The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.

OBJECTIVETo observe the inhibitory effect of different extract fractions from Longdan Xiegan decoction on biofilms of Candida albicans, and discuss its possible mechanism.

METHODThe micro-dilution method and the XTT reduction assay were adopted to explore the antifungal activity of different extract fractions from Longdan Xiegan decoction and detect the inhibitory effect of different extracts on biofilms of C. albicans. The expression quantity of the adhesion related gene ALS1 and hypha formation SUN41 were detected by qRT-PCR.

RESULTThe MICs of extracts from Longdan Xiegan decoction, including petroleum ether, water, butanol, methanol and ethyl acetate, against C. albicans were > 1 000, > 1 000, > 1 000, 125, 125 mg x L(-1). The SMIC50 against biofilms of C. albicanswere > 1 000, > 1000, > 1 000, 500, 500 mg x L(-1). The SMIC50 were > 1 000, > 1 000, > 1 000, > 1 000 and 1 000 mg x L(-1). 1 000 mg x L(-1) ethyl acetate extracts could considerably inhibit the expression of the adhesion related gene ALS1 and hypha formation SUN41.

CONCLUSIONThe ethyl acetate extract showed the greatest activity against Candida albicans biofilms.

Antifungal Agents ; pharmacology ; Biofilms ; drug effects ; growth & development ; Candida albicans ; drug effects ; growth & development ; Candidiasis ; drug therapy ; microbiology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Hyphae ; drug effects ; growth & development ; Microbial Sensitivity Tests

Adult ; Female ; Gastrointestinal Hemorrhage ; metabolism ; Glutathione ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Humans ; Lipid Peroxidation ; Liver ; blood supply ; Liver Cirrhosis ; complications ; metabolism ; Male ; Middle Aged ; Reperfusion Injury ; prevention & control

Objective To investigate the characteristics and distribution of human eehinococcosis in Hobukesar Mongolian Autonomous County (HMAC) in Xinjiang. Methods Using cluster sampling methods, the 2 counties (Tiebukenwusa and Narenhebuke) in HMAC were chosen as focusing areas for investigation. A survey of human echinococcosis including questionnaire, serological test and abdominal ultrasonic scan was carried out. Results The prevalence of human echinococcosis was 9.0% (64/712) by ultrasound and surgical history, including 8.7% (62/712) for cystic eehinococcosis(CE), 0.3%(2/712) for alveolar echinococcosis(AE) and 15.6%(111/712) for total of serological positives in HMAC. CE prevalence rate of different occupations, age, family slaughtering livestock and drinking water source had significant differences(P<0.05). Herdsmen as the highest risk group showed a CE prevalence of the 13.4% (27/201) in comparison with other occupations. The ages between 20 to<40 year-old were at the highest risk stage with 12.8% incidence. But CE prevalence rate of different gender, ethnic and education groups had not significant differences(P>0.05). Conclusions HMAC could be considered as a high endemic human CE region in Xinjiang. The current study reported the main risk factors may include occupations, age difference and drinking water source.

Sarcopenia is a syndrome associated with decreased muscle mass,decreased muscle strength,and reduced physical performance. Due to multiple factors such as tumor metabolism,systemic inflammatory response,disease progression,and reduced physical activity associated with treatment itself,the risk of sarcopenia in patients with lung cancer is higher than that of the general population. Sarcopenia is closely related to the clinical outcomes,including increased risk for mortality,and significantly impacts patients' long-term quality of life and mental health. This study systematic reviewed the risk factors for sarcopenia in patients with lung cancer,its negative effects on clinical outcomes,long-term quality of life and mental health,and the interventions for sarcopenia. Given the significant impact of sarcopenia on patients with lung cancer,it is urgent to explore a multidisciplinary intervention model to improve their survival and quality of life.

OBJECTIVETo investigate the clinical effect of spermatic cord seal-up injection on acute epididymitis and its mechanisms.

