Danshen (Salvia miltiorrhiza) protects ovariectomized rats fed with high-saturated fat-sucrose diet from bone loss.

Dietary patterns may interfere with the efficacy of herbal intervention. Our results demonstrated the protective effects of Salvia miltiorrhiza aqueous extract (SMA) on bone metabolism were influenced by levels of dietary fat and sucrose in ovariectomized (OVX) rats through its actions on attenuating lipid deposition and oxidative stress in rats. INTRODUCTION: Salvia miltiorrhiza (SM), also known as Danshen, has been tested as an osteoporosis treatment in a series of small, short human trials that generally report improvements in bone property. However, dietary patterns may interfere with the effects of herbal intervention. We hypothesized that dietary fat and sucrose levels could influence the effects of SM supplementation on bone in estrogen-deficient animals. METHODS: Six-month-old Sprague-Dawley sham or OVX rats were fed either a low-saturated fat-sucrose (LFS, a diet that was similar in composition to normal rat chow) or a high-fat-sucrose (HFS) diet and OVX rats were treated (8 rats/group) with SM aqueous extract (SMA, 600 mg/kg/day), 17ß-estradiol (1 mg/kg/day), or vehicle for 12 weeks. RESULTS: SMA significantly improved bone properties as revealed by the increase in trabecular bone mineral density and decrease in trabecular separation at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats, but not in LFS-fed OVX rats. SMA greatly reduced lipid deposition and malondialdehyde levels, improved the activities of superoxide dismutase, catalase, and glutathione peroxidase in the livers of HFS-fed OVX rats. SMA could directly improve the proliferation and differentiation in vitro in an H2O2-induced preosteoblast cell model by attenuating cellular reactive oxygen species levels. CONCLUSIONS: The protective effects of SMA on bone metabolism were influenced by dietary fat and sucrose levels in OVX rats. The ability of SMA to reduce bone loss in HFS-fed OVX rats was associated with the attenuation of lipid deposition and oxidative stress levels.

[Analysis of prognostic factors on multidisciplinary team for diagnosis, treatment and prevention of hepatocellular carcinoma].

Objective: To analyze the prognostic factors on multidisciplinary team patients for diagnosis, and treatment of hepatocellular carcinoma. Methods: This retrospective study enrolled 132 HBsAg positive patients with HCC. MDT diagnostic approach was conducted at our hospital between 1 January 2015 and 31 December 2015, and all patients were followed up to 31 December 2017. Groups were arranged according to variables such as Barcelona stage, MDT compliance, and multidisciplinary combination therapy. TTP and OS were statistically analyzed. Results: The survival of the MDT compliance group was better than the non-compliance group. The difference in survival curves was statistically significant (χ(2) = 4.062, P < 0.05). The 1- and 2-year survival rates of the former group were 72.0%, 60.9%, and the latter was 64.3%, 40.3%. The survival of the combined treatment group was better than the non-combination group. The survival curves of the two groups were statistically significant (χ(2) = 9.502, P < 0.05), and they were independent influencing factors of survival (HR = 0.451, 95% CI, 0.210-0.968). The 1- and 2-year survival rates of the former group were 82.2% and 75.4%, and the latter was 63.1% and 44.6%. The median survival time of the follow-up group was 29.4 months, and the non-compliance and the uncombined group were 17.0 months. The difference was statistically significant (χ(2) = 13.336, P < 0.001). The median tumor progression time was 15.7 months in the combination group and 10.1 months in the non-compliance group (χ(2) = 7.263, P < 0.05). Conclusion: An advanced MDT compliance with implementation of multidisciplinary combination therapy may help to improve the prognosis of MDT patients with liver cancer.

[Role of brain and muscle ARNT-like protein 1 in the rat periodontitis-induced liver injury model].

