Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

ObjectiveTo determine the prevalence of hepatitis C virus （HCV） infection and identify the underlying risk factors among drug users in Taizhou City of Zhejiang Province during 2009‒2020. MethodsA consecutive cross-sectional survey was conducted. A total of 400 drug users in correctional settings were randomly selected from April to August. The drug users were interviewed with a questionnaire to collect demographic characteristics， AIDS-related knowledge， detoxification service， drug use， and sexual behavior. Blood samples were then collected for anti-HCV antibody testing. Chi-square test and multivariate conditional logistic regression were used. ResultsA total of 5 042 drug users were included in this study. Seroprevalence of HCV was determined to be 22.7%. From 2009 to 2019， the seroprevalence showed a significant downward trend， from 34.9% to 8.8% （χ²=221.025， P<0.001）. However， in 2020， the seroprevalence was 12.7%. The multivariate logistic regression analysis showed that senior age （≥25 years old）， cohabitation， taking traditional or mixed drugs， injection drug use， and needle sharing were risk factors associated with HCV seroprevalence. ConclusionSince 2009， HCV seroprevalence among drug users in Taizhou City has shown a downward trend， however， it has increased slightly in 2020. It warrants strengthening prevention and treatment measures in response to risk factors related to HCV infection among drug users.

8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
Dimethylallyltranstransferase/metabolism* ; Flavonoids/metabolism* ; Molecular Docking Simulation ; Prenylation ; Saccharomyces cerevisiae/metabolism* ; Sophora/metabolism*

Saccharomyces cerevisiae is one of the most important hosts in metabolic engineering. Advanced gene editing technology has been widely used in the design and construction of S. cerevisiae cell factories. With the rapid development of gene editing technology, early gene editing technologies based on recombinase and homologous recombination have been gradually replaced by new editing systems. In this review, the principle and application of gene editing technology in S. cerevisiae are summarized. Here, we first briefly describe the classical gene editing techniques of S. cerevisiae. Then elaborate the genome editing system of MegNs, ZFNs and TALENs based on endonuclease. The latest research progress is especially introduced and discussed, including the CRISPR/Cas system, multi-copy integration of heterologous metabolic pathways, and genome-scale gene editing. Finally, we envisage the application prospects and development directions of Saccharomyces cerevisiae gene editing technology.
CRISPR-Cas Systems/genetics* ; Endonucleases/genetics* ; Gene Editing ; Saccharomyces cerevisiae/genetics* ; Technology

Relapse or metastatic esophageal squamous cell carcinoma (ESCC) has poor prognosis and limited treatment options. Chemotherapy based on platinum agents combined with fluorouracil or taxanes is the standard first-line treatment for it. Molecular-targeting agents, mainly epidermal growth factor receptor inhibitors including cetuximab, panitumumab, nimotuzumab and gefitinib, have failed to improve the survival of patients with advanced ESCC. Anlotinib, one of the small molecule multi-target tyrosine kinase inhibitors, can prolong the median progression free survival in patients treated with above the second line. Compared with chemotherapy, immune checkpoint inhibitors (including nivolumab, pembrolizumab and camrelizumab) significant improve overall survival times in patients with ESCC who fail to the first line chemotherapy, and can be selected as the standard second line treatment. Immunotherapy combined with chemotherapy or anti-angiogenic therapy for first-line treatment of advanced ESCC is also being studied.

Objective:To understand the personal dose level of nuclear medical workers in a hospital, and to provide basis for health management of nuclear medicine occupational population.Methods:From January 2014 to December 2018, 147 radiation workers in a hospital were selected as the monitoring objects, and the individual dose monitoring data were analyzed. The correlation between individual dose and clinical workload was analyzed.Results:The average annual personal dose of 147 staff members was below the national dose limit. Compared with the radiation department, the average annual personal dose of nuclear medical staff was higher, and the difference was statistically significant ( P<0.05) . There was a positive correlation between the annual average personal dose and the corresponding injection workload (Rs=0.69, P<0.05) . Conclusion:The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose. Conclusion The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose.

Objective:To understand the personal dose level of nuclear medical workers in a hospital, and to provide basis for health management of nuclear medicine occupational population.Methods:From January 2014 to December 2018, 147 radiation workers in a hospital were selected as the monitoring objects, and the individual dose monitoring data were analyzed. The correlation between individual dose and clinical workload was analyzed.Results:The average annual personal dose of 147 staff members was below the national dose limit. Compared with the radiation department, the average annual personal dose of nuclear medical staff was higher, and the difference was statistically significant ( P<0.05) . There was a positive correlation between the annual average personal dose and the corresponding injection workload (Rs=0.69, P<0.05) . Conclusion:The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose. Conclusion The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose.

