Objective To evaluate the value of transrectal real-time tissue elastography (RTE) targeted prostate biopsy in the peripheral zone combined with peak strain index.Methods One hundred and forty-one patients with suspicious prostate lesions in the peripheral zone were evaluated from February 2011 to February 2014.All the patients underwent RTE with a mean age of 71.6 years,PSA of 30 ng/ml,prostate volume of 50.3 ml and measured peak strain index (PSI).The diagnostic value of PSI was assessed by receiver operating characteristic (ROC) curve.Two-core RTE combined with PSI targeted prostate biopsy was taken and subsequently a 10-core systematic biopsy was taken.The value of RTE was evaluated.The data of targeted biopsy and systematic biopsy in prostate were both reviewed and statistically compared.Results Cancer was detected in 72 of 141 patients (PSI,mean 24.79),and 69 patients had benign prostate disease (PSI,mean 3.02).PSI value of prostate cancer was significantly higher than that of the benign lesions (P ＜ 0.05).Prostate cancer could be predicted with the highest sensitivity (87.5％) and specificity (88.6％) using the cutoff value of PSI ≥ 5.97 with an area under the curve of 0.95.RTE targeted biopsy combined with PSI could detect 95.6％ of moderate or high risk prostate cancer.One hundred and fifty-nine suspicious areas detected by RTE in 141 patients were biopsied with 2 cores for each area.The positive incidence of prostate cancer in RTE-targeted biopsy cores was 44％ and in systematic biopsy was 30.2％ (P ＜ 0.05).Among the 72 prostate cancer patients,63 cases (87.5％) were detected by RTE-targeted biopsy,62 cases (86.1％) by systematic biopsy (P ＞ 0.05).Conclusions RTE combined PSI can improve the detection rate of prostate cancer in the peripheral zone and likewise guide targeted biopsy combined with svstematic biopsy to detect more moderate or high risk prostate cancer.

@@

OBJECTIVETo prepare purified and concentrated coltivirus high titer antigen in order to further detect antibodies against coltivirus in serum sample of patients.

METHODSThe coltivirus in C6/36 cells was cultured and harvested at different time, and the titer was titrated. The virus was purified and concentrated by polyethylene glycol (PEG), and stored at -20 degrees and 4 degrees, with and without glycerol, respectively, then the titer of coltivirus antigen was tested by indirect ELISA. By using the antigen, coltivirus antibodies in serum samples from both suspected Japanese encephalitis (JE) and viral encephalitis (VE) patients were detected.

RESULTSThe highest titer of coltivirus was found at 3-4 weeks of culturing. The antigen titer could be maintained at least for 6 months, especially antigen with glycerol either at 4 degrees or at -30 degrees even for two years. Totally 1141 serum samples from patients diagnosed clinically as JE and VE were tested. The results showed that 130 samples were coltivirus IgM antibody positive and the average positive rate was 11.4% (130/1141). Among 41 samples of paired-serum from patients in Guangzhou Children's Hospital, 9 samples were positive, the positive rate was 22.0% (9/41) in which 5 samples were diagnosed clinically as VE.

CONCLUSIONSStable and purified coltivirus antigen was obtained in order to test coltivirus antibodies as well as development of kits. Coltivirus probably can cause summer-autumn encephalitis in China.

Antibodies, Viral ; blood ; Antigens, Viral ; isolation & purification ; Cell Line ; Coltivirus ; immunology ; Cryopreservation ; methods ; Enzyme-Linked Immunosorbent Assay ; Humans ; Reoviridae Infections ; blood

Catheter-associated bloodstream infection(CRBSI) is one of the most common hospital-associated infections, and the incidence of central line-associated blood stream Infections (CLABSI) is the highest in CRBSI. This paper analyzes the current monitoring system of CLABSI in China, and compares the concept and method of National Healthcare Safety Network (NHSN) monitoring system, in order to make suggestions for the CLABSI monitoring system in China, and further improve the quality of medical safety.

Objective To evaluate the correlation of CT enhancement parameters with Fuhrman grade in T1 (≤7 cm) clear cell renal carcinoma(ccRCC).Methods From September 2011 to November 2017,102 post-operation cases in our hospital proven to be T1 ccRCC were retrospectively analyzed.There were 71 males and 31 females,with a mean age of (59.1 ± 12.7)years (26 ～79 years),mean body mass index(BMI) of (24.0 ± 2.8)kg/m2 (14.3 ～ 31.6 kg/m2).Tumors of 55 patients were in left kidneys,47 in right kidneys.Fuhrman grade 1 and 2 were defined as low-grade group,meanwhile high-grade group included grade 3 and 4.There were 46 males and 21 females in low-grade group,with a mean age of (59.0 ± 13.2) years,mean BMI of (24.0 ± 2.9) kg/m2.In high-grade group,there were 25 males and 10 females,with a mean age of (58.8 ± 11.8) years,mean BMI of (24.2 ± 2.7) kg/m2.The maximum diameter and tumor enhancement value (TEVX),relative enhancement value (REVX) were measured and calculated.In arterial phase,X =1;in venous phase X =2.The total consumption amount of iodine was recorded.Comparisons of maximum diameter,TEV1,TEV2,REV1,REV2 and the total consumption of iodine between the two different groups were performed.The ROC curves of TEV1,TEV2,REV1,and REV2 were drawn to predict the grade of tumors..Results The TEV1 [(146.1 ± 29.1) HU vs.(100.2 ± 32.1) HU],TEV2 [(98.2 ± 22.9) HU vs.(75.6 ± 25.7) HU],REV1 (1.12 ± 0.24 vs.0.70 ± 0.16),REV2(0.67 ± 0.17 vs.0.54 ± 0.18) between low-grade group and high-grade group had statistical difference (P ＜ 0.05).There was no significant difference in the maximum diameter[(41.8 ± 15.4)mm vs.(45.3 ± 17.0)mm] and the total consumption of iodine [(33.3 ± 5.0)g vs.(34.2 ± 4.4)g] between the two groups (P ＞ 0.05).The area under ROC curve of TEV1,TEV2,REV1 and REV2 were 0.856,0.755,0.901 and 0.728,respectively.REV1 had the highest distinguish efficiency and the best critical value was 0.93.Conclusions The enhancement parameters of T1 ccRCC could contribute to predicting the Fuhrman grade.When the REV1 ≤0.93,the tumor tended to be high-grade tumor(Fuhrman grade 3-4).

