The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

[Objective]Embedding data information literacy in postgraduate education of traditional Chinese medicine,to provide an innovative approach to improve the quality of graduate theses.[Methods]By collecting blind review data of 891 doctoral dissertations submitted from 2016 to 2021 in Zhejiang Chinese Medical University,the quality of graduate theses based on factors such as postgraduate training category,subject,submission year,affiliated unit,thesis review indicators,proposes current problems and relevant countermeasures and suggestions was statistically analyzed.[Results]The proportion of articles in grades A,B and C was 85.07%,12.01%and 2.92%,respectively,with statistically significant differences among grades(P<0.001).According to the classification of first level disciplines,the results show that the overall quality of doctoral dissertations in traditional Chinese medicine is superior to other disciplines;according to the classification of training categories,the results show that the overall quality of non-directed doctoral dissertations is better than that of directed categories;classified by the year of submission for review,the results show that with the increasing of doctoral blind review papers in recent years,the overall quality of doctoral theses has gradually been improved;according to the classification of affiliations,the results show that the overall quality of doctoral dissertations from the second school of clinical medicine,school of pharmacy,and school of basic medicine is better than other colleges.A comprehensive explanation of factors such as the training category,discipline and major,year of submission for review affiliation and evaluation indicators for the doctoral thesis effectively provides feedback on the overall quality of the thesis.[Conclusion]Embedding data information literacy in postgraduate education is of great significance for improving the quality of postgraduate education,especially the quality of graduate theses.

Objective:To examine the clinical value of rapid detection of drug-resistant bacteria by immunochromatography and the effects of rapid detection on the prognosis of patients with severe intra-abdominal infection complicated by carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection.Methods:This was a retrospective cohort study. We analyzed clinical data of 73 patients with severe abdominal infections with sepsis or septic shock complicated by CRE bloodstream infection admitted to the general surgery department of Jinling Hospital between February 2022 and February 2023. Patients were divided into a colloidal gold immunochromatographic assay (GICA) group (17 patients) and conventional testing group (56 patients) based on whether a GICA for CRE had been performed on the patients' first blood culture sample during the diagnosis and treatment process. There were no statistically significant differences between the GICA and conventional testing groups in age ([55.9±17.3] vs. [47.6±16.4] years), sex ([16 men vs. one woman ] vs. [41 men vs. 15 women]), median Charlson comorbidity index (3.0[2.0,4.0] vs. 3.0[2.0, 4.8]), septic shock (10 vs. 39), or acute kidney injury (8 vs. 40) (all P>0.05). Both groups routinely underwent traditional bacterial identification and drug susceptibility testing. Additionally, patients in the GICA group were tested directly for positive blood cultures using a GICA carbapenemase test kit. The main outcomes were mortality rates on Days 28 and 90 after the first identification of CRE bloodstream infection in both groups. We also compared the microbial clearance rate, duration of hospitalization and intensive care unit stay, and time from onset of CRE bloodstream infection to initiation of targeted and appropriate antibiotics between the two groups. Results:The rate of microbial clearance of bloodstream infection was significantly greater in the GICA group than in the conventional testing group (15/17 vs. 34/56 [60.7%], χ 2=4.476, P=0.034), whereas the 28-day mortality tended to be lower in the GICA than conventional testing group [5/17 vs. 44.6% [25/56], χ 2=1.250, P=0.264). The 90-day mortality (8/17 vs. 53.6% [30/56], χ 2=0.222, P=0.638), median duration of hospitalization (37.0 [18.0, 46.5] days vs. 45.5 [32.2, 64.8] days, Z=-1.867, P=0.062), and median duration of intensive care unit stay (18.0 [6.5, 35.0] days vs. 32.0 [5.0, 51.8] days, Z=-1.251, P=0.209). The median time between the onset of bloodstream infection and administration of antibiotics was 49.0 (38.0, 69.0) hours in the GICA group, which is significantly shorter than the 163.0 (111.8, 190.0) hours in the conventional testing group ( Z=-5.731, P<0.001). The median time between the onset of bloodstream infection and administration of appropriate antibiotics was 40.0 (34.0, 80.0) hours in the GICA group, which is shorter than in the conventional testing group (68.0 [38.2, 118.8]) hours; however, this difference is not statistically significant ( Z=-1.686, P=0.093). Conclusions:GICA can provide information on carbapenemase- producing pathogens faster than traditional drug sensitivity testing, enabling early administration of the optimal antibiotics. The strategy of 'carbapenemase detection first' for managing bacterial infection has the potential to improve prognosis of patients and reduce mortality rate.

Objective:To examine the clinical value of rapid detection of drug-resistant bacteria by immunochromatography and the effects of rapid detection on the prognosis of patients with severe intra-abdominal infection complicated by carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection.Methods:This was a retrospective cohort study. We analyzed clinical data of 73 patients with severe abdominal infections with sepsis or septic shock complicated by CRE bloodstream infection admitted to the general surgery department of Jinling Hospital between February 2022 and February 2023. Patients were divided into a colloidal gold immunochromatographic assay (GICA) group (17 patients) and conventional testing group (56 patients) based on whether a GICA for CRE had been performed on the patients' first blood culture sample during the diagnosis and treatment process. There were no statistically significant differences between the GICA and conventional testing groups in age ([55.9±17.3] vs. [47.6±16.4] years), sex ([16 men vs. one woman ] vs. [41 men vs. 15 women]), median Charlson comorbidity index (3.0[2.0,4.0] vs. 3.0[2.0, 4.8]), septic shock (10 vs. 39), or acute kidney injury (8 vs. 40) (all P>0.05). Both groups routinely underwent traditional bacterial identification and drug susceptibility testing. Additionally, patients in the GICA group were tested directly for positive blood cultures using a GICA carbapenemase test kit. The main outcomes were mortality rates on Days 28 and 90 after the first identification of CRE bloodstream infection in both groups. We also compared the microbial clearance rate, duration of hospitalization and intensive care unit stay, and time from onset of CRE bloodstream infection to initiation of targeted and appropriate antibiotics between the two groups. Results:The rate of microbial clearance of bloodstream infection was significantly greater in the GICA group than in the conventional testing group (15/17 vs. 34/56 [60.7%], χ 2=4.476, P=0.034), whereas the 28-day mortality tended to be lower in the GICA than conventional testing group [5/17 vs. 44.6% [25/56], χ 2=1.250, P=0.264). The 90-day mortality (8/17 vs. 53.6% [30/56], χ 2=0.222, P=0.638), median duration of hospitalization (37.0 [18.0, 46.5] days vs. 45.5 [32.2, 64.8] days, Z=-1.867, P=0.062), and median duration of intensive care unit stay (18.0 [6.5, 35.0] days vs. 32.0 [5.0, 51.8] days, Z=-1.251, P=0.209). The median time between the onset of bloodstream infection and administration of antibiotics was 49.0 (38.0, 69.0) hours in the GICA group, which is significantly shorter than the 163.0 (111.8, 190.0) hours in the conventional testing group ( Z=-5.731, P<0.001). The median time between the onset of bloodstream infection and administration of appropriate antibiotics was 40.0 (34.0, 80.0) hours in the GICA group, which is shorter than in the conventional testing group (68.0 [38.2, 118.8]) hours; however, this difference is not statistically significant ( Z=-1.686, P=0.093). Conclusions:GICA can provide information on carbapenemase- producing pathogens faster than traditional drug sensitivity testing, enabling early administration of the optimal antibiotics. The strategy of 'carbapenemase detection first' for managing bacterial infection has the potential to improve prognosis of patients and reduce mortality rate.