Objective To explore the clinical efficacy of bone grafting in the treatment of type Ⅱ odontoid fracture with pedicle screw fixation .Methods Of 14 cases with type Ⅱ odontoid fractures ,8 patients in group A received pedicle screw,lamina autologous bone grafts,6 cases of group B received simple posterior pedicle screw fixation.The operative time ,the amount of surgical bleeding and the postoperative cervical spine flexion and rotationwere observed at 3 months postoperatively ,and the patients were followed up for 5-45 months.Results All patients were followed up for 5-45 months,with an average of 26.5 months.The operation time was (1.83 ±0.5) h in the bone graft group,and (1.58 ±0.9)h in the non-bone graft group,the difference was statistically significant (t=2.842,P>0.05).The blood loss of the bone graft group was (150 ±16)mL,which of the non-bone graft group was (120 ±14) mL,the difference between the two groups was statistically significant (t =3.57,P >0.05).After 3 months,the flexion of the cervical spine of the bone graft group was (31.2 ±4.6)°,which in the non -grafted group was (32.3 ±5.7)°,the difference was statistically significant (t=0.675,P<0.05).The rotation of the bone graft group was (40.6 ±4.5)°,which in the non -graft group was (41.3 ±3.5)°,the difference was statistically significant (t=0.278,P<0.05).Both two groups had no vertebral artery and spinal cord injury ,wound healing. During the follow-up period,the two groups of patients had a good reduction of cervical spine ,no internal fixation lossening,fracture,fracture healing well,group A bone graft fusion.Conclusion For this type of fracture,simple atlantoaxial pedicle screw fixation compared with autologous iliac bone graft fusion treatment ,can save the operation time,reduce the amount of bleeding .

Objective To observe the effects and safety of oxycodone hydrochloride combined with parecoxib sodium in preventing postoperative hyperalgesia induced by remifentanil. Methods Eighty-eight ASA Ⅰ or Ⅱ patients undergoing elective laparoscopic myomectomy surgery were randomly divided into four groups (C,O,P,PO) with 22 cases in each group. Patients in group C,O,P,PO were given with 10 mL saline, 0.1 mg?kg-1 oxycodone hydrochloride, 40 mg parecoxib sodium, 0.1 mg?kg-1 oxycodone hydrochloride and 40 mg parecoxib sodium 30 min before the end of the surgery, respectively. The VAS scores were recorded at the end of surgery 30 min, 1 h, 2 h, 4 h, 8 h, and the cases of agitation, rigor, vomiting and increasing of analgesics were recorded. Results Compared with group C, the VAS scores in group O, P,PO were significantly lower(P<0.05). The VAS scores in group PO were lower than those in group O,P(P<0.05). The cases of agitation and rigor in group PO (0.0%, 5.0%) were less than those in group C (45.0%,23.0%) (P<0.05). The increased doses of analgesics in group PO(0) were less than those in groups C (12), group P (5), and group O (5)(P<0.05). Conclusion Oxycodone hydrochloride combined with parecoxib sodium can effectively prevent postoperative hyperalgesia induced by remifentanil, and reduce the incidence of postoperative agitation.

Objective To evaluate the diagnostic ability of fusion images of SWI and DWI in ischemic penumbra(IP)of patients with acute ischemic stroke(AIS).Methods 47 AIS patients were retrospective analyzed.Two neuroradiologists analyzed the fusion images of SWI and DWI respectively.SDM was defined as that the hypo-intensity signals of intramedullary or sulcal veins were dilated or increased on fusion images compared with contralateral areas.The results compared with the PDM,which was considered as the“gold standard”.Areas under the receiver operating characteristic curve(AUC)were used to assess the efficacy of SDM which determined by fusion images and compared to PDM.Chi-square test was used to analyze the consistency between the two neuroradiologists and also the consistency between SDM and PDM in IP assessment Results The fusion images of SWI and DWI had a high diagnostic efficacy compared to PDM, AUC of the two radiologists were 0.885,0.877,the diagnostic sensitivity were 84.2%,78.9% and specificity were 92.9%,96.4%respectively.There was also a high consistency in SDM assessment through fusion images between the two neuroradiologists (Kappa=0.908,P >0.05). Conclusion Fusion images of SWI and DWI have a high diagnostic efficacy in IP assessment,which may be considered as a simple approach for IP assessment in patients with AIS.