Objective: Brain and muscle ARNT-like protein 1 (BMAL1) is a core component of hepatocyte molecular clock and plays an important role in the regulation of other related rhythmic genes in the body through a transcriptional-translational feedback loop in molecular circadian oscillations. Therefore, the aim of this study was to investigate the role of BMAL1 in the rat periodontitis-induced liver injury. Methods: Twelve male Wistar rats were divided into the control group and the periodontitis group according to the random number table method. The rats in the control group were untreated. The periodontitis models were established by ligating the necks of the bilateral maxillary first molars in the periodontitis group rats. After 8 weeks, periodontal clinical indexes of rats in both groups were examined and executed. Micro-CT scans of the maxilla were performed and levels of the alveolar bone resorption were analyzed. Pathological changes in periodontal and liver tissue of rats in two groups were detected by HE and oil red O staining. Biochemical kits were used to detect glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), total cholesterol (TC) and triglycerides (TG) in serum. The gene and protein expression levels of BMAL1, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) in liver tissue were measured by real time fluorescent quantitative-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) assays. Apoptosis was detected in liver tissues by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) kit staining. Results: The results of HE staining of maxillary first molars and micro-CT results of maxillary bones showed that alveolar bone resorption was significant in the periodontitis group of rats. The liver histopathology results showed infiltrated inflammatory cells in the liver tissue, disorganized liver cords and a large number of lipid droplets formed in the hepatocytes of the periodontitis group compared with the control group. The results of serum biochemical assay showed that the levels of GOT [(62.77±2.59) U/L], GPT [(47.54±1.04) U/L], TC [(3.19±0.23) mmol/L] and TG [(1.11±0.09) mmol/L] in the serum of rats with periodontitis were significantly higher than that in the control group respectively [GOT: (38.66±2.47) U/L, GPT: (31.48±1.57) U/L, TC: (1.60±0.05) mmol/L and TG: (0.61±0.09) mmol/L](P=0.003, P=0.001, P=0.002, P=0.038). qRT-PCR results showed that the mRNA expression level of BMAL1 was significantly decreased in liver tissue of the periodontitis group [(0.60±0.04)%] compared to the control group [(1.01±0.07)%] (t=4.80, P=0.009), while the mRNA expression levels of NF-κB and TNF-α [(1.62±0.12)%, (2.69±0.16)%] were significantly increased compared to the control group [(1.00±0.03)%, (1.03±0.16)%] (P=0.008, P=0.002); IHC results showed that the protein expression level of BMAL1 in liver tissue of the periodontitis group (averaged optical density, AOD) (11.58±2.15) was down-regulated compared to the control group (AOD) (22.66±1.67) (P=0.015), while NF-κB and TNF-α (AOD) (31.77±2.69, 24.31±2.32) were up-regulated compared to the control group (AOD) (19.40±1.82, 11.92±0.94) (P=0.019, P=0.008). WB results showed that the protein expression level of BMAL1 in liver tissue was down-regulated in the periodontitis group [(0.63±0.10)%] compared to the control group [(1.00±0.06)%] (t=3.19, P=0.033), while NF-κB and TNF-α [(1.61±0.12)%, (2.82±0.23)%] were up-regulated compared to the control group [(1.00±0.12)%, (1.00±0.11)%] (P=0.022, P=0.002). TUNEL staining showed increased apoptotic cells in the liver tissue of the periodontitis group of rats compared to the control group. Conclusions: Periodontitis may induce liver injury by down-regulating the BMAL1 expression levels in liver tissue, which in turn activates NF-κB signaling molecules, leading to the elevated levels of inflammation and apoptosis in rat liver.

[Epidemiological investigation of tinnitus in Sichuan and Chongqing].

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.

Effects of rapamycin on osteosarcoma cell proliferation and apoptosis by inducing autophagy.