METHODSA total of 120 cases of acute epididymitis were allocated to a trial group (n = 56), aged 18 - 78 (38.4 +/- 9.6) years, and a control group (n = 64), aged 14 -82 (41.3 +/- 7.2) years. The patients in the trial group were given seal-up injections of a mixture of lidocaine, gentamicin (or Amikacin) and dexamethasone into the spermatic cord, qd or bid, for 2 courses of 5 days each, with an interval of 3 to 5 days. Those in the control group were treated by intravenous drip of penicillin, qd, intramuscular injection of Streptomycin, bid, and oral medication of SMZCo (SMZ-TMP), bid, with the initial dose doubled. After less than 2 weeks of treatment, we compared the therapeutic effects between the two groups of patients.

RESULTSIn the trial group, 53.6% of the patients were basically cured, 37.5% obviously improved and 91.1% improved (total rate of effectiveness). The average treatment time for the improved cases was (9.2 +/- 0.5) d. In the control group, 40.6% of the patients were basically cured, 31.2% obviously improved and 71.8% improved (total rate of effectiveness). The average treatment time for the improved cases was (12.8 +/- 0.7) d. There were significant differences between the two groups in the total rate of effectiveness and the average treatment time for the improved cases (P < 0.05).

CONCLUSIONSpermatic cord seal-up injection for acute epididymitis deserves wide clinical application for its simple operation, good tolerance, short therapeutic course and high safety and efficacy.

Acute Disease ; Administration, Topical ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Epididymitis ; therapy ; Humans ; Male ; Middle Aged ; Spermatic Cord ; Young Adult

Objective:To investigate the effect of mandibular angle osteotomy on the morphological changes of mandible by using cone beam computed tomography (CBCT) scanning data and three-dimensional cephalometry.Methods:According to included and excluded criteria, the complete CBCT data of 20 female patients (aged 20-35 years with an average age of 25.5 years) from January 2016 to June 2018 who underwent curved mandibular angle osteotomy combined with splitting cortiectomy were selected. Seven items reflecting mandibular morphology before and after surgery were measured respectively. All the data were analyzed by the means of SPSS 12.0; linear correlation analysis and paired t test were used to evaluate the change of andibular morphology.Results:The measurement results of the mandible pre- and post-operative 10 days showed as follows: Go-Go decreased, both sides of Cd-Go, Go-Ri and MR-MA decreased, both sides of Go-Me became longer, both sides of Ar-Go-Me and MP-FH increased. The paired t-test results showed that there was significant difference before and after operation ( P<0.05), but there was no significant difference between the left and right measurement items ( P>0.05). Compared with that in 10 days after operation, the measurement items also changed 6 months after operation. There was no statistical difference between the above measurement items 6 months after surgery and 10 days after surgery ( P>0.05), and no statistical difference between the left and right sides ( P>0.05). Conclusions:The mandibular three-dimensional model which is reconstructed based on CBCT data, not only displays the three-dimensional anatomical structure that cannot be presented on X-ray film visually and comprehensively by means zoom, rotation and other operations, but also precisely and accurately shows the change of the shape of the mandible from the sagittal, coronal and horizontal plane with arbitrary cutting and rotation. The measurement of mandible is more accurate and reliable, and the surgical plan of mandibular angle osteotomy can be accurately planned preoperatively, and the operative effect can be quantitatively evaluated postoperatively.

BACKGROUNDNoninvasive cardiac imaging is now central to the diagnosis and management of patients with moderate probability for coronary artery disease. The aim of this study was to assess the impact of stress myocardial perfusion single photon emission computerized tomography (SPECT) on in-hospital coronary angiography and revascularization for such patients.

METHODSBetween January 2005 and June 2007, 1053 consecutive in-hospital patients (423 women, the average age of (57.2 ± 11.2) years) with suspected coronary artery disease but without any prior interventional treatment were retrospectively analyzed. All patients underwent a 2-day stress/rest (99m)Tc-methoxyisobutylisonitrile (MIBI) myocardial perfusion SPECT, including 984 exercise test and 69 adenosine test.

