[Application of Padua prediction score and serum albumin level in evaluating venous thromboembolism in rheumatic inpatients].

OBJECTIVE: To investigate the status of venous thromboembolism (VTE) in rheumatic inpatients, and to explore the efficiency of Padua prediction score (PPS) in the patient population. In addition, to analyze the relationship between serum albumin and VTE in rheumatic inpatients. METHODS: Data of inpatients with rheumatology were retrospectively collected and analyzed at Sichuan Provincial People's Hospital from September 2018 to September 2019. Occurrence of VTE was compared between high (PPS≥4) and low (PPS < 4) risk groups. PPS were analyzed in the VTE and non-VTE patients. Multivariate Logistic regression model was used to analyze the risk factors in PPS and the relationship between serum albumin and VTE. RESULTS: A total of 1 547 patients were included in this study, and 27 (1.7%) had symptomatic VTE. Among the symptomatic VTE cases, 19 (1.2%) had deep vein thrombosis (DVT) only, 6 (0.4%) had pulmonary thromboembolism (PTE) only, and 2 (0.1%) were diagnosed with DVT and PTE. PPS in the VTE and non-VTE groups were 3.33±1.78 and 1.80±0.97 respectively (P < 0.05).The number of patients with PPS≥4 in the VTE group and non-VTE group was 37.0% and 4.3% respectively (P < 0.01). The average serum albumin level in the VTE group was lower than that in non-VTE group [(29.79±6.36) g/L vs. (35.17±6.31) g/L, P < 0.001]. Seventy-six cases was divided into high-risk group of VTE, while 1 471 cases were in the low-risk group, and the incidence of VTE was 13.2% and 1.2% respectively (P < 0.001). Logistic regression analysis showed that ongoing hormonal treatment, age≥70 years, trauma and/or surgery ≤30 d, reduced mobility and previous VTE were risk factors of VTE in the rheumatology patients, OR values were 7.11, 7.07, 3.40, 2.40 and 2.00, respectively. Lower serum albumin level was the risk factor of VTE in the rheumatology patients [OR=0.88 (95%CI: 0.82-0.94)]. CONCLUSION: The incidence of VTE was relatively higher in the hospitalized patients in Department of Rheumatology and Immunology. Glucocorticoid therapy was the highest risk factor of VTE and lower serum albumin level also was the risk factor. Although the PPS can reflect the risk of VTE in rheumatic inpatients to some extent, its effectiveness is limited. PPS can be optimized for quantitative VTE risk assessment of rheumatic inpatients in the future.

[National external quality assessment for molecular detection of severe acute respiratory syndrome coronavirus 2 Delta variant].

Objective: To clarify the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant on the performance of existing molecular diagnostic assays, and investigate the detection ability of clinical laboratories across China. Methods: The first nationwide external quality assessment (EQA) for molecular detection of Delta variant was carried out based on the non-infectious phage virus-like particles samples, which were prepared by genetic engineering methods and distributed to 8 488 laboratories nationwide. The EQA panel was composed of three Delta variant samples (7.5×102, 1.5×103 and 6.0×103 copies/ml), one non-variant weak positive sample and one negative sample. The percentage of agreement (PA) of Delta variant samples with different concentration, the PA of Delta variant and non-variant samples with 7.5×102 copies/ml, the PA of assays used by more than 100 laboratories for Delta variant samples with different concentration and the PA of Delta variant and non-variant samples with 7.5×102 copies/ml were calculated and analyzed. Results: The data from 8 127 laboratories were available for evaluation. The testing capability of 98.77% (8 027/8 127) of the participating laboratories was found to be competent in reporting correct results for all samples. The overall percentage of agreement (OPA), negative percentage of agreement (NPA) and positive percentage of agreement (PPA) of the samples were 99.64% (40 490/40 635), 99.73% (8 105/8 127), 99.62% (32 385/32 508), respectively. With the decrease of the concentration of the samples, the PPA of Delta variant samples decreased. The PPAs were 99.41% and 99.51% for Delta variant and non-variant samples with 7.5×102 copies/ml, respectively, with no statistical difference (P=0.392). The OPA, NPA and PPA of the assays used by more than 100 laboratories were all greater than 98%, and no statistical difference of the PPAs was identified between Delta variant and non-variant samples with 7.5×102 copies/ml (P>0.05). Conclusions: Delta variant fails to impair the performance of current molecular diagnostic assays in China. The clinical laboratories have the same detection capabilities for Delta variant and non-variant samples. However, in certain laboratories, further improvement is required to ensure the accurate detection of weak positive samples.

