Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

OBJECTIVE：To establish the method for content determination of 6 components in Fuzheng guben granules ，such as 2，3，5，4′-tetrahydroxystilbene glucoside ，baicalin，icariin，scutellarin，baicalein and wogonin. METHODS ：HPLC method was adopted. The determination was performed on Dikma Diamonsil C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid aqueous solution （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelengths were set at 275 nm （0-8 min），320 nm（8-9 min）and 275 nm（9-33 min）. The column temperature was set at 25 ℃，and sample size was 10 μL. With baicalin as reference material ，the relative corr ection factors （fk/s） of other five components were calculated by multi-point correction method and slope correction method ；the retention time difference method was used to locate the chromatographic peaks ； the calculation values obtained by above 2 QAMS were compared with measured values of external standard method. RESULTS ： The linear range of 2，3，5，4′-tetrahydroxystilbene glucoside ，baicalin，icariin，scutellarin，baicalein and wogonin were 0.053-2.12， 0.163-6.52，0.059-2.36，0.021 6-0.864，0.03-1.2，0.021-0.84 μg（r＞0.999），respectively. RSDs of precision ，stability（12 h）and reproducibility tests were all lower than 3％. Average recoveries were 98.72％-99.82％（RSDs were 0.89％-1.24％，n＝9）. Using baicalin as reference material ，fk/s of multi-point correction method for 2，3，5，4′-tetrahydroxystilbene glucoside ，icariin，scutellarin， baicalein and wogonin were 1.172，0.528，1.479，1.820 and 2.534，respectively；fk/s of slope correction method were 1.234， 0.550，1.559，1.939，2.664. RSDs of 6 components in 10 batches of Fuzheng guben granules by 3 methods were 0.29％-2.77％ （n＝10），respectively. Pearson correlation coefficient was not lower than 0.999 9（P＜0.001）in measured values between QAMS and external standard method. CONCLUSIONS ：QAMS method is established successfully for simultaneous determination of 6 components in Fuzheng guben granules.

Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

[Objective] To measure the diameter of the superior rectal vein (SRV) & theinferior mesenteric vein (IMV) by CT and analyze their relationship with lymphatic metastasis of rectal carcinoma.And to discuss the feasibility of utilizing SRV to prcdict lymph node metastasis of rectal cancer.[Methods] The CT imaging and pathological data of 105 rectal carcinoma patients were analyzed retrospectively.We measured and compared the diameter of every patient's SRV & IMV by CT in the presence and absence of microvascular tumor thrombus,signet ring cell,lymph node metastasis and distant metastasis.The accuracy of predicting lymph node metastasis for rectal carcinoma by the diameter of SRV were evaluated by ROC curve.[Results] There were statistical differences in the diameters of SRV and IMV between rectal cancer group with lymph node metastasis (D =4.34 mm,D =5.00 mm) and without (D =3.56 mm,D =4.81 mm;P ＜ 0.001,P =0.023).The differences were significant in the diameter of SRV between rectal cancer group with microvascular tumor thrombus or signet ring cell and without (P =0.019,P =0.044).However,the diameter of IMV showed no statistical difference between rectal cancer group with microvascular tumor thrombus or signet ring cell and without (P =0.605,P =0.663).And there was no statistical difference in the diameter of SRV or IMV between rectal cancer patients with distant metastasis and without (P ＞ 0.05).Regarding 3.75 mm as the cut-off value for the diameter of SRV to predict lymph node metastasis for rectal cancer patients,the sensitivity was 90.9％ and the specificity was 82.0％.Regarding 4.65 mm as the cut-off value for the diameter of IMV to predict lymph node metastasis for rectal cancer patients,the sensitivity was 87.3％ and the specificity was 38％.[Conclusions] It is completely feasible to utilize the diameter of SRV measured by CT to predict lymph node metastasis of rectal carcinoma with high sensitivity,accuracy,and relatively high specificity.

OBJECTIVETo discuss the operation method and characteristic of correcting upper eyelid depression by transposition of orbital septum fat.

METHODSDuring the double eyelid surgery, we set.the lateral orbital septum fat completely free, while the bottom is still connected with the middle orbital septum fat. We separate a tunnel from the middle to the inner side in orbital septum, and the separated orbital septum fat is transposed to the inner side of orbital septum by the tunnel with suturing fixation.

RESULTSFrom March 2008 to October 2013, 51 cases with upper eyelid depression were treated successfully. Patients were followed up for 3 months to 3 years (average, 7. 5 months) with sustained aesthetic results.

CONCLUSIONSOrbital septum fat transposition can successfully correct the upper eyelid depression. It should become a regular procedure in blepharoplasty.

