Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals.

Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively explore the mechanisms underlying this age-related disparity, we conducted the integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, and elucidated six functionally and spatially distinctive macrophage groups and lymphocytes surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we characterized the dysfunction of Spp1+ macrophages in aged mice impeded the activation of the type Ⅱ immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.

Neoadjuvant immunotherapy combined with chemotherapy in the treatment of stage III lung squamous cell carcinoma: a retrospective cohort study.

Background: Neoadjuvant immunochemotherapy has been proven to be a successful therapeutic strategy for patients with locally advanced non-small cell lung cancer (NSCLC). Nevertheless, there is a paucity of information regarding surgical feasibility and safety as well as tumor response. The present study aimed to investigate the therapeutic and surgical outcomes for patients with stage III lung squamous cell carcinoma (LSCC). Methods: Patients with stage III potentially resectable LSCC treated with neoadjuvant immunochemotherapy at The First Affiliated Hospital of Ningbo University between March 2020 and June 2022 were retrospectively included. Oncologic outcomes and intraoperative and postoperative variables were assessed. Results: A total of 17 locally advanced LSCC patients were included in the study. Patients in stages IIIA and IIIB were represented by 10 (58.8%) and 7 (41.2%) cases, respectively. A minimally invasive procedure was successfully completed in 12 out of 17 cases (70.6%). A total of 10 patients (58.8%) had standard lobectomies performed, 1 (5.9%) had a bilobectomy, 3 (17.6%) had pneumonectomies, and 1 (5.9%) had a wedge resection. A total of 7 patients (41.2%) experienced postoperative complications, and there were no 30- or 90-day mortalities. The 2-year disease-free survival (DFS) and overall survival (OS) rates were 76.6% and 82.5%, respectively. The rate of major pathological response (MPR) was 70.6%. Conclusions: Lung resection after immunochemotherapy for potentially resectable stage III LSCC is feasible and safe. This treatment strategy results in a significant pathologic response and promising rates of OS at 2 years.

Association of biopsy core number and location with pain in patients undergoing a transperineal prostate biopsy under local anaesthesia: a secondary analysis of the APROPOS trial.

BACKGROUND: APROPOS was a multicentre, randomized, blinded trial focus on investigating the perineal nerve block versus the periprostatic block in pain control for men undergoing a transperineal prostate biopsy. In the analysis reported here, the authors aimed to evaluate the association of biopsy core count and location with pain outcomes in patients undergoing a transperineal prostate biopsy under local anesthesia. METHODS: APROPOS was performed at six medical centers in China. Patients with suspected prostate cancer were randomized to receive either a perineal nerve block or a periprostatic block (1:1), followed by a transperineal prostate biopsy. The secondary analysis outcomes were the worst pain experienced during the prostate biopsy and postbiopsy pain at 1,6, and 24 h. RESULTS: Between 12 August 2020 and 20 July 2022, a total of 192 patients were randomized in the original trial, and 188 were involved in this analysis, with 94 patients per group. Participants had a median (IQR) age of 68 (63-72) and a median (IQR) prostate volume of 42.51 (30.04-62.84). The patient population had a median (IQR) number of biopsy cores of 15 (12-17.50), and 26.06% of patients had a biopsy cores count of more than 15. After adjusting the baseline characteristics, the number of biopsy cores was associated with the worst pain during the biopsy procedure in both the perineal nerve block group ( ß 0.19, 95% CI: 0.12-0.26, P <0.001) and the periprostatic block group ( ß 0.16, 95% CI: 0.07-0.24, P <0.001). A similar association was also evident for the postbiopsy pain at 1, 6, and 24 h. A lesser degree of pain in both groups at any time (r range -0.57 to -0.01 for both groups) was associated with biopsy cores from the peripheral zone of the middle gland, while other locations were associated with a higher degree of pain. In addition, the location of the biopsy core had less of an effect on pain during the biopsy (r range -0.01-0.25 for both groups) than it did on postbiopsy pain (r range -0.57-0.60 for both groups). CONCLUSIONS: In this secondary analysis of a randomized trial, biopsy core count and location were associated with pain in patients undergoing a transperineal prostate biopsy under local anesthesia. These results may be helpful for making clinical decisions about the anesthetic approach for scheduled transperineal prostate biopsies.

Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

Preparation of colloidal gold test strips for the detection of antibodies to peste des petits ruminants based on monoclonal antibodies to N protein / 生物工程学报

A simple, fast, and visual method for detecting antibodies against peste des petits ruminants virus (PPRV) using colloidal gold strips was developed. In this study, the pET-32a-N was transformed into Escherichia coli Rosetta (DE3) for expression. Hybridoma cell lines were generated by fusing SP2/0 myeloma cells with splenocytes from immunized mice with the expressed and purified N protein of PPRV. The PPRV N protein was labeled with colloidal gold particles as the gold-labeled antigen. The N protein served as the gold standard antigen and as the test (T) line-coated antigen, while the monoclonal antibody served as the quality control (C) line-coated antibody to assemble the colloidal gold immunochromatographic test strips for detecting antibodies against the N protein of PPRV. Hybridoma cell line designated as 1F1 was able to stably secrete the monoclonal antibody against the N protein of PPRV. The titer of 1F1 monoclonal antibody in ascites was 1:128 000 determined by indirect enzyme-linked immunosorbent assays (ELISA), and the immunoglobulin subtype of the monoclonal antibody was IgG1, with kappa chain. The obtained monoclonal antibody was able to specifically recognize the N protein of PPRV, as shown by Western blotting and indirect immunofluorescent assay (IFA). The developed colloidal gold test strip method was able to detect PPRV antibodies specifically, and there was no difference between different batches of the test strips. Testing of a total of 122 clinical sera showed that the compliance rate of the test strip with ELISA test was 97.6%.The test strip assay developed in this study has good specificity, reproducibility, and sensitivity, and it can be used for the rapid detection of PPRV antibodies.

Effectiveness and safety of transcatheter aortic valve replacement in treatment of aortic regurgitation: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To investigate effectiveness and safety of transcatheter aortic valve replacement in the treatment of aortic regurgitation. Methods     PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data and VIP were searched from inception to August 2021. According to the criteria of inclusion and exclusion, two reviewers independently screened the literature, extracted the data and evaluated the quality of the included studies. Then, Stata 16.0 software was used for meta-analysis. Subgroup meta-analysis of valve type used and study type was performed. Results    Twenty-five studies (12 cohort studies and 13 single-arm studies) were included with 4 370 patients. Meta-analysis results showed that an incidence of device success was 87% (95%CI 0.81-0.92). The success rate of the new generation valve subgroup was 93% (95%CI 0.89-0.96), and the early generation valve subgroup was 66% (95%CI 0.56-0.75). In addition, the 30-day all-cause mortality was 7% (95%CI 0.05-0.10), the 30-day cardiac mortality was 4% (95%CI 0.01-0.07), the incidence of pacemaker implantation was 10% (95%CI 0.08-0.13), and the incidence of conversion to thoraco-tomy was 2% (95%CI 0.01-0.04). The incidence of moderate or higher paravalvular aortic regurgitation was 6% (95%CI  0.03-0.09). Conclusion     Transcatheter aortic valve replacement for aortic regurgitation is safe and yields good results, but some limitations can not be overcome. Therefore, multicenter randomized controlled trials are needed to confirm our results.

Progress of Biomarkers to Predict Response to Immune Checkpoint Inhibitors in Microsatellite Stability Colorectal Cancer / 肿瘤防治研究

The exploration of biomarkers predicting response to immune checkpoint inhibitors in microsatellite stability colorectal cancer can enable more patients to benefit from immunotherapy. Tumor mutational burden (TMB), POLE/POLD1 mutation, CMS classifications, MGMT methylation, and other indicators own the potential and value of predicting response to immune checkpoint inhibitors in microsatellite stability colorectal cancer. In this paper, we reviewed the related research on predictive biomarkers of immune checkpoint inhibitors in microsatellite stability colorectal cancer, provide a reference for the best treatment strategy for microsatellite stability colorectal cancer.