More efficient drug delivery system and formulation with less adverse effects are needed for the clinical application of broad-spectrum antineoplastic agent doxorubicin (DOX). Here we obtained outer-membrane vesicles (OMVs), a nano-sized proteoliposomes naturally released by Gram-negative bacteria, from attenuated and prepared doxorubicin-loaded O0MVs (DOX-OMV). Confocal microscopy and distribution study observed that DOX encapsulated in OMVs was efficiently transported into NSCLC A549 cells. DOX-OMV resulted in intensive cytotoxic effects and cell apoptosis as evident from MTT assay, Western blotting and flow cytometry due to the rapid cellular uptake of DOX. In A549 tumor-bearing BALB/c nude mice, DOX-OMV presented a substantial tumor growth inhibition with favorable tolerability and pharmacokinetic profile, and TUNEL assay and H&E staining displayed extensive apoptotic cells and necrosis in tumor tissues. More importantly, OMVs' appropriate immunogenicity enabled the recruitment of macrophages in tumor microenvironment which might synergize with their cargo DOX . Our results suggest that OMVs can not only function as biological nanocarriers for chemotherapeutic agents but also elicit suitable immune responses, thus having a great potential for the tumor chemoimmunotherapy.

Objective To explore the effect of the Jaw‐tracking with RapidArc(JT‐RapidArc) plans for upper thoracic e‐sophageal cancer .Methods Treatment planning was designed by using RapidArc and JT‐RapidArc techniques for 11 consecutive patients .The dose‐volume histogram parameters of PTV and the organs at risk ,conformity index(CI) ,heterogeneity index(HI) , low dose volume of normal tissue (B‐P ) and monitor units (MU ) were compared between the different techniques . Results Compared with the RapidArc plan ,JT‐RapidArc had increased coverage of PTV1(64) D98 and HI(P<0 .05) ,lower Dmean , D2 of PTV1(64) and PTV2(54) ,but no statistically difference in CI(P>0 .05) .Plans with JT‐RapidArc had lower Lung(V5 ,V10 , V13 ,V20 ,V30 ,Dmean ,P<0 .05) ,heart(V20 ,Dmean ,P<0 .05) ,and B‐P(V5 ,V10 ,V15 ,V20 ,V30 ,P<0 .05) ,but no significantly different in spinal cord and SC‐PRV as compared with RapidArc plans(P>0 .05) .JT‐RapidArc plans increaseed the MU by 1% (349 ± 29 vs .345 ± 16 ,P>0 .05) as compared with RapidArc plans .Conclusion All of the plans had met the requirements of clinical dosime‐try .JT‐RapidArc plans as compared with RapidArc plans ,showing better part of target coverage ,part of lung and heart and B‐P sparing ,which MU was slightly increased .

Objective To perform a routine quality assurance procedure for Truebeam multi-leaf collimator (MLC) using MLC quality assurance (QA) phantom,verifying the reliability of MLC during the treatment.Methods MLC QA phantom was a specialized phantom for multi-leaf collimator QA,and contained five radio-opaque spheres that were embedded in an L-shape.The phantom was placed isocentrically on the Truebeam treatment couch for the tests.A quality assurance plan was settled up in the Eclipse v10.0 so that the fields for acquiring the necessary images could be created.The images were acquired by the electronic portal imaging device (EPID),and imported into the PIPSpro software for the analysis.The tests were delivered once a week for six weeks to verify consistency of the delivery,and the images were acquired in the same manner each time.Results For the leaf position test,the average position error was (0.21 ± 0.02) mm.The leaf width was measured at the isocenter,and the average error was (0.04±0.02) mm for the leaf width test.Multi-Port test showed the dynamic leaf shift error,the average error was (0.26 ± 0.04) mm.For the leaf transmission test,the average inter-leaf leakage value was 1.0％ ± 0.14％.Conclusions The MLC system of Truebeam could operate very well and the QA phantom is a useful test tool for the MLC QA.

