,but positively correlated with the P300 amplitude.Conclusions Collateral circulation can protect the cognitive function of patients with unilateral stenosis or occlusion of the internal carotid artery to some extent,with multicollateral circulation being more effective than monocollateral and AcoA circulation superior to both PcoA and OA circulation.The MoCA score is significantly correlated with the latency period of P300 in such cases.

Objective To explore the serum levels of fibroblast growth factor 23 (FGF23) in patients with rheumatoid arthritis (RA) and to investigate the relationship between FGF23 and RA disease activity and the occurrence of osteoporosis (OP).Methods Serum levels of FGF23 from 174 cases of patients with RA and 88 normal subjects were detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry.All the clinical and laboratory indexes of RA patients were recorded in details,disease activity score (DAS28) and health assess questionnaire (HAQ) were also calculated in the meantime.Radiographic changes in both hands of RA patients were assessed by Sharp's method.T test,nonparametric test,x2 test,correlation analysis and Logistic regressive analysis were used for statistical analysis.Results Serum levels of FGF3 [145.46(67.67,245.93) pg/ml] in RA patients were higher than the control group [32.64(12.34,44.70) pg/ml,Z=11.416,P＜0.01].The positive rate of serum levels of FGF23 (≥71.95 pg/ml) in RA was 74.7％(130/174),while the positive rate in control was 4.5％(4/88,x2=115.16,P＜0.01).The threshold of FGF23 serum levels for diagnosing RA was 48.56 pg/ml (AUC=0.932,Youden index=0.743,P＜0.01,sensitivity 89.1％,specificity 85.2％).In RA patients with serum FGF23 ≥48.56 pg/ml,compared with negative FGF23 group,VAS,HAQ,number of joint swelling and BMD at femoral neck,Ward,GT,Total hip,L4 and L1-4 were significantly higher in FGF23 positive group (P＜0.05).Linear correlation analysis found that in RA patients with serum FGF23 ≥48.56 pg/ml,anti-CCP was negatively correlated with serum FGF23 levels (r=-0.171,P=0.035).And DAS28 was positively correlated with serum FGF23 (r=0.163,P=0.045).BMD at femoral neck,Ward,GT,Total hip,L4 and L1-4 were negatively correlated with serum FGF23 (P＜0.05).Results of logistic regression analysis showed that sex (OR=8.518,95％CI (2.636,27.522),P＜0.01,age [OR=1.129,95％CI (1.079,1.180),P＜0.01] and Sharp score [OR=1.008,95％CI(1.003,1.013),P=0.001]were risk factors for OP in RA patients.BMI[OR=0.801,95％CI(0.707,0.909),P=0.001] was a protective factor for OP in RA patients.Conclusion Serum FGF23 level is significantly higher in RA patients.Meanwhile,the serum FGF23 level correlates with RA disease activity and BMD.