Design and synthesis of peptide-drug conjugates and fluorescent probe based on α-conotoxin ArIBV11L,V16D / 药学学报

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC50 values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Comparison of transfemoral transcatheter aortic valve replacement under local versus general anesthesia in patients with aortic stenosis: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically review the efficacy and safety of transfemoral transcatheter aortic valve replacement (TFTAVR) under local anesthesia (LA) and general anesthesia (GA). Methods    Electronic databases including PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang and CBM were searched to collect randomized controlled trial and cohort studies on clinical outcomes of TFTAVR under LA and GA from inception to September 2020. Two authors independently screened literature, extracted data and assessed the quality of studies, and a meta-analysis was performed by using Stata 16.0 software. Results    A total of 30 studies involving 52 087 patients were included in this study. There were 18 719 patients in the LA group and 33 368 patients in the GA group. The results of meta-analysis showed that the in-hospital all-cause mortality rate [RR=0.65, 95%CI (0.45, 0.94), P=0.021], 30-day all-cause mortality rate [RR=0.73, 95%CI (0.62, 0.86), P<0.001], 30-day stroke [RR=0.82, 95%CI (0.68, 0.98), P=0.025], cardiac arrest [RR=0.50, 95%CI (0.34, 0.73), P<0.001], ICU stay time [RR=−6.86, 95%CI (−12.31, −1.42), P=0.013], and total hospital stay  time [RR=−2.02, 95%CI (−2.59, −1.45), P<0.001] in the LA group were all better than those in the GA group. There was no significant difference in the in-hospital stroke [RR=0.83, 95%CI (0.69, 1.00), P=0.053], in-hospital myocardial infarction (MI) [RR=1.74, 95%CI (0.43, 7.00), P=0.434], or 30-day MI [RR=0.77, 95%CI (0.42, 1.42), P=0.404] between the two groups. Conclusion    LA provides a safe and effective way to induce sedation without intubation, and may be a good alternative to GA for TFTAVR.

Gross tumor volume delineation in primary prostate cancer on 18F-PSMA-1007 PET/MRI and 68Ga-PSMA-11 PET/MRI.

BACKGROUND: We aimed to assess the clinical value of 18F-PSMA-1007 and 68Ga-PSMA-11 PET/MRI in the gross tumor volume (GTV) delineation of radiotherapy for prostate cancer (PCa). METHODS: Sixty-nine patients were retrospectively enrolled (57 in the 18F subgroup and 12 in the 68Ga subgroup). Three physicians delineated the GTV and tumor length by the visual method and threshold method with thresholds of 30%, 40%, 50%, and 60% SUVmax. The volume correlation and differences in GTVs were assessed. The dice similarity coefficient (DSC) was applied to estimate the spatial overlap between GTVs. For 51 patients undergoing radical prostatectomy, the tumor length (Lpath) of the maximum area was measured, and compared with the longest tumor length obtained based on the images (LMRI, LPET/MRI, LPET, LPET30%, LPET40%, LPET50%, LPET60%) to determine the best delineation method. RESULTS: In the 18F subgroup, (1) GTV-PET/MRI (p < 0.001) was significantly different from the reference GTV-MRI. DSC between them was > 0.7. (2) GTV-MRI (R2 = 0.462, p < 0.05) was the influencing factor of DSC. In the 68Ga subgroup, (1) GTV-PET/MRI (p < 0.05) was significantly different from the reference GTV-MRI. DSC between them was > 0.7. (2) There was a significant correlation between GTV-MRI (r = 0.580, p < 0.05) and DSC. The longest tumor length measured by PET/MRI was in good agreement with that measured by histopathological analysis in both subgroups. CONCLUSION: It is feasible to visually delineate GTV on PSMA PET/MRI in PCa radiotherapy, and we emphasize the utility of PET/MRI fusion images in GTV delineation. In addition, the overlap degree was the highest between GTV-MRI and GTV-PET/MRI, and it increased with increasing volume.

Cryopreservation Conditions of Carthamus tinctorius Seeds / 中国实验方剂学杂志

ObjectiveTo study on the suitable cryopreservation conditions of Carthamus tinctorius seeds. MethodThe germination rate，relative conductivity，soluble sugar，soluble protein， and related enzyme activities of C. tinctorius seeds， as well as the hydroxysafflor yellow A （HSYA） content in Carthami Flos after storage and breeding for four months were detected under different temperature conditions （long-term storage，medium-term storage，short-term storage，room temperature，and ultra-low temperature refrigerator），different water content （8.1%，6.6%，5.2%，and 3.9%），and different storage time （2，4，6，8， 10 months）. SPSS 20.0 was used for statistical analysis. ResultDuring the storage for 10 months，the changing trend of the germination rate of C. tinctorius seeds revealed that it was more suitable to store seeds with low water content at a lower temperature. The differences in germination rate of seeds caused by storage temperature，seeds water content， and storage time were statistically significant. After storage for 10 months，the germination rate was significantly correlated with other detection indexes. ConclusionThe proper water content of C. tinctorius seeds in long-term and medium-term storage is 5.2% or 6.6%，and that in short-term and ultra-low temperature refrigerator is 3.9% or 5.2%. As revealed by the comparison results， the optimal storage conditions for C. tinctorius seeds were long-term storage and water content of 5.2%， which resulted in the highest germination rate and content of soluble sugar and soluble protein and the lowest relative conductivity after storage for 10 months. Additionally， the content of hydroxy safflor yellow A （HSYA） in Carthami Flos obtained after breeding and regeneration for four months was higher than that obtained after room temperature storage.

