A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.
Humans ; Depression/therapy* ; Acupuncture Points ; Acupuncture Therapy/methods* ; Medicine, Chinese Traditional ; Acupuncture

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

The present study was designed to perform structural modifications of of neobavaisoflavone (NBIF), using an in vitro enzymatic glycosylation reaction, in order to improve its water-solubility. Two novel glucosides of NBIF were obtained from an enzymatic glycosylation by UDP-glycosyltransferase. The glycosylated products were elucidated by LC-MS, HR-ESI-MS, and NMR analysis. The HPLC peaks were integrated and the concentrations in sample solutions were calculated. The MTT assay was used to detect the cytotoxic activity of compounds in cancer cell lines. Based on the spectroscopic analyses, the two novel glucosides were identified as neobavaisoflavone-4'-O-β-D-glucopyranoside (1) and neobavaisoflavone-4', 7-di-O-β-D-glucopyranoside (2). Additionally, the water-solubilities of compounds 1 and 2 were approximately 175.1- and 4 031.9-fold higher than that of the substrate, respectively. Among the test compounds, only NBIF exhibited weak cytotoxicity against four human cancer cell lines, with IC values ranging from 63.47 to 72.81 µmol·L. These results suggest that in vitro enzymatic glycosylation is a powerful approach to structural modification, improving water-solubility.
Antineoplastic Agents ; metabolism ; pharmacology ; Bacillus ; enzymology ; Cell Line, Tumor ; Colorimetry ; Drug Screening Assays, Antitumor ; Glucosides ; biosynthesis ; chemistry ; Glycosyltransferases ; metabolism ; Humans ; Isoflavones ; biosynthesis ; chemistry ; Molecular Structure ; Solubility

OBJECTIVETo modify the structure of psoralidin using in vitro enzymatic glycosylation to improve its water solubility and stability.

METHODSA new psoralidin glucoside (1) was obtained by enzymatic glycosylation using a UDP- glycosyltransferase. The chemical structure of compound 1 was elucidated by HR-ESI-MS and nuclear magnetic resonance (NMR) analysis. The high-performance liquid chromatography (HPLC) peaks were integrated and sample solution concentrations were calculated. MTT assay was used to detect the cytotoxicity of the compounds against 3 cancer cell lines in vitro. Results Based on the spectroscopic data, the new psoralidin glucoside was identified as psoralidin-6',7-di-O-β-D- glucopyranoside (1), whose water solubility was 32.6-fold higher than that of the substrate. Analyses of pH and temperature stability demonstrated that compound 1 was more stable than psoralidin at pH 8.8 and at high temperatures. Only psoralidin exhibited a moderate cytotoxicity against 3 human cancer cell lines. Conclusion In vitro enzymatic glycosylation is a powerful approach for structural modification and improving water solubility and stability of compounds.

Antineoplastic Agents ; metabolism ; Benzofurans ; metabolism ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Coumarins ; metabolism ; Glucosides ; biosynthesis ; Glycosylation ; Glycosyltransferases ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Solubility

Objective To investigate the MRI and pathological features of different molecular subtypes of breast cancer.Methods The data of 202 patients who underwent primary breast cancer resection were retrospectively reviewed.All of the patients had MRI preoperatively.The molecular subtypes of breast cancer defined by immunohistochemistry were classified as basal-like,luminal and HER-2 overexpression.Morphology (including mass or non-mass like enhancement,shape and margin of masses,unifocal or multifocal masses) and enhancement characteristics on MRI,histologic types and grades of tumors were analyzed with Chi-square test,exact test,Fisher exact test,Kruskal-Wallis H test,and Wilcoxon test.Results Among the 202 patients,34 were basal-like,144 were luminal and 24 were HER-2 overexpression.The number of mass cases in each subtype was 29,133 and 19 respectively,making no significant difference (x2 =4.136,P =0.126).As for the shape of basal-like lesions,8 were round,19 were lobular and 2 were irregular,while this distribution was 23,58,52 in luminal subtype and 1,11,7 in HER-2 overexpression subtype (x2 =13.391,P ＜ 0.05).The margin was also strikingly different among three groups (smooth,spiculated,irregular):20,5,4 respectively in basal-like,27,53,53 respectively in luminal,and 4,7,8 respectively in HER-2 overexpression (x2 =28.515,P ＜ 0.01).52.6％ (10/19) of HER-2 overexpression cases were multifocal,while only 6.9％ (2/29) of luminal and 8.0％ (24/133) of basal-like ones were multifocal (x2 =16.140,P ＜ 0.01).Characteristics in dynamic contrast-enhanced MRI were statistically different,with homogeneous,heterogeneous,and rim enhancement 0,13,16 respectively in basal-like cases,28,93,11 respectively in luminal cases and 2,11,6 respectively in HER-2 overexpression cases (P ＜ 0.01).However,the difference for enhancement curve did not reach significance (P =0.457).Histologic types were significantly different among molecular subtypes (P ＜ 0.01).Luminal breast cancer consisted of various histologic types,32.6％ (47/144) of which were mixed type.The majority of the other two molecular subtypes were invasive ductal carcinoma.Furthermore,invasive ductal carcinomas with different molecular subtypes showed different histologic grades (Hc =30.014,P ＜ 0.01).Basal-like breast cancer was more likely associated with a higher grade of malignancy.Conclusions Different molecular subtypes of breast showed distinct MRI features and pathologic characteristics.MRI might be a useful tool for preoperative prediction of molecular subtypes of breast cancer.