[Clinical characteristics and related factors of rheumatoid arthritis complicated with tuberculosis infection].

OBJECTIVE: To investigate the clinical characteristics and high risk factors of Rheumatoid arthritis (RA) complicated with tuberculosis infection. METHODS: Patients with rheumatoid arthritis diagnosed in the hospital of Sichuan Provincial People's Hospital from January 2007 to January 2017 was retrospectively collected, who were enrolled in the study group. A control group was randomly selected from the RA patients hospitalized in the same period without co-infection at a ratio of 1 :2. The general data, clinical data, laboratory test data, treatment plan, etc. of the two groups were collected in detail for single factor statistical analysis. Then multivariate Logistic regression was used to analyze the independent risk factors of RA complicated with tuberculosis infection with statistical significance in univariate analysis. RESULTS: The clinical manifestations of fever (83.3%) were most common, followed by cough (69%) and body mass loss (45.2%). In the infected group, pulmonary tuberculosis accounted for 73.3%. In the infected group the chest CT showed two or more cases, accounting for 59%. There were 9 cases (33.3%) occurring in the typical tuberculosis occurrence site. Compared with the control group, the erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) levels, and the daily average dose of glucocorticoid in 1 year in the infected group were higher than those in the control group. And those differences were statistically significant(P < 0.05). There were no significant differences in gender, age, disease duration, disease activity score, white blood cell (WBC), platelet (PLT), hemoglobin (Hb), immunoglobulin G (IgG), complement (C), Anti cyclic citrullinated peptide antibody (anti-CCP), CD4+T cell count, and immunosuppressant use (P > 0.05). Multivariate Logistic regression analysis showed that CRP levels(OR=1.016, 95%CI:1.002-1.031) and the daily average dose of glucocorticoid in 1 year(OR=1.229, 95%CI:1.066-1.418)were the independent risk factors of RA complica-ted with tuberculosis infection. CONCLUSION: RA patients with tuberculosis infection are mainly phthisis. The clinical manifestations of RA combined with tuberculosis infection are lack of specificity, and the chest imaging features of pulmonary tuberculosis are diverse, which are easy to be misdiagnosed. CRP levels and the daily average dose level of glucocorticoid in 1 year were risk factors for RA and tuberculosis infection.

[Effect of convection enhanced delivery on the microstructure of brain extracellular space in aged rats].

OBJECTIVE: To compare the changes of extracellular space (ECS) structure and local drug distribution in adult brain and aged brain at different drug delivery rates in minimally invasive treatment of encephalopathy by convection enhanced delivery (CED) via ECS pathway. METHODS: Thirty-six SD male rats were divided into adult rats group (2-8 months, n=18) and aged rats group (18-24 months, n=18) according to the age of the month. According to the drug rates (0.1 µL/min, 0.2 µL/min, and 0.3 µL/min), they were randomly divided into 3 subgroups, 6 in each subgroup. Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) with a concentration of 10 mmol/L were introduced into the caudate nucleus of each group of rats by stereotactic injection. Tracer-based magnetic resonance imaging (MRI) was used to dynamically monitor the diffusion and distribution images of the Gd-DTPA in the brain interstitial system (ISS). Using the self-developed MRI image measurement and analysis system software to process and analyze the obtained images, the diffusion coefficient, clearance rate, volume fraction, and half-life of each group of rats in the caudate nucleus ECS could be acquired. The effects and differences of drug clearance and ECS structural function in the brain of aged rats and adult rats were compared and analyzed at different drug delivery rates. Magnetic tracer DECS-mapping technique was used to observe the distribution and drainage of tracer in caudate nucleus. RESULTS: At the injection rate of 0.1 µL/min, the volume fraction in the aged rats was increased compared with that in the adult rats (18.20%±0.04% vs. 17.20%±0.03%, t=3.752, P=0.004), and the degree of tortuosity was decreased (1.63±0.04 vs. 1.78±0.09, t=-3.680, P=0.004), the drug clearance rate was decreased [(1.94±0.68) mm2/s vs. (3.25±0.43) mm2/s, t=-3.971, P=0.003], and the molecular diffusion in ECS was increased [(3.99±0.21)×10-4 mm2/s vs. (3.36±0.37)×10-4 mm2/s, t=3.663, P=0.004]. When the rate of injection increased to 0.2 µL/min, the drug clearance in ECS of the aged rats was slowed down [(2.53±0.45) mmol/L vs. (3.37±0.72) mmol/L, t=-1.828, P=0.021]. However, there were no significant differences in volume fraction, molecular diffusion in ECS and macroscopic drug metabolism parameters. When the rate of injection increased to 0.3 µL/min, the volume fraction in the aged rats was decreased (17.20%±0.03% vs. 18.20%±0.05%, t=-0.869, P=0.045), and the drug clearance rate in ECS was significantly accelerated [(4.04±0.76) mmol/L vs. (3.26±0.55) mmol/L, t=1.786, P=0.014], and there was no significant difference in tortuosity and the rate of molecular diffusion in the ECS. CONCLUSION: The drug clearance and ECS structural parameters of brain ECS in aged brain with CED administration were changed at different rates, and it has the least effect on ECS in the aged brain at the injection rate of 0.2 µL/min. For the application of CED for the treatment of encephalopathy, we should consider the influence of factors such as age and injection rate, and provide reference for the development of individualized clinical treatment plan for minimally invasive treatment of encephalopathy via ECS pathway.