Prognosis of new-onset left bundle branch block after transcatheter aortic valve replacement in patients with aortic stenosis: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically review the clinical outcome of patients with new-onset left bundle branch block (LBBB) following transcatheter aortic valve replacement (TAVR). Methods    Electronic search was performed in PubMed, EMbase, Cochrane Library, Web of Science, CNKI, Wanfang and CBM databases to identify studies about the new-onset LBBB after TAVR from inception to March 19, 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 15.0 software. Results    A total of 17 cohort studies were included, covering 9 205 patients, including 2 202 patients with new-onset LBBB and 7 003 without new-onset LBBB after TAVR. The results of meta-analysis showed that patients with new-onset LBBB after TAVR at 30-day (RR=1.65, 95%CI 1.30 to 2.10, P<0.001) and 1-year (RR=1.30, 95%CI 1.16 to 1.45, P<0.001) all-cause mortality was higher than no new-onset LBBB group. One-year cardiovascular mortality was higher in the new-onset LBBB group (RR=1.47, 95%CI 1.21 to 1.79, P<0.001). In the occurrence of 30-day (RR=1.51, 95%CI 1.10 to 2.08, P=0.011) and 1-year (RR=1.34, 95%CI 1.14 to 1.58, P=0.001) rehospitalization rate, 30-day (RR=3.05, 95% CI 1.49 to   6.22, P=0.002) and 1-year (RR=2.15, 95%CI 1.52 to 3.03, P<0.001) pacemaker implantation, the incidence of patients with new-onset LBBB was higher than that of the no new-onset LBBB group. Conclusion    Compared with the patients without LBBB after TAVR, the clinical prognosis of patients with new-onset LBBB after TAVR is poor. In the future, the management and follow-up of the patients with LBBB after TAVR should be further strengthened to improve the prognosis of patients.

Roles of STAT3 in radiation response, tumor progression and tissue repair / 中华放射医学与防护杂志

Signal transducer and activator of transcription (STAT) is a family of cytoplasmic transcription factors including seven proteins of STAT-1, -2, -3, -4, -5A, -5B and -6. The genes encoding the STAT family are located on are located on chromosome 2 (STAT1 and STAT4), chromosome 12 (STAT2 and STAT6) and chromosome 17 (STAT3, STAT5A and STAT5B). Among these seven proteins, STAT3 and STAT5 have the strongest correlation with tumor progression, and ionizing radiation can affect STAT3 level. Continuous activation of STAT3 can regulate a variety of functions, including cell proliferation, cell cycle progression, apoptosis, angiogenesis and immune escape. STAT3 is highly complex in its biological function and activator action. Therefore, it is of great significance to further study the biological function and signaling pathway of STAT3.

A Multicenter Single-Arm Objective Performance Criteria Trial to Determine the Efficacy and Safety of High-Frequency Irreversible Electroporation as Primary Treatment for Localized Prostate Cancer: A Study Protocol.