Adipose Tissue ; transplantation ; Blepharoplasty ; methods ; Esthetics ; Eyelids ; abnormalities ; surgery ; Humans ; Orbit

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F-Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F-Tau. The cellular uptake of F-Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F-Tau compared with fluorescein. As compared with fluorescein, F-Tau showed little toxicity, and was retained longer by cells in uptake experiments. F-Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.

Typodont models of bilateral canines gingival displaced vertically for 3 mm and bilateral lateral incisors palatal displaced horizontally for 3 mm are made and every kind of the two kind models was divided into four groups: MDD, MBT, self-ligating and Tip-Edge. Each group of the two kinds of models had 5 models, so a total of 40 models for the two kinds of models were set up. The experimental models were aligned with a 0.30 mm of nickel titanium round wire in a water-bath with constant temperature 45 degrees C for 30 minutes. The three-dimensional digital images of the experimental models before and after the water bath were obtained by scanning with the three dimensional optical scanner ATOS. Geomagic software was used to overlap the digital images taken before and after the water bath treatment. The vertical changes of sign points of canines, the movements of sign points of lateral incisors in the sagittal plane and the horizontal plane were quantified by using the Color map. The data was then processed by a two-factor analysis of variance by using SAS 9.2 software package. Analysis of the results shows that the vertical changes of sign points of canines , the movements of sign points of lateral incisors in the sagittal plane and the horizontal plane of MDD group are all less than those in the other three groups, a statistically significant difference (P < 0.0001). And the size of the teeth displacement is directly related to the size of orthodontic force on the typodont models. Thus the preliminary results suggest that MDD appliance might have advantages of light force in the alignment stage, and that the possible relevant factors are the improvement of its sub-slot and the single ligation wing design.
Cuspid ; Dental Models ; Humans ; Imaging, Three-Dimensional ; methods ; Incisor ; anatomy & histology ; Malocclusion ; therapy ; Orthodontic Appliance Design ; Tooth Movement Techniques ; instrumentation ; methods

The mitogen activated protein kinases-extracellular signal regulated kinases (MAPK-ERK) pathway is involved in regulation of multiple cellular processes including the cell cycle.In the present study using a Huh7 cell line Con1 with an HCV replicon,we have shown that the MAPK-ERK pathway plays a significant role in the modulation of HCV replication and protein expression and might influence IFN-α signalling.Epithelial growth factor (EGF) was able to stimulate ERK activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 led to an elevated HCV RNA load and higher NS5A protein amounts in Con1 cells.It could be further demonstrated that the inhibition of the MAPK-ERK pathway facilitated the translation directed by the HCV internal ribosome entry site.Consistently,a U0126 treatment enhanced activity of the HCV reporter replicon in transient transfection assays.Thus,the MAPK-ERK pathway plays an important role in the regulation of HCV gene expression and replication.In addition,cyclin-dependent kinases (CDKs) downstream of ERK may also be involved in the modulation of HCV replication since roscovitine,an inhibitor of CDKs had a similar effect to that of U0126.Modulation of the cell cycle progression by cell cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels.Further,the replication of HCV replicon in Conl cells was inhibited by IFN-α.The inhibitory effect of IFN-α could be partly reversed by pre-incubation of Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs.It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes.

Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV)usually result in altered hepatitis B surface antigen(HBsAg)secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs)synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.

OBJECTIVE: To study the clinical value of ultrasonography in diagnosing nasopharyngeal carcinoma. METHOD: Seventy-five patients with suspicious clinical symptoms of recurrent nasopharyngeal carcinoma were studied 0.5-3.0 years after radiotherapy. All received ultrasonography, computed tomography examination, nasendoscopy and nasopharyngeal biopsy. The diagnostic value of ultrasonography were then evaluated. RESULT: Of 75 cases, recurrent nasopharyngeal carcinomas were detected in 35 cases by ultrasonography. There were 26 cases confirmed pathologically, 9 cases false positive, 25 cases true negative and 15 cases false negative. Meanwhile, of 75 cases recurrent nasopharyngeal carcinomas were indicated in 35 cases by computed tomography. There were 27 cases confirmed pathologically, 8 cases false positive, 26 cases true negative and 14 cases false negative. There were no significant difference between the sensitivity, specificity and accuracy of ultrasonography and computed tomography in diagnosing recurrent nasopharyngeal carcinoma. CONCLUSION Either ultrasonography or computed tomography has good diagnostic values in detecting recurrent nasopharyngeal carcinoma. Furthermore, both of them can complement each other.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnostic imaging ; pathology ; Neck ; Neoplasm Recurrence, Local ; diagnostic imaging ; Sensitivity and Specificity ; Ultrasonography ; methods