Immunoregulatory Effect of Jiedu Tongluo Shengjin Prescription on Sjögren's Syndrome Mice Based on Stability of Treg Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect of different doses of Jiedu Tongluo Shengjin prescription （JTSP） on serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and forkhead box P3 （FoxP3） in submandibular gland of NOD/Ltj mice with Sjögren's syndrome， and to explore the mechanism of JTSP on immune regulation in NOD/Ltj mice. MethodThirty NOD/Ltj mice （eight weeks old） were randomly divided into model group， JTSP low-dose group， JTSP medium-dose group， JTSP high-dose group and hydroxychloroquine group， and were administrated with normal saline， JTSP 9， 18， and 36 g·kg-1， and hydroxychloroquine 60 mg·kg-1 daily， respectively from the age of 12 weeks. Six ICR mice were given an equal amount of normal saline by gavage as the control group. During the experiment， daily water consumption and saliva secretion of mice at the age of 9， 12， 16 weeks were recorded. After 4 weeks of administration， submandibular gland and spleen tissues were dissected to calculate corresponding indexes. The pathological morphology of submandibular gland was observed by hematoxylin-eosin （HE） staining. Meso Scale Discovery （MSD） and immunohistochemistry were employed to detect the serum levels of IL-6， TNF-α and IL-10， and the expression and distribution of FoxP3 in submandibular gland， respectively. The protein expression of FoxP3 in mouse submandibular gland was determined by Western blot， and the mRNA expressions of FoxP3 and TNF-α were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group presented increased daily water consumption， decreased saliva secretion， lowered submandibular gland index， elevated pathological score of submandibular gland， up-regulated serum IL-6 and TNF-α and mRNA expression of TNF-α while down-regulated serum IL-10 and protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. Compared with the conditions in model group， daily water consumption in JTSP groups was reduced while saliva secretion was increased， especially in medium-dose and high-dose groups （P<0.05）， and there was an increase in the submandibular gland index of JTSP medium-dose group （P<0.05） while a decrease in the spleen index of JTSP high-dose group （P<0.05）. Additionally， JTSP groups had lower pathological score of submandibular gland than the model group （P<0.05）， especially high-dose group， as well as lower serum IL-6 and TNF-α and mRNA expression of TNF-α while higher serum IL-10 （P<0.05）. JTSP at medium and high doses up-regulated the protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. ConclusionJTSP may inhibit the secretion of inflammatory cytokines by regulating the stability of FoxP3+ regulatory T （Treg） cells， thus alleviating the systemic immune inflammation in Sjögren's syndrome.

Theoretical insights into selective extraction of uranium from seawater with tetradentate N,O-mixed donor ligands.

The competition of uranium and vanadium ions is a major challenge in extracting uranium from seawater. In-depth exploration of the complexation of uranium and vanadium ions with promising ligands is essential to design highly efficient ligands for selective recovery of uranium. In this work, we systematically explored the uranyl and vanadium extraction complexes with three tetradentate N,O-mixed donor analogues including the rigid backbone ligands 1,10-phenanthroline-2,9-dicarboxylic acid (PDA, L1) and 5H-cyclopenta[2,1-b:3,4-b']dipyridine-2,8-dicarboxylate acid (L3), as well as the flexible ligand [2,2'-bipyridine]-6,6'-dicarboxylate acid (L2) using density functional theory (DFT). These ligands coordinate to the uranyl cation in a tetradentate fashion, while L1 and L3 act as tridentate ligands toward VO2+ due to the smaller ionic radius of VO2+ and larger cleft sizes of L1 and L3. Bonding analyses show that the metal-ligand bonding orbitals of the uranyl complexes [UO2L(CO3)]2-, [UO2L(OH)]-, and [UO2L(H2O)] mainly arise from the interactions of the U 5f, 6d orbitals and N, O 2p orbitals. Because of the rigid structure and more suitable chelate ring size, the L1 ligand possesses a stronger complexing ability for uranyl ions than other ligands, while the L3 ligand has weaker binding affinity than L1 and L2. All these ligands prefer to coordinate with the uranyl cation rather than vanadium ion, indicating the selectivity of these ligands to [UO2(CO3)3]4- over H2VO4- and HVO42- in seawater. This is mainly attributed to the metal ion size-based selectivity and structural preorganization of the ligands. These results demonstrate that the backbone of these ligands affect their extraction behaviors. It is expected that this work might prove useful in designing efficient ligands for uranium extraction from seawater.

