Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

In this study, the transmittance of tanshinone Ⅱ_A(Tan Ⅱ_A) and cryptotanshinone(CTS) through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E) treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo. First, the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model, and the transmission of Tan Ⅱ_A and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components. Second, SD rats were administrated with 700 mg·kg~(-1) Tan E, 29 mg·kg~(-1) CTS, and 50 mg·kg~(-1) Tan Ⅱ_A by gavage, and plasma and prostate tissue samples were collected at the time points of 2, 4, 8, 12, and 24 h. The Tan Ⅱ_A and CTS concentrations in the samples were determined. The results showed that in the cell model, the cumulative transmission amounts of CTS and Tan Ⅱ_A in the extract at each time point were higher than those of the corresponding single active components(P<0.01). In rats, after the administration of Tan E, the concentrations of Tan Ⅱ_A and CTS in rat plasma and prostate were higher than those of the corresponding single active components. This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components Tan Ⅱ_A and CTS through the blood-prostate barrier. The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.
Male ; Rats ; Humans ; Animals ; Prostate ; Rats, Sprague-Dawley ; Abietanes/pharmacology* ; Permeability

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Objective: To study the effects of superficial temporal artery and vein as recipient vessels for the free anterolateral thigh flap on the appearance and functions after maxillectomy. Methods: Clinical data of 21 patients with malignant maxillary tumors in Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital of Central South University from January 2014 to November 2019, who were treated by free anterolateral thigh flap with temporal superficial vessels as the recipient vessels were analyzed retrospectively. There were 18 males and 3 females, with the age ranging from 29 to 73 years old, including 19 cases of squamous carcinoma, 1 case of adenoid cystic carcinoma and 1 case of osteosarcoma. Of those 7 patients underwent primary surgery, 14 patients received resurgery, and 6 patients had a history of postoperative radiotherapy and chemotherapy. Among 14 patients with resurgery, 13 had recurrent ipsilateral second site tumor and 1 had recurrent tumor, and all of them received the maxillectomy and reconstructive surgery with the free anterolateral thigh flap. Patients were evaluated with water swallow test and speech intelligibility score in 1, 3 and 6 months after operation. The data were statistically analyzed with SPSS 22.0 statistical software. Water swallow test results before and after operation were compared using the Wilcoxon rank sum test. The mean speech intelligibility scores before and after operation were compared by the paired t test. Results: Patients were followed up for 10-60 months. All free flaps survived after operation. No diplopia occurred. Breathing, swallowing and speaking functions were normal. No movement disorders caused by the donor of thigh flap. Water swallow test showed no phenomenon of water flowing into the nasal cavity or oral and nasal leakage with level Ⅰ for 4 cases, level Ⅱ for 13 cases, level Ⅲ for 3 cases and level Ⅳ for 1 case. The mean speech intelligibility scores before surgery and 1, 3 and 6 months after surgery were 4.31±0.13, 1.46±0.21, 2.15±0.45 and 2.87±0.76 respectively. There was statistically significant difference in the mean speech intelligibility scores between 1 and 6 months after surgery (F=78.456, P<0.05). Conclusion: It is safe and reliable to use the superficial temporal vessels as recipient vessels for free anterolateral thigh flap in the reconstruction of defect after maxillectomy in malignant tumors, with good outcomes of functions and a satisfactory restoration of outward appearance.
Adult ; Aged ; Female ; Free Tissue Flaps ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Thigh/surgery*

OBJECTIVE: To analyze the characteristics of volatile organic compounds (VOCs) in expiratory air components of patients with acute promyelocytic leukemia (APL), and assess the feasibility of VOCs for the diagnosis and prognostic evaluation of APL. METHODS: The VOCs exhaled from the patients with APL and healthy volunteers should be analyzed with SPME-GC/MS, and compared between newly-diagnosed group, relapse group, remission group, and healthy group with Wilcoxon/Kruskal-Wallis one-way analysis of variance and Dunn-Bonferroni test. RESULTS: Dimethyl sulfide, toluene, and dodecane obtained of newly-diagnosed APL patients were significantly higher, while ethanol, n-hexanal, and benzaldehyde were significantly lower than those of healthy people (P<0.05). Compared with the newly-diagnosed group, dimethylsulfide, toluene, and dodecane of the remission group significantly decreased, while ethanol, n-hexanal, and benzaldehyde significantly increased (P<0.05), which was just opposite from the relapse group. CONCLUSION Dimethyl sulfide, toluene, dodecane, ethanol, n-hexanal, and benzaldehyde can be used as biomarkers for the diagnosis and prognosis assessment of APL patients.
Exhalation ; Gas Chromatography-Mass Spectrometry ; Granulocyte Precursor Cells ; Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Volatile Organic Compounds/analysis*

