Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective:To assess the occurrence, prognosis and possible early risk factors of jaundice in polytrauma patients.Methods:This study was a single-center, prospective study. Polytrauma patients (age>18 years) admitted to Tongji Trauma Center from October 2020 to January 2023 were enrolled. The patients with liver, biliary tract or pancreatic traumatic injury, previously suffered from chronic liver disease were excluded. The clinical characteristics of patients, laboratory test results, imaging examination results, Injury Severity Score (ISS), Glasgow Coma Score and APACHEⅡ score were collected. The incidence of jaundice, the classification of jaundice or the severity of jaundice after multiple injuries, the mortality rate of polytrauma patients with jaundice, and the early independent risk factors of jaundice in polytrauma were analyzed. The differences between the groups were compared by Student’s t test or χ2 test. The independent risk factors of jaundice were analyzed by Logistic regression analyzed. Results:A total of 742 polytrauma patients were included, 34.09% polytrauma patients were accompanied by jaundice, and the ratio of both moderate and severe jaundice were as high as 32.41%. The main type of jaundice was intrahepatic cholestatic jaundice (47.03%). The mortality rate of polytrauma patients accompanied by jaundice was significantly higher than that of polytrauma patients without jaundice (12.25% vs. 3.47%, P<0.001). Logistic regression analysis showed that ISS score ( OR=3.405, 95% CI: 1.962-7.438, P=0.026), plasma lactate ( OR=2.216, 95% CI: 1.203-4.862, P=0.017), interleukin-6 levels ( OR=2.431, 95% CI: 1.424-3.793, P=0.007), the overall duration of parenteral nutrition ( OR=3.011, 95% CI: 1.624-5.041, P=0.022), and the total duration of mechanical ventilation ( OR=3.572, 95% CI: 1.497-4.601, P=0.031) were the early independent risk factors for jaundice in patients after polytrauma. Conclusions:Polytrauma patients are prone to developing jaundice after injury, which is more harmful, especially for intrahepatic cholestatic jaundice after injury. Early identification and early intervention of risk factors associated with jaundice after injury should be strengthened.

Abstract Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.

This paper introduces the composition of the Chinese version of the European quality of life five-dimension scale (EQ-5D), including two different level scales, EQ-5D-3L and EQ-5D-5L, and summarizes the status quo of the application of the above scales. This paper sorts out the utility value sets of the EQ-5D-3L and EQ-5D-5L scales currently developed based on the Chinese population, and provide an important reference for Chinese researchers to choose suitable scales for research on health-related quality of life and health economics cost-utility analysis in the future.

Objective:Based on the principle that the aggregation-induced emission (AIE) fluorescent probe 6PD-DPAN could bind and aggregate with bacteria, and the fluorescence intensity could reflect the quantity of bacteria, a new method for rapid, convenient, and accurate bacterial drug sensitivity testing was established, which provided a basis for rapid and accurate clinical drug use.Methods:This was a methodological evaluation study. A total of 107 clinical isolates were collected from Houjie Hospital of Dongguan City from January to December 2022, among which 46 isolates were used for the establishment of the new method, and 61 isolates were used for methodological validation. The minimum inhibitory concentration (MIC) determined by broth microdilution method was used as the gold standard, and three antibacterial drugs, gentamicin, levofloxacin, and cefotaxime, were used as experimental drugs. The AIE plate was incubated for 4 hours, and the fluorescence intensity was measured every half an hour to draw a fluorescence change curve. The MIC results were compared with the CLSI breakpoints to determine the bacteria as sensitive, intermediate, or resistant. To simplify the detection process, the ratio of fluorescence intensity at 4 hours(R) was calculated, and the ROC curve was used to analyze the efficacy of R in determining bacterial growth and establish its cutoff value. The new method was used to determine the MIC of 61 clinical isolates, with broth microdilution method as the gold standard. The basic consistency, categorical consistency, very major errors, and major errors of the new method were analyzed, and the consistency between the two methods was determined by the Kappa test.Results:ROC curve analysis of the R after 4 hours of culture: The cut-off value was 3.0, with both sensitivity and specificity for determining bacterial growth being 100%. The median (interquartile) R for bacterial growth inhibition was 11.1 (8.6, 14.4); the median R-value for bacterial growth was 1.1 (1.0, 1.2). Compared to the gold standard, the newly established method showed 100% (61/61) essential agreement in detecting MICs of 61 clinical isolates, with a categorical agreement of 96.7% (59/61). There were no very major or major errors, and the Kappa value was 0.94, indicating good consistency between the newly established method and the microbroth dilution method.Conclusions:This study successfully established a new method for bacterial drug sensitivity testing based on AIE technology, which could obtain satisfactory results within 5 hours, providing a basis for early precision drug treatment in clinical practice.