INTRODUCTION: The classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. An alternative pathway is to perform an ablation by some energy to the localized lesion, known as focal therapy. High-frequency irreversible electroporation (H-FIRE) is nonthermal energy that can be used in cancer ablation to deliver pulsed high-voltage but low-energy electric current to the cell membrane and to invoke cell death. An H-FIRE pathway has been reported to be tissue-selective, which leads to fewer side effects. METHODS AND ANALYSIS: This is a multicenter and single-arm objective performance criteria (OPC) study, in which all men with localized prostate cancer are allocated to H-FIRE ablation. This trial will assess the efficacy and safety of the H-FIRE ablation for prostate cancer. Efficacy will be assessed by prostate biopsy 6 months after treatment while safety will be assessed by adverse event reports and questionnaires. The main inclusion criteria are moderate to low-risk prostate cancer in NCCN risk classification and had no previous therapy for prostate cancer. A sample size of 110 participants is required. The primary objective is to determine whether the detection rate of clinically significant cancer by prostate biopsy is less than 20% after the H-FIRE ablation. ETHICS AND DISSEMINATION: This study has obtained ethical approval by the ethics committee of all participating centers. The results of the study will be submitted for dissemination and publication in peer-reviewed journals. CONCLUSIONS: This multicenter single-arm objective performance criteria trial will evaluate the efficacy and safety of the use of high-frequency irreversible electroporation in treating prostate cancer. STRENGTHS AND LIMITATIONS OF THIS STUDY: A comprehensive evaluation of imaging and histopathology is used to determine the effect of treatment. Questionnaires were used to assess the treatment side effects. Multicenter and pragmatic designs capacitate higher generalizability. A limitation of this trial is that the prostate biopsy as an endpoint may not be as accurate as of the specimen from prostate prostatectomy. Another limitation is the 6-month follow-up time, making this trial challenging to come to firm conclusions regarding the efficacy and safety of IRE in the long term. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03838432.

Cyclization of α-conotoxin A10LPnIA with lysine assisted cyanuric chloride linker / 药学学报

The cyanuric chloride linkers have been used for cyclizing polypeptide, but not used for α-conotoxin, the peptides with rich disulfide bonds and more amino acid residues. In this study, cyclic peptides c[A10L]PnIA-1-4 were synthesized efficiently by lysine assisted cyanuric chloride linkers with 28.92%-52.00% yields. The activity evaluation showed that the IC50 values of c[A10L]PnIA-1 against α7 and α3β2 nAChR subtypes were 5 and 7 times higher than [A10L]PnIA respectively, and the subtype selectivity was maintained. The results of circular dichroism show that this cyclization method had no significant effect on its secondary structure. Compared with the commonly used head-to-tail cyclization in conotoxin cyclization, this method has the advantages of rapid reaction and high yield, which is expected to be further applied to the cyclization study of various α-conotoxins.

Study on the Effect and Mechanism of Ganoderic Acid C 2 on Lipid Metabolism of Hepatocytes by Regulating S6K/SREBPs Signaling Pathway / 中国药房

OBJECTIVE：To stu dy in vitro lipid-lowering effect of ganoderic acid C 2（GAC2），and to investigate its potential mechanism on the basis of S 6K/SREBPs signaling pathway. METHODS ：Using human liver cells HL- 7702 as objects ，MTT assay was used to test relative cell viability after treated with low ，medium and high doses （5，10，20 μmol/L，hereinafter）of GAC 2. Using lovastatin as positive control ，ELISA method was used to detect the contents of TC and TG in cells after treated with low ， medium and high doses of GAC 2. Nile red staining was used to observe the accumulation of lipids in cells. After transfected SREBPs report gene plasmid ，using 25-HC as positive control ，relative viability of SREBPs luciferase in cells were determined by luciferase assay after treated with low ，medium and high doses of GAC 2. Using 25-HC as positive control ，real-time fluorescent quantitative PCR was used to measure the mRNA expression of SREBPs and their downstream genes in cells after treated with medium and high doses of GAC 2. Using SREBPs inhibitor （25-HC）and S 6K inhibitor （rapamycin）as control ，Western blotting assay was adopted to determine the expression of SREBP- 1 and SREBP- 2（in the case of n-SREBPs ），relative expression ratio of phosphorylated S 6K to S 6K（p-S6K/S6K ratio ）. AutoDock 4.0 and other softwares were used for molecular docking of S 6K and GAC2. RESULTS ：There was no significant effect of low ， 0.05）. Compared with blank control group ，the content of TC qq.com in lovastatin group and GAC 2 high-dose group as well as thecontent of TG in lovastatin group ， GAC2 medium- and 床应用。电话：0371-65962746。E-mail：whui3697@126.com high-dose groups were decreased significantly （P＜0.05 or P＜ 0.01）；the number of lipid droplets in the cells of all medication groups decreased. Compared with blank control group ，relative viability of SREBPs luciferase in 25-HC group ，GAC2 low-，medium- and high-dose groups were decreased significantly ；mRNA expression of HMGCS1，MVK，SCD，HMGCR gene in 25-HC group and GAC 2 medium-，high-dose groups ，mRNA expression of DHCR7 gene in 25-HC group ，mRNA expression of SREBP-2 gene in GAC- 2 high-dose group as well as mRNA expression of DHCR24 and MSMO2 gene in 25-HC group and GAC 2 high-dose group were all decreased significantly ；relative protein expression of n-SREBP- 1 in 25-HC group ，GAC2 low-，medium- and high-dose groups ，relative protein expression of n-SREBP- 2 in 25-HC group and GAC 2 high-dose group as well as p-S 6K/S6K ratio in rapamycin group and GAC 2 groups were decreased significantly （P＜0.05 or P＜0.01）. The molecular docking results showed that GAC 2 could bound to amino acid residues Arg 335，Arg330 and Ala332 of S 6K via hydrogen bond. CONCLUSIONS ：GAC2 can reduce the lipid level of HL- 7702 cells，which may be associated with inhibiting the expression of S 6K/SREBPs signaling pathway.

