Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Aim To explore how Danzhi Jiangtang cap-sules(DJC)safeguard the mitochondrial activity of vascular smooth muscle cells(VSMCs)by controlling the LncRNA TUG1/β-catenin signaling pathway to de-crease vascular calcification(VC).Methods Vascu-lar smooth muscle cell calcification models were in-duced with β-glycerin and diabetic vascular calcifica-tion rat models were induced with vitamin D3+high-fat diet.Von Kossa staining was applied to detect cal-cification of cells and vascular tissue.Colorimetric method of phthalein complex was used to determine calcium content.P-nitrobenzene phosphate colorimetry was employed to assess alkaline phosphatase(ALP)activity.RT-qPCR was used to analyze the expression of VSMCs'osteoblast transformation related genes bone morphogenetic protein2(BMP2),smooth muscle actin alpha(α-SMA),taurine up-regulated1,LncRNA Tug1(Lnc-RNA TUG1),and β-catenin.Western blotting was utilized to detect the protein expression of BMP2,α-SMA and β-catenin.The mitochondrial membrane potential was detected by JC-1 fluorescence probe.Mitochondrial structure was observed by trans-mission electron microscope.Results DJC reduced LncRNA TUG1 expression,down-regulated β-catenin expression,decreased ALP activity and calcium depo-sition,protected mitochondrial function,restored mem-brane potential,and decreased osteoblastic transforma-tion of VSMCs induced by glycerin phosphate.Impor-tantly,DJC attenuated diabetic lower limb VC by down-regulating the expression of LncRNA TUG1,β-catenin,and elevating the expression of α-SMA.Con-clusions DJC capsules significantly improved VSMCs by protecting mitochondrial function by LncRNA TUG1/β-catenin signaling to reduce VSMCs'osteo-blast transformation.

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

AIM: To evaluate the clinical efficacy of adalimumab(ADA)with dose-reduced glucocorticoid for the treatment of Vogt-Koyanagi-Harada disease(VKH).METHODS: A total of 21 patients(37 eyes)with VKH who received ADA therapy in the Department of Ophthalmology of our hospital from August 2020 to December 2021 were included. The interval of ADA administration was progressively extended after intraocular inflammation controlled and lasted for 3mo, and it returned to the initial treatment interval once the inflammation recurred. After follow-up for 12mo, anterior chamber cell(ACC)grade, vitreous haze(VH)grade, retinal/choroidal lesions, serous retinal detachment(SRD), best corrected visual acuity(BCVA), central macular thickness(CMT)and doses of glucocorticoid and immunosuppressant were compared before and after the first ADA injection. Treatment failure events and adverse reactions were recorded.RESULTS: Compared with baseline, the proportion of eyes with ACC grade ≤1+ and VH grade ≤1+ increased(P<0.05), the proportion of eyes with retinal/choroidal lesions decreased significantly(P<0.01), BCVA and CMT were significantly improved(P<0.01), and the average dose of glucocorticoid reduced significantly(P<0.01)at 2wk, 1, 3 and 6mo after treatment. At the final follow-up, 82% of patients received glucocorticoid ≤5 mg, and all patients stopped using immunosuppressant. There were 13 treatment failure events during the follow-up period, and 12 patients(57%)extended the ADA treatment interval, with no serious adverse events related to ADA treatment observed.CONCLUSION: ADA is effective and safe for the treatment of VKH, reducing the need for glucocorticoid and immunosuppressant. In addition, extending the interval of ADA treatment is effective, which has a lower recurrence rate.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
Biomarkers/metabolism* ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Spermatozoa/metabolism*

Coronary Angiography ; Coronary Disease ; Humans ; Liver ; Non-alcoholic Fatty Liver Disease/complications*