Background: and Purpose To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). Methods: Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. Results: A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4–53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8–15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. Conclusion TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.

Objective:To retrospectively assess early risk factor of persistent inflammation, immunosuppression and catabolism syndrome (PICS) in patients with severe polytrauma, in order to deepen the understanding of the pathological changes of chronic critical illness (CCI) after severe polytrauma.Methods:A total of 276 patients with severe polytrauma admitted to Department of Trauma Surgery of Tongji Hospital from March 2019 to December 2020 were enrolled. Inclusion criteria included patients who suffered severe polytrauma, and injury severity score (ISS) ≥27, age ≥18 years old, and had length of hospital stay >15 days. Exclusion criteria included previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. The patient’s clinical characteristics, ISS scores, Glasgow coma scale (GCS), sequential organ failure assessment, APACHEⅡ scores, and nutrition and immune indexes on day 3 after injury were collected. The difference between the PICS group and N-PICS group were performed by Student’s t test, χ2 test or Mann-Whitney U test. The early risk factors were assessed in patients with PICS after severe polytrauma by logistic regression analysis. Results:According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group ( n=102) and N-PICS group (without PICS, n=174). Compared with the N-PICS group, patients in the PICS group were older and associated with more brain and chest injuries. On the third day after injury, serum levels of IL-6 and IL-10, and the ratio of Treg cells were significantly higher, the number and ratio of NK cells subset, and the ratio of activated T lymphocyte were significantly lower in the PICS group than in the N-PICS group ( P<0.05). Logistic regression analysis showed that the age>65 years old ( OR=2.375, 95% CI: 1.442-4.531), GCS ≤8 scores ( OR=3.431, 95% CI: 1.843-8.512), IL-10 >10 pg/mL ( OR=2.173, 95% CI: 1.751-5.614), the ratio of Treg cells >7% ( OR=3.871, 95% CI: 1.723-6.312), and the occurrence of traumatic brain and chest injuries ( OR=2.846, 95% CI: 1.522-5.361) were the early risk factors in patients with PICS after severe polytrauma. Conclusions:Age>65 years old, GCS score, IL-10, the ratio of Treg cells, and the occurrence of traumatic brain and chest injuries could be used as the early risk factors in patients with PICS after severe polytrauma. The discovery of early risk factors will help identify patients at high risk of PICS after severe polytrauma, and create the possibility for early intervention.

Objective To explore the application value of chest dual-energy subtraction (DES) technology in the diagnosis of occupational pneumoconiosis. Methods A total of 86 patients with suspected pneumoconiosis and 21 dust-exposure workers were selected as the research subjects using random sampling method. The posterior and anterior chest radiographs were taken by digital radiography (DR) and DES technology, and the difference of chest radiographs of DR, DES and combined groups were compared. Results The positive rate of superior chest radiographs in DR group was higher than that in DES group (72.9% vs 56.1%, P<0.05). The determination of shadow shape and size, total density and stage of pneumoconiosis on chest radiographs in DES group and combined group were consistent with those in DR group (all Kappa values >0.75, all P<0.01). However, the judgment of small shadow intensity, small shadow aggregation and large shadow distribution in the two groups were not superior to those in the DR group (Kappa value was 0.67, 0.74, both P<0.01). There was no significant difference between DES group and DR group in the determination of small shadow intensity, small shadow aggregation and large shadow distribution (P>0.05). However, there were statistically significant difference in this index between the combined group and DES group and DR group (all P<0.01). There was no statistically significant difference in shadow shape and size, total density and stage of pneumoconiosis in chest radiographs among these three groups (all P>0.05). Conclusion There was no difference between DES alone and DES combined with DR for the diagnosis of pneumoconiosis in terms of shadow shape and size, total density and stage of pneumoconiosis when compared with the gold standard DR. The value of DES in the diagnosis of pneumoconiosis needs further study.