Objective To explore the antitumor small molecules targeting the ubiquitin–proteasome system (UPS) on the basis of active molecules from traditional Chinese medicine. Methods Ub^G76V-GFP stably expressing cell line was constructed to screen novel small molecule inhibitors targeting UPS. The fluorogenic substrates of Suc-LLVY-AMC, Z-LLE-AMC, and Boc-LRR-AMC were used to assess the effect of dioscin on the 20S proteasome hydrolase activity. The Ub-AMC substrate was used to evaluate the effect of dioscin on the intracellular deubiquitinating enzyme activity. Western blot was used to detect the effect of dioscin on intracellular ubiquitination levels. CCK-8 and colony formation assays were used to detect the inhibitory effect of dioscin on the tumor cell proliferation. Results Dioscin is a UPS inhibitor discovered through the Ub^G76V-GFP reporter system. It enhances intracellular ubiquitination and inhibits tumor cell proliferation and colony formation by targeting deubiquitinating enzymes. Conclusion Dioscin could significantly inhibit tumor cell proliferation by targeting ubiquitin–proteasome.

Objective To analyze the important abnormal results of physical examination of the staff in our hospital in recent 2 years,and to provide evidence for the health management of the staff in our hospital.Methods The physical examina-tion data of hospital staff in recent 2 years were retrospectively analyzed,and the important abnormal results were statistically ana-lyzed.Results A total of 3 584 employees participated in physical examination,including753 males and 2831 females.There were 92 cases with significant abnormal results,and the total detection rate was 2.57%.The detection rate of significant abnor-mal results was slightly lower in males(17cases,2.26%)than in females(75cases,2.65%),and the age of females[(48.89±19.53)years]was lower than that of males[(55.68±17.43)years].The age group with the most significant detec-tion rate of important abnormal results was 50-59 years old(3.07%),and the diseases detected by important abnormal results were as follows:There were 26 thyroid tumors,19 lung tumors,13 breast tumors,12 space occupying cases(3 liver,4 kidney,2 adrenal glands,1 adnexa,1 pancreas,1 mediastinum),9 vascular lesions,6 abnormal tumor markers,5 cervical lesions,1 tuberculosis,and 1 subdural hematoma.Among them,thyroid tumors,breast tumors,lung tumors and cervical lesions were the main cases in women,and vascular diseases,lung tumors,space-occupying lesions(liver and kidney)and thyroid tumors were the main cases in men.Conclusion Physical examination is of great significance in detecting important abnormal diseases.We should attach great importance to physical examination,detect serious diseases as early as possible,and strengthen health man-agement accordingly.

Objective:To evaluate the autogenous arteriovenous fistula(AVF) insufficiency by ultrasound monitoring of brachial artery resistance index(RI).Methods:The brachial artery RI and blood flow volume(FV) data of 828 patients who underwent color-Doppler ultrasound detection after AVF in the General Hospital of Western Theater Command from January 2019 to June 2021 were retrospectively analyzed. The patients were grouped according to the adequacy of clinical dialysis, including 668 patients in the group with normal AVF function and 160 patients in the group with insufficient AVF function. The general information and ultrasonic measurement parameters were compared between the two groups. The correlation between brachial artery FV and RI was analyzed. The evaluation of brachial artery flow RI for AVF insufficiency was analyzed by ROC curve.Results:There were statistically significant differences between the two groups in brachial artery RI and FV(both P<0.001). The results of Pearson correlation analysis showed that brachial artery FV was negatively correlated to RI ( r=-0.657, P<0.001). The area under ROC curve for assessing AVF function by brachial artery RI was 0.970, with 95% CI was 0.955-0.986, the optimal cut-off value was 0.665, and the sensitivity and specificity were 0.888 and 0.955, respectively. Conclusions:Brachial artery RI in patients with AVF insufficiency is significantly higher than that in patients with normal AVF function. The optimal cutoff value of brachial artery RI can be used as an evaluation parameter for rapid screening of AVF function.

Objective To explore the prognostic values of telomerase reverse transcriptase promoter (TERTp) mutation and 1p/19q co-deletion in newly-diagnosed O6-methylguanine-DNA methyltransferase (MGMT) promoter un-methylated/isocitrate dehydrogenase (IDH) wild-type glioblastoma multiform (GBM). Methods A total of 82 patients pathologically newly-diagnosed MGMT promoter un-methylated/IDH wild-type GBM, admitted to our hospitals from March 2016 to November 2018, were included in this study. TERTp mutations (TERTp wild-type and TERTp mutation [C228 mutation and C250 mutation]) in GBM specimens were detected by PCR sequencing, 1p/19q co-deletion in GBM specimens was detected by fluorescence in situ hybridization (FISH), and clinical data, adverse reactions and prognoses of patients with different molecular typing were compared. Results There were 33 patients in the TERTp wild type group with mean age of 48 years, and 49 patients in the TERTp mutation group with mean age of 59 years; the difference of age was significant (P<0.05); there were no statistical differences in gender distribution, Karnofsky performance status (KPS) scores, tumor sites and surgical resection degrees between the two groups (P>0.05). There were 8 patients with 1p/19q co-deletion and 74 patients without 1p/19q co-deletion; no significant differences in above clinical parameters were noted between the two groups. There were no statistically significant differences in the incidences of bone marrow suppression, digestive tract response and fatigue, disease progression rate, or survival rate between patients from TERTp wild type group and TERTp mutation group, and between patients with 1p/19q co-deletion and patients without 1p/19q co-deletion (P>0.05). No significant differences in above clinical parameters, disease progression rate, and survival rate were noted between patients with C228 mutation and C250 mutation (P>0.05). Conclusion TERTp typing and 1p/19q co-deletion status do not have prognostic value in newly-diagnosed MGMT un-methylated/IDH wild-type GBM patients; patients with TERTp mutations have older age than wild-type patients; patients with C250 mutation trend to have higher survival rate than those with C228 mutation.