OBJECTIVE: To investigate the influences of rapamycin on proliferation and apoptosis of human osteosarcoma MG-63 cells and the mechanisms of action. MATERIALS AND METHODS: The human osteosarcoma MG-63 cells were randomly divided into Control group, Rapamycin group, and Rapamycin + Beclin-1 plasmid transfection group. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to detect the viability of MG-63 cells in each group, and the 5-Ethynyl-2'-deoxyuridine (EdU) staining and Hoechst staining were applied to determine the proliferation and apoptosis, respectively, of MG-63 cells in each group. The levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured using enzyme-linked immunosorbent assay (ELISA) kits, and the protein expression levels of Beclin-1 and Vps34 in each group of MG-63 cells were tested using the Western blotting. RESULTS: Compared with the Control group, Rapamycin group, and Rapamycin + Beclin-1 plasmid transfection group had markedly weakened the viability of MG-63 cells, inhibited cell proliferation, remarkably increased cell apoptosis rate, elevated Bax level, notably declined Bcl-2 level, and significantly raised the levels of Beclin-1 and Vps34 proteins in MG-63 cells. Besides, the effects in Beclin-1 plasmid transfection group were stronger. CONCLUSIONS: Rapamycin may decrease the viability, inhibit the proliferation, and promote the apoptosis of MG-63 cells by activating autophagy.

[Clinicopathological analysis of 187 cases of external nose skin tumors].

Objective:To explore the pathological types, distribution and characteristics of external nose skin tumors, in order to improve the diagnosis and treatment of such diseases, and provide reference for the clinical diagnosis and treatment of external nose skin tumors. Method: The gender, age of onset, lesion location, lesion size, pathological type, course of disease and related risk factors of all 187 cases with external nose skin tumors in our hospital from January 2008 to December 2017 were analyzed retrospectively. Result:The sex ratio of patients with external nasal skin benign tumors was 1.10：1.00, and that of patients with external nasal skin malignant tumors was 0.97：1.00. There was no significant difference in the composition of benign and malignant patients(χ²=0.169,P=0.681). The peak age of skin tumors of the external nose is over 60 years old, accounting for 71.1%(133/187). There was a significant difference in the ratio of benign to malignant tumors among different age groups(χ²=31.378,P<0.001). The ratio of malignant tumors increased with age(χ²trend=28.741, P<0.001). The most common benign external nasal skin tumors were alar nasi(28 cases, 22.2%), nasal root(25 cases,19.8%), dorsal nasal(23 cases, 18.3%), tip nasi(22 cases, 17.5%) and paranasal(18 cases,14.3%). Malignant external nasal skin tumors were alar nasi(18 cases,28.5%), dorsal nasal(15 cases,24.6%) and tip nasi(11 cases,18.0%). Epidermal cellderived basal cell carcinoma was the most common malignant tumor(44 cases,72.1%), followed by squamous cell carcinoma(11 cases,18.0%). Conclusion: External nasal skin malignancies have the characteristics of the elderly at the peak age of onset, skin basal cell carcinoma is the most common, for the incidence of basal cell carcinoma constitutes the largest, so that early detection, early diagnosis, early treatment.

[Research progress in the pathogenic mechanisms of Porphyromonas gingivalis fimbriae].

FimA has been characterized as an important virulence factor for Porphyromonas gingivalis (Pg). These structures play a major role in the mechanisms of adhesion and invasion of Pg to host cells, and can induce cellular activation and cytokines release. FimA can also promote biofilm formation and induce immuno-inflammatory response of host cells. Many studies have characterized FimA to be associated with periodontitis and cardiovascular disease. Pg strains are classified into six types based on divergent nucleotide sequences of the fimA gene (types Ⅰ、Ⅰb、Ⅱ、Ⅲ、Ⅳ andⅤ). The expression of fimbriae is regulated by the fimA gene, which may be the key factor that leads to virulence diversities of Pg, At present, the research on the pathogenesis of FimA mainly focuses on periodontitis and atherosclerosis, which is of great significance for the prevention and treatment of diseases. This paper reviewed the pathogenic effect of FimA in the development of above mentioned two diseases and its application in the prevention.

An orthogonal moment-based method for automatic verification of radiation field shape.