Objective::To explore the effect of modified Qingyitang combined with continuous blood purification in the adjuvant treatment of severe acute pancreatitis (SAP) complicated with multiple organ dysfunction (MODS) caused by heat accumulation of viscera. Method::Totally 100 cases of patients of SAP complicated with MODS, who were diagnosed as heat accumulation of viscera by traditional Chinese medicine(TCM) and treated in ICU of the First Affiliated Hospital of Hunan University of Chinese Medicine during May 2015 and May 2019, were randomly divided into two groups, namely control group and observation group, with 50 cases in each group. The patients in control group were treated with fasting and abstinence, gastrointestinal decompression, inhibition of trypsin secretion, gastric mucosal protection, early jejunal nutrition, reduction of inflammatory reaction, continuous blood purification (CBP), mechanical ventilation and circulatory support. The patients in observation group were treated by nasojejunal tube according to syndrome differentiation in addition to routine comprehensive therapy. Modified Qingyitang was injected for 7 days. The remission time of abdominal pain and distention, the time of first exhaust and defecation, the time of ICU residence, the number of samples falling off, the cause of death and the number of cases were recorded. Relevant indexes were measured before treatment, on the 3^rd and 7^th day of treatment, including the evaluation indexes of pancreatitis: blood amylase (AMS), blood lipase (LPS), and modified computed tomography severity index (MCTSI), inflammatory response indexes were interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP). Organ function indexes included APACHE-Ⅱ, arterial partial pressure of oxygen (PaO₂), oxygenation index (PaO₂/FiO₂), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyltransferase (γ-GGT), urine volume, creatinine (CREA), urea nitrogen (UREA), glomerular filtration rate (GFR), creatine kinase (CK), creatine kinase isoenzymes (CKMB), lactate dehydrogenase (LDH), myoglobin (Mb). Tissue perfusion evaluation indexes included acute physiology and chronic health score, serum lactic acid (Lac) and central venous pressure (CVP). TCM treatment score was based on the syndrome score of acute pancreatitis with heat accumulation of viscera syndrome. Result::The total effective rate of TCM syndromes was 86.67%(39/45) in observation group and 73.91%(34/46) in control group (χ² =13.524, P<0.01). On the 7^th day of treatment, the symptoms and indicators of the two groups were improved. Compared with before treatment, AMS, LPS, IL-6, hs-CRP, MCTSI, APACHE-Ⅱ, Lac, CVP, PaO₂, PaO₂/FiO₂, ALT and AST were improved on the 3^rd and 7^th day after treatment in observation group and control group. The levels of AMS, LPS, IL-6, hs-CRP, MCTSI, APACHE-Ⅱ, Lac, CVP, PaO₂, PaO₂/FiO₂, ALT, AST, ALP, γ-GGT, urine volume were significantly improved (P<0.05). Compared with control group on the 3^rd and 7^th day, the levels of AMS, LPS, IL-6, hs-CRP, MCTSI, APACHE-Ⅱ, Lac, CVP, PaO₂, PaO₂/FiO₂, ALT, AST, ALP, γ-GGT, urine volume were significantly improved (P<0.05). CREA, UREA, GFR, CK, CKMB, LDH and Mb were significantly improved (P<0.05). Compared with control group, the abdominal pain, abdominal distension relief time, first exhaust/defecation time, ICU stay time in observation group were significantly shortened (P<0.05), and the mortality rate in observation group was significantly reduced (P<0.05). Conclusion::Patients of SAP accompanied with MODS can be treated with blood purification combined with modified Qingyitang by promoting pancreas repair, inhibiting inflammation and improving organ function. It plays an important role in improving symptoms, alleviating TCM syndromes, delaying progression of disease, reducing hospital stay and reducing mortality.