The activation of p21 kinase 2 (PAK2) has a certain value in cancer research, since its participation in a series of intracellular biological activities. There is a relatively little research on its relationship with the development of tumors. PAK2 can be activated by a variety of upstream signals, especially small G protein Rho family of Rac and Cdc42, and it participates in a variety of important signaling pathways and cell function regulation. Abnormal expression of PAK 2 has been reported in various tumors, which involves in cytoskeletal remodeling, cell motility, apoptosis, signal transduction, gene transcription, translation and angiogenesis. Therefore, PAK2 plays an important role in tumor occurrence and development. The study on PAK2 and the targeting therapy for anti-PAK2 provides a new sight on the treatment and prevention of tumor.

Objective By studying clinical features, treatment and prognosis of eosinophilic gastroenteritis of infants resulted from milk protein allergy an, to improve the diagnosis and treatment level of eosinophilic gastroenteritis. Methods 24 cases of infants which diagnosed eosinophilic gastroenteritis were chosen from June of 2010 to January of 2014 in children’s Hospital of XX province and By retrospective analysis clinical manifestations, endoscopic features, histopathology, treatment and prognosis of the 24 cases. Results The 24 cases who were vomiting, paroxysmal crying, abdominal distension (100.00%), which accompanied by haematemesis 23 cases (95.83%), 1case (4.17%) hematochezia, 17cases (70.83%) eczema, 21 cases (87.50%) mild to moderate anemia, 1 cases (4.17%) severe anemia, 19 cases (79.17%) the increasing of peripheral blood eosinophil cells, 8 cases (33.33%)the increasing of IgE of the serum and 4 cases (16.67%) the test of antibody of the Helicobacter pylori in Serum was positive; 3 cases (12.50%) were milk protein allergy by the detecting of food allergen-speciifc IgE antibodies, the endoscopic characteristics were hyperemia, edema, erosion, ulcer of gastric and duodenal mucosa. Among them, 24 cases (100.00%) were gastritis, 5 cases (20.83%) duodenitis and 1 cases (4.17%) duodenal ulcer. The histopathology of the 24 cases revealed that there were gastric or duodenal eosinophils infiltration (> 20/HPF) and were all associated with mast cell infiltration; By antisecretory, protection of the gastrointestinal mucosa and the obviating of milk protein had a satisfactory treatment effect, 24 cases of children with oral general formula milk test conifrmed that the milk protein allergy, The 3 cases of the patients were reviewed by 8~12 weeks after gastroscope, and the mucosa of the duodenum was smooth, Eosinophils were/HPF<8, mast cells were/HPF<5. Conclusion There are no speciifc clinical and endoscopic manifestations in eosinophilic gastroenteritis of infants resulted from milk protein allergy, gastrointestinal mucosa eosinophil inifltration and simultaneously are accompanied by abnormal mast cell inifltration;Mucosal type without the use of corticosteroids, through milk protein avoidance treatment can achieve satisfactory results, But definite diagnosis must rely on biopsy and eosinophils, combined with avoidance stimulation test of milk protein can further confirmed, But the excitation test should be at least 10 days of observation of children, and carefully recorded symptoms, so as not to delay the missed diagnosis of CMPA.

Objective Observation and discussion about the treatment effect with home-made vacuum drainage and Algoplaque on severe pressure ulcers. Methods The patients with severe pressure ulcers selected from Yuebei Peole′s Hospital of Shaoguan city from January to December 2016 were randomly divided into three groups:experimental group, control group A and group B (30 cases in each). The patients were treated with home-made vacuum drainage and Algoplaque in the experimental group, meanwhile a simple use of Algoplaque treatment in control group A and VSD technology in control group B only. Observed and compared the effect in the three groups on the time of dressing change, wound healing time and the total cost. Results The wound healing time of experimental group.contral group A and group B were (24.10 ± 2.12), (33.26 ± 1.71), (27.87 ± 1.95) days, the times of dressing change were 5.52 ± 0.96, 35.84 ± 1.81, 7.23 ± 1.09, dressing costs were (629.95 ± 28.10) yuan, (1354.29 ± 301.63) yuan, (10825.38±1678.21) yuan, and the differences were statistically significant (F=175.961, 5017.527, 1029.377, all P<0.01), and the wound healing time, dressing times, dressing costs were lower than the control group A and B in the observation group. Conclusion The treatment of home-made vacuum drainage and Algoplaque on patients with severe pressure ulcers can obviously reduce the time of dressing change and wound recovery, and the cost also. It is worthy to promote in clinic.

