Objective To determine if activation of AMP-activated protein kinase (AMPK) is involved in ropivacaine-induced reactive oxygen species (ROS) production and apoptosis in human neuroblastoma cell line SHSY5Y.Methods SH-SY5Y cell line was purchased from cell center of Shanghai life Science Research Institute,Chinese Academy of Sciences and cultured in DMEM/F12 liquid culture medium containing 15 % bovine calf serum at 37 ℃ in incubator filled with 5% CO2 . Plasmids pGPU6/GFP/Neo-shRNA AMPKα2 and pEGFP-N1-AMPKα2were transfected into the SH-SY5Y cell line. The expression of AMPKα2 was determined by Western blot analysis.The SH-SY5Y cells transfected with recombinant plasmids were exposed to 3 mol/L ropivacaine. Intracellular ROS was detected by flow cytometry. Cell viability was quantitatively determined by MTT colorimetry assay. Apoptosis was assessed by flow cytometry and Hoechst33258 staining. Results The plasmid pEGFP-N1-AMPKα2 upregulated while pGPU6/GFP/Neo-shRNA AMPKα2 down-regulated the expression of AMPKα2 ( P < 0.01). Down-regulation of AMPKα2 expression attenuated while up-regulation of. AMPKα2 expression promoted intracellular ROS production and cell apoptosis induced by ropivacaine ( P < 0.01) . Conclusion AMPK probably mediates ROS production and cell apoptosis induced by ropivacaine.

Objective: To introduce the application and practice of information technology in the management of charitable donated injection drugs in our hospital, and explore the information management mode of injection-type charitable drugs in the new era. Meth-ods: Taking herceptin injection as an example, the injection-type drug management system was introduced by comparing October 2016-April 2017 (before the implementation of the information system) and May 2017-October 2017 (after the implementation of the infor-mation system). The comparison items included infusion qualified rate, consumption time for the management and deployment of hu-man resources of each bottle of herceptin, and satisfaction of related doctors, nurses and patients during the drug management process. Results: The qualified rate of finished infusion before and after the implementation of the information system was 94. 29% and 99. 05% , respectively. The consumption time for the management and deployment of human resources of each bottle of herceptin was 2. 11 and 0. 36 working hours before and after the implementation of the system. The overall satisfaction of doctors, nurses and patients was 78% , 42% and 62% before the implementation, and 98% , 96% and 98% after the implementation. The differences in the above indices between pre-implementation and post-implementation were significant (P<0. 01). Conclusion: The use of information man-agement in the growing number of injection-type charitable drugs can ensure the safety, effectiveness and convenience, and the system is worthy of promotion and application.

Preoperative patients′ preparedness for selective surgery is of great significance in improving surgical efficiency, improving treatment outcomes, and optimizing the quality of medical care. The lack of unified standards for existing evaluation tools hinders their clinical application. This article provides a review of the development, content, reliability, validity, and application of existing evaluation tools, and compares and analyzes them, in order to provide reference for medical workers to select suitable evaluation tools and construct a patient-centered preoperative preparation strategy.

Objective:To analyze the differences in clinical outcomes and toxicities between postoperative radiotherapy alone and postoperative radiochemotherapy for soft tissue sarcoma (STS), as well as the related factors affecting clinical prognosis of STS patients.Methods:Retrospective analysis of patients diagnosed with primary STS admitted to Zhejiang Cancer Hospital from May 2012 to May 2019 was performed, who received adjuvant radiotherapy after surgery, combined with or without postoperative chemotherapy. A total of 100 patients were enrolled and divided into postoperative radiotherapy group ( n=52) and postoperative radiochemotherapy group ( n=48). The median follow-up time was 65 months (24-124 months). The local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-related toxicities were recorded in two groups. The survival rate was calculated by Kaplan-Meier analysis. Log-rank test was used for univariate analysis, and Cox model was used for multivariate analysis. Results:In multivariate analysis, the maximum tumor diameter was an independent predictor of local tumor recurrence ( HR=4.80, 95% CI=1.16-19.85, P=0.031), distant metastasis ( HR=4.67, 95% CI=1.53-14.26, P=0.007) and OS ( HR=4.10, 95% CI=1.35-12.48, P=0.013). In addition, the degree of myelosuppression in patients in postoperative radiochemotherapy was significantly higher than that in their counterparts in postoperative radiotherapy group ( P<0.001). Conclusions:In the limited number of patients, radiochemotherapy has no advantages over radiotherapy alone in distant metastasis or survival rate. Besides, it increases toxicities, but the overall tolerability is favorable. It is necessary to conduct prospective randomized studies in a large population and subgroup analysis of histological subtypes, aiming to obtain results with better reference value.

Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.

Female ; Humans ; Kidney ; pathology ; Kidney Neoplasms ; diagnosis ; Rhabdoid Tumor ; diagnosis

OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.

BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca