The deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.

Objective: To investigate the impact of surgical treatment on quality of life in patients with locally recurrent rectal cancer (LRRC). Methods: A descriptive case series study was performed. The complete clinical data of 62 patients who met the diagnostic criteria of LRRC and treated by surgical procedures in Huashan Hospital of Fudan University from January 2012 to November 2019 were analyzed retrospectively. All the patients were followed up at least 12 months. Assessments of urinary function, sexual function, mobility function of lower limb and quality of life were documented. Patients with distant metastasis and surgical history of the urinary system were excluded. According to the criteria of Memorial Sloan Kettering Cancer Center (MSKCC), recurrence were divided into central (n=27), anterior (n=20), posterior (n=7), and lateral (n=8) subtypes. Baseline characteristics, surgical procedures and short-term complications were analyzed. International prostate symptom score (IPSS) and grade of voiding dysfunction were used to evaluate the urinary function. Higher score of IPSS and higher grade of voiding dysfunction indicated worse voiding function. Sexual function for both genders was assessed preoperatively and postoperatively. International index of erectile function-5 (IIEF-5) was used for assessment of male patients and higher score indicated better function. Female sexual function index (FSFI) was used in females and higher score indicated better function. Short-form health survey with 36 items (SF-36), yielding an 8-scale profile of functional health (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, emotional health and mental health) was used to evaluate the quality of life. The higher score indicated the better quality of life. Results: All the operations of 62 patients completed successfully and R0 resection rate was 88.7% (55/62). Postoperative surgical complications occurred in 16 cases (25.8%), including 3 patients of Clavien-Dindo classification III. At postoperative 3-month, 42 patients without ileum cystectomy or ureterostomy suffered from different grade of voiding dysfunction. IPSS increased significantly after the surgery (before surgery: 12.36±4.75, after surgery: 18.40±4.77, t=-9.128, P<0.001). There was no significant difference among the subtypes (P>0.05). At postoperative 12-month, IIEF-5 decreased from 14 (0~25) to 9 (0~19) in males (Z=-5.174, P<0.001) and FSFI deceased from 8.4 (2.0-27.0) to 2.0 (2.0-18.4) in females (Z=-3.522, P<0.001). Scores of physical functioning and role-physical decreased significantly [physical functioning: before surgery 70 (35-85), after surgery 65 (30-80), Z=-3.685, P<0.001; role-physical: before surgery 50 (0-50), after surgery 25(0-75), Z=-4.065, P<0.001], while those of social functioning role-emotional and mental health increased significantly after the surgery [social functioning: before surgery 44 (22-78), after surgery 56 (0-89), Z=-3.509, P<0.001; role-emotional: before surgery 17 (0-100), after surgery 33 (0-100), Z=-2.439, P=0.015; mental health: before surgery 40 (36-76), after surgery 52 (24-80), Z=-3.395, P<0.001]. All surgical procedures decreased the voiding function of LRRC patients and the sexual function of male patients (all P<0.01). However, only total pelvic exenteration and posterior pelvic exenteration decreased FSFI in female patients [before surgery: 8.4 (2.0-27.0) after surgery: 2.0 (2.0-18.4), Z=-2.810, P=0.005]. Conclusions: Multi-visceral resection in LRRC patients may damage voiding and sexual function. However, successful and effective surgical treatment can improve the psychosocial health of LRRC patients.
Female ; Humans ; Male ; Neoplasm Recurrence, Local ; Quality of Life ; Rectal Neoplasms/surgery* ; Rectum ; Retrospective Studies

This study using traditional Chinese medicine inheritance support software(TCMISS) to analyze the prescription rules of Tibetan medicine containing Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine, Tibetan Medicine Composition Preparation of Modern Research and Clinical Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5) was used to build a prescription database of Tibetan medicine containing T. chebula.The software statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze the common herbs, combination rules and core combination of prescriptions containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed and 14 common herbal combinations were summarized, whose ingredients mostly had the functions of clearing heat and detoxicating, promoting blood circulation and stopping pain, warming the middle-jiao and promoting the circulation of Qi. Prescriptions containing T. chebula were commonly used to treat 640 kinds of diseases, there are 22 kinds with high frequency(≥12) in which the representative "Tripa" disease, antiquated febrile symptoms, food poisoning had the highest frequency.T. chebula had different therapeutic effects through different compatibility.The complex composing and medication regularities of Tibetan medicine containing T. chebula have been clarified by TCMISS. That will provide reference for the clinical application of T. chebula and the new development.