Comparing clinical outcomes between bicuspid and tricuspid aortic valve stenosis after transcatheter aortic valve replacement: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To compare the clinical outcomes of bicuspid aortic valve stenosis (BAV) and tricuspid aortic valve stenosis (TAV) after transcatheter aortic valve replacement (TAVR). Methods    A computer-based search in PubMed, EMbase, The Cochrane Library, CBM, CNKI and Wanfang databases from their date of inception to March 2019 was conducted. Two reviewers independently screened the articles, extracted data and evaluated their quality. RevMan 5.3 and Stata 15.0 softwares were used for meta-analysis. Results    The selected 15 cohort studies contained 45 770 patients, including 1 500 of BAV patients and 44 270 of TAV patients. The results showed that no statistical difference was found in postoperative in-hospital mortality [OR=1.29, 95%CI (0.91, 1.83), P=0.15], 30-day mortality [OR=1.23, 95%CI (0.86, 1.77), P=0.25], and 1-year mortality [OR=1.14, 95%CI (0.87, 1.50), P=0.33] between the two groups. The surgical success rate [OR=0.57, 95%CI (0.44, 0.74), P<0.01], postoperative bleeding events [OR=0.72, 95%CI (0.58, 0.91), P<0.01] and postoperative vascular injury [OR=0.68, 95%CI (0.47, 0.97), P=0.03] of patients in the BAV group were lower than those in the TAV group. The incidence of paravalvular leak in the BAV group was higher than that in the TAV group [OR=1.47, 95%CI (1.13, 1.90), P<0.01]. No significant difference was found between the two groups in terms of conversion to surgery, postoperative myocardial infarction, postoperative renal failure, postoperative neurologic events, postoperative valve gradient difference and pacemaker implantation. Conclusion    Compared with TAV, the application of TAVR in BAV patients is feasible and effective.

Application of three-in-one intelligent screening in outpatient department of children's hospital during COVID-19 epidemic / 浙江大学学报·医学版

OBJECTIVE@#To evaluate the application of three-in-one intelligent screening in outpatient pre-inspection in children's hospital.@*METHODS@#We randomly enrolled 100 children pre-screened by traditional method in the outpatient department of Children's Hospital of Zhejiang University from February 6th to 16th, 2020, and another 100 children by the intelligent three-in-one mode from February 17th to 27th, 2020. The traditional triage was conducted by nurses based on face-to-face, one-by-one interview of the epidemiological history and consultation department, and the temperature was measured before manual triage. The intelligent three-in-one model combined online rapid pre-inspection and triage, on-site manual confirmation, as well as synchronized online health education system. For on-line registered patients, the system automatically sent the COVID-19 epidemiological pre-screening triage questionnaire one hour before the appointment, requiring parents to complete and submit online before arriving at the hospital. The on-site registered patients were controlled at 100 m away from the hospital entrance. The nurses guided the parents to scan the QR code and fill in the COVID-19 epidemiological pre-examination triage questionnaire. At the entrance of the hospital, the nurse checked the guidance sheet and took the temperature again. The children with red guidance sheet were checked again and confirmed by pre-examination nurses, and accompanied to the isolation clinic through COVID-19 patients-only entrance. The children with yellow guidance sheet were guided to fever clinic. The children with green guidance sheet could go with their parents to the designated area, and then went to the corresponding consultation area. Health education was carried out throughout the treatment, and the system automatically posted the corresponding outpatient instructions and education courses. Parents would read the courses on their mobile phones and counsel online. The time of pre-examination and the coincidence rate of triage were compared between the two groups.@*RESULTS@#The three-in-one intelligent pre-inspection mode took an average of (25.6±8.0) s for each child, which was significantly shorter than the traditional pre-inspection mode (74.8±36.4) s (@*CONCLUSIONS@#The three-in-one intelligent pre-inspection model can effectively shorten the patient pre-check time, with similar triage coincidence rate to traditional model.

