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.

Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC₅₀ as 4.77, 1.59, 11.11 and 25.87 μmol·L^-1, resepectively.

Two new labdane diterpenoids were isolated from 95% ethanol extract of the leaves of Callicarpa formosana Rolfe by using silica gel column, MCI column, ODS column and HPLC. Their structures were elucidated by HR-ESI-MS, NMR and ECD spectral data. All of them are new compounds, named 13E-6β-hydroxylabda-8(17),13-dien-15-oic acid (1) and 13E-7α-hydroxylabda-8(17),13-dien-15-oic acid (2). Compounds 1 and 2 were tested for antioxidant activity, and none of them had obvious activity.

Objective To evaluate the preliminary clinical effect of anterior anatomical reduction plate fixation on the treatment of atlantoaxial dislocation. Methods A retrospective case series study was conducted to analyze the 13 patients with atlantoaxial dislocation admitted to the second affiliated hospital of Xi'an Jiaotong University from January 2016 to December 2017. There were eight males and five females, aged 20-57 years, with an average age of 42 years. All patients received transoropharyngeal reconstruction and atlantoaxial anterior anatomical reduction plate fixation, 12 of which underwent the surgery for the first time but one had the revision surgery. The operation time and intraoperative bleeding were recorded. The angle of the clivus axis was measured, and the reduction of the atlantoaxial spine and the fusion of bone graft were observed. The neurological function was evaluated by Japanese Orthopedic Association ( JOA ) score and the improvement rate of spinal cord function was calculated. The complications were also recorded. Results All patients were followed up for 10-30 months [(14. 2 ± 5. 0)months]. The operation time was 150-285 minutes [(216. 8 ± 36. 7)minutes]. The intraoperative blood loss was 50-130 ml [(80. 5 ± 19. 7)ml]. The slope axis angle was (113. 2 ± 9. 1)° before operation and (145. 8 ± 6. 7)° after operation, with an average increase of 32. 6° (P<0. 01). Anatomical reduction was obtained in nine patients, and partial reduction in four patients. At the last follow-up, the atlantoaxial fusion was obtained in all patients, and the healing time was ( 4. 6 ± 1. 1 ) months. Postoperative neurological symptoms were improved compared with those before operation. The JOA score was improved from preoperative (8. 7 ± 1. 7) points to postoperative (14. 3 ± 1. 2) points, with an average increase of 5. 6 points (P<0. 01). The average improvement rate of spinal cord function was 69％. Except for one patient with cerebrospinal fluid leakage, there were no complications such as spinal cord, nerve, blood vessel injury or wound infection after operation. Conclusions Anterior atlantoaxial anatomical reduction plate fixation can effectively restore the dislocated atlantoaxial joint, restore slope axis angle, improve bone fusion rate, and improve nerve function. It can be used as an alternative or supplement to posterior fixation.

OBJECTIVE: To explore long-term outcomes of Chiari osteotomy for Legg-Calvé-Perthes disease in children with type Catterall III or IV, and to analyze clinical effect of osteotomy angle on clinical and radiographic results. METHODS: From March 2005 to July 2013, 26 children with Legg-Calvé-Perthes disease with type Catterall III or IV were treated by Chiari osteotomy, including 17 males and 9 females, aged from 4 to 13 years old with an average of (8.9±2.6) years old. Children were divided into low osteotomy angle group and high osteotomy angle group. according to osteotomy angle. There were 10 children in low osteotomy angle group with an osteotomy angle of 10 degrees, including 8 boys and 2 girls, aged from 4 to 13 years old with an average of (9.2±3.3) years old; while there were 16 children in high osteotomy angle group with an osteotomy angle of 15 degress, including 9 boys and 7 girls, aged from 6 to 12 years old with an average of (8.8±2.1) years old. HHS score before operation and at the latest follow-up were recorded to observe clinical results. CE angle of hip joint, acetabular index, Sharp angle, Shenton's line continuity, femoral head coverage, acetabular depth ratio were recorded to compare radiographic results. Stulberg classification was analyzed to compare reshaping ability of femoral head. RESULTS: Twenty-six children were followed up for 4.5 to 12.0 years with an average of (7.9±1.8) years. All incisions were healed at stage I for 10 to 14 days, with an average of(12.3±1.1) days. No inflammation, skin necrosis and injury of vessel and nerve occurred. All osteotomies achieved bone union for 8 to 13 weeks, with an average of(9.8±1.4) weeks. HHS score increased from 75.8±6.5 before operation to 93.5±2.5 at the latest follow-up in low osteotomy angle group(<0.05), and form 77.6±6.2 to 97.8±1.6 in high osteotomy angle group (<0.05). HHS score of high osteotomy angle group at the latest follow-up was higher than that of low osteotomy angle group (<0.05). The acetabular index decreased from (10.1±2.5)° before operation to (4.5±1.3)° at the latest follow-up in low osteotomy angle group (<0.05), and from (10.7±3.3)° before operation to (2.0±1.1)° in high osteotomy angle group (<0.05). The acetabular index of high osteotomy angle group at the latest followup was better than low osteotomy angle group(<0.05). There was no significant difference in CE angle, Sharp angle, Shenton's continuity, femoral head coverage, acetabular depth ratio between two groups. According to Stulberg classification, the femoral head reshaping ability in high osteotomy angle group was better than that of low osteotomy angle group(<0.05). CONCLUSIONS Chiari osteotomy with 15° for Legg-Calvé-Perthes disease in children with type Catterall III or IV could effectively decrease index of acetabulum, and helpful for femoral head reshaping ability, then in further improve clinical effects.
Acetabulum ; Adolescent ; Child ; Child, Preschool ; Female ; Femur Head ; Hip Joint ; Humans ; Inflammation ; Male ; Osteotomy ; Treatment Outcome