Bisimidazolium Salt Glycosyltransferase Inhibitors Suppress Hepatocellular Carcinoma Progression In Vitro and In Vivo.

Hepatocellular carcinoma is a leading cause of cancer death, and the disease progression has been related to glycophenotype modifications. Previously synthesized bisimidazolium salts (C20 and C22) have been shown to selectively inhibit the activity of glycosyltransferases in cultured cancer cell homogenates. The current study investigated the anticancer effects of C20/C22 and the possible pathways through which these effects are achieved. The therapeutic value of C20/C22 in terms of inhibiting cancer cell proliferation, metastasis, and angiogenesis, as well as inducing apoptosis, were examined with hepatic cancer cell line HepG2 and a xenograft mouse model. C20/C22 treatment downregulated the synthesis of SLex and Ley sugar epitopes and suppressed selectin-mediated cancer cell metastasis. C20/C22 inhibited HepG2 proliferation, induced cell-cycle arrest, increased intracellular ROS level, led to ER stress, and eventually induced apoptosis through the intrinsic pathway. Furthermore, C20/C22 upregulated the expressions of death receptors DR4 and DR5, substantially increasing the sensitivity of HepG2 to TRAIL-triggered apoptosis. In vivo, C20/C22 effectively inhibited tumor growth and angiogenesis in the xenograft mouse model without adverse effects on major organs. In summary, C20 and C22 are new promising anti-hepatic cancer agents with multiple mechanisms in controlling cancer cell growth, metastasis, and apoptosis, and they merit further development into anticancer drugs.

N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats.

Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1ß and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1ß and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.

Diagnostic Value of Neutrophil/lymphocyte Ratio and Platelet/lymphocyte Ratio in Premature Rupture of Membranes Complicated by Sepsis.

OBJECTIVE: To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in premature rupture of membranes complicated by sepsis. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Paediatrics, Affiliated Hospital of Yanbian University, China, from January 2020 to June 2021. METHODOLOGY: Ninety-nine children with premature rupture of membranes and sepsis were included as group A and 99 children without sepsis were included as group B. Logistic regression analysis was used to analyse the risk factors for premature rupture of membranes complicated by sepsis. The diagnostic value of PLR and NLR in sepsis complicated by premature rupture of membranes was assessed by subject operating characteristic curve (ROC) curves. RESULTS: Univariate analysis showed significant differences between groups A and B in terms of mode of delivery, lymphocyte count, platelets, PLR and NLR (p <0.05). Logistic regression analysis showed that mode of delivery, platelets, PLR and NLR were independent risk factors for premature rupture of membranes complicated by sepsis (p <0.05). The ROC area for PLR was 0.781 (95% CI: 0.718-0.844, p <0.001), which was greater than that for NLR when premature rupture of membranes complicated by sepsis was predicted. When the PLR was >93.072, the sensitivity of predicting premature rupture of membranes complicated by sepsis was 67.7% and the specificity was 79.8%. CONCLUSION: PLR and NLR have a high predictive value for premature rupture of membranes complicated by sepsis. Among them, the predictive value of PLR was greater than NLR. KEY WORDS: Premature rupture of membranes, Sepsis, PLR, NLR, Subject operating characteristic curve (ROC).

Insulin-like growth factor-1: A potential target for bronchopulmonary dysplasia treatment (Review).

Bronchopulmonary dysplasia (BPD) is a common respiratory disorder among preterm infants, particularly low-birth-weight infants (LBWIs) and very-low-birth-weight infants (VLBWIs). Although BPD was first reported 50 years ago, no specific drugs or efficient measures are yet available for prevention or treatment. Insulin-like growth factor-1 (IGF-1) belongs to the insulin family. It promotes mitosis and stimulates cell proliferation and DNA synthesis, the primary factors involved in pulmonary development during the fetal and postnatal periods. Several studies have reported that IGF-1 exerts certain effects on BPD genesis and progression by regulating BPD-related biological processes. In addition, exogenous addition of IGF-1 can alleviate lung inflammation, cell apoptosis and eliminate alveolar development disorders in children with BPD. These findings suggest that IGF-1 could be a new target for treating BPD. Here, we summarize and analyze the definition, pathogenesis, and research status of BPD, as well as the pathogenesis of IGF-1 in BPD and the latest findings in related biological processes.

