This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg^-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

The single-chain antibody gene (ox26-scFv) to transferrin receptor (TfR) was synthesized and amplified by three-step PCR. After sequencing, the gene was cloned into prokaryotic expression vector pTIG-Trx which carried thioredoxin (Trx) gene and a C-terminal His.tag. The Ox26-scFv proteins achieved 31% yields of total bacteria proteins at 20 degrees C, after 0.02mM IPTG induction using the strain E. coli BL21 (DE3). The soluble scFv proteins in cytoplasm suspension were about 35% and the inclusion bodies were about 65%. The soluble products were purified by immobilized metal chelation affinity chromatography (Ni-NTA), a single band with molecular weight 29 kD appeared on SDS-PAGE gel. Rat GH3 cell immunocytochemistry staining showed that Ox26-scFv protein could recognize and bind to transferrin receptor. Injected SD rats with Ox26-scFv proteins by tail veins, the antibodies were detected from brain tissues specially on the brain capillaries 4 h later which indicate that Ox26-scFv proteins have a good target function to brain capillaries and can permeate the blood-brain barrier mediated by the transferrin receptors.
Animals ; Antibodies ; administration & dosage ; genetics ; metabolism ; Antibody Formation ; Base Sequence ; Blood-Brain Barrier ; drug effects ; Drug Delivery Systems ; Genetic Vectors ; Molecular Sequence Data ; Rats ; Rats, Sprague-Dawley ; Receptors, Transferrin ; immunology

Objective To explore the feasibility and application of determining the center of the inferior portion of the glenoid on a standard anteroposterior view of the normal glenoid. Methods Seventy shoulders of 35 mature adults were measured in this study. A 64-slice CT 3D reconstruction was performed for each glenoid. A standard anteroposterior view and the scale of glenoid were made at a 3D workstation by one radiologist, and then transferred to software AutoCAD as 2D images. The 2D images were analyzed with AutoCAD respectively by 3 radiologists. The line was drawn between the most anterior and the most inferior points of the glenoid bony rim. On the same image, another line was drawn between the most posterior and the most inferior points of the glenoid bony rim. Two perpendicular bisectors of the 2 lines were drawn. The cross point of the 2 perpendicular bisectors was regarded as the circle center of the inferior part of the glenoid. The distances from the circle center to the anteroinferior and the posteroinferoir rims of the glenoid and the most posterior point were measured. Measurements were expressed as the mean ± standard deviation. Several related samples Friedman rank sum test was used to compare the measurements (the distance from the circle center to the most posterior point) by the 3 radiologists. Paired t tests were used to compare the differences between the left and right glenoids. Results The mean distance from the circle center to the most posterior point was ( 14. 1 ± 1.6) mm, the anteroinferior rim was ( 14. 0 ± 1.7) mm, and the posteroinferoir rim was ( 14. 1 ±1.6) mm. No significant differences were found ( P>0. 05) between measurements by the 3 radiologists. No significant differences were found ( P>0. 05) between the measurements of the both-side glenoids. Conclusions The method of determining the center of the inferior portion of the glenoid based on the most anterior,posterior and inferior points of the glenoid on a standard 3D anteroinferior view of the normal glenoid is easy,practical and highly repeatable. The radius of the left glenoid is comparable to the radius of the right side in normal shoulders. This method can be used to quantify a glenoid bone defect precisely.

Aim The effect of extracts of astralus(EA) on learning, memory and immune function of CTX treated mice was observed.Methods The step-down test was adopted to investigate learning and memory in mice; the method of enveloping CRBC was adopted to explore the function of macrophage in abdominal cavity; 3H-TdR marking method was used to observe the prolifernation of T lymphocytes and the method of ELISA was applied to measure the concentration of IFN-? in blood. Results EA (25 mg?kg-1, 50 mg?kg-1,ig, 21 d ) could boost learning and memory , enhance the phagocytic activity of monocytes and the proliferation of T lymphocytes of CTX treated mice, and increase the concentration of IFN-? in blood of CTX treated mice. Conclusion EA not only promote learning and memory, but regulate immune function.