OBJECTIVETo investigate the changes in the range of motion (ROM) and stress of the intervertebral disc and facet joint of the adjacent segments following anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) using finite element analysis.

METHODSA three-dimensional finite element model of the lower cervical vertebrae was constructed and validated by comparing the ROM of the finite element model against the published data. After the validation of successful modeling, finite element models of ACDF and ACCF were constructed. The ROM and the stress of the intervertebral disc and facet joint of the adjacent segments were compared between the intact lower cervical vertebrae and the cervical vertebrae after ACDF and ACCF.

RESULTSThe ROM of the finite element model was consistent with the published data. The total ROM and the ROM of the fusion segments with ACDF and ACCF were significantly decreased compared with the intact cervical vertebrae. In the adjacent segments following ACDF and ACCF, the ROM the adjacent segments and the stress peak of the intervertebral disc and facet joint all increased obviously compared with those of intact cervical vertebrae.

CONCLUSIONAfter fusion surgeries, the total ROM of the cervical vertebrae decreases and the ROM of the adjacent segment increases. The stress peak of the intervertebral disc and facet joint of the adjacent segments also increases to significantly alter the physiological characteristics of the intact cervical vertebrae.

OBJECTIVETo investigate the pathogenic mechanisms of airway inflammation and recurrent wheezing induced by recurrent respiratory virus infection after respiratory syncytial virus (RSV) infection.

METHODSSixty-four female BALB/c mice (aged 6-8 weeks) were randomly divided into four groups: control, RSV, Poly(I:C), and RSV+Poly(I:C) (n=16 each). The bronchoalveolar lavage fluid (BALF) was collected on the 3rd day after Poly(I:C) administration, and the total cell number and differential counts in BALF were determined. Hematoxylin-eosin staining was used to observe pulmonary pathological changes. The airway responsiveness was detected. ELISA was used to measure the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-13 (IL-13), matrix metallopeptidase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in BALF.

RESULTSCompared with the other three groups, the RSV+Poly(I:C) group had significant increases in the total number of inflammatory infiltrating cells in the airway, airway responsiveness, and MMP-9 level in BALF (P<0.05). The RSV+Poly(I:C) group showed more severe pulmonary tissue injuries compared with the control and RSV groups (P<0.01). Compared with the RSV group, the RSV+Poly(I:C) group showed significant reductions in the levels of IL-4 and TIMP-1 in BALF (P<0.01).

CONCLUSIONSViral re-infection in the late stage of RSV infection may cause an imbalance of MMP-9/TIMP-1 expression and thus contribute to aggravated airway inflammation.

Animals ; Asthma ; etiology ; Bronchoalveolar Lavage Fluid ; chemistry ; Female ; Lung ; pathology ; Matrix Metalloproteinase 9 ; analysis ; Mice ; Mice, Inbred BALB C ; Poly I-C ; pharmacology ; Respiratory Syncytial Virus Infections ; complications ; Tissue Inhibitor of Metalloproteinase-1 ; analysis

OBJECTIVEThis study was designed to evaluate the prevalence of thyroid nodules (TNs) and its relationship with urine iodine concentrations (UICs) after the regional rapid economic growth and lifestyle changes.