PtrHAT22, as a higher hierarchy regulator, coordinately regulates secondary cell wall component biosynthesis in Populus trichocarpa.

Homeodomain-leucine zipper (HD-Zip) II transcription factors (TFs) have been reported to play vital roles in diverse biological processes of plants. However, it remains unclear whether HD-Zip II TFs regulate secondary cell wall (SCW) in woody plants. In this study, we performed the functional characterization of a Populus trichocarpa HD-Zip II TF, PtrHAT22, which encodes a nuclear localized transcription repressor predominantly expressing in secondary developing tissues. Overexpression of PtrHAT22 showed arrested growths, including reduced heights and diameters above the ground, small leaves, and decreased biomass. Meanwhile, the contents of lignin, cellulose, and thickness of SCW significantly decreased, whilst the content of hemicellulose obviously increased in PtrHAT22 transgenic poplar. The expressions of some wood-associated TFs and structural genes significantly changed accordingly with the alternations of SCW characteristics in PtrHAT22 transgenic poplar. Furthermore, PtrHAT22 directly repressed the promoter activities of PtrMYB20, PtrMYB28, and PtrCOMT2, and bind two cis-acting elements that were specifically enriched in their promoter regions. Taken together, our results suggested that PtrHAT22, as a higher hierarchy TF like PtrWNDs, exerted coordination regulation of poplar SCW component biosynthesis through directly and indirectly regulating structural genes and different hierarchy TFs of SCW formation network.

Theoretical Insights on Improving Amidoxime Selectivity for Potential Uranium Extraction from Seawater.

Extraction of uranium from seawater is one of the important ways to solve the shortage of terrestrial uranium resources. Thereinto, the competition between uranyl and vanadium cations is a significant challenge in the commonly used amidoxime-based adsorbents for extracting uranium from seawater. An in-depth understanding of the extraction behaviors of modified amidoxime groups with uranyl and vanadium ions is one of the effective means to design and develop efficient adsorbents for selective uranium sequestration. In this work, we have designed and systematically investigated the alkyl and amino functionalized amidoxime, (Z)-2-amino-N'-hydroxy-N,N-dimethylbenzimidamide (L1), and its phenyl and methoxy derivatives ((Z)-3-amino-N'-hydroxy-N,N-dimethyl-2-naphthimidamide (L2) and (Z)-2-amino-N'-hydroxy-4-methoxy-N,N-dimethylbenzimidamide (L3)) by quantum chemistry calculations. In the uranyl complexes, the amidoxime groups prefer to act as η2-coordinated ligands as the amidoximes increase, and there exist substantial hydrogen bond interactions, which are different from the vanadium complexes. Various bonding analyses show that the L1 ligand possesses a stronger binding affinity to UO22+, and the -C6H5 and -CH3O substituent groups seem to have no effect on the improvement of extraction ability. Thermodynamic analysis confirms that the L1 ligand has a stronger extraction capability to uranyl ion compared to L2 and L3. According to the calculations of the vanadium (V) (VO2+ and VO3+) complexes with the L1 ligand, L1 is more likely to react with [H2VO4]- and [HVO4]2- to form VO2+ complexes. Expectantly, thermodynamic analysis displays a higher extraction capacity for uranyl ions than vanadium ions. Therefore, these alkyl and amino functionalized amidoxime ligands demonstrate high selectivity for uranyl over vanadium ions, which is mainly due to the coordination mode changes of these ligands toward vanadium in conjunction with the considerable hydrogen bonds in the uranyl complexes. These results are expected to afford useful clues for the design of efficient adsorbents for uranium extraction from seawater.

Salidroside Mitigates Airway Inflammation in Asthmatic Mice via the AMPK/Akt/GSK3ß Signaling Pathway.