Application of three-in-one intelligent screening in outpatient department of children's hospital during the COVID-19 epidemic / 浙江大学学报·医学版

OBJECTIVE@#: To evaluate the application of three-in-one intelligent screening in outpatient pre-inspection in Children's Hospital.@*METHODS@#We randomly enrolled 100 children pre-screened by traditional in the outpatient department of Children's Hospital Zhejiang University School of Medicine from February 6th to 16th, 2020, and another 100 children by the intelligent three-in-one mode from February 17th to 27th, 2020. The traditional triage was conducted by nurses based on face-to-face, one-by-one interview of the epidemiological history and consultation department, and the temperature was measured before manual triage. The intelligent three-in-one model of pre-inspection and triage combined online rapid pre-inspection and triage, on-site manual confirmation, as well as synchronized online health education system. For on-line registered patients, the system automatically sent the COVID-19 epidemiological pre-screening triage questionnaire one hour before the appointment, requiring parents to complete and submit online before arriving at the hospital. The on-site registered patients were controlled at 100 m outside of the hospital entrance. The nurses guided the parents to scan the QR code and fill in the COVID-19 epidemiological pre-examination triage questionnaire. At the entrance of the hospital, the nurse checked the guide sheet and took the temperature again. The children with red guidance sheet for isolation clinic were checked again and confirmed by pre-examination nurses, and accompanied to the isolation clinic by a special channel. The children with yellow guidance sheet were guided to fever clinic; parents with green guidance sheet took their children to the designated area by themselves, and then went to the corresponding consultation area after on-site manual pre inspection and registration. The whole process of health education was associated with outpatient notes, and the system automatically posted the corresponding outpatient instructions and education courses. Parents would read the courses on their mobile phones and counsel online. The time of pre-examination and the coincidence rate of triage were compared between the two groups.@*RESULTS@#The three-in-one intelligent pre-inspection mode took an average of (25.6±8.0) seconds for each child, which was significantly shorter than the traditional pre-inspection mode (74.8±36.4 seconds) (=13.182, 0.05).@*CONCLUSIONS@#The three-in-one intelligent pre-inspection model can effectively shorten the patient pre-check time, with similar triage coincidence rate to traditional model.

Role of MDM2-p53 signaling pathway in the development of colorectal cancer / 国际生物医学工程杂志

Objective To investigate the mechanism of MDM2-p53 signaling pathway in the development of colorectal cancer and correlation between p53 with clinicopathological parameters, so as to further analyze the effect of p53 on prognosis. Methods The colorectal cancer tissues and the adjacent normal tissues from 86 cases of patients with colorectal cancer were collected . The expression of p53 and murine double minute 2 (MDM2) in colorectal cancer and adjacent normal tissues were detected by immunohistochemistry, Western Blot and real-time fluorescence quantitative polymerase chain reaction (RT-PCR). The prognosis of the patients was analyzed by the Kaplan-Meier survival curves. Results The protein expression and the mRNA expression of p53 and MDM2 in colorectal cancer tissues were significantly higher than that in the adjacent non-cancerous tissues (all P<0.01). A positive correlation was observed between the expression of p53 and MDM2 (r=0.785). The expression of p53 in colorectal cancer tissues were correlated well with the degree of tumor differentiation, TNM stage, lymph node metastasis and infiltration depth (all P<0.05). Survival analysis demonstrated that the mean overall survival time in p53 high expression group was (53.92±1.56) months which was significantly lower than that in p53 low expression group of (69.16±3.72) months, and the difference was statistically significant (χ2=14.78, P<0.01). Conclusions The risk and prognosis of colorectal cancer are closely related to the MDM2-p53 signaling pathway. p53 can be used as a potential target for the prognosis and treatment of colorectal cancer.