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

OBJECTIVE: To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. METHODS: A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. RESULTS: The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. CONCLUSION: The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

[Research progress in autophagy in the development of pulp inflammation and dental pulp injury reparation and regeneration].

Pulpitis is an infectious disease characterized by persistent inflammation of dental pulp and severe pain of patients, root canal treatment increases the risk of tooth fracture, discoloration and reinfection. Therefore, pulp injury repair and pulp regeneration become the new targets of pulpitis treatment. Autophagy is considered as an important defense and protective mechanism, thus plays an important role in preventing the host from excessive inflammatory reaction. There are few reports on the regulative mechanisms and therapeutic strategies of autophagy on pulp inflammation progression, therefore, this paper reviewed the role of autophagy on the progression of pulpitis, also reviewed the research progress of autophagy on dental pulp injury repair and regeneration, aiming to provide theoretical support for further research and clinical application.

Annealing effect on the structure and electronic transport properties in La5/8Ca3/8MnO3/ErMnO3 multilayer thin films.

Ferromagnetic La5/8Ca3/8MnO3 (LCMO) and Ferroelectric ErMnO3 (EMO) multilayer thin films with sandwich structure (LCMO/EMO/LCMO) were grown on (LaAlO3)0.3(Sr2AlTaO6)0.7 (001) [LSAT (001)] substrates by pulsed laser deposition (PLD) method. For these films, the structural characterization was carried out by X-ray diffraction (XRD), and the temperature-dependence resistivity (p-T) showing the metal-insulator transition (Tp) also was measured. In the multilayer thin films the LCMO (002) peak move to lower Bragg angles after annealing at 900 degrees C for 30 hours under 1atm Oxygen pressure, and this condition is much different from the LCMO single layer films where the (002) peak moves to higher Bragg angle after annealing due to the lattice mismatch between the LCMO layer and the substrate. By increasing the thickness of LCMO, the multilayer samples show two MR peaks in a wide temperature range during the process of M-l transition. This phenomenon is attributed to a new (La5/8Ca3/8)xEr(1-x)MnO3 layer produced by the solubility between LCMO and EMO layers after high-temperature annealing. In this paper, we provide some evidence of dissolution between LCMO and EMO layers, and discuss the influence on structure and electronic transport properties in the composite thin films by annealing.

Handgrip strength is associated with dyspnoea and functional exercise capacity in male patients with stable COPD.

Handgrip strength (HGS) is widely used to evaluate nutrition and adverse outcomes in several diseases. However, the relationship between HGS and the parameters of chronic obstructive pulmonary disease (COPD) are not known. To evaluate HGS in male patients with stable COPD, and to assess its correlation with dyspnoea and functional exercise capacity. We recruited 116 male out-patients with stable COPD from a general hospital in China between February and December 2017. For each patient, we recorded demographic characteristics and measured pulmonary function, dyspnoea, exercise capacity, body composition and HGS. HGS had a significantly positive correlation with muscle mass, lung function, and 6-min walking distance (6MWD) and a negative correlation with the modified Medical Research Council dyspnoea score. Multiple linear regression analysis showed that combining age, fat-free mass (FFM), 6MWD and duration of COPD accounted for 43.1% of the total variance in HGS. HGS was correlated with dyspnoea and exercise capacity. Aging and disease could alter upper limb muscle strength in COPD patients. Hence, HGS might be a simple method for assessing muscle function and for identifying patients with a noticeable reduction in HGS, who will need early, multidisciplinary intervention. .

