OBJECTIVE: To observe the effect of moxibustion on Toll-like receptor 4/nuclear factor-κB (TLR 4/NF-κB) signaling in the synovial tissue of the ankle joint in rats with rheumatoid arthritis (RA), so as to analyze its biological mechanism underlying improvement of RA. METHODS: Fifty male SD rats were randomly divided into normal control, model, moxibustion, moxibustion ＋ TLR 4 agonist, and moxibustion ＋ TLR 4 antagonist groups (n＝10 rats in each). The RA model was established by subcutaneous injection of Freund's complete adjuvant (FCA, 0.1 mL/rat) at the right hind-paw and by being raised in a wind (air fan blowing), cold (about 10 ℃) and wet (purling) environment for 20 days. After 3 days of modeling, mild moxibustion was applied to bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 minutes, once daily for successive 10 days. The TLR 4 agonist (lipopolysaccharide) or TLR 4 antagonist (TAK-242) (1 mg/mL) was separately administered via the tail vein 30 min before performing moxibustion every time in the agonist group and the antagonist group. The expression of NF-κB inhibitory factor ɑ (IκBɑ), IκB kinase complex β(IκKβ), myeloid differentiation factor 88 (MyD 88), TLR 4, and NF-κB p 65 proteins in the synovial tissue of the ankle joint was detected by using Western blot. RESULTS: Following modeling, the girth of the swollen ankle joint was obviously bigger (P<0.01), and the expression levels of IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 proteins in the synovial tissue were considerably increased in the model group relevant to the normal control group (P<0.01). After moxibustion intervention, the girth of the swollen ankle joint and the expression levels of IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 proteins were significantly down-regulated in the moxibustion, moxibustion ＋TLR 4 agonist, moxibustion＋TLR 4 antagonist groups compared with the model group (P<0.01, P<0.05). Comparison among the 3 moxibustion groups showed that the lowered levels of ankle-joint girth, and IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 expression were significantly smaller in the moxibustion＋TLR 4 agonist group than in the simple moxibustion and moxibustion＋TLR 4 antagonist groups (P<0.05，P<0.01). No significant differences were found between the moxibustion and moxibustion＋TLR 4 antagonist groups in the decreased ankle joint girth and IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 expression levels (P>0.05), suggesting that activation of TLR 4 reduced the anti-inflammatory effect of moxibustion intervention. CONCLUSION: Moxibustion can reduce the ankle joint swelling in RA rats, which may be closely associated with its effect in down-regulating the expression of IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 proteins and in inhibiting TLR 4/NF-κB signaling in the synovial tissue of the ankle joint.

AIM:To observe the recovery of corneal subbasal nerves after laser - assisted subepithelial keratomileusis (LASEK), laser in situ keratomileusis ( LASIK), femto-second lenticule extraction ( FLEx ) and small incision lenticule extraction ( SMILE) .
METHODS: Confocal microscopy was used to observe subbasal nerves 1mo after surgery in 12 eyes of 12 LASEK patients, 12 eyes of 12 LASIK patients, 12 eyes of 12 FLEx patients and 12 eyes of 12 SMILE patients as well as some other follow-up times.
RESULTS: Subbasal nerves 1mo after SMILE were almost complete and regular, showing no significant differences from those 2wk after surgery or even unoperated eyes. The nerves cut off at the incision were well involuted 1mo after surgery. Subbasal nerves were damaged in different degrees and got repaired to form communicating branches with time lapse after LASEK, LASIK and FLEx.
CONCLUSION: SMILE exerted small infections on subbasal nerves. It may be superior to other corneal refractive surgeries in terms of postoperative nerve recovery.

Objective:To evaluate the safety and feasibility of the in-situ needle fenestration combined with the in vitro physician modified fenestration technique to reconstruct supra-aortic branches during thoracic endovascular aortic repair (TEVAR) for aortic arch lesions requiring landing at Z0 and Z1.Methods:From Nov 2017 to Dec 2019, eighteen patients who underwent both the in-situ needle fenestration and the in vitro physician modified fenestration techniques to extend the proximal landing zone to Z0 and Z1 during TEVAR were included in our study.Results:Sixteen patients underwent in vitro physician modified fenestration ,two patients underwent in vitro physician modified fenestration to reconstruct both the left common carotid artery and the innominate artery. All eighteen patients received in-situ needle fenestration to preserve the left subclavian artery. Supra aortic branches were preserved in all patients (38/38, 100%). There was no Type Ⅰ endoleak. Type Ⅱ endoleak was found in four paitnets (4/18). Type Ⅲ endoleak occurred in one patient (1/18). Type Ⅳ endoleak in four patients (4/18). Type Ⅲ endoleak needed open aortic arch repair 6 months later. The median follow-up time was 12 months. One (1/18) died in 12 months and the other patients were doing well.Conclusions:The joint application of the in-situ needle fenestration and the in vitro physician modified fenestration to reconstruct supra-aortic branches during TEVAR for aortic arch pathologies requiring landing at Z0 and Z1 was satisfactory.