INTRODUCTION: This study aimed to explore the effects and mechanisms of salidroside (SAL) in airway inflammation in asthmatic mice. METHODS: Mice were sensitized with ovalbumin (OVA) to establish an asthma model. They were divided into the control group, OVA group, SAL low-dose group (SAL-L), SAL high-dose group (SAL-H), and dexamethasone (DXM) group. The airway reactivity of the mice was measured, and the total cells, neutrophils, eosinophils, and lymphocytes were counted, respectively. The levels of IL-4, IL-5, IL-13, and IFN-γ in bronchoalveolar lavage fluid (BALF) were detected by ELISA. Immunohistochemistry was used to detect the expression levels of p-AMPK, p-Akt, and p-GSK3ß. Western blot was used to detect cytokine levels in lung tissue and p-AMPK, p-Akt, and p-GSK3ß levels in LPS-induced 16HBE cells. RESULTS: The airway hyperresponsiveness of asthmatic mice in the SAL-H group decreased (p < 0.05), and the total number of cells, neutrophils, eosinophils, and lymphocytes decreased significantly (p < 0.05). In addition, the airways of mice showed airway inflammatory infiltration and goblet cell proliferation, and the corresponding cellular inflammatory factors IL-4, IL-5, and IL-13 were significantly decreased. However, the expression of IFN-γ in BALF and lung tissues was increased (p < 0.05). Moreover, after the mice were treated with SAL, the phosphorylation level of AMPK was significantly increased, which further reduced the phosphorylation levels of Akt and GSK3ß (p < 0.05). Both SAL and AMPK inhibitors exerted effects on LPS-induced 16HBE cells, consistent with in vivo results. CONCLUSION: SAL can inhibit bronchial hyperresponsiveness and reduce tracheal inflammation by increasing AMPK phosphorylation and inhibiting Akt and GSK3ß signaling pathways.

Pompe Disease Complicated with Appendicular Torsion: A Rare Concurrence.

Pompe disease, also known as Glycogen Storage Disease Type II, is a rare disorder of glucose metabolism caused by congenital acid alpha-glucosidase (GAA) deficiency. A large amount of glycogen accumulates in the lysosomes, causing these to swell and rupture. Its incidence is about 1 in 40,000 to 1 in 50,000 newborns. The main features are hypotonia and cardiomyopathy. Only a few clinical cases of Pompe disease have been reported, and appendicular torsion has rarely been observed. Herein, we report a case of Pompe disease combined with appendicular torsion, both of which were diagnosed on autopsy pathology. The clinical diagnosis of this disease is difficult in developing countries, and it is mostly misdiagnosed as other types of heart disease. Once the clinical symptoms worsen, most of them die within a short period. Therefore, screening for neonatal genetic metabolic diseases for early diagnosis and treatment should be carried out. Key Words: Glycogen storage disease type II, Metabolic disease, Enzyme replacement therapy, Neonatal screening.

Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratio as Predictive Biomarkers for Early-onset Neonatal Sepsis.

OBJECTIVE: To determine the predictive significance of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in early-onset neonatal sepsis (EONS). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: The Neonatal Intensive Care Unit (NICU), Affiliated Hospital of Yanbian University, Jilin, China, from January 2018 to January 2020. METHODOLOGY: Of the total 124 children, 74 children with EONS were enrolled in group A and 50 children without infection-related diseases were enrolled in group B (control). The EONS risk factors were evaluated by logistic regression. Besides, the PLR and NLR diagnostic performances in EONS were evaluated by plotting the receiving operating characteristic (ROC) curves. RESULTS: In the univariate analysis, the differences for platelet count, lymphocyte number, neutrophil number, NLR, and PLR, between group A and group B were of statistical significance (p = 0.02, 0.021, <0.001, <0.001, and <0.001 respectively). As suggested by logistic regression, PLR and NLR were identified as the factors to independently predict the risk of EONS (p = 0.012, and 0.003, respectively). In addition, the value of area under the ROC curve (AUC) of NLR in predicting EONS was 0.788 (95% CI: 0.708-0.868; p <0.001), which was greater than that of PLR. At the NLR value of ≥3.169, the sensitivity of predicting EONS was 77%, and the specificity was 78%. CONCLUSION: Peripheral blood NLR and PLR have high predictive value for EONS. The predictive value of NLR as a biomarker for EONS evaluation was greater than that of PLR. Key Words: Neonatal sepsis, Logistic models, ROC curve, Blood cell count.

Role of Glycans on Key Cell Surface Receptors That Regulate Cell Proliferation and Cell Death.