Objective To evaluate the clinical effect of itraconazole in prevention of invasive fungal infections in allogeneic hema-topoietic stem cell transplantion .Methods In this retrospective study ,110 patients receiving allogeneic hematopoietic stem cell transplants were administed itraconazole or fluconazole for prevention of fungal infection .The occurrence and prognosis of invasive fungal infection ,and the side effect of both pyrroles were observed .Results Proven and probable invasive fungal infections occurred in 5 of 69 itraconazole recipients(7 .2% ) and in 8 of 41 fluconazole recipients(19 .5% ) during the first 180 days after transplanta-tion ,the difference had statistical significance(P<0 .05) .The fatality rate related to fungal infection had no statistical difference be-tween the two groups(2 .9% vs .7 .3% ) .The occurrence of itraconazole adverse reactions were more than fluconazole (26 .9% vs . 7 .0% ) ,and both itraconazole and fluconazole were well tolerated .Conclusion Itraconazole significantly reduces the incidence of inva-sive fungal infection in the patients receiving allogeneic hematopoietic stem cell transplants ,and it is a effective and safe prophylaxis .

Objective To observe the position and mobility of the tape after tension-free vaginal tape-obturator(TVT-O) surgery using transperineal two and three dimensional ultrasonography in patients with stress urinary incontinence.Methods A total of 32 patients with stress urinary incontinence who had TVT-O surgery and cured were enrolled.Transperineal two and three dimensional ultrasonography were performed after operation 3 months later.Both the position,morphology and mobility of the tape at rest and during Valsalva menuaver were observed.Results The tapes were mainly located in the 1/3 connection of the middle and distal urethra.The length of the urethra and the length of the urethra between the bladder neck and the proximal tape at valsalva menuaver were longer than those at rest.The tapes moved front-down at valsalva manuaver according to the mean distance between the tape and the symphysis pubis.The angles of the tapes were smaller at valsalva manuaver without significant difference.Conclusion It is useful to observe the position,morphology and mobility of the tape using transperineal two and three dimensional ultrasonography.The changes of the position and morphology of the tapes at valsalva menuaver were not significant.But the tapes can strengthen the urine control in the middle of urethra.

Objective To detect the expression of urinary nuclear matrix protein 22(NMP22) and cytokeratin 20(CK20) mRNA in the monitoring of bladder tumor recurrence ,and to explore the clinical value of combined detection of urinary NMP22 and CK20 mRNA in the monitoring of bladder tumor recurrence .Methods Enzyme‐linked immunosorbent assay(ELISA) and nested reverse transcriptase polymerase chain reaction(Nested RT‐PCR) were used to detect the expression of NMP22 and CK20 mRNA in the u‐rine of 46 patients with recurrent bladder cancer tumor (recurrent group) ,66 patients without recurrent tumor (no‐recurrent group) and 40 healthy volunteers(control group) respectively .Results The expression of NMP22 and CK20 mRNA in the urine of control group were negative .There was statistically significant difference between the positive expression rate of NMP 22 and CK20 mRNA in the urines of the recurrent group[78 .3% (36/46) ,80 .4% (37/46))] and that of the no‐recurrent group[6 .1% (4/62) , 6 .1% (4/62)] and the control group respectively (P<0 .01) .There was no statistically significant difference between the no‐recur‐rent group and the control group(P>0 .05) .The expression level of NMP22 in recurrent tumor increased obviously along with the progression of the pathological grade and clinical classification of tumor (P<0 .05) .The positive rate of CK20 mRNA expression in the recurrent group increased obviously along with the increase of the tumor number (P<0 .05) .The sensitivity and specificity of NMP22 for monitoring bladder cancer recurrence were 78 .3% and 93 .9% ,of CK20 mRNA were 80 .4% and 93 .9% .Combined de‐tection of both sensitivity and specificity were 95 .7% and 92 .4% .Statistical significance was observed between combined sensitivi‐ty and that of single detection(P<0 .05) .No significant difference was observed between combined specificity and that of single de‐tection(P>0 .05) .Conclusion The positive expression of CK20 mRNA may also indicate tumor multiplicity .Combined detection of NM P22 and CK20 mRNA significantly increases the sensitivity and specificity in clinical detection .