Adult ; Antineoplastic Agents ; toxicity ; CD4-Positive T-Lymphocytes ; drug effects ; Female ; Humans ; Killer Cells, Natural ; drug effects ; Middle Aged ; Nurses ; statistics & numerical data ; Occupational Exposure ; T-Lymphocyte Subsets ; drug effects

Objective To investigate the effects of quetiapine and risperidone in the treatment of behavior and psychiatric symptom of dementia(BPSD).Methods 56 cases of Alzheimer's disease and vascular dementia pa- tients were all met for the classification and diagnostic criteria for mental illness in China(CCMD-3)and randomly divided into two groups(27 in quetiapine group,29 in risperidone group),experimental dosage were 0.05～0.3g/d and 1～2mg/d,respectively.The treatment lasted for 8 weeks.Results The total efficiency of quetiapine was 66.67% and that of risperidone was 65.5%,and the statistical difference was significant.As for the adverse effects, there was no significant difference,but incidence of EPS in quetiapine group was less than that of risperidone group. Conclusion Quetiapine can be widely administrated in clinic application as the high efficacy of control BPSD with low minor adverse effect.

Objective To explore the clinical symptoms and neuroimaging features of a patient with atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (H-ABC) caused by a novel TUBB4A mutation.Methods We analyzed the clinical data, imaging features and the result of genetic testing of a case diagnosed as atypical H-ABC.Results The initial symptoms were progressive spasticity, mild cerebellar ataxia and mild cognitive impairment.MRI showed regional blurring of slight high signal on T2-weight and FLAIR image in white matter of the bilateral midbrain ventral, internal capsule, posteior horn of lateral ventricle and centrum semiovale, with normal bilateral cerebellar and caudoputamen nucleus.Compared with normal subjects of the same age and gender, hypometabolism was found by 18F-FDG-PET in brainstem, cerebellar and caudoputamen nucleus in the patient.Genetic testing revealed a de novo pathogenic exome missense heterozygous mutations c.70G>A in TUBB4A, which was not reported in the human gene mutation database (HGMDpro) and was assessed to be a pathogenic mutation by pathogenic mutation prediction software.Conclusions The diversity of TUBB4A gene mutations may cause different functional and/or structural impairment in subcortical white matter, cerebellar and caudoputamen nucleus, leading to atypical symptoms and neuroimaging features.Genetic testing for pathogenic mutation in TUBB4A gene is a key for the diagnosis of H-ABC.