Objective To evaluate the effect of the bird exercises of Wuqinxi bird exercises combined with simple breath exercises on the quality of life and immune function in patients with chronic obstructive pulmonary disease (COPD). Methods Sixty-eight COPD patients were allocated into observation group (N=32) and control group (N=36)according to the intention of the patients. The control group was given conventional inhalation of Seretide and Tiotropium Bromide,and the observation group did Wuqinxi bird exercises and simple breath exercises plus the conventional inhalation therapy. Before and after treatment,we compared the BODE indexes such as body mass index (BMI), air flow obstruction index of forced expiratory volume in one second (FEV1%), dyspnea scores,exercise capacity (6-min walking distance)as well as COPD assessment test (CAT)scores between the two groups before and after treatment. Meanwhile, the changes of T lymphocyte subtype CD3, CD4, CD8, CD4/CD8 levels and serum immunoglobulin M (IgM),IgA,IgG levels were also monitored. Results(1)After intervention, dyspnea scores of the observation group were obviously improved (P < 0.01), while the control group showed no obvious changes in dyspnea scores (P > 0.05). The observation group had better effect on improving dyspnea scores and 6-min walking distance than the control group (P < 0.05 or P <0.01).(2)After intervention,BODE index and CAT scores were improved in the observation group(P<0.01),BODE index was improved in the control group (P < 0.05), and the improvement of BODE index and CAT scores in the observation group was superior to that in the control group (P < 0.05 or P < 0.01). (3)After intervention, T lymphocyte subtype CD3 and CD4 levels as well as the serum IgM, IgA, IgG levels in the observation group were increased (P < 0.05 or P < 0.01),and IgA level in the control group was also increased (P < 0.05). The observation group had stronger effect on increasing T lymphocyte subtype CD3 and CD4 levels than the control group(P < 0.05 or P < 0.01).(4)The difference of adverse reaction incidence was insignificant between the two groups (P > 0.05). Conclusion Application of Wuqinxi bird exercises and simple breath exercises based on conventional inhalation therapy is effective on improving dyspnea, 6-min walking distance, BODE index and CAT scores, and on increasing T lymphocyte subtype CD3 and CD4 levels as well as the serum IgM and IgG levels of COPD patients.

BACKGROUNDProlonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients.

METHODSThis was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17-30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests.

RESULTSHigher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all p<0.05). IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P < 0.05). Basal serum ACTH (9.91 ± 4.98 pmol/L vs. 7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 μg/L vs. 1417.1 ± 498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05). We also found that basal serum ACTH levels were positively correlated with NAFLD (r = 0.289,p<0.05) and triglyceride levels (r = 0.268, P< 0.05) in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis.

CONCLUSIONSThe male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Adolescent ; Adrenocorticotropic Hormone ; blood ; Adult ; Humans ; Hydrocortisone ; blood ; Hypogonadism ; blood ; Linear Models ; Male ; Non-alcoholic Fatty Liver Disease ; blood ; drug therapy ; Retrospective Studies ; Young Adult

Tibetan medicine "Dida" isoccasionally misused due to its complex origins, which ultimately affects its clinical efficacy. The accurate name, origin, property, and efficacy of "Dida"are highly important for its further research and development. In the present study, by viewing the classic Tibetan medicine and modern literature, and combining the clinical practice of Tibetan medicine, the origins, properties and the clinic effects of "Dida" were defined. "Dida" originated from multiple plant species of Swertia, Gentianopsis, Halenia, Lomatogonium, Comastoma(Gentianaceae), Hedyotis (Saxifragaceae) and Erysimum (Cruciferae). The medicinal properties of "Dida" is mainly bitter and cold. It has been commonly used to treat febrile diseases and hepatic and gall diseases. This study suggested that the relevant herbalogical study, species identification and pharmacological effects of "Dida" should be taken based on the Tibetan medicine theories and clinical practice. Thus the medicine can be better used and ensure its safety and quality simultaneously.