Objective:To artificially design and express a recombinant protein named as ScFv-pLLO by fusing ScFv gene of Rituximab(C2B8)and dominant antigen epitopes from listeriolysin O(LLO),and studying its anti-tumor activity.Methods:VH and VL gene sequences of C2B8 against CD20 were acquired by searching United States Patent database,and ScFv sequence was constructed by linking VL and VH with a short peptide linker.Two CD4+T cell epitopes from LLO were selected and designed to splice ScFv sequence.The recombinant gene of ScFv-pLLO was cloned into prokaryotic expression vector and purified after induction.The capacity of ScFv-pLLO target-binding to B-cell lymphomas was evaluated by flow cytometry ( FCM ) and co-immunoprecipitation ( Co-IP ) .The effects of ScFv-pLLO on B-cell lymphomas proliferation and apoptosis were detected respectively.The immunogenicity of ScFv-pLLO was assessed by lymphocyte proliferation assay.Results: ScFv-pLLO was successfully expressed.It could bind to different B-cell lymphomas cell lines and obviously inhibit the growth of Raji cells as well as inducing apoptosis.Moreover,ScFv-pLLO was able to stimulate proliferation of spleen lymphocytes of immunized mice.Conclusion: The recombinant protein ScFv-pLLO can target-bind to B-cell lymphomas,and perform inhibitory effect and induce apoptosis on Raji cells that indicate ScFv-pLLO retain the capacity of ScFv derived from monoclonal antibody against CD20.Besides, ScFv-pLLO can induce immune response.This study provides a basis for further research about the role of ScFv-pLLO on simulating tumor cell antigens as well as being tumor vaccine adjuvant.

Rivaroxaban is one of the new oral anticoagulants (NOAC) for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation. It has clear pharmacokinetic parameters, stable plasma concentration, less drug-drug interaction and higher compliance of patients. However, the discrepancy of pharmacokinetics between individuals and drug-induced hemorrhage events frequently occur clinically, therefore the association of gene polymorphism with drug metabolism has become a research hotspot. This article reviews the research progress on pharmacokinetic characteristics of rivaroxaban and its relationship with gene polymorphism, to provide a reference for the individualized rational use of rivaroxaban.

Objective:To explore the regional brain activities in healthy adolescent subjects after sleep deprivation (SD) using amplitude of low-frequency fluctuation (ALFF) method.Methods:Total of 16 healthy adolescent subjects (8 males,8 females;aged 13-20 years) were recruited in the community and the campus through the internet and posters.Each of the 16 healthy adolescent subject underwent the attention network test and magnetic resonance imaging (MRI) session twice:once was after rested wakefulness (RW condition),and the other was after SD condition.Amplitude of low frequency fluctuation (ALFF) method was used to assess the local brain features.The mean ALFF signal values of the different brain areas were performed to investigate their relationships with the accuracy rate,reaction time and lapse rate in the attention network test,and were analyzed with a receiver operating characteristic (ROC) curve to investigate their sensitivities and specificities to distinguish the SD condition from the RW condition.Results:Subjects showed a lower response accuracy rate [(83 ± 12) ％ vs.(97 ± 4) ％,P ＜ 0.05],a longer response time [(832 ± 134) ms vs.(715 ± 97) ms,P ＜ 0.05] and a higher lapse rate [(15 ± 11)％ vs.(2.4 ±7.3)％,P ＜0.05] under SD condition than under RW condition.They showed higher ALFF area in the right cuneus (BA 17,BA 18),and lower ALFF areas in the right lentiform nucleus,right claustrum,left dorsolateral prefrontal cortex (BA 46) and left inferior parietal cortex (BA 39) under SD condition than under RW condition.Under SD condition,the mean ALFF signal value of the right claustrum showed a significant positive correlation with the accuracy rate (r =0.69,P ＜0.05),and a negative correlation with the lapse rate (r =-0.71,P ＜0.05).The mean ALFF signal value of the dorsolateral prefrontal cortex showed a significant positive correlation with the reaction time (r =0.68,P ＜ 0.05).The values of area under the curve of the right cuneus,right lentiform nucleus,right claustrum,left dorsolateral prefrontal cortex and left inferior parietal cortice were 0.9,0.8,0.9,0.8 and 0.9,respectively.These different ALFF areas also showed high degree of sensitivities and specificities.Conclusion:Sleep deprivation leads to the dysfunction in the default mode network,anticorrelatedtask-positive network,and advanced cognitive function brain areas,and the functional compensation in the visual network.