Objective:To analyze the effect of immersive scenario simulation training on improving the competency of infection prevention for health-care workers (HCWs).Methods:Taking the implementation time of immersive scenario simulation teaching training in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (August 2020) as the boundary, 352 new HCWs entered the hospital before the training (August 2019) were included as control group taking traditional teaching method, and 298 new HCWs entered the hospital after the training (August 2020) were included as observation group taking immersive scenario simulation combined with theoretical training. The mastery status of nosocomial infection-related knowledge and the implementation status of infection control measures (hand hygiene compliance, hand hygiene accuracy, correct personal protective equipment (PPE) selection, 100% of pass rate of PPE on and off, and qualified disposal of medical waste) were compared between the two groups of HCWs after theoretical teaching and different forms of practical training. The training effect (final assessment results) and training satisfaction (Minnesota satisfaction questionnaire, MSQ) of the two groups of HCWs were compared. SPSS 22.0 was used for t test and chi-square test. Results:The assessment results of the two groups of new HCWs trained by theoretical lecturing and immersive scenario simulation training were significantly improved compared with those just received theoretical lecturing, and the results of observation group were significantly higher than those of control group ( P<0.05). The implementation status of infection control measures after practical training were obviously improved in the two groups of HCWs compared to after theoretical lecturing, and the correct rates of PPE selection and all the procedure of donning and doffing PPE of observation group were significantly higher than those of control group ( P<0.05), but there were no significant differences in the hand hygiene accuracy and qualified disposal of medical waste between the two groups ( P>0.05). At the end of training, the final assessment results and satisfaction MSQ score of HCWs in observation group were significantly higher than those in control group ( P<0.05). Conclusion:Immersive scenario simulation teaching and training intervention is beneficial to improve the mastery of nosocomial infection knowledge of new HCWs, standardize their clinical infection control behaviors such as hand hygiene and aseptic operation, and finally obtain good training effect of infection prevention competency.

Objective:To investigate the effects of hyperuricemia on the prognosis of IgA nephropathy (IgAN) using propensity score matching (PSM) method.Methods:IgAN patients proven by biopsy were included. PSM was used to match patients. Kaplan-Meier method was used for survival analysis, and Cox regression analysis was used to analyze the effects of hyperuricemia on IgAN prognosis. Primary outcome events were defined as death, or end-stage renal disease (dialysis, transplantation), or a decrease in estimated glomerular filtration rate (eGFR) greater than 40%. Renal outcome was defined as end-stage renal disease (dialysis, transplantation), or a decrease in eGFR greater than 40%.Results:A total of 1 454 IgAN patients were included in this study, including 850 females and 604 males. Uric acid level was (368.26±92.87) μmol/L in the males, and (277.23±92.71) μmol/L in the females. The median follow-up time was 85.00(56.10, 106.33) months. During the follow-up period, a total of 134 patients reached the primary outcome events, including 5 deaths, 24 dialysis patients, 5 kidney transplant patients, and 100 patients with eGFR decreased by more than 40%. After 1∶1 matching, 131 males and 159 females in the hyperuricemia group were successfully matched with 131 males and 159 females in the normal uric acid group, and there was no significant statistical difference in each parameter in baseline between the hyperuricemia group and normal uric acid group after matching. Kaplan-Meier survival analysis showed that either before or after matching, the incidence of primary outcome events in male or female patients with hyperuricemia was higher than those with normal uric acid, but there was no statistically significant difference in incidence of primary outcome events between female hyperuricemia group and female normal uric acid group after matching (Log-rank test, χ2=3.586, P=0.058). Cox proportional hazard regression model showed that, in the pre-match fully adjusted model, the hazard ratio ( HR) of entering primary outcome events was 2.29-fold (95% CI 1.27-4.11, P=0.006) for men with hyperuricemia and 1.85-fold (95% CI 1.01-3.37, P=0.045) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering primary outcome events was 2.41-fold (95% CI 1.18-4.93, P=0.016) for men with hyperuricemia and 1.83-fold (95% CI 0.91-3.67, P=0.091) for women with hyperuricemia compared with those with normal uric acid. In the pre-match fully adjusted model, the HR of entering renal outcome events was 2.68-fold (95% CI 1.47-4.88, P=0.001) for men with hyperuricemia and 1.81-fold (95% CI 0.99-3.33, P=0.056) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering renal outcome events was 2.89-fold (95% CI 1.36-6.15, P=0.006) for men with hyperuricemia and 1.81-fold (95% CI 0.88-3.72, P=0.106) for women with hyperuricemia compared with those with normal uric acid. Conclusion:Hyperuricemia may be associated with IgAN progression, and it has a more significant effect on male IgAN patients.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.
Aging/physiology* ; Brain/physiology* ; Brain Mapping ; Humans ; Magnetic Resonance Imaging/methods* ; Nerve Net/physiology* ; Transcranial Direct Current Stimulation/methods*

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC