[The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis].

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

[The characteristics and associated factors of functional limitation in patients with rheumatoid arthritis].

Objective: To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA). Methods: Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI. Results: A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age (OR=1.019, 95%CI 1.004-1.035),pain VAS (OR=1.820, 95%CI 1.616-2.050), ESR (OR=1.009, 95%CI 1.001-1.017), CDAI (OR=1.080, 95%CI 1.059-1.102) and modified total Sharp score (OR=1.010, 95%CI 1.004-1.015) were associated factors of functional limitation. Conclusion: The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

Knockdown of lncRNA ZFAS1 inhibits progression of nasopharyngeal carcinoma by sponging miR-135a.

Nasopharyngeal carcinoma (NPC) is one common head and neck malignancy with leading cause of cancer-related death. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in progression, prognosis and treatment of NPC. However, the exact role of lncRNA zinc finger antisense 1 (ZFAS1) in NPC progression and its potential mechanism remain largely unknown.The expressions of ZFAS1 and microRNA-135a (miR-135a) were measured in NPC tissues or cells by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between ZFAS1 and miR-135a was explored by luciferase reporter assay and RNA immunoprecipitation (RIP). Cell proliferation, apoptosis, migration and invasion were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5 -diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry or trans-well assay, respectively. Our data showed the expression of ZFAS1 was up-regulated and miR-135a was down-regulated in NPC tissues and cells. miR-135a was bound to ZFAS1 in NPC cells. Moreover, knockdown of ZFAS1 or addition of miR-135a inhibited cell proliferation, migration and invasion but promoted apoptosis in NPC cells. Besides, down-regulation of miR-135a reversed abrogation of ZFAS1-mediated inhibition of proliferation, migration and invasion and increase of apoptosis in NPC cells. Our data suggested Inhibition of ZFAS1 protected against proliferation, migration and invasion but contributed to apoptosis by sponging miR-135a in NPC cells, providing a novel avenue for NPC treatment.

[Therapeutic effects of rutaecarpine on dextran sodium sulfate-induced experimental colitis in mice].

Objective: To determine the therapic effects of rutaecarpine in dextran sodium sulfate (DSS)induced experimental colitis and explore whether the protective role of rutaecarpine is related to the synthesis and release of CGRP. Methods: Fifty female BABL/c strain mice were randomly divided into untreated model control group and DSS-exposed groups.DSS-exposed groups were given administration of 5% DSS for 7 days and respectively treated with vehicle, rutacarpine(30 mg/kg, 100 mg/kg) , prednisone by intragastric administration from day 8 to day 14.The disease activity index (DAI) scores, the histological scores, the mRNA and protein concentrations of CGRP in colonic tissues were measured. Results: On day 7, the DAI scores of the DSS-exposed groups[vehicle group (8.9±0.9), low-dose Rut group(8.9±0.6), high-dose Rut group(8.2±0.8), prednisone group(8.7±1.6)] were much higher, compared with the untreated model control group(0±0)(P<0.01). The DAI scores on day 14 of the vehicle, rutaecarpine or prednisone treated groups were respectively markedly lower than on day 7(3.2±0.6, 0.9±0.6, 3.1±0.7 vs 8.9±0.6, 8.2±0.8, 8.7±1.6, P<0.05). The DAI score of mice treated with high-dose rutaecarpine was significantly lower, compared with those treated with low-dose rutaecarpine and prednisone.Compared to the untreated model control group, the histological scores in other four groups significantly increased.Comparisons of values among the post-treatment groups had statistical significance (0.2±0.4 vs 6.9±0.9, 4.5±0.9, 2.8±0.8, 5.7±0.7, P<0.01), while the high-dose rutaecarpine group presented the lowest score.The colonic mucosal CGRP mRNA and CGRP protein expressions in groups receiving vehicle, low-dose rutaecarpine and prednisone were significantly reduced than those in the untreated model control group(0.32±0.03 vs 0.15±0.02, 0.18±0.01, 0.22±0.01, P<0.01). The CGRP mRNA and CGRP protein expressions in the untreated model control group was similar to those in the DSS+ high-dose rutaecarpine group with no statistic significance between them(0.32±0.03 vs 0.31±0.02, P>0.05). Pearson correlation analysis between CGRP mRNA levels, CGRP immunohistochemisty levels and DAI, histological scores showed a statistically negative relationship respectively(r=-0.797, -0.819, -0.863, -0.845, all P<0.01). Conclusions: Rutaecarpine can ameliorate the DAI scores and histological scores of ulcerative colitis in mice.Rutaecarpine can upregulate the expressions of CGRP mRNA and CGRP protein.Correlation between CGRP mRNA, CGRP protein levels and DAI scores, histological scores respectively showed a statistically negative relationship.

[Preliminary study on reading speed test with IReST for normally-sighted young Chinese readers].