OBJECTIVE: To build bridges between anti-α enolase antibody (anti-enolase 1 antibody, anti-ENO1 antibody) and common clinical and laboratory characteristics of systemic lupus erythematosus (SLE) and to analyze the role of anti-ENO1 antibody in the evaluation of SLE disease activity. METHODS: The SLE patients with retinopathy and without retinopathy were enrolled in the study, as well as healthy individuals whose gender and age matched with those of the SLE patients. Serum anti-ENO1 antibodies were measured using enzyme-linked immunosorbent assay (ELISA), presenting as intra-group positive rate and arbitrary units (AU) value. Clinical and laboratory data were obtained from medical records. RESULTS: The SLE retinopathy patients represented various fundus abnormalities. Ranked by percentage, the top three retinopathies were retinal hemorrhage (14/32, 43.75%), cotton-wool spots (8/32, 25.00%) and retinal vein occlusion (3/32, 9.38%). Among the 32 SLE retinopathy patients, 13 (40.63%) suffered from two or more fundus abnormalities. The positive rate and AU value of the SLE patients were higher than of the SLE patients without retinopathy (68.75% vs. 46.00%, P=0.043; 16.11%±10.35% vs. 12.06%±6.47%, P=0.045). Besides, the positive rate and AU value of the two SLE groups were both significantly higher than those of the healthy control group (P < 0.001). Compared with the SLE-without-retinopathy group, the systemic lupus erythematosus disease activity index (SLEDAI)-2000 of the SLE retinopathy patients were significantly higher than those of the SLE patients without retinopathy (17.41±4.25 vs. 9.48±5.35, P < 0.001). Dividing all the SLE patients into an anti-ENO1-positive group and an anti-ENO1-negative group, we found that anti-ENO1-positive was more likely to be correlated to developing fever and positive result of urine occult blood (P=0.011, P=0.042). Comparing with the patients with negative anti-ENO1 antibodies, the patients with positive anti-ENO1 antibodies had significantly higher erythrocyte sedimentation rate (ESR) [the median (range) was 29.50 (1.52-110.00) mg/L vs. 12.00 (4.00-101.00) mg/L, P=0.001], higher immunoglobulin G (IgG) [the median (range) was 14.30 (4.02-37.80) g/L vs. 10.46 (2.50-25.73) g/L, P=0.000 3], and higher blood platelet count (PLT) [(205.87×10⁹±67.98×10⁹) /L vs. (164.57×10⁹±69.57×10⁹) /L, P=0.008], as well as higher immunoglobulin A (IgA) [the median (range) was 2.85 (0.07-27.00) g/L vs. 2.05 (0.42-4.36) g/L, P=0.014]. CONCLUSION The positive rate and AU value of anti-ENO1 antibody suggested higher SLE disease activity and they were elevated in SLE and SLE retinopathy.
Humans ; Autoantibodies ; Lupus Erythematosus, Systemic ; Enzyme-Linked Immunosorbent Assay ; Retinal Diseases/etiology* ; Immunoglobulin G

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg^-1·day^-1) and high-dose RUT group (45 mg·kg^-1·day^-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.

Aim To observe the protective effect of Gancao Xiexin Decoction (GXD) on intestinal epithelial cells (IECs) under endoplasmic reticulum stress from the perspective of PERK-elF2α-CH0P signaling pathway. Methods Caco-2 cells were cultured and divided into normal control group (NC), model control group(MC), low-dose GXD group(GXD-L), mediumdose GXD group (GXD-M) and high-dose GXD group (GXD-H). Models of the stress epithelial cells were induced by tunicamycin(Tm), and GXD groups were treated with GXD contained serum at the same time. The cell survival rate was assessed by CCK-8 method, the cell apoptotic rate and cell cycle distribution were determined by flow cytometry, and the cell barrier permeability was determined by TEER and FITC-dextran method; the expression levels of core proteins of PERK-elF2α-CH0P signaling pathway were detected by Western blot. Results Compared with MC group, GXD intervention could improve cell survival rate(P < 0. 05), reduce their apoptotic rate(P <0. 01), relieve cell cycle arrest(P < 0. 01), improve cell barrier permeability by increasing cell TEER value (P < 0. 01) and decreasing FITC-dextran concentration (P < 0.05), and the levels of p-PERK, p-elF2α, ATF4 and CHOP in GXD-M and GXD-H groups all visibly descended (P < 0. 01). Conclusions GXD can reduce the excessive apoptosis of IECs and protect intestinal epithelial cell barrier homeostasis by inhibiting the signal transduction of PERK-elF2α-CH0P apoptotic pathway.