Objective·To explore the diagnostic,therapeutic,and prognostic value of metagenomics next-generation sequencing(mNGS)in patients with pneumonia-induced sepsis.Methods·This study consisted of a multicenter,prospective,non-randomized controlled trial and a diagnostic test.Patients with pneumonia-induced sepsis who were hospitalized in four hospitals across China were enrolled between March 2020 and October 2021.All patients met the Sepsis-3 criteria issued by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine,as well as the clinical diagnostic standard of pneumonia.Enrolled patients were assigned based on their preference to either the conventional test-only group[receiving only conventional test(CMT)]or the combined mNGS test group(receiving CMT and mNGS concurrently).The primary outcome was the 7-day all-cause mortality rate,and secondary outcomes included the changes in SOFA and APACHE Ⅱ scores from baseline to day 7,28-day all-cause mortality rate,the composite endpoint of mechanical ventilation or death within 28 d,28 d ventilation-free days,28 d hospital-free days,and the average daily hospitalization cost.Propensity score matching was used to balance covariates between the two groups.Kaplan-Meier curves were plotted and Cox proportional hazards models were built to compare the risk of death between the two groups.Pathogen detection results from infection site samples in the combined mNGS test group were used for the diagnostic test.The clinically-adjudicated causative pathogens was used as the reference standard.The results of traditional pathogen detection and mNGS detection were compared respectively with the reference standard.The positive percent agreement,negative percent agreement,positive predictive value,and negative predictive value between the two methods and the reference standard were calculated.McNemar's χ2 test was used to evaluate the causative pathogen detection capabilities of the two methods.Results·A total of 533 patients were enrolled,of whom 311 opted for additional mNGS testing,while 222 received only conventional pathogenetic testing.In the non-randomized controlled trial,after propensity score matching to balance covariates,the 7-day all-cause mortality was lower in the combined mNGS test group compared to the conventional test-only group[4.8%vs 8.6%,HR 0.37(95%CI 0.15?0.91),P=0.031].Additionally,the 28-day ventilation-free days were increased in the combined mNGS test group(19.9 d vs 18.4 d,P=0.041).No significant difference was observed between the two groups in terms of 28-day all-cause mortality or the average daily hospitalization costs.In the diagnostic test,compared to the reference standard,the positive percent agreement of mNGS with the clinical composite judgment for causative pathogens was higher than that of CMT[91.9%(95%CI 87.7%?95.0%)vs 56.1%(95%CI 49.7%?62.4%),P<0.001].Conversely,the negative percent agreement of mNGS was lower than that of CMT[29.2%(95%CI 18.6%?41.8%)vs 69.2%95%CI 56.6%?80.1%),P<0.001].The negative predictive value of nNGS was higher than that of CMT[48.7%(95%CI 32.4%?65.2%)vs 29.4%(95%CI 22.3%?37.3%),P=0.001].Conclusion·In patients with pneumonia-induced sepsis,mNGS of infection site samples demonstrated a higher detection rate of causative pathogen compared to CMT.Furthermore,the combination of mNGS with CMT may help reduce the 7-day all-cause mortality,suggesting that mNGS has clinical value and potential for application in the management of sepsis caused by pulmonary infections.

Objective: Intrathyroid thymic carcinoma（ITTC） is a rare thyroid tumor that lacks typical clinical manifestations and imaging features, making preoperative diagnosis challenging.The primary treatment for ITTC is radical surgery; however, the effectiveness of adjuvant radiotherapy and chemotherapy post-surgery is not well-established. This paper presents a case of ITTC , analyzing the clinical data and correlating it with the literature to explore the clinical manifestations, diagnostic approach, treatment, and prognosis of ITTC.
Humans ; Prognosis ; Thymoma ; Thymus Neoplasms/diagnosis* ; Thyroid Neoplasms/pathology*