Objective To explore preliminarily the role of the E2 subunit of pymvate dehydrogenase (PDC-E2) modified by xenobiotics (e.g.2-octynic acid,2-OA) in the pathogenesis of primary biliary cirrhosis (PBC).Methods Patients of PBC (102 cases),primary sclerosing cholangitis (PSC,34 cases) and healthy controls (HC,50 cases) were selected.The anti-PDC-E2,anti-2-OA and anti-lipoic acid (LA) antibody in the peripheral blood of the 3 groups were tested by enzyme linked immunosorbent assay (ELISA).By inhibitive ELISA (iELISA),30 of the 102 PBC patients with anti-PDC-E2 antibody but without anti-2-OA antibody were selected to detect whether there was any new epitope on the PEC-E2 conjugated with 2-OA.The chi-square test and Fisher exact test were taken to analyze the enumeration data.The two-tailed unpaired t test with Welch's correction was used to compare the measurement data.Spearman rank correlation analysis was also employed for proper test.Results The positive rate of anti-PDC-E2,anti-LA and anti-2-OA antibody in PBC patients was 94.1％(96/102),73.5％(73/102) and 53.9％(55/102) respectively,all of which were statistically significantly higher than those in healthy controls group but were of no significant difference between PSC and healthy controls group.There was no significant relevance between the levels of Anti-LA and anti-2-OA antibody in the PBC group (r=-0.065,P=0.520).The iELISA results showed that the antibody,which only identified the epitopes on 2-OA-PDC-E2 induced by the 2-OA conjugation with PDC-E2,existed in 40％(12/30) of the PBC patients,and more interestingly,this antibody was predominantly appeared in PBC patients at their early clinical stage.Conclusion There are anti-LA antibody and anti-2-OA antibody in PBC patients,which have shown no significant association with each other.It is very likely that new antigenic conformational epitopes on PDC-E2 modified by 2-OA would emerge,which might led to the immune response in the individuals who are susceptible to PBC,and thus contribute for the breaking of PDC-E2 immune tolerance,and PBC occurrence finally.

Objective To investigate the effect of continuing nursing on elderly patients with high risk of pressure sores. Methods High-risk elderly patients with pressure sores healed in our hospital in January 2014 to December 2014 were divided into control group and observation group with 130 cases in each group by random number table. The control group received routine follow-up service, while the observation group were intervened by continuing nursing care. To observe the differences before and after the interventions in both groups on the patient's quality of life and the incidence of pressure sores. Results There was statistically significance on mental function scores (t=12.393, P=0.000), social function score (t=8.459, P=0.000) and overall quality of life score (t=12.750, P=0.000) between the two groups after the interventions. Meanwhile, there was no statistically significance on material life score (t =-1.913, P=0.057) and physical function score (t=-0.328, P=0.744). The difference of the re-occurrence of pressure sores in the two groups was statistically significant (χ2=35.96, P=0.000), either. Conclusions Continuing nursing intervention can obviously reduce the risk the re-occurrence of pressure sores on high-risk elderly patients, in particular to improve the quality of life aspects of mental function and social function in patients, meanwhile with no obvious improvement in that of material life and body functions.

We wished to select a cold-adapted genotype G1P[8] ZTR-68 rotavirus (China southwest strain) in MA104 cells for possible use as a live vaccine. ZTR-68 was recovered originally from children with diarrhea. The virus was cultivated at 37 degrees C at the first passage. Then, the cultivation temperature was decreased stepwise by 3 degrees C per eight passages. In total, the virus was passaged 32 times, and cultivation was terminated at 28 degrees C. Biological characteristics of the virus were analyzed during serial passages. There was no difference between the migration patterns of genomic dsRNA segments according to polyacrylamide gel electrophoresis of original and cold-adapted viruses. Infectious and red cell-agglutination titers of cold-adapted virus were lower than those of the parent virus. Also, the virus formed small-size plaques with irregular shapes at 31 degrees C and 28 degrees C. These results suggested that a genetically stable attenuated virus can be obtained through serial cold-adapted passages. Thus, an alternative strategy is provided by cold-adaption for development of attenuated live rotavirus vaccines.
Adaptation, Physiological ; China ; Cold Temperature ; Diarrhea ; virology ; Female ; Genotype ; Humans ; Infant ; Male ; Rotavirus ; genetics ; growth & development ; isolation & purification ; physiology ; Serial Passage ; Virus Cultivation ; Virus Replication