Impaired learning and memory in rats induced by a high-fat diet: Involvement with the imbalance of nesfatin-1 abundance and copine 6 expression.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and behaviour was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST) and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin and insulin were measured via enzyme-linked immunosorbent assay, and the protein expressions of p-glycogen synthase kinase-3ß (GSK-3ß), GSK-3ß, p-ß-catenin, ß-catenin, cyclinD and copine 6 in the hippocampus and prefrontal cortex (PFC) were detected using western blotting. After 4 consecutive weeks of feeding with a high-fat diet, the rats showed obesity; increased plasma concentrations of ALT, glucose, FFA, TC, TG, HDL-C and LDL-C; decreased plasma levels of leptin and insulin; and inflammation and mild hepatocyte steatosis in the liver. Although there was no significant difference between groups with regard to performance in the OFT, EPM or FST, the NAFLD rats showed a decreased sucrose preference index in the SPT and impaired learning and memory in the MWM task. Moreover, the present study provides the first evidence of an increased plasma nesfatin-1 concentration in NAFLD rats, which was significantly correlated with plasma lipid concentrations and behavioural performance. Furthermore, copine 6 and p-ß-catenin protein expression decreased and p-GSK-3ß increased in the hippocampus and PFC of NAFLD rats. These results suggest that consuming of a high-fat diet for 4 consecutive weeks could successfully induce a NAFLD rat model. More importantly, these results provide the first evidence that impaired learning and memory in NAFLD rats was, at least partly, associated with increased plasma nesfatin-1 concentration and decreased copine 6 expression in the hippocampus and PFC.

[Effect of miR- 155 on immune- factors and its mechanism in mesenchymal stem cells under hypoxic environment].

OBJECTIVE: To investigate the effect of miR-155 on immune-factors and its mechanism in mesenchymal stem cells under hypoxia. METHODS: The microRNA sequences targeting miR-155 mimic and mimic NC gene was designed and transfected into MSC by lipofectamineTM 2000. Lipopolysaccharide was used to stimulate the immunity of MSC under hypoxic environment. Transfection efficiency of miR- 155 and immune-related genes (IL-6, IL-8, iNOS, TGF-ß, HIF-1α) were detected by real-time RT-PCR. The cell surface antigens (CD29, CD73, CD90, CD105, CD31, CD45) and supernatant cytokines (IL- 6, IL- 8, TGF- ß, SDF- 1α) were analyzed by flow cytometry and ELISA, respectively. Western Blot was applied to evaluate related proteins, iNOS and HIF- 1α. RESULT: miR- 155 was transfected into MSC effectively (53.447±8.361 vs 1.070±0.174, P<0.01). In miR-155 high-expressed groups, the expressions of IL-6 and IL-8 were up-regulated [(24.201±1.536) vs (1.802±0.058), P<0.01; (24.406±4.611) vs (7.407± 1.553), P<0.01] and iNOS was markedly suppressed [(0.151 ±0.035) vs (32.925±1.632), P<0.01]. Hypoxia up-regulated expressions of HIF-1α [(45.093±3.371) vs (2.210±0.498), P<0.01] and promoted the regulation of miR-155. MiR-155 and hypoxia had effect on mRNA expression of SDF-1α and TGF-ß [(5.690±1.655) vs (0.841±0.194), P<0.01; (6.982±1.353) vs (0.632±0.184), P<0.01]. However, there was no influence on cytokines of SDF- 1α and TGF- ß [(24.609±2.584) vs (25.359±2.455), P=0.760;(0.568±0.019) vs (0.345±0.037), P=0.002]. CONCLUSION: Hypoxia environment may promote miR-155 to positively modulate immune factors of MSC through up-regulating the expression of HIF-1α, which down-regulated iNOS protein.

[Changes of potassium and sodium content in erythrocyte of rabbit cardiac blood after death and timing of death].

We studied the changes of potassium and sodium contents in erythrocytes and the activity of erythrocyte membrane Na(+)-K(+)-ATPase in 40 cardiac blood samples of rabbit corpses at different postmortem intervals (PMI). The erythrocyte potassium content (RBCK) decreased linearly as the PMI increased (R = -0.829, P < 0.025). during postmortem 48 hours. The erythrocyte potassium content and the time after death had significant correlation. The activity of erythrocyte membrane Na(+)-K(+)-ATPase had no significant changes over postmortem 48 hours.

Status epilepticus stimulates peroxisome proliferator-activated receptor γ coactivator 1-α/mitochondrial antioxidant system pathway by a nitric oxide-dependent mechanism.

Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1-α (PGC-1α) is a transcriptional coactivator identified as an upstream regulator of lipid catabolism, mitochondrial number and function. PGC-1α protects neurons against oxidative damage by inducing several members of the mitochondrial antioxidant system such as superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Its role in seizure-induced oxidative stress has not been studied. Here we showed that pilocarpine-induced status epilepticus (SE) stimulates the PGC-1α/mitochondrial antioxidant system signaling pathway in the rat hippocampus. Because nitric oxide (NO) is the key factor of mitochondrial biogenesis through the transcriptional induction of PGC-1α, we investigated whether NO is involved in activation of the PGC-1α/mitochondrial antioxidant system after SE. Treatment with the NO synthase (NOS) inhibitor N(G)-nitro-l-argininemethyl ester (l-NAME) attenuated the increased expression of the PGC-1α/mitochondrial antioxidant system after SE and enhanced oxidative stress. These results suggest that SE can induce the PGC-1α/mitochondrial antioxidant system signaling pathway, which may represent a protective mechanism against SE-induced oxidative stress. Furthermore, NO may positively regulate the mitochondrial antioxidant system by inducing PGC-1α in pilocarpine-induced SE.

Renal cortical mitochondria are the source of oxygen free radicals enhanced by gentamicin.

Rat renal cortical mitochondria were isolated from Wistar male rats weighing 80 to 120 g to investigate whether the source of oxygen free radicals was renal cortical mitochondria enhanced by gentamicin. In renal cortical mitochondria with or without the addition of gentamicin, DMSO, DFO, CAT, SOD, and MT1 were added separately, then incubated at 37 degrees C for 90 min. Superoxide anions and hydroxyl radicals were then determined. The results showed that superoxide anions and hydroxyl radicals generated in mitochondria were enhanced by the addition of in vitro gentamicin (12.4 mg/mL) when compared to those without the addition of gentamicin. Dimethylsulfoxide (DMSO), catalase (CAT), and deferoxamine (DFO) significantly inhibited hydroxyl radicals enhanced by gentamicin, but superoxide dismutase (SOD) and metallothionein-1 (MT1) did not. SOD significantly inhibited the production of superoxide anions. Our data indicated that renal cortical mitochondria are the source of oxygen free radicals and that production is enhanced by gentamicin. This provides more insight on the pathogenetic role of hydroxyl radicals and superoxide anions in gentamicin-induced nephrotoxicity in vitro.

Zinc-induced metallothionein synthesis could protect from gentamicin nephrotoxicity in suspended proximal tubules of rats.

We have reported that preinjection of zinc could ameliorate gentamicin-induced nephrotoxicity in vivo via the induction of metallothionein. The present project was designed to study whether preinjection of zinc could protect from the harmful effects of gentamicin on DNA synthesis, Na(+)-K(+)-ATPase activity, and free radical production in rat renal proximal tubules (PT) in vitro. PT were prepared and cultured from normal, saline-preinjected, and Zn-preinjected (Zn 10 mg/k/day s.c. 5 days) Wistar male rats weighing 80-120 g. The results showed that DNA synthesis and Na(+)-K(+)-ATPase activity were significantly suppressed in the normal and saline-preinjected rats' PT by addition of gentamicin to the media in the concentration of 12.4 mg/mL; however, these reactions were not suppressed by gentamicin in Zn-preinjected rats' PT, and malondialdehyde and hydroxyl radical production in Zn-preinjected rats' PT were significantly lower than those in the normal and saline-preinjected rats' PT (p < .01). On the other hand, the metallothionein in Zn-preinjected rats' PT was very significantly higher than that in the normal and saline-preinjected rats' PT (p < .001). Our data indicate that gentamicin-induced suppression of DNA synthesis and Na(+)-K(+)-ATPase activity in rat PT, which lead to renal injury, may be relevant to free radicals generated by gentamicin; and that preinjection of zinc could ameliorate gentamicin-induced nephrotoxicity via the induction of the metallothionein synthesis in rat PT to scavenge free radicals generated by gentamicin.

Effect of acute trauma on the levels of intracellular cAMP, cGMP and DNA: studies on endocrinology and metabolism.

In this experiment, we used morgrel dogs to study the effect of trauma on the neuro-endocrine and metabolic organs and the effects of hormones on metabolism by determining the levels of intracellular cAMP, cGMP and DNA. From the changes in intracellular nucleotides, we learned that many neuro-endocrine organs and the main metabolic organs are characteristic of predominance in alpha-adrenoreceptor after trauma, thereby leading to high blood sugar.