Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of Aspergillus nidulans, and its titer in fermentation is significantly affected by the ECB synthesis pathway and cell morphology. In this study, the key genes related to the transcription activation, hydroxylation, and cell morphology during ECB biosynthesis were investigated to increase the fermentation titer of ECB and to change the cell morphology of Aspergillus nidulans to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of ecdB and ecdK, the ECB titer increased by 25.8% and 23.7%, respectively, compared with that of the wild-type strain, reaching (2 030.5±99.2) mg/L and (1 996.4±151.4) mg/L. However, the deletion of fksA associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing ecdB was fermented in a 50-L bioreactor, in which the ECB titer reached 2 234.5 mg/L. The findings laid a research foundation for the subsequent metabolic engineering of this strain.
Fermentation ; Aspergillus nidulans/genetics* ; Echinocandins/genetics* ; Bioreactors/microbiology* ; Fungal Proteins/biosynthesis* ; Metabolic Engineering

Objective To investigate the clinical efficacy of Qi Shi Shen Shu Capsule combined with dapagliflozin in treating type 2 diabetic nephropathy.Methods 120 patients with type 2 diabetic nephropathy(qi-yin liangxu syndrome)admitted to the endocrinology department in the inpatient and outpatient depart-ments of endocrinology from May 2022 to December 2023 were randomly divided into control and observation groups(60 cases each).The control group received dapagliflozin plus placebo capsules,while the observation group received dapagliflozin plus Qi Shi Shen Shu Capsule for 6 months.The therapeutic effects were observed between the two groups.Parameters including serum creatinine(Scr),urinary albumin-to-creatinine ratio(uACR),24-hour urinary protein quantification(24hUP),glycated hemoglobin(HbA1c),and tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and high sensitivity-C reactive protein(hs-CRP)were measured be-fore and after treatment.Results The total effective rate was higher(P＜0.05)in the observation group(93.33％)than in the control group(78.33％).After treatment,both groups showed decreased levels of uACR,Scr,24hUP,HbA1c,TNF-α,IL-6,and hs-CRP compared with baseline,with lower levels in the obser-vation group(P＜0.05).Conclusion Qi Shi Shen Shu Capsule combined with dapagliflozin can effectively re-duce uACR,Scr levels and serum inflammatory cytokines levels in patients with type 2 diabetic nephropathy.

Objective This study aims to evaluate the safety and efficacy of internal carotid artery(ICA)embolization for the resection of head and neck tumors invading the ICA.Methods A retrospective analysis was conducted on eight patients with ICA-invading head and neck tumors treated between August 2022 and June 2024 in Beijing Tongren Hospital,Capital Medical University.All patients underwent a preoperative balloon occlusion test(BOT),which yielded negative results before undergoing ICA embolization.Parameters from BOT,technical success rates of embolization procedures,perioperative complications,and follow-up outcomes were recorded.Results During BOT assessments,the mean reflux pressure was found to be 75.4％±10.3％of the pre-occlusion pressure.Patency of both anterior and posterior communicating arteries was observed in three cases;four cases exhibited patency solely in the anterior communicating artery,while one case showed patency only in the posterior communicating artery.The technical success rate of embolization was 100％.One patient experienced acute cerebral infarction following embolization treatment,while two patients had migraine attacks post-procedure.All patients achieved complete tumor resection without new-onset neurological deficits.Conclusion For patients with head and neck tumors invading the ICA who are negative on BOT,preoperative ICA embolization is a safe and feasible approach that enhances surgical safety during tumor resection.

Objective:To explore the application value of multimodal MRI imaging in early neurological deterioration (END) and clinical prognosis prediction of acute ischemic stroke (AIS).Methods:A total of 200 AIS patients admitted to the Chengde Central Hospital from October 2019 to October 2022 were selected as the study subjects. Based on whether END occurred within 7 days of enrollment, there were 40 cases in the occurrence group and 160 cases in the non occurrence group. The influencing factors of END occurrence in AIS patients and the predictive value of multimodal magnetic resonance imaging (MRI) parameters on END were analyzed; According to the modified Rankin (mRS) score, patients were divided into good prognosis and poor prognosis groups, and the impact of multimodal MRI imaging parameters on the risk of poor prognosis in AIS patients was analyzed.Results:There were statistically significant differences in the apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and their differences before and after thrombolysis in multimodal MRI imaging parameters between the END group and the non END group, as well as in the National Institutes of Health Stroke Scale (NIHSS) score at admission, age, and time from onset to admission (all P<0.05). The difference between ADC and CBF before and after thrombolysis, time from onset to admission, NIHSS score at admission, and age were all independent influencing factors for the occurrence of END in AIS patients (all P<0.05). The area under the curve (AUC) of the combined prediction of the difference between ADC and CBF before and after thrombolysis for the occurrence of END in AIS patients was 0.924, which was higher than that predicted by a single indicator ( P<0.05). The incidence of poor prognosis in patients with END was significantly higher than that in patients without END ( P<0.05). The risk of poor prognosis in AIS patients with a difference of less than <45.83×10 -9 mm 2/s before and after ADC thrombolysis was 3.136 times higher than that in patients with ≥45.83×10 -6 mm 2/s. The risk of poor prognosis in AIS patients with a difference of less than 10.52 ml/(min·100 g) before and after ADC thrombolysis was 2.640 times higher than that in patients with ≥10.52 ml/(min·100 g). Conclusions:Multimodal MRI imaging can be used for END evaluation in AIS patients and can provide reference for clinical prognosis evaluation.

OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

BACKGROUND:For the patients who have undergone unicompartmental knee arthroplasty,although the surgical effect is clear,there is still a lack of effective quantitative evaluation tools,and it is necessary to further explore the early postoperative gait and stability changes. OBJECTIVE:To investigate the changes in gait and stability before and after unicompartmental knee arthroplasty. METHODS:From May 2021 to May 2022,30 patients aged(63.80±9.31)years who planned to perform unilateral unicompartmental knee arthroplasty in the Department of Joint Surgery,Affiliated Hospital of Xuzhou Medical University were selected as the unicompartmental knee arthroplasty group.15 healthy elderly patients aged(61.28±8.60)years without a history of hip and knee pain and hip and knee joint dysfunction were recruited as the control group.Hospital for special surgery scores,stability parameters(center of pressure path length,95%confidence ellipse area)and gait parameters(pace,stride length,stride frequency,gait cycle,and the proportion of single support period)were recorded and compared in the control group and unicompartmental knee arthroplasty group before operation,1 and 3 months after operation. RESULTS AND CONCLUSION:(1)There was no significant difference in the step frequency between the patients 1 month after operation and those before operation in the unicompartmental knee arthroplasty group(P＞0.05).The stability of 1 month after operation was worse than that before operation,and other parameters of 1 month after operation were better than those before operation,and the difference was statistically significant(P＜0.05).(2)Hospital for special surgery score,gait and stability parameters at 3 months after operation were better than those before operation(P＜0.05).(3)Compared with the control group,the pace,stride length,stride frequency,and the proportion of single support period of the unicompartmental knee arthroplasty group were significantly lower before and 3 months after operation.Center of pressure path length,95%confidence ellipse area and gait cycle were greater in the unicompartmental knee arthroplasty group than those in the control group,with statistically significant differences(P＜0.05).(4)It is indicated that gait analysis is an effective means to quantitatively evaluate the rehabilitation status after unicompartmental knee arthroplasty.The early gait recovery after unicompartmental knee arthroplasty is good,but the gait frequency improvement is not obvious and the stability is poor 1 month after the operation.

Objective To explore the effect of transcutaneous electrical acupoint stimulation bracelet at Neiguan acupoint on the postoperative nausea and vomiting after thyroidectomy under general an-esthesia.Methods Seventy-two female patients underwent thyroidectomy,aged 18-50 years,ASA physical status Ⅰ or Ⅱ,were enrolled.The patients were assigned 1 ∶ 1 to two groups by permuted block randomization:the electrical stimulation group and the control group,36 patients in each group.Before an-esthesia induction,patients in both groups wore domestic transcutaneous electrical acupoint stimulation bracelets,and the electrodes were aimed at Neiguan acupoint.The electrical stimulation group started to stimulate Neiguan acupoint,and adjusted the proper intensity to make the patient feel tingling in the related area of the hand.When the bracelet was fixed firmly,turned it off.At the end of the operation,the bracelet was turned on with the stimulation intensity set before induction for 24 hours.Patients in the control group also wore the bracelet for 24 hours,but it was never turned on.The number of cases of postoperative nausea and vomiting(PONV)and the number of remedial cases of antiemetic drugs were recorded.Results Compared with the control group,the incidence of PONV and postoperative vomiting in the electrical stimula-tion group were significantly reduced within 24 hours after surgery(P＜0.05),and the differences were mainly in 1-6 hours after surgery(P＜0.05).There was no significant difference in the rate of remedial ca-ses of antiemetic drugs between the two groups at different time periods.Conclusion Transcutaneous electri-cal stimulation bracelet at Neiguan acupoint can effectively reduce the incidence of PONV within 24 hours after thyroidectomy.

Objective:To evaluate the quality of test papers and to analyze students'mastery of knowledge through the analysis of test papers,so as to provide reference for the reform of test proposition and correction teaching.Methods:Using paper analysis software(Ver 2.0),the paper quality,the students'scores and the answers to the questions of the final exam paper of Physiology of grade 2021 students majoring in nursing were analyzed.Results:The composition of the test paper was consistent with the requirements of the teaching programme,the difficulty of subjective and objective test questions was moderate,the differentiation of subjective test questions was good,the differentiation of objective test questions was general,and the reliability and validity were good.The overall performance was basically normal distribution.The full score ratio of objective test questions was higher than that of subjective test questions,and the zero score test questions were mostly concentrated in chapter 10 and chapter 4.Conclusion:Test paper analysis can feedback the problems and shortcomings of test paper proposition and teaching process,promote the quality of test paper and teaching model innovation,and improve the quality of teaching.

Objective:To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency.Methods:This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups.Results:Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was ( M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group ( P<0.01). Conclusions:Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.