Cells undergo proliferation and apoptosis, migration and differentiation via a number of cell surface receptors, most of which are heavily glycosylated. This review discusses receptor glycosylation and the known roles of glycans on the functions of receptors expressed in diverse cell types. We included growth factor receptors that have an intracellular tyrosine kinase domain, growth factor receptors that have a serine/threonine kinase domain, and cell-death-inducing receptors. N- and O-glycans have a wide range of functions including roles in receptor conformation, ligand binding, oligomerization, and activation of signaling cascades. A better understanding of these functions will enable control of cell survival and cell death in diseases such as cancer and in immune responses.

Effects of 10 Hz repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in the vegetative state.

The aim of the present study was to investigate the effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) during vegetative state (VS). Between May 2017 and November 2018, 95 patients were treated in the Coma Recovery Department of the Central Hospital of Jinzhou. According to the inclusion and exclusion criteria, a total of 32 patients in VS caused by brain injury were enrolled. The patients were assigned into rTMS and control groups in a non-randomized manner. All patients received JFK Coma Recovery Scale-Revised (CRS-R) scores and underwent motor evoked potential (MEP) latency and central motor conduction time (CMCT) measurement before the first treatment and after 20 days of treatment, which was the end of the study. Following 20 days of treatment, a significant increase was observed in the CRS-R scores of patients in the rTMS group compared with those obtained at pretreatment (P<0.001). An increase in the CRS-R scores of the control group was also observed compared with the pretreatment scores (P=0.035). The change in CRS-R scores (P<0.001) and improved conscious state rate (P=0.0016) were significantly different between the two groups. A significant decrease in MEP (P<0.001) and CMCT (P<0.001) was observed in the rTMS group compared with measurements obtained at pretreatment, whereas no significant decrease was observed in the control group (P=0.693; P=0.070). The changes in MEP (P<0.001) and CMCT (P<0.001) between the two groups were statistically significant. In conclusion, 10 Hz rTMS of the right DLPFC in early disorders of consciousness is feasible and efficient. rTMS treatment could improve patient state of awareness and accelerate patient recovery in VS.

In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer.

BACKGROUND: Chemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin. METHODS: Four kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice. RESULTS: The ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin. CONCLUSION: In this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic.

Comparing the clinical characteristics and prognosis of seropositive and seronegative rheumatoid arthritis patients in China: a real-world study / 中华风湿病学杂志

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Uncontrolled central hyperthermia by standard dose of bromocriptine: A case report.

BACKGROUND: Some patients present to the intensive care unit due to noninfectious pathologies resulting in fever, especially acute neurological injuries, including brain trauma and intracranial haemorrhage. The cause has been identified to be central hyperthermia characterized by a high core temperature and a poor response to antipyretics and antibiotics. However, no proper guidelines on how to treat central hyperthermia have been developed for clinical practice. CASE SUMMARY: A 63-year-old woman was transferred to our hospital due to injury after a traffic accident. Eight hours after admission, her pupils enlarged bilaterally from 2.5 mm to 4.0 mm. She developed severe coma and underwent decompressive craniectomy. She was diagnosed with central hyperthermia after surgery and was prescribed bromocriptine. The standard dose of bromocriptine could not control her hyperpyrexia, and we prescribed 30 mg a day to control her temperature. CONCLUSION: Bromocriptine may be effective in controlling central hyperthermia and have a dosage effect.

The expression and functional analysis of the sialyl-T antigen in prostate cancer.

Aberrant glycosylation is a featured characteristic of cancer and plays a role in cancer pathology; thus an understanding of the compositions and functions of glycans is critical for discovering diagnostic biomarkers and therapeutic targets for cancer. In this study, we used MALDI-TOF-MS analysis to determine the O-glycan profiles of prostate cancer cells metastasized to bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP) in comparison to immortalized RWPE-1 cells derived from normal prostatic tissue. Prostate cancer (CaP) cells exhibited an elevation of simple/short O-glycans, with a reduction of complex O-glycans, increased O-glycan sialylation and decreased fucosylation. Core 1 sialylation was increased dramatically in all CaP cells, and especially in PC-3 cells. The expression of Neu5Acα2-3Galß1-3GalNAc- (sialyl-3T antigen) which is the product of α2,3-sialyltransferase-I (ST3Gal-I) was substantially increased. We therefore focused on exploring the possible function of ST3Gal-I in PC-3 cells. ST3Gal-I silencing studies showed that ST3Gal-I was associated with PC-3 cell proliferation, migration and apoptosis. Further in vivo studies demonstrated that down regulation of ST3Gal-I reduced the tumor size in xenograft mouse model, indicating that sialyl-3T can serve as a biomarker for metastatic prostate cancer prognosis, and that ST3Gal-I could be a target for therapeutic intervention in cancer treatment.