Objective: To assess the reading speed of normally-sighted young Chinese with the International Reading Speed Texts (IReST) Chinese version, and evaluate the normal range of the texts, the equivalence of the ten different texts and the potential clinical value. Methods: Evaluation of diagnostic techniques. Participants aged 18 to 35 years old with junior high school or above education and best corrected visual acuity no less than 0.6 were recruited. Best corrected visions of both eyes and binocular vision were tested, and ocular and nervous system diseases were excluded with slit-lamp microscope and funduscope. All the ten texts were read aloud at a distance of 40cm one by one according to a random sequence for each participant. Reading speeds were calculated based on the reading time measured with a stopwatch and number of characters read correctly. The procedure was repeated once again a week later. Data were collected with Epidata and further analyzed with R software. Data accorded with normal distribution and homogeneity of variance were compared by t-test, or by rank sum test. Results: One hundred and three volunteers aged (26.0±2.8) years old participated in the survey. Among them, 66% were female, 96.1% had college education, 53.4% wear glasses in daily life. The best corrected vision of both distance and near were 1.0 (decimal). For the first test, average reading speed for all the participants and texts was (295±51) characters/min,much faster than the normal range provided by the reading cards. No significant difference was found between different texts, and the biggest variance between texts was 11 characters/min(P>0.05). The average reading speed of the second test was (315±53) characters/min, which was faster than the first one (P<0.05) . No statistic relationship was found between reading speed and age, education level or wearing of glasses. However, women read faster than men, and significant difference was found between male and female volunteers in 5 texts during the first test. Conclusions: Normally-sighted young Chinese readers read faster than the normal range provided by IReST cards. There is significant variance of reading speed between different individuals. Although learning effect due to the repeated tests should be considered, the ten texts are of favorable consistency. IReST can be a useful tool for assessing reading performance, especially for comparing results before and after interventions with different texts. (Chin J Ophthalmol, 2018, 54: 120-124).

Combustion smoke-induced inflammation in the cerebellum and hippocampus of adult rats.

AIMS: The effect of combustion smoke inhalation on the respiratory system is widely reported but its effects on the central nervous system remain unclear. Here, we aimed to determine the effects of smoke inhalation on the cerebellum and hippocampus which are areas vulnerable to hypoxia injury. METHODS: Adult male Sprague-Dawley rats were subjected to combustion smoke inhalation and sacrificed at 0.5, 3, 24 and 72 h after exposure. The cerebellum and hippocampus were subjected to Western analysis for VEGF, iNOS, eNOS, nNOS and AQP4 expression; ELISA analysis for cytokine and chemokine levels; and immunohistochemistry for GFAP/AQP4, RECA-1/RITC and TUNEL. Aminoguanidine (AG) was administered to determine the effects of iNOS after smoke inhalation. RESULTS: Both the cerebellum and hippocampus showed a significant increase in VEGF, iNOS, eNOS, nNOS and AQP4 expression with corresponding increases in inflammatory cytokines and chemokines and increased AQP4 expression and RITC permeability after smoke exposure. AG was able to decrease the expression of iNOS, followed by VEGF, eNOS, nNOS, RITC and AQP4 after smoke exposure. There was also a significant increase in TUNEL+ cells in the cerebellum and hippocampus which were not significantly reduced by AG. Beam walk test revealed immediate deficits after smoke inhalation which was attenuated with AG. CONCLUSION: The findings suggest that iNOS plays a major role in the central nervous system inflammatory pathophysiology after smoke inhalation exposure with concomitant increase in proinflammatory molecules, vascular permeability and oedema, for which the cerebellum appears to be more vulnerable to smoke exposure than the hippocampus.

Combustion smoke exposure induces up-regulated expression of vascular endothelial growth factor, aquaporin 4, nitric oxide synthases and vascular permeability in the retina of adult rats.

Retinal cells respond to various experimental stimuli including hypoxia, yet it remains to be investigated whether they react to smoke inhalation. We show here that retinal cells in rats, notably the ganglion cells, Müller cells, astrocytes and blood vessels responded vigorously to a smoke challenge. The major changes included up-regulated expression of vascular endothelial growth factor (VEGF), aquaporin 4 (AQP4) and nitric oxide synthase (NOS). VEGF expression was localized in the ganglion cells, Müller cells, astrocytes and associated blood vessels. AQP4 was markedly enhanced in both astrocytes and Müller cells. Increase in vascular permeability after smoke exposure was evidenced by extravasation of serum derived rhodamine isothiocyanate which was internalized by Müller cells and ganglion cells. The tracer leakage was attenuated by aminoguanidine and N(G)-nitro-L-arginine methyl ester (L-NAME) treatment which suppressed retinal tissue NOS and nitric oxide (NO) levels concomitantly. It is suggested that VEGF, AQP4 and NO are involved in increased vascular permeability following acute smoke exposure in which hypoxia was ultimately implicated as shown by blood gases analysis. NOS inhibitors effectively reduced the vascular leakage and hence may ameliorate possible retinal edema in smoke inhalation.

Seroprevalence of Helicobacter pylori infection in patients with hepatitis B.