This study is to establish an HPLC-DAD-ELSD method for simultaneous determination of 5 flavones and saponins in Rhizoma Anemarrhenae including neo-mangiferin, mangiferin, timosaponin B II, timosaponin B III and timosaponin A III. Samples were analyzed on a Merck Purospher STAR column(4.6 mm x 250 mm, 5 μm). The mobile phase consisted of acetonitrile( A) and 0. 1% formic acid (B) with gradient elution at a flow rate of 1.0 mL · min(-1). The column temperature was set at 40 °C. The DAD detector wavelength was set at 254 nm. The ELSD conditions were as follows: the nebulizing gas flow rate was 2.0 L · min(-1) and temperature of drift tube was 105 °C. The volume was 10 μL. The five compounds were well separated with good linear correlations. The mean recoveries were between 102.0%-104.0%. This method was quick and reliable which provides a foundation for quality control of R. Anemarrhenae.
Anemarrhena ; chemistry ; Chromatography, High Pressure Liquid ; instrumentation ; methods ; Drugs, Chinese Herbal ; analysis ; Flavones ; analysis ; Rhizome ; chemistry ; Saponins ; analysis

Delphi Technique ; Humans ; Radiculopathy ; drug therapy ; surgery ; therapy

BACKGROUNDDespite extensive research, the mechanism of immature dendritic cells (DCs) induced immune hyporesponsiveness remains incompletely understood.

METHODSRecipient DCs from C3H mouse bone marrow cells were incubated with donor antigen from splenic lymphocytes of C57BL/6 mouse; these DCs were transfected with CD80/86 specific siRNA using lentiviral vectors. Flow cytometry was used to evaluate expression of CD80/86 on the antigen-pulsed recipient DCs. Immune regulatory activity was examined by mixed lymphocyte reaction, in which irradiated DCs were cultured with C3H spleen T cells. After the reaction, interleukin (IL)-2, IL-4, IL-10, and interferon (INF)-γ levels of mixed lymphocyte reaction culture supernatant were measured by enzyme-linked immunosorbent assay. The apoptotic T lymphocytes were identified by Annexin V and CD3 staining.

RESULTSThere was a significant inhibition of CD80/86 expression in DCs transfected with CD80/86 lentiviral vectors compared with the control groups (P < 0.05), indicating the specificity of RNA interference. Enzyme-linked immunosorbent assay results showed a significant reduction of INF-γ, IL-2 and IL-10 in the CD80/86 lentivirus transfected group compared to the control groups (P < 0.05). There was no significant difference in IL-4 levels between the groups (P > 0.05). We also showed that CD80/86 low DCs loaded with alloantigen (1) stimulated low T cell proliferative responses via the indirect recognition pathway and (2) enhanced apoptotic activity (P < 0.05) in co-cultured T cells.

CONCLUSIONSLentiviral vector transfection can effectively and specifically knock down target genes in DCs. The CD80/86 low DCs may show tolerogenic activity via induction of T-cell apoptosis, thereby modulating the activity of recipient-derived DCs. The use of this approach may potentially be clinically applicable.

Animals ; Apoptosis ; B7-1 Antigen ; genetics ; physiology ; B7-2 Antigen ; genetics ; physiology ; Dendritic Cells ; immunology ; Lentivirus ; genetics ; Lymphocyte Activation ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; RNA Interference ; T-Lymphocytes ; cytology ; immunology

AIM: To study the effect of sphingosine 1-phosphate (S1P) on the increase in microvessel permeability induced by platelet activating factor (PAF). METHODS: The microvessel permeability was assessed by measuring hydraulic conductivity (Lp). To observe the effect of S1P and PAF on vascular endothelial-cadherin (VE-Cadherin), the microvessels were stained with immunofluorescence and examined by laser confocal microscopy. RESULTS: After giving PAF at concentration of 10 nmol/L, the Lp value of rat mesentery microvessel was significantly increased. However, after pretreatment with S1P, PAF did not give rise to a further significant change. The effect of PAF on microvascular endothelial cells could be seen: the formation of endothelial gap was induced, the microvascular fluorescence intensity significantly increased, a large number of fluorescent microspheres (FMs) distributed in the space among the endothelial cells. However, after pretreated with S1P, no obvious gap opening and the FMs accumulation were observed. Compared to normal control, no significant difference of the microvascular fluorescence intensity was found. CONCLUSION: PAF changes the structure of VE-Cadherin, leading to detachment of adherent junction, formation of intercellular gaps, which contributes to the increase in the permeability. S1P improves the increase in the microvessel permeability caused by PAF, which might be mediated by strengthening adherent junction and inhibiting the formation of endothelial gaps.