Objective·To explore the diagnostic,therapeutic,and prognostic value of metagenomics next-generation sequencing(mNGS)in patients with pneumonia-induced sepsis.Methods·This study consisted of a multicenter,prospective,non-randomized controlled trial and a diagnostic test.Patients with pneumonia-induced sepsis who were hospitalized in four hospitals across China were enrolled between March 2020 and October 2021.All patients met the Sepsis-3 criteria issued by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine,as well as the clinical diagnostic standard of pneumonia.Enrolled patients were assigned based on their preference to either the conventional test-only group[receiving only conventional test(CMT)]or the combined mNGS test group(receiving CMT and mNGS concurrently).The primary outcome was the 7-day all-cause mortality rate,and secondary outcomes included the changes in SOFA and APACHE Ⅱ scores from baseline to day 7,28-day all-cause mortality rate,the composite endpoint of mechanical ventilation or death within 28 d,28 d ventilation-free days,28 d hospital-free days,and the average daily hospitalization cost.Propensity score matching was used to balance covariates between the two groups.Kaplan-Meier curves were plotted and Cox proportional hazards models were built to compare the risk of death between the two groups.Pathogen detection results from infection site samples in the combined mNGS test group were used for the diagnostic test.The clinically-adjudicated causative pathogens was used as the reference standard.The results of traditional pathogen detection and mNGS detection were compared respectively with the reference standard.The positive percent agreement,negative percent agreement,positive predictive value,and negative predictive value between the two methods and the reference standard were calculated.McNemar's χ2 test was used to evaluate the causative pathogen detection capabilities of the two methods.Results·A total of 533 patients were enrolled,of whom 311 opted for additional mNGS testing,while 222 received only conventional pathogenetic testing.In the non-randomized controlled trial,after propensity score matching to balance covariates,the 7-day all-cause mortality was lower in the combined mNGS test group compared to the conventional test-only group[4.8%vs 8.6%,HR 0.37(95%CI 0.15?0.91),P=0.031].Additionally,the 28-day ventilation-free days were increased in the combined mNGS test group(19.9 d vs 18.4 d,P=0.041).No significant difference was observed between the two groups in terms of 28-day all-cause mortality or the average daily hospitalization costs.In the diagnostic test,compared to the reference standard,the positive percent agreement of mNGS with the clinical composite judgment for causative pathogens was higher than that of CMT[91.9%(95%CI 87.7%?95.0%)vs 56.1%(95%CI 49.7%?62.4%),P<0.001].Conversely,the negative percent agreement of mNGS was lower than that of CMT[29.2%(95%CI 18.6%?41.8%)vs 69.2%95%CI 56.6%?80.1%),P<0.001].The negative predictive value of nNGS was higher than that of CMT[48.7%(95%CI 32.4%?65.2%)vs 29.4%(95%CI 22.3%?37.3%),P=0.001].Conclusion·In patients with pneumonia-induced sepsis,mNGS of infection site samples demonstrated a higher detection rate of causative pathogen compared to CMT.Furthermore,the combination of mNGS with CMT may help reduce the 7-day all-cause mortality,suggesting that mNGS has clinical value and potential for application in the management of sepsis caused by pulmonary infections.

Establishing a comprehensive mechanism for the initiation and review of investigator-initiated trial(IIT) plays an important role in ensuring the scientific validity of clinical research and improving research quality.Since 2021, Zhongshan Hospital affiliated to Fudan University had actively explored improvements in the project management of IIT. The hospital had established a standardized grading review management process, developed an integrated clinical research management system, established a three-level clinical research training system, built a methodological support platform, and formulated research plan templates, gradually formed a standardized grading project approval review management mode. As of February 2024, the hospital had completed 400 quick reviews and more than 400 expert letter reviews based on the integrated clinical research management system. The efficiency and quality of IIT project approval had been improved. At the same time, over 40 academic salons and forums had been held, cultivating a group of young clinical research talents, providing data management training for more than 30 clinical departments, and promoting the improvement of the quality of research protocol. In the future, hospitals should further optimize their information systems, expand the influence of their training systems, enhance the capabilities of their methodological support platforms, and improve the efficiency of the application of clinical research protocol templates, so as to escort the establishment and implementation of high-quality clinical research projects and provide references for other hospitals′ IIT project management.

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7％,22.0％and 31.5％,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P＜0.05).On day 1,the SIC score with a cut-off value＞3 had a significantly higher sensitivity(72.00％)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00％,SAC status 52.00％;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P＜0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95％confidence interval[95％CI]:0.060-0.783,P=0.018)and SAC(adjusted HR=0.146,95％CI:0.041-0.513,P=0.003). CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Objective:Dysregulated host immune responses contribute to the pathogenesis of sepsis. G protein-coupled receptor 174 (GPR174) was found to be involved in the immune responses and associated with the susceptibility to autoimmune diseases. This study aimed to investigate the association of GPR174 variants with sepsis susceptibility and the contribution of GPR174 in sepsis development.Methods:From May 2005 to December 2017, a total of 575 sepsis patients and 579 non-septic controls admitted to our Emergency ICU were enrolled in this case-control study. The non-synonymous SNP rs3827440 in GPR174 was genotyped using TaqMan Real-time PCR assays on ABI7900 platform. Then the correlation between rs3827440 and serum levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were investigated in septic patients. Gpr174-deficient mice were generated and subjected to cecal ligation and puncture (CLP). The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA).Results:Rs3827440 TT/T genotype in GPR174 was positively associated with sepsis risk after logistic regression analysis adjusted for sex [odds ratio ( OR) = 1.68, 95% confidence interval ( CI): 1.19-2.20, P = 0.0004]. IL-6 and TNF-α serum levels in female TT and male T allele carriers of septic patients were significantly higher than those in female CC and male C allele carriers ( P < 0.05). Preclinical validation of Gpr174 gene was performed in Gpr174 knockout (KO) mice using CLP models. Gpr174 KO mice had higher survival rate. Moreover, Gpr174 KO mice had significantly decreased serum concentrations of IL-1β, IL-6 and TNF-α compared with WT mice, while the levels of IL-10 was increased ( P < 0.01). Conclusions:GPR174 as a novel sepsis susceptibility gene in Chinese Han population is involved in the development and physiopathology of sepsis.