Objective:To explore the clinical value of sarcopenia and vitamin D deficiency on gluco-corticoid induced osteoporosis (GIOP) in patients with rheumatoid arthritis (RA).Methods:Three hundred and eleven patients with RA from January 2017 to December 2018 were enrolled in the study. One hundred and fifty-eight sex, age-matched normal subjects were recruited as control group. Clinical and laboratory features, daily dosage and treatment duration of glucocorticoid (GC) were recorded in detail. Skeletal muscle mass was measured by biological electrical impedance. Serum levels of 25-hydroxy vitamin D [25(OH)D] were examined using electro-chemiluminescence. Bone mineral density (BMD) at total hip and lumbar vertebra were detected by dual energy X-ray absorptiometry (DEXA). Numerical data and categorical data comparisons were analyzed using χ2 test, non-parametric test, Logistic regression analysis test. Results:① The prevalence of osteoporosis (OP) in RA patients was 33.4%(104/311), which was higher than that in the control group 12.7%(20/158)( χ2=23.267, P<0.01). Percentage of GC taking in 311 RA patients was 56.6%(176/311), and the prevalence of GIOP was 40.9%(72/176). The prevalence of sarcopenia in RA patients was 61.7%(192/311), which was higher than that in the control group [9.0%(14/156), χ2=117.310, P<0.01]. The prevalence of vitamin D deficiency in RA patients was 81.7%(254/311), which was higher than that in control group [38.0%(60/158), χ2=90.415, P<0.01]. ② The prevalence of OP in RA without sarcopenia was 17.6% (21/119), which was lower than that in patients with sarcopenia [43.2%(83/192), χ2=21.601, P<0.01]. In condition without GC, the prevalence of OP in RA without sarcopenia was 9.8%(6/61), which was significantly lower than that in patients with sarcopenia [35.1%(26/74), χ2=11.834, P<0.01]. Under circumstances with GC, the prevalence of OP in RA without sarcopenia (25.9%, 15/58), which was significantly lower than that in patients with sarcopenia (48.3%, 57/118, χ2=8.103, P<0.01). ③ No matter whether existing vitamin D deficiency or not, the prevalence of OP in RA without GC was 23.7%(32/135), which was significantly lower than that in patients with GC [40.9%(72/176), χ2=10.161, P<0.01]. In patients without vitamin D deficiency, the prevalence of OP in RA without GC was 21.4%(6/28), which was similar to that in patients with GC [31.0%(9/29), χ2=0.678, P>0.05]. In the case of vitamin D deficiency, the prevalence of OP in RA without GC was 24.3%(24/107), which was significantly lower than that in patients with GC [42.9% (63/147), χ2=9.370 2, P<0.01]. ④ In RA patients with GC, age( t=5.313, P<0.01), Sharp score ( Z=2.999, P<0.01), disease duration ( Z=2.141, P<0.05) and treatment duration of GC ( Z=2.460, P<0.05) were higher in group with GIOP than that in group without GIOP, while erythrocyte sedimentation rate (ESR)( Z=2.262, P<0.05), C-reactive protein levels (CRP) ( Z=2.551, P<0.05) and body mass index (BMI) ( t=2.425, P<0.05) were lower and the composition ratio of X-ray staging was worse ( χ2=12.484, P<0.01).⑤ Logistic regression analysis (LR Backward) showed that female gender [ OR(95% CI)=14.240(3.878, 52.288), P<0.01], age [ OR(95% CI)=1.079(1.042, 1.118), P<0.01] and sarcopenia [ OR(95% CI)=2.470(1.192, 5.120), P<0.05] were the risk factors for GIOP in RA patients. Conclusion:The proportion of treatment with GC in RA patients is very high (about 60%), and the prevalence of GIOP is 40.9%, which is closely related to sarcopenia and vitamin D deficiency.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

OBJECTIVETo compare the effects of acupuncture, electroacupuncture (EA) and moxibustion on functional constipation in rats.

METHODSSixty male Sprague-Dawley rats were divided into a control group (=8), a model group (=11), a medication group (=8), an acupuncture group (=11), an EA group (=11) and a moxibustion group (=11) by random number table. The rats in the model group, medication group, acupuncture group, EA group and moxibustion group were treated with intragastric administration of loperamide hydrochloride for 6 days continuously to establish the functional constipation models, while equal volume of drinking water was administrated to rats in the control group at the same time. The rats in the acupuncture group, EA group and moxibustion group were respectively treated with acupuncture, EA and moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) one hour after intragastric administration; rats in the medication group were treated with intragastric administration of cisapride suspension. All the treatment was given once a day for 6 days. At the last day of intervention, the 24-hour food intake, stool quantity and its water content were measured in each group; the pushing rate of intestine was measured; the structure of colon tissue and acidic mucus in its mucous layer were observed by hematoxylin-eosin dyeing and alcian blue dyeing; the expression of stem cell factor (SCF) and c-kit mRNA was detected by real-time PCR.