RESULTSOverall, stress/rest myocardial perfusion SPECT was normal in 973 patients (92.4%) and abnormal in 80 patients (7.6%). A total of 190 patients underwent coronary angiography, 46 underwent percutaneous coronary intervention and 10 coronary artery bypass grafting during hospitalization. From the whole perspective, only 14.7% of patients with normal SPECT underwent coronary angiography, so did 58.8% of patients with abnormal SPECT (χ(2) = 97.0, P < 0.001); furthermore, the rates of revascularization in patients with normal and abnormal SPECT were 2.8% and 36.3%, respectively (27 out of 973 vs. 29 out of 80, χ(2) = 157.9, P < 0.001). The extent and severity of ischemia did not add more predictive value for subsequent coronary angiography, but did have impact on revascularization. Multivariate analysis showed that reversible perfusion defect was the most predictive variable for referral rate to coronary angiography (odds ratio = 7.5, P < 0.001).

CONCLUSIONSAbnormal myocardial perfusion SPECT is a powerful referral for in-hospital coronary angiography and revascularization during the same hospitalization. Thus, stress/rest SPECT is an effective gatekeeper for early coronary angiography and invasive treatment for patients with suspected coronary artery disease.

Aged ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; pathology ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon ; methods

OBJECTIVETo study the expressions of CD55 and CD59 in patients with hyperlipidemia and the effects of atorvastatin on it, and to identify the possible influential factors.

METHODSWe selected 67 patients with hyperlipidemia, and 24 healthy people matched in terms of age, sex and body weight as control. The expressions of CD55 and CD59 on white blood cells were detected by flow cytometry, and their relationships to blood lipids, complement activation indexes (C(5a), sC(5b-9)), inflammatory factors (high sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6 were analyzed. 24 patients with hyperlipidemia were treated with atorvastatin for 8-12 weeks and the expressions of CD55 and CD59 were measured before and after atorvastatin therapy.

RESULTSThe mean fluorescence intensity (MFI) of CD55 lymphocytes and monocytes were decreased in patients with hyperlipidemia compared with control (2.07 +/- 0.28 vs 2.29 +/- 0.44 and 3.45 +/- 1.02 vs 4.33 +/- 2.32, P < 0.01 and P < 0.05, respectively). CD55 positive lymphocyte MFI was negatively correlated with waist circumference, waist-hip ratio, hsCRP and C(5a). C(5a) was negatively correlated with the MFIs of CD55 positive lymphocytes, monocytes, granulocytes, and positively with TG and diastolic blood pressure. After atorvastatin therapy, the MFIs of CD59 positive lymphocytes, monocytes and granulocytes increased (4.34 +/- 1.16 vs 3.69 +/- 0.76, 4.52 +/- 1.36 vs 3.91 +/- 0.89, 5.67 +/- 1.72 vs 4.56 +/- 1.03, P < 0.05, < 0.05 and < 0.01 respectively), which were not correlated with changes of blood lipids.

CONCLUSIONSThe expression of CD55 is down-regulated in hyperlipidemia, which might be influenced by obesity, abdominal distribution of adipose tissue and inflammatory status of hyperlipidemia, but not by blood lipids. The expression of CD55 is related with complement activation; The expression of CD59 is up-regulated after atorvastatin treatment independently of blood lipids.

Aged ; Atorvastatin Calcium ; CD55 Antigens ; metabolism ; CD59 Antigens ; metabolism ; Case-Control Studies ; Complement Activation ; Gene Expression Regulation ; Heptanoic Acids ; therapeutic use ; Humans ; Hyperlipidemias ; drug therapy ; immunology ; metabolism ; Hypolipidemic Agents ; therapeutic use ; Male ; Middle Aged ; Pyrroles ; therapeutic use

Adult ; Antibodies, Monoclonal ; pharmacology ; Bronchoalveolar Lavage Fluid ; cytology ; Cells, Cultured ; Cytokines ; biosynthesis ; blood ; secretion ; Fas Ligand Protein ; antagonists & inhibitors ; metabolism ; Humans ; Macrophages, Alveolar ; immunology ; metabolism ; Middle Aged ; Occupational Exposure ; analysis ; Signal Transduction ; Silicon Dioxide ; adverse effects ; Silicosis ; blood ; immunology ; fas Receptor ; antagonists & inhibitors ; metabolism