Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.

OBJECTIVE To study the effects of transferrin-targeting peptide T7 （7pep） on intracellular transportation of polyethylene glycol-polycaprolactone （PEG-PCL） micelles in human cervical cancer HeLa cells. METHODS Using coumarin-6 （C6） as fluorescent indicator probe， both coumarin-6 （C6）-loaded PEG-PCL （PEG-PCL-C6） micelles and 7pep-modified PEG- PCL （7pep-PEG-PCL-C6） micelles were prepared by film-dispersion method. The particle size， polydispersity index and appearance morphology were compared between two types of micelles； the real-time uptake of two types of micelles by HeLa cells was compared， and the colocalization of two types of micelles with early endosomes （EE）， endocytic recycling compartments （ERC） and late endosomes （LE） after entry into the cells was observed. RESULTS The particle sizes of PEG-PCL-C6 and 7pep-PEG-PCL- C6 micelles were（75.0±2.3）and（82.0±1.5）nm； the polymer dispersity indexes were 0.17±0.20 and 0.17±0.32， respectively， with a regular spherical appearance. The colocalization results showed that entry speed and amount of 7pep-PEG-PCL-C6 micelles were significantly faster/more than those of PEG-PCL-C6 micelles. 7pep-PEG-PCL-C6 micelles entered EE faster than PEG-PCL-C6 micelles， while PEG-PCL-C6 micelles entered ERC at a faster rate than 7pep-PEG-PCL-C6 micelles， and both PEG-PCL-C6 micelles and 7pep-PEG-PCL-C6 micelles tended to accumulate gradually in LE； Pearson coefficient， signal overlap ratio， and colocalization ratio of 7pep-PEG-PCL-C6 micelles with LE were significantly lower 60 minutes after entering the cell than those 30 minutes after entering the cell （P＜0.05 or P＜0.01）. CONCLUSIONS Targeting 7pep modification can increase the entry speed and amount of PEG-PCL-C6 micelles， and also alter their intracellular transportation behavior.

Objective This research aims to investigate the impact of Orff music therapy on long-term schizophrenic patients in hospitals.Methods The study was a randomized,single-blind controlled trial conducted from April,2023 to September,2023.From April to September 2023,sixty-eight individuals diagnosed with persistent schizophrenia were enrolled and evenly distributed into a pair of cohorts:a treatment group of thirty-four people receiving the intervention,and an equal number forming the control group for comparative purposes.Individuals enrolled in the experimental arm of the study were administered Orff-music therapy alongside routine rehabilitation treatment across a span of two months.For a period of 8 weeks,the control group was given only standard rehabilitation treatment,whereas the research group underwent Orff-music therapy in addition to the standard rehabilitation treatment.Results Before treatment,there were no significant differences in the positive and negative symptoms scale(PANSS),the inpatient psychosis rehabilitation observe scale(IPROS)and the personal and social performance scale(psp)between two groups.After intervention,the PANSS showed that the changes were better in the study group than in the control group in 3 indicators:negative symptoms(-3.20±4.13 vs.-0.17±2.43,P<0.001),general symptoms(-2.79±3.83 vs.-0.17±2.99,P=0.003)and the total scores(-5.88±6.36 vs.0.00±4.08,P<0.001),but not in positive symptoms(P>0.05).The IPROS showed that the performances of patients in the study group were better than the control group in terms of participation in work therapy(-0.82±2.08 vs.0.23±2.10,P=0.041),socialization(-0.59±1.94 vs.0.53±1.69,P=0.014)and ability to live(-0.94±2.50 vs.0.15±1.48,P=0.033),the changes in scores before and after the intervention were significantly different when compared to the control group.The PSP showed that the changes in scores before and after the treatment of the study group was better than the control group in terms of social activity[0(-1,0)vs.0(0,0),P=0.011],and self-care[0(-1,0)vs.0(-0.25,0),P=0.012]were better than the control group.Conclusion For long-term hospitalized patients with chronic schizophrenia.Orff-music therapy can be a powerful tool for alleviating mental issues,fostering social functioning,and enhancing rehabilitation results.