Helicobacter pylori infection has been investigated extensively in immunocompromised hosts, such as those with acquired immunodeficiency syndrome (AIDS) and organ transplant recipients. However, few reports on H. pylori prevalence in individuals with chronic HBV infection are available. The aim of this serological study is to investigate H. pylori prevalence in patients with hepatitis B. Ninety-six consecutive hospitalised patients with chronic hepatitis B were studied, together with 104 age-matched healthy individuals of similar socioeconomic status and with no evidence of hepatitis B virus infection or liver diseases. Serum samples from both groups were tested for specific IgG antibodies to H. pylori, using enzyme-linked immunosorbent assay (ELISA). Of the 96 patients with hepatitis B, 55 (57.3%) were positive for serum IgG anti-H. pylori, significantly greater than in the control group of 104, where 44 (42.3%) were positive (P < 0.05). In addition, the seroprevalence of H. pylori in the 45 patients who were positive for hepatitis B envelope antigen (HBeAg) and/or HBV-DNA was 75.6% (34), compared to 41.2% (21) in the 51 patients who were negative (P < 0.005). An increase in H. pylori prevalence is present in patients with chronic hepatitis B. Further study is needed to determine whether eradication of H. pylori will benefit these patients.

[Investigation of temperature sensitive liposome encapsulated adriamycin injected into hepatic artery for targeted behavior and cancer therapy].

Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 degrees C and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The 14C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery-injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W256 carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and iv injected liposome group.

[Temperature sensitive liposome encapsulated adriamycin combined with hepatic artery embolization].

A temperature sensitive liposome composed of a vesicle membrane of dipalmitoyl phosphatidylcholine and encapsulated adriamycin was made by the modified reverse-phase evaporation method. The encapsulation efficiency measured with a centrifugal filtration method was about 38%. The phase-transition temperature of the liposome determined by DSC was 41 degrees C. The liposome size was 851 +/- 50 nm, and the size distribution was from 772 to 952 nm as measured by laser particle analyzer with dynamic light scatter method. Eighty-four percent of the encapsulated drug could be released at precisely the phase-transition temperature of liposome in vitro. The results show that the liposomal drug is sensitive to temperature-controlled release.

Targeting behavior of hepatic artery injected temperature sensitive liposomal adriamycin on tumor-bearing rats.

Temperature sensitive liposomal Adriamycin (LADM) was injected into the hepatic artery of rats bearing implanted hepatic tumors. Two hours after the injection, the liver was heated at 42 degrees C and maintained for six minutes at that temperature using local hyperthermia. Blood samples were taken at regular intervals until 8 hours after injection, at which time the animals were sacrificed and the drug distribution in the tissues was examined. Results indicate that the Adriamycin was released from the liposome, with the drug concentration in circulation peaking at 30 minutes after heating. High drug levels (25.2 micrograms/g of wet tissue) in the tumor and high tumor/liver Adriamycin level ratios (TLAR; 4.1) were found. The drug levels and the TLAR of the liposomal Adriamycin injection combined with heating (LADM H) were significantly different from those of the same dose of aqueous Adriamycin with heating (ADM H) or aqueous Adriamycin (ADM) and LADM without heating. The experiment shows that the LADM is cleared from the liver slowly, and when hyperthermia treatment at phase-transition temperature of the liposome is performed, the drug level in an implanted hepatic tumor is increased, and in the parenchyma is decreased. The results imply that targeting the hepatic tumor in this way may be an effective therapeutic method, and the drug release from the liposome may be controlled externally. This method appears promising for clinical practice.

[Basic study on hepatic artery chemoembolization and tumor selective drug targeting by temperature-sensitive liposome with local hyperthermia].

Temperature-sensitive liposome entrapping adriamycin (L-ADM) was administered into the hepatic artery of hepatic tumor-bearing rats. The embolization of the hepatic artery with liposome and bio-distribution of ADM were examined. ADM concentration in blood showed a peak at 30 min after local heating on tumor (the heating had been performed for 6 min at 41-42 degrees C 2 hr. after injection). The value at the peak was about 3 times higher than that just before heating. ADM administered in liposomal form showed a high accumulative property to tumor with heating; ADM concentration in tumor 8 hr. after administration of ADM in liposomal form was about 5 times higher than that in liver and about 30 times higher than that in the heart, and about 20 times higher than that in tumor after administration in free form.

[Studies on the stability and some other important physical properties of polysaccharides polyphase liposome (PPL)].

The stability and some other important physical properties of PPL were investigated by means of electron microscopy and MPV-TAS experiments. The results are rated as follows: Good integrity of liposome homogeneity of its particle size were reached, and at 100 degrees C PPL was found to undergo sterilization without causing changes of its shape and encapsulation efficiency for 1 h. Also, the distribution of PPL particle size and the regularity of the change of PPL particle in size were determined by Coulter counter. Using this method, the kinetic equation of coalescence of polyphase liposome and the activation energy for coalescence were obtained, and through these results the stability of PPL is elucidated.