METHODSA cross-sectional survey was conducted in the general population aged 15-69 years. A questionnaire regarding general and personal characteristics and relevant information was administered. Ultrasonography of the thyroid was performed, and serum triiodothyronine (T3), tetraiodothyronine (T4), serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and TSH receptor antibody (TRAb) levels were measured for each individual subject.

RESULTSThe prevalence rates of TNs in the whole population, females and males were 27.76%, 34.04%, and 21.60%, respectively. The prevalence of multiple nodules increased with age, whereas the prevalence peaks differed between males and females. The median UICs in the whole population and females with non-TNs were higher than those of subjects with TNs (P=0.0035, P=0.0068). The median UICs in subjects with a single TN were higher than those in subjects with multiple TNs (P=0.0164, P=0.0127). The result showed a U-shaped curve relationship between UIC and prevalence of TNs. The prevalence of TNs was the lowest when the UIC was 140-400 μg/L.

CONCLUSIONThe prevalence of TNs was nearly 30% and increased with age. The relationship between UIC and prevalence of TNs is U-shaped, with an increase in risk when the UIC was <140 μg/L and >400 μg/L. Very low or high UIC levels need attention and correction.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Iodine ; urine ; Male ; Middle Aged ; Nutritional Status ; Prevalence ; Thyroid Nodule ; chemically induced ; epidemiology ; Young Adult

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Objective The aim of the study was to investigate the epidemic situation,clinical symptom,diagnosis and epidemiological characteristics of human Fasciola gigantica infection in Dali,Yunnan province.It will also provide a scientific basis for fasciolosis control and prevention.Methods Epidemic data were collected and patient's clinical signs and symptoms were studied.Serum soluble antigen of Fasciola gigantica of patients and part of family members and health people in the same village was detected using enzyme-linked immunosorbent assay (ELISA) and the eggs of Fasciola gigantica in stool were observed under microscope.Sequencing and PCR amplification of Fasciola gigantica eggs had been done.Sequencing results were analyzed using basic local alignment search tool (BLAST) program of the U.S.National Center for Biotechnology Information (NCBI) and the similarity of the two in the sequence of nucleic acid was compared.Furthermore,patients were experimentally given orally therapeutic doses of Triclabendazole 10 mg·kg-1·d-1 daily for 2 days,and kept in the hospital for observation for one week.Moreover,host and vector were investigated in the surrounding ditches of Dali prefecture and Limnaea peregra snail samples were collected.All the snails were squashed by glass sheet in order to detect the cercarie.Cow dung and sheep manure was collected in the Limnaea peregra distribution environment,and the eggs in the feces were checked by microscope after washing and precipitation.Results All the 26 patients had a continued hyperpyrexia with distinct alimentary system symptoms of nausea,vomiting,stomachache,abdominal distension as well as hepatomegaly,sensitive to percussion,different levels of liver damage detected by CT.All the patients had an eaten history of raw Herba Houttuyniae and other aquatic plants,and the course of the disease was similar,with the same epidemiological characteristics.ELISA detection was used in the 26 patients,family members and other healthy population,the results of all the 26 patients were positive(100.0％,26/26) ; the positive rates of the 57 family members and other health people of the same village were 31.6％ (18/57) and 17.1％ (6/35),respectively.The results of sequencing and BLAST program showed that the pathogen was Fasciola gigantica with the similarity between 99％-100％.PCR amplification also confirmed that the eggs were Fasciola gigantica eggs with an approximately 1000 bp band on agarose gel.After treatment with Triclabendazole,body temperature of the patients dropped to normal and symptoms improved markedly.Moreover,329 Limnaea peregra snails were collected including 5 ones with redia and one-tailed cercariae which were preliminary identified as the larva of Fasciola gigantica.There were also eggs of Fasciola gigantica detected in one stool of cattle and one of goat.Conclusions Eating raw food is the leading cause of the onset of the disease.Triclabendazole is the drug of choice to treat Fasciolasis.Health education should be strengthened by government and disease prevention and control departments in order to make the local residents to understand the potential hazard of eating raw aquatic vegetable and drinking unboiled water,which is the key to prevent the occurrence of the disease.