Preparation, Characterization, and Pharmacokinetic Study of a Novel Long-Acting Targeted Paclitaxel Liposome with Antitumor Activity.

BACKGROUND: Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting. METHODS: Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models. RESULTS: ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects. CONCLUSION: ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.

Co-delivery of epirubicin and paclitaxel using an estrone-targeted PEGylated liposomal nanoparticle for breast cancer.

Breast cancer is one of the most frequent malignancies in the female population. Recently, the development of medical products has been advanced for this disease; however, patients still suffer from the failure of current treatments and new therapeutic strategies are urgently required. In this study, due to the overexpression of the estrogen receptor (ER) in breast cancer and the ability of ER to specifically bind to its ligand estrone (ES), an ES-targeted PEGylated epirubicin (EPI) and paclitaxel (PTX) co-loaded liposomal nanoparticle (NP) (termed as ES-SSL-EPI/PTX) was developed. Physicochemical studies demonstrated that the ES-SSL-EPI/PTX had a nanoscaled particle size (~120 nm) and a neutral zeta potential (~-5 mV) and presented favorable stability in physiological media. In vitro, the ES-SSL-EPI/PTX showed a significantly higher cellular uptake in human breast cancer MCF-7 cells mainly via the receptor-ligand mediated pathway resulting in effective cytotoxic activity. In vivo targeting study, the accumulation of targeted liposomes in tumor was significantly improved. The systemic circulation time and biodistribution in main organs of EPI and PTX delivered by ES-SSL-Liposomes were increased. Consequently, the ES-SSL-EPI/PTX significantly suppressed tumor growth in the MCF-7-derived tumor-bearing mouse model without inducing toxicity. These results suggested that the ES-SSL-EPI/PTX was a promising formulation for co-delivery of chemotherapeutics in the treatment of breast cancer.

The clinical significance of serum CXC-chemokine ligand 13 in primary Sj?gren's syndrome / 中华风湿病学杂志

Objective:To investigate the clinical significance of serum CXCL13 in primary Sj?gren's syndrome (pSS).Methods:Thirty patients with pSS were enrolled as pSS group and 30 healthy individuals were selected as control group. Serum CXC-chemokine ligand 13 (CXCL13) level were detected by enzyme- linked immuno sorbent assay (ELISA), which was analyzed with the related immune parameters (eg. B cell pro-portion, immunoglobulin (Ig)G, IgA, IgM, complement (C)3, C4 and autoantibodies), the index of gland structure and function, and the related disease index of pSS[EULAR Sj?gren's syndrome disease activity index (ESSDAI), EULAR Sjogren's syndrome patient reported inde (ESSPRI)] by Pearson or Spearman analysis method.Results:The level of serum CXCL13 in pSS patients [(139±94) pg/ml]was significantly higher than that in healthy individuals [(36±20) pg/ml] ( t=5.838, P<0.01). The level of serum CXCL13 was positively cor-related with the proportion of B cells ( r=0.364, P=0.048), the level of serum IgG ( r=0.369, P=0.045), focus score ( r=0.592, P=0.001), ESSDAI ( r=0.415, P=0.023) and ESSPRI ( r=0.431, P=0.017). Meanwhile, it was negatively correlated with unstimulated salivary flow rate ( r=-0.381, P=0.038). There were 24 pSS patients with systemic involvement. The serum CXCL13 level of pSS patients with systemic involvement was signifi-cantly higher than that of patients without systemic involvement, and the difference was statistically significant ( Z=-2.256, P=0.024), but there was no significant correlation with the number of systemic involvement ( r=0.344, P=0.062). Conclusion:The level of serum CXCL13 is a useful index in estimating disease activity and gland destruction.