The purpose of the present study was to investigate the effect of luteolin on the angiogenesis and invasion of breast cancer cells. MTT assay was used to examine breast cancer proliferation. The chick chorioallantoic membrane model was used to assess the angiogenesis effect. Wound healing assay was used to assess cell invasion ability. Western blot was used to analyze Bcl-2, AEG-1 and MMP-2 expression levels. The results showed luteolin inhibited MCF-7 cells proliferation in a dose- and time-dependent manner, and the expression of Bcl-2 protein was decreased. Luteolin had a strong anti-angiogenesis of chick chorioallantoic membrane. After treatment of MCF-7 cells with luteolin at 60 μmol/L for 48 h, migration rate was reduced by 71.07% compared with control (P < 0.01). After treatment of MCF-7 cells with luteolin at 60 μmol/L for 48 h, the expression of AEG-1 and MMP-2 was reduced by 82.34% (P < 0.05) and 85.70% (P < 0.05) respectively, compared with control. In conclusion, the results suggest that luteolin can inhibit the proliferation of breast cancer cells, and suppress the expression of Bcl-2. Furthermore, luteolin has strong anti-angiogenesis of chick chorioallantoic membrane and anti-invasive activity on breast cancer cells, and down-regulates the expression of AEG-1 and MMP-2.
Animals ; Breast Neoplasms ; pathology ; Cell Adhesion Molecules ; metabolism ; Cell Proliferation ; Chickens ; Chorioallantoic Membrane ; drug effects ; Down-Regulation ; Female ; Humans ; Luteolin ; pharmacology ; MCF-7 Cells ; Matrix Metalloproteinase 2 ; metabolism ; Neovascularization, Pathologic ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism

Estrogen signaling pathways play an important role in the regulation of the physiological function of breast cancer cell proliferation and apoptosis. The article used MTT assay, flow cytometer analysis and Western blot to detect the inhibition of fraxetin on MCF-7 cell cycle distribution and apoptosis, ERα, cyclin D1 and Bcl-2 expression levels, MAPK and PI3K signaling pathway to investigate the mechanism of anti-breast cancer of fraxetin. The results showed fraxetin inhibited E2β-stimulated MCF-7 cell proliferation in a dose- and time-dependent manner, reversed E2β-induced anti-apoptosis and promoted G0/G1 phase arrest. After treatment with fraxetin, the expression of ERα in MCF-7 cell was decreased, and estrogen genomic signaling pathway was inhibited by down-regulating the expression of cyclin D1 and Bcl-2 proteins. After MCF-7 cells were treated with fraxetin, the expressions of MAPK/Erk1/2 protein were reduced, which affected estrogen non-genomic signaling pathway. The results suggest fraxetin plays a part in anti-breast cancer function through E2β-mediated genomic and non-genomic signaling pathways.
Apoptosis ; Breast Neoplasms ; metabolism ; Cell Proliferation ; Coumarins ; pharmacology ; Cyclin D1 ; metabolism ; Estrogen Receptor alpha ; metabolism ; Estrogens ; pharmacology ; Humans ; MCF-7 Cells ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Signal Transduction

Glucokinase (GK) is a new target for the treatment of type II diabetes mellitus (T2DM). In order to find a structure-simplified small molecule GK activator, 19 salicylic acid derivatives were designed and synthesized based on new lead compound (1). Experimental results showed that the potency of compound 8h is superior to control RO-28-0450 in GK activation.
Drug Design ; Enzyme Activation ; drug effects ; Enzyme Activators ; chemical synthesis ; chemistry ; pharmacology ; Glucokinase ; metabolism ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Salicylates ; chemical synthesis ; chemistry ; pharmacology ; Thiazoles ; pharmacology

The aim of the present study was to investigate the involvements of insulin-like growth factor-1 (IGF-1) and estrogen receptor α (ERα) in the inhibitory effect of wogonin on the breast adenocarcinoma growth. Moreover, the effect of wogonin on the angiogenesis of chick chorioallantoic membrane (CAM) was also investigated. MCF-7 cells (human breast adenocarcinoma cell line) were subjected to several drugs, including IGF-1, wogonin and ER inhibitor ICI182780, alone or in combination. MTT assay was used to detect breast cancer proliferation. Western blot was used to analyze ERα and p-Akt expression levels. CAM models prepared from 6-day chicken eggs were employed to evaluate angiogenesis inhibition. The results showed wogonin and ICI182780 both exhibited a potent ability to blunt IGF-1-stimulated MCF-7 cell growth. Either of wogonin and ICI182780 significantly inhibited ERα and p-Akt expressions in IGF-1-treated cells. The inhibitory effect of wogonin showed no difference from that of ICI182780 on IGF-1-stimulated expressions of ERα and p-Akt. Meanwhile, wogonin at different concentrations showed significant inhibitory effect on CAM angiogenesis. These results suggest the inhibitory effect of wogonin on breast adenocarcinoma growth via inhibiting IGF-1-mediated PI3K-Akt pathway and regulating ERα expression. Furthermore, wogonin has a strong anti-angiogenic effect on CAM model.
Adenocarcinoma ; metabolism ; pathology ; Angiogenesis Inhibitors ; pharmacology ; Animals ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chick Embryo ; Chorioallantoic Membrane ; blood supply ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Flavanones ; pharmacology ; Humans ; Insulin-Like Growth Factor I ; antagonists & inhibitors ; pharmacology ; Scutellaria ; chemistry