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m²·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.
Humans ; Aged ; Azacitidine/therapeutic use* ; Prospective Studies ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols ; Leukemia, Myeloid, Acute/etiology* ; Proto-Oncogene Proteins c-bcl-2

The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.
Escherichia coli/genetics* ; Glutamine ; Zeolites/chemistry* ; Amino Acids

Objective To investigate the value of endovascular therapy for cognitive dysfunction in patients with moderate or severe vertebrobasilar artery stenosis. Methods A total of 78 patients with cognitive dysfunction due to basilar artery stenosis who were treated in the Outpatient and Inpatient Department of Neurology,People's Hospital of Rizhao,China from March 2019 to November 2022 were prospectively enrolled and divided into endovascular stenting(EVS) group and non-EVS group according to whether they underwent endovascular therapy. Before and after treatment,attention and processing speed-trail making test(TMT)-A,executive function-TMT-B,and mini-mental state examination(MMSE) were conducted. These neuropsychological tests were carried out again after 6 months of follow-up. Computed tomography perfusion examination was performed twice before and after treatment to evaluate the patients' cerebral blood perfusion. The clinical data of the two groups were compared to summarize the therapeutic effect on cognitive dysfunction. Results A total of 78 patients,aged(45.03±13.00)years,with a male-to-female ratio of 1.79∶1,were included in the study. There were no significant differences between the EVS group and the non-EVS group in age,sex,years of education,hypertension,diabetes,stroke history,smoking history,and drinking history(P>0.05). Within one week after treatment,MMSE improvement was significantly different between the EVS group and the non-EVS group(P<0.001). There were no significant differences in the changes in TMT-A and TMT-B between the two groups(P>0.05). After 6 months of follow-up,the improvements in MMSE,TMT-A,and TMT-B in the EVS group were better than those in the non-EVS group(P<0.05). In the EVS group,cerebral blood perfusion was significantly improved,the time to peak was significantly shortened,and the cerebral blood flow was increased. No similar changes were observed in the non-EVS group. Conclusion Endovascular stenting for vertebrobasilar artery stenosis has a certain clinical value in improving cognitive function,and the effect becomes more obvious with the extension of time.

Aim To investigate the inhibitory effect of copper gluconate and disulfiran on the PLpro of SARS-CoV-2 and to explore the effect of combination of them on PLpro.Methods SARS-CoV-2 PLpro was purified by recombinant expression technology of he effects of copper gluconate and disulfiram on PLpro activity were studied by enzyme kinetic method.Results Copper gluconate and disulfiram had high inhibitory activity on SARS-CoV-2 PLpro,Ubiquitin-7-Amino-4-methylcoumarin(Ub-AMC)was used as the fluorescent substrate.The IC50 of copper gluconate was 33.02 nmol·L-1,showing competitive inhibition,and the IC50 of disulfiram was 480.4 nmol·L-1,showing non competitive inhibition,and the combination of the two inhibitors showed the advantage of synergistic inhibition.Conclusions Copper gluconate and disulfiram have a high inhibitory effect on SARS-CoV-2 PLpro protein,and the combination shows the advantage of synergistic inhibition.

Objective　To study the clinical characteristics and differentiation between TS-AMCI and AF-AMCI.It aims to help clinicians better distinguish and treat patients with two diseases.Methods　The clinical symptoms,imaging tests,prognostic data of 30 TS-AMCI (TS-AMCI group) and 39 AF-AMCI (AF-AMCI group) who received hospital treatment from June 2017 to June 2020 in Rizhao people’s Hospital were retrospectively analyzed.Results　The proportion of hypertension,diabetes and stroke history in TS-AMCI group was lower than that in AF-AMCI group (P＜0.05);But the plasma fibrinogen and D-dimer in TS-AMCI group were significantly higher than those in AF-AMCI group (P<0.001).The proportion of the number of cerebral infarction lesions less than 10 in DWI of TS-AMCI group was significantly lower than that in AF-AMCI group (P<0.001).The number of cerebral infarction lesions in bilateral anterior and posterior circulation in TS-AMCI group was significantly higher than that in AF-AMCI group(P＜0.001),while,AF-AMCI group was characterized by unilateral anterior circulation,which was significantly higher than that in TS-AMCI group (P＜0.001).The mRS score and the Death cases at 30 days of follow-up in TS-AMCI group were significantly higher than those in AF-AMCI group (P＜0.05).Conclusion　Compared with the AF-AMCI group.The traditional risk factors of stroke such as hypertension and diabetes in TS-AMCI group were more rare than those in AF-AMCI group.The plasma fibrinogen and D-dimer value increased more obviously and multiple small lesions in the blood supply area of multiple arteries were more common in TS-AMCI group.There was no significant difference in clinical manifestations at the onset of the disease between the two groups,but the prognosis of TS-AMCI group was poor at 30 days.