Objective:To observe the effects of moxibustion on serum levels of interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α), and to explore the effects of moxibustion on inflammatory damaging factors in experimental rheumatoid arthritis (RA) model rats; the relationship between the therapeutic effect of moxibustion on RA and the change in the Toll-like receptor (TLR) signaling pathway was analyzed using Toll-like receptor 4 (TLR4) antagonists and agonists. Methods:Fifty Sprague-Dawley (SD) rats were divided into a normal group, a model group, a moxibustion group, a moxibustion plus TLR4 agonist group (agonist group) and a moxibustion plus TLR4 antagonist group (antagonist group) according to the random number table, with 10 rats in each group. Except the normal group, rats in the other four groups were subjected to model preparation with the wind, cold and wet environmental factors plus Freund's complete adjuvant (FCA). Rats in the normal and model groups were not treated; rats in the moxibustion, agonist and antagonist groups started to be treated with the moxibustion (cigarette-type moxa) at bilateral Shenshu (BL 23) and Zusanli (ST 36) from the 4th day after the successful modeling, for 20 min each time with a total of 10 d. Rats in the agonist and the antagonist groups were injected with TLR4 agonist or antagonist [0.1 mg/(kg·bw)] via the tail vein 30 min before moxibustion. The concentrations of serum IL-6, IL-8 and TNF-α in each group were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the normal group, in the model group, the rat's right hind paw swelling was significantly obvious (P<0.01), there was a lot of inflammatory infiltration in the synovial tissues, the surface of the synovial membrane was unsmooth, the synovial membrane was hyperplasia and thicker, and the serum IL-6, IL-8 and TNF-α concentrations increased significantly (P<0.05). Compared with the model group, the paw swelling degrees of the rats in the moxibustion, the agonist and the antagonist groups reduced significantly (allP<0.01); the swelling degree in the antagonist group was milder than that in the agonist group, but the between-group difference was not statistically significant (P>0.05); inflammatory infiltration and synovial membrane hyperplasia in the synovial tissues of the moxibustion group and the antagonist group were all relieved differently; the decrease of synovial layer number in the moxibustion group was more obvious, and there were no obvious improvements in inflammatory infiltration and synovial thickness in the agonist group; the concentrations of IL-6, IL-8 and TNF-α in the moxibustion group were decreased, and the differences in the IL-6 and TNF-α concentrations were statistically significant (allP<0.01); there was no significant between-group difference in the IL-8 concentration (P>0.05); the concentrations of serum IL-8 and TNF-α in the agonist group increased significantly (both P<0.01), while the IL-6 concentration decreased without significant difference (P>0.05); the concentrations of IL-6 and IL-8 in the antagonist group decreased but the between-group differences were statistically insignificant (bothP>0.05), and the TNF-α concentration significantly increased (P<0.05). Compared with the moxibustion group, IL-6, IL-8 and TNF-α concentrations increased in the agonist group, and the differences in the IL-8 and TNF-α concentrations were statistically significant (both P<0.01); the concentrations of IL-6, IL-8 and TNF-α increased in the antagonist group, and the differences in the IL-6 and TNF-α concentrations were statistically significant (bothP<0.01); there was no significant difference in the IL-8 concentration between the groups (P>0.05). The serum levels of IL-6, IL-8 and TNF-α in the antagonist group were lower than those in the agonist group (allP<0.05). Conclusion:Moxibustion at Shenshu (BL 23) and Zusanli (ST 36) can reduce the joint swelling degree and inflammation in synovial tissue of RA model rats, decrease the serum levels of IL-6, IL-8 and TNF-α in RA model rats; the decreases of IL-6 and TNF-α are more significant than the decrease of IL-8; TLR4 agonist and antagonist can significantly attenuate the effect of moxibustion in inhibiting releases of IL-6, IL-8 and TNF-α, so that the change in TLR signaling pathway affects the effect of moxibustion in inhibiting the releases of IL-6, IL-8 and TNF-α.

To evaluate the immunogenicity of inactivated SARS coronavirus (SARS-CoV), three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant, adjuvant,and normal saline respectively. Eight batchs of serum were sampled from the auricular vein at day 7 to day 51, and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test. Antibody specificity was identified by proteinchip assay.Histopathological changes were detected by H&E staining. The results showed that, rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity, which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses. The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively. In the experimental group, no obvious histopathological changes was detected in the H&E stained slides of heart, spleen, kidney and testis samples, but the livers had slight histopathological changes, and the lungs presented remarkable histopathological changes. These findings are of importance for SARS-CoV inactivated vaccine development.

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
Antineoplastic Agents ; pharmacology ; Calixarenes ; Crown Compounds ; Cyclodextrins ; Drug Delivery Systems ; Humans ; Macrocyclic Compounds ; pharmacology ; Neoplasms ; drug therapy ; Platinum Compounds ; pharmacology

Objective To investigate and compare the different effects of soluble adult wornl antigen(SWA)and soluble egg antigen(SEA)of Schistosoma japonicum on the apoptosis and cell-cycle of routine CD4~+T cells.Methods Purified CD4~+T ceUs from normal C57BL/6 mice were cultured with CFSE labeled antigen presenting clls in the presence of different stimuli for 36 h.Flow cytometry(FCM)was used to detect the apoptosis of CD4~+T cells by fluorescence conjugated caspase-3 antibodie staining.The flow cytometry was used to analyze the cell-cycle of CD4~+T cells cultured as described above for 96 h by propidium iodide staining.Results Compared with the apoptosis percentage of CD4~+T cells[(1.24±0.29)%]in the SEA stimulated group,that in the SWA stimulated group[(1.52±0.38)%]did not show statistically significant difference(P>0.05).Compared with the cell percentages in G1 phase[(78.91±2.98)%],S phase[(7.39±0.85)%]and G2/M phase[(10.69±1.05)%] in the SWA stimulated group,that of the G1 phase[(59.42±1.32)%]was significantly lower,but those in the S phase[(21.07±O.88)%] and G2/M phase[(18.88±1.21)%]were significantly increased in the SEA stimulated group(P<0.01).Conclusions There is no statistically significant difference between the apoptosis levels of CD4~+T ceHs stimulated by SWA and SEA.However,SEA significantly promotes the progression of the cell-cycle of CD4~+T cells compared with SWA.