Objective To investigate the effect of miR-132-3p on the proliferation of endothelial progenitor cells and its regulatory mechanism in order to provide a new theoretical basis for the treatment of deep venous thrombosis. Methods Real-time quantitative PCR (qPCR) was used to detect the expression of miR-132-3p in the plasma and endothelial progenitor cells of 27 healthy volunteers and 22 thrombus patients, and in endothelial progenitor cells under normoxic and hypoxic conditions. The miR-132-3p analogue and the specific siRNA were transferred into endothelial progenitor cells by the electroporation method. The effect of miR-132-3p on the proliferation of endothelial progenitor cells was detected using MMT and Cell Counting Kit-8 (CCK-8) methods. The effects of miR-132-3p on the expression of FOXO1 in endothelial cells were analyzed using the luciferase assay and western blots. Results The expression of miR-132-3p in clinical patients with thrombosis was significantly decreased to 0.45 ± 0.05 times of that of the healthy volunteers (P＜0.05). The expression of miR-132-3p in endothelial progenitor cells under hypoxia was down-regulated to (0.23 ± 0.13) times of that of under normoxia (P＜0.05). The expression of miR-132-3p of experiment group under hypoxia was up-regulated to (15.72 ± 2.06) times of that of control group (P＜0.05). MMT assay showed that the proliferation of cells in the experimental group under hypoxic condition was up-regulated to (7.79 ± 1.37) times of that in the control group (P＜0.01). CCK-8 assay showed that cell proliferation in experimental group was up-regulated to (6.46 ± 0.38) times of that in the control group (P＜0.01). Software analysis showed that FOXO1 was a direct target of miR-132-3p. Luciferase activity of miR-132-3p mimics transfected endothelial progenitor cells under hypoxic conditions were 0.47 times of that in siRNA treatment group. Western blot showed that the expression of FOXO1 protein in endothelial progenitor cells transfected with miR-132-3p mimics in hypoxia was 0.18 times of that in siRNA treatment group. Conclusions Compared with healthy volunteers, miR-132-3p expression in the blood of patients with thrombosis was significantly reduced that can promote transcription of the FOXO1 gene (and protein expression) and inhibit the proliferation of endothelial progenitor cells. It could be closely related to the formation of venous thrombosis.

Objective: To explore the imaging manifestations of multi-slice spiral CT angiography (CTA) and relationship with in-hospital death in patients with aortic dissection (AD). Methods: The clinical data of 429 patients with AD who underwent CTA in Zhongshan Hospital of Fudan University between January 2009 and January 2016 were retrospectively analyzed. AD patients were divided into 2 groups, including operation group who underwent surgery or interventional therapy (370 cases) and non-operation group who underwent medical conservative treatment(59 cases). The multi-slice spiral CTA imaging features of AD were analyzed, and multivariate logistic regression analysis was used to investigate the relationship between imaging manifestations and in-hospital death in AD patients. Results: There were 12 cases (3.24%) of in-hospital death in operation group, and 28 cases (47.46%) of in-hospital death in non-operation group(P<0.001). AD involved different vascular branches. Multi-slice spiral CTA can clearly show the dissection of true and false lumen, and intimal tear was detected in 363 (84.62%) cases, outer wall calcification was revealed in 63 (14.69%) cases, and thrombus formation was present in 227 (52.91%) cases. The multivariate logistic regression analysis showed that the number of branch vessels involved (OR=1.374, 95%CI 1.081-1.745, P=0.009) and tearing false lumen range(OR=2.059, 95%CI 1.252-3.385, P=0.004) were independent risk factors of in-hospital death in AD patients, and the number of branch vessels involved (OR=1.600, 95%CI 1.062-2.411, P=0.025) was independent risk factor of in-hospital death in the operation group, while the tearing false lumen range (OR=2.315, 95%CI 1.019-5.262, P=0.045) was independent risk factor of in-hospital death of non-operation group. Conclusions Multi-slice spiral CTA can clearly show the entire AD, true and false lumen, intimal tear, wall calcification and thrombosis of AD patients. The number of branch vessels involved and tearing false lumen range are the independent risk factors of in-hospital death in AD patients.