Objective To evaluate the dosimetric characteristics of base dose plan compensation (BDPC) optimization method applied on the intensity-modulated radiotherapy (IMRT) for upper esophageal carcinoma,based on the Eclipse treatment planning system.Methods Nineteen patients were included.For each case initial IMRT plan was generated and further optimized respectively by the two following methods:the BDPC method and hot and cold spot control (HCSC) method.Then the BDPC and HCSC plans were compared concerning planning-target-volume (PTV) coverage,conformity index (CI),and homogeneity index (HI),as well as organ-at-risk (OAR) sparing,planning time,monitor unit (MU) and delivery time.Results Compared with the HCSC plans,the BDPC plans provided superior CI and HI (Z =-3.662,-3.745,P ＜ 0.05),as well as lower D2％ (near-maximum dose) (Z =-3.823,P ＜ 0.05) and comparable D98％ (near-minimum dose) (P ＞ 0.05) for PTV64 (high-risk PTV),and provided superiorCI (Z=-3.340,P＜0.05),lower D95％ and D98％ (Z=-3.582,-2.616,P＜0.05) for PTV54 (low-risk PTV).The BDPC plans also provided slightly lower doses to the spinal cord and lung compared with the HCSC plans (Z =-3.625--3.369,P ＜ 0.05).Moreover,the planning time [(26.05 ±0.88) min] for BDPC plans was less than that of the HCSC plans [(33.73 ± 3.24) min] (Z =-3.823,P ＜0.05).The MU of the BDPC plans (1 019 ± 167) was higher than that of the HCSC plans (1 003 ±159) (Z=-2.616,P＜0.05),while the delivery time [(3.52 ±0.29) min] was more than that of the HCSC plans [(3.50±0.28) min] (Z=-2.548,P＜0.05).Conclusions The BDPC optimization method can significantly improve target dose homogeneity and conformity with effective reduction of the dose to OARs for upper esophageal carcinoma.Moreover,it is simple and can improve the treatment planning efficiency.

Objective To compare the dosimetric differences of volumetric modulated arc therapy (VMAT) for preoperative radiotherapy of rectal cancer using 6MV X-ray flattening filter-free (FFF) and flattening filter (FF) modes.Methods FF-VMAT and FFF-VMAT plans were designed for 15 rectal cancer patients with preoperative radiotherapy by planning treatment system (Eclipse 10.0),respectively.Prescription dose of PTV was 50 Gy in 25 fractions.When the plans were normalized to 50 Gy to 95 ％ of PTV,the dose volume histogram (DVH),target and risk organ doses,conformity indexes (CI),homogeneity indexes (HI),low dose volume of normal tissue (B-P),monitor units (MU) and treatment time (TT) were compared between the two kinds of plans.Results FF-VMAT provided the lower Dmean,V105,HI (P ＜ 0.05),and higher CI (P ＜ 0.05) compared with FFF-VMAT.Small intestine (D5),Bladder (D5,Dmean V40,V50),L-femoral head (V40),R-femoral head (Dmean) were lower in FF-VMAT than those in FFF-VMAT (P ＜ 0.05).FF-VMAT had higher B-P (V5) compared with FFF-VMAT (P ＜ 0.05).FF-VMAT reduced the monitor units (MU) by 21％ (382±53 vs 483±26,P ＜ 0.05),as well as the treatment time (TT) in FF-VMAT was no significant difference compared with that in FFF-VMAT [(148±4) s vs (146±3) s,P ＞ 0.05)].Conclusions The qualities of FF-VMAT and FFF-VMAT plans were comparable and both clinically acceptable.When comparing two plans,FF-VMAT showed better target coverage and some of OARs sparing.The MUs of FFF-VMAT were higher than those of FF-VMAT,yet were not delivered within the same time.

Objective To compare IMSure QA and MatriXX for intensity modulated radiotherapy plans,and to investigate the credibility of IMSure QA software.Methods Ten patients receiving intensity modulated radiotherapy were randomly chosen for the quality assurance plans with IMSure QA and MatriXX.Results The overall average of percentage pass points in 3％ and 3 mm were (98.1 ± 0.8) ％ with IMSure QA,and (97.9 ±0.6)％ with MatriXX(t =0.86,P ＞0.05).Conclusion IMSure QA can be a reliable verification tool for IMRT QA.