The purpose of this paper is to develop a new method for automated on-line verification of the treatment field shape during radiotherapy. The treatment field boundary is extracted from the digital portal image and is then approximated by a polygon. The proposed procedure used one of the approved field shapes as the reference boundary for automated comparison with subsequent portal field boundaries. The orthogonal moment-based method was applied to align treatment field boundaries that include the translational shifts, scaling factor and rotation angle. Firstly, the moments of order up to one were used to adjust the magnification and translation of the test field boundary related to the reference one; this step created a common coordinate system for the two images. Then a quadratic least-square objective function based on the orthogonal moments (e.g. Legendre moments) of the two field shapes was employed to perform rotational correction. Since moment computation by a straightforward method required a large number of multiplication and addition operations, a fast method for computing Legendre moments was also developed to decrease the calculation time. Application of the method to some simulated cases showed that our alignment procedure has an accuracy of 0.5 mm in detecting translational shift, 0.004 in detecting magnification and less than 0.3 degrees in detecting rotation angle between the test shape and the reference shape. The alignment procedure using the proposed method can be done within 2 s on a Pentium II personal computer. Therefore, our method is potentially useful for automated real-time treatment field shape verification.

Percutaneous balloon mitral valvuloplasty. An observation of 50 patients.

Percutaneous balloon mitral valvuloplasty (PBMV) was successfully performed in 50 selected patients with mitral stenosis by using Inoue pillow-shaped balloon and Inoue technique. The average diameter of balloon used was 26.9 +/- 0.9 mm. 90% (45/50) of cases had either double or single mitral commissura split. Of the rest 5 cases, 1 had a mitral score 13 and 4 had a history of mitral valve commissurotomy. Totally they had a mean mitral valve area increase from 1.13 +/- 0.32 to 2.21 +/- 0.43 cm2, left atrial pressure decrease from 31.8 +/- 9.3 to 14.7 +/- 5.6 mmHg, left atrial diameter reduction from 44.9 +/- 7.7 to 37.4 +/- 4.9 mm, and transmitral gradient decrease from 21.7 +/- 9.8 to 4.0 +/- 5.2 mmHg. Most patients had a obvious cardiac function improvement, especially in patients with mitral score of 8 or less. 30% patients (15/50) had a mild mitral regurgitation, but relieved 3-6 months after procedure. During one year of follow up, the majority of patients (16/20) were found in a good cardiac function, mitral area and the left atrial diameter, except in 4 patients with a high mitral score of more than 10. It is suggested that for patient with lower mitral morphological score and good general health, a larger diameter balloon might be suitable for effectively improving patient's symptom, but for patients with a previous surgical mitral commissurotomy, PBMV should not be selected.

HGFK1 inhibits bone metastasis in breast cancer through the TAK1/p38 MAPK signaling pathway.

Breast cancer metastasis to bone represents a devastating complication of advanced breast cancer, frequently resulting in significant increases in morbidity and mortality. An understanding of the mechanisms that govern breast cancer metastasis at the molecular level should lead to more effective therapies. Recently, the kringle 1 domain of human hepatocyte growth factor (HGFK1) was identified as a candidate metastasis suppressor gene. Here, we investigated whether HGFK1 is a key regulator of breast cancer bone metastasis. Of the 193 human breast carcinoma tissue samples examined, HGFK1 expression was relative higher in 82 (42.4%) by western blot and in 84 (43.5%) by quantitative real-time PCR. The higher expression of HGFK1 was significantly associated with a better prognostic value (P<0.001) and inversely correlated with bone metastasis (P=0.003). The efficacy of adeno-associated virus carrying HGFK1 (AAV-HGFK1) in osteolytic bone metastasis was then evaluated using an in vivo bone metastasis model. AAV-HGFK1 significantly inhibited osteolytic bone metastasis and prolonged the survival of mice in this model (P<0.01). In vitro, HGFK1 expression resulted in significant anti-invasion effects, enhanced the phosphorylation of TAK1 (transforming growth factor-ß-activated kinase 1), p38 MAPK (mitogen-activated protein kinase) and MAPKAPK2 (MAPK-activated protein kinase 2) and decreased the expression of receptor activator of nuclear factor-κB (RANK), which was abrogated by the p38 MAPK inhibitor SB203580. This study shows for the first time that HGFK1 significantly inhibits the metastasis of breast cancer to bone by activating the TAK1/p38 MAPK signaling pathway and inhibiting RANK expression. Thus, AAV-HGFK1 treatment represents a potential therapy for bone metastasis in breast cancer.