Objective To investigate the effect of hyperbaric oxygen (HBO) coupled with cisplatin on the apoptosis of human hypopharyngeal cancer Fadu cells in vitro and also to observe the effect of HBO exposure at different time points on the efficacy of cisplatin.Methods Human hypopharyngeal cancer Fadu cells for culture were bought from the Tumor Research Institute,Shanghai Jiaotong University.MTT assay was applied to observe the effect of different concentrations of cisplatin on the proliferation inhibition of Fadu cells in vitro.In accordance with different treatment,Fadu cells were divided into 6 groups:group C (the control group),group HBO (the HBO group),group CHT (the chemotherapy group),group HBO + CHT (the HBO + chemotherapy group),group CHT + HBO (the chemotherapy + HBO group and group IC (the HBO immediately combined with chemotherapy group).Cells of various groups were detected by flow cytometry 48 hours after experiment to observe changes in apoptosis,and adenosine triphosphate (ATP) changes in the cells of various groups were measured by ATP kit.Results Apoptosis rates of group C,HBO,CHT,HBO + CHT,CT + HBO and IC were respectively(2.00 ±0.17)％,(2.07 ±0.22)％,(8.73 ±0.74)％,(11.9 ±0.68)％,(9.92 ±0.27)％ and(10.4 ±0.72)％.No statistical significance could be noticed in the apoptosis rates of group C and HBO(P ＞0.05).The apoptosis rates of group CHT,HBO + CHT,CHT + HBO and IC were all higher that those of group C and HBO,and statistical significance could be noted when comparisons were made between them(P ＜0.01).Experiments showed that the apoptosis rate of group HBO + CHT was higher than those of the other groups,with statistical significance(P ＜ 0.05).Suppose the ATP level of group C was 100％,the ATP levels of other groups were respectively 98.7％,83.9％,61.3％,78.5％ and 77.1％.There was statistical significance in the ATP levels of group C and HBO(P ＞0.05).However,the ATP levels of group CHT,HBO + CHT,CHT + HBO and IC were all lower than those of group C and HBO,also with statistical significance (P ＜0.01).The ATP level of group HBO + CHT was significantly lower than those of the other groups,also with statistical significance(P ＜ 0.05).Conclusions Single HBO exposure had no effect on the apoptosis of hypopharyngeal cancer Fadu cells.HBO coupled with cisplatin could enhance the therapeutic efficacy of cisplatin,promote apoptosis,and the efficacy might be associated with the time points of the combined treatment of HBO.

Objective To investigate the effect of hyperbaric oxygen (HBO) coupled with cisplatin on the apoptosis of human hypopharyngeal cancer Fadu cells in vitro and also to observe the effect of HBO exposure at different time points on the efficacy of cisplatin.Methods Human hypopharyngeal cancer Fadu cells for culture were bought from the Tumor Research Institute,Shanghai Jiaotong University.MTT assay was applied to observe the effect of different concentrations of cisplatin on the proliferation inhibition of Fadu cells in vitro.In accordance with different treatment,Fadu cells were divided into 6 groups:group C (the control group),group HBO (the HBO group),group CHT (the chemotherapy group),group HBO + CHT (the HBO + chemotherapy group),group CHT + HBO (the chemotherapy + HBO group and group IC (the HBO immediately combined with chemotherapy group).Cells of various groups were detected by flow cytometry 48 hours after experiment to observe changes in apoptosis,and adenosine triphosphate (ATP) changes in the cells of various groups were measured by ATP kit.Results Apoptosis rates of group C,HBO,CHT,HBO + CHT,CT + HBO and IC were respectively(2.00 ±0.17)％,(2.07 ±0.22)％,(8.73 ±0.74)％,(11.9 ±0.68)％,(9.92 ±0.27)％ and(10.4 ±0.72)％.No statistical significance could be noticed in the apoptosis rates of group C and HBO(P ＞0.05).The apoptosis rates of group CHT,HBO + CHT,CHT + HBO and IC were all higher that those of group C and HBO,and statistical significance could be noted when comparisons were made between them(P ＜0.01).Experiments showed that the apoptosis rate of group HBO + CHT was higher than those of the other groups,with statistical significance(P ＜ 0.05).Suppose the ATP level of group C was 100％,the ATP levels of other groups were respectively 98.7％,83.9％,61.3％,78.5％ and 77.1％.There was statistical significance in the ATP levels of group C and HBO(P ＞0.05).However,the ATP levels of group CHT,HBO + CHT,CHT + HBO and IC were all lower than those of group C and HBO,also with statistical significance (P ＜0.01).The ATP level of group HBO + CHT was significantly lower than those of the other groups,also with statistical significance(P ＜ 0.05).Conclusions Single HBO exposure had no effect on the apoptosis of hypopharyngeal cancer Fadu cells.HBO coupled with cisplatin could enhance the therapeutic efficacy of cisplatin,promote apoptosis,and the efficacy might be associated with the time points of the combined treatment of HBO.