RESULTSCompared with the control group, the 24-hour food intake and stool quantity were reduced in the model group (both<0.01), and the water content of stool and pushing rate of intestine were reduced (both<0.01); compared with the model group, the stool quantity and its water content were increased in the medication group, acupuncture group, EA group (<0.05,<0.01), which were not significantly different from those in the moxibustion group (both>0.05). The pushing rate of intestine in each intervention group was increased (all<0.01). The 24-hour food intake and stool quantity in the medication group were not significantly different from those in the acupuncture group, EA group and moxibustion group (all>0.05), and the water content of stool was only reduced in the moxibustion group (<0.01). The pushing rate of intestine in the acupuncture group and moxibustion group was lower than that in the medication group (both<0.01), while that in the EA group was not significantly different from that in the medication group (>0.05). The water content of stool in the moxibustion group was lower than that in the acupuncture group and EA group (both<0.01). The pushing rate of intestine in the acupuncture group and moxibustion group was lower than that in the EA group (both<0.01). The HE staining result indicated the structure of colon tissue was normal, complete and similar in each group; the alcian blue staining indicated the acidic mucosubstance in the model group was lower than that in the control group; compared with the model group, the acidic mucosubstance in the medication group, acupuncture group, EA group and moxibustion group was all increased. Compared with the control group, the expression of SCF and c-kit mRNA was reduced in the model group (both<0.05); compared with the model group, the expression of SCF and c-kit mRNA was increased in the medication group, acupuncture group, EA group and moxibustion group (all<0.05); compared with the moxibustion group, the expression of c-kit mRNA was reduced in the acupuncture group and EA group (both<0.05).

CONCLUSIONSAcupuncture, EA and moxibustion all can play a positive regulative role on functional constipation in rats, in which EA has the best efficacy, followed by acupuncture.

Zinc oxide quantum dots (ZnO QDs) were synthesized by gel-sol method and employed as the transdermal aloesin (Alo) carriers. ZnO QDs were surface-functionalized with amino using aminopropyltriethoxysilane (APTES). Alo was covalently bonded on the surface of ZnO QDs via N,N'-carbonyldiimidazole to obtain Alo NPs, which were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analyzer (TGA). TEM images showed that ZnO QDs were analogously sphere and monodisperse with a reasonably narrow size distribution, of which was around 4 nm. The size of Alo NPs increased to around 8 nm due to the surface modification. The intense bands at around 3 400 cm and 1 200 cm in the FTIR spectrum of Alo NPs from the vibration of -OH indicated the linkage of Alo on the surface of ZnO QDs. The results of TGA analysis showed that the mass ratio of ZnO QDs and Alo were 39.27% and 35.14%, respectively. The penetration of Alo NPs was much higher than raw Alo according to the passive penetration experiments with Franz-type diffusion cells instrument using full-thickness cavy skin, which manifested the improvement of the penetration for Alo delivered by ZnO QDs. The pH-controlled drug release behavior was investigated. At pH 7.4, only a small amount of Alo (1.45% ± 0.21%) had been released after 2 h. In contrast, as incubation at pH 5.0 of which pH was similar to endosomal environment, Alo was released very fast (87.63% ± 0.46% in 2 h) from Alo NPs, confirming that Alo NPs could response to the pH and realize the intracellular drug release. The inhibitory effect of Alo NPs on tyrosinase was in a dose dependent manner. When the concentration of Alo NPs was 12.5 μg/mL, the inhibition rate was up to 40.32% ± 1.57%. All the results show that the Alo NPs hold a great potential in transdermal tyrosinase inhibition.
Administration, Cutaneous ; Animals ; Chromones ; administration & dosage ; Drug Delivery Systems ; Glucosides ; administration & dosage ; Guinea Pigs ; Monophenol Monooxygenase ; metabolism ; Nanoparticles ; Quantum Dots ; Zinc Oxide