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.

Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

Objective: To analyze the association between exposure patterns of adverse childhood experiences (ACEs) and anxiety symptom trajectories in medical college students. Methods: A survey was conducted on first-year students from Anhui Medical College and Anqing Medical College, using the Childhood Abuse Questionnaire, Family Disability Questionnaire, Childhood Adverse Social Experience Item, and Anxiety Self Rating Scale. The baseline survey was conducted from November to December 2019, and two follow-up visits were conducted once every six months until November to December 2020. The latent class analysis (LCA) was used to analyze the exposure patterns of ACEs. The latent class growth analysis (LCGA) was used to analyze the development trajectory of anxiety symptoms. The multiple logistic regression model was used to analyze the correlation between different exposure patterns of ACEs and the trajectory of anxiety symptom trajectories. Results: A total of 3 662 college students aged (19.2±1.0) were surveyed. The LCA showed that the exposure patterns of ACEs could be divided into the "high ACEs" group (13.4%), "high neglect/emotional abuse" group (25.7%), "high family dysfunction" group (6.9%), "high neglect" group (27.1%), and "low ACEs" group (26.3%). The LCGA divided anxiety trajectories into four groups: "high anxiety decline" (7.1%),"anxiety increase "(4.1%), "moderate anxiety"(52.9%), and "low anxiety"(35.9%). Using the low ACEs group as a reference group, compared with the low anxiety trajectory, the high ACEs group, high neglect/emotional abuse group, high family dysfunction group, high neglect group, and medium to high-level anxiety trajectory were all associated with an increased risk (P<0.05). Conclusion: There is heterogeneity in ACEs exposure patterns among medical college students, and ACEs exposure patterns are important influencing factors for anxiety symptom trajectories.
Humans ; Adverse Childhood Experiences ; Anxiety/epidemiology* ; Child Abuse/psychology* ; Students/psychology* ; Surveys and Questionnaires ; Adolescent ; Young Adult

Objective To compare the image quality of three high-resolution dynamic MRI methods for evaluating the motion of temporomandibular joint disc and condyle. Methods Twenty-five patients with suspected temporomandibular joint disorders were examined by single-shot fast spin-echo (SSFSE),fast imaging employing steady-state acquisition (FIESTA),and spoiled gradient echo (SPGR) on the oblique sagittal position.Two radiologists performed subjective and objective evaluation on the images with double-blind method.The subjective evaluation included the signal intensity of mandibular condyle,articular disc,soft tissue around articular disc,and lateral pterygoid muscle,the contrast between articular disc and condyle,the contrast between articular disc and surrounding soft tissue,condylar motion,and disc movement.The objective evaluation indexes included image signal intensity,signal-to-noise ratio (SNR),and contrast-to-noise ratio (CNR).The subjective and objective indexes of the image quality were compared between the three sequences. Results The SSFSE sequence had lower signal intensity of articular disc and higher signal intensity of condyle and surrounding soft tissue than FIESTA and SPGR sequences (all P<0.001).The SPGR sequence showed higher signal intensity of lateral pterygoid muscle than the SSFSE and FIESTA sequences (P=0.017,P<0.001).Among the three sequences,SSFSE sequence showed the clearest articular disc structure (χ²=41.952,P<0.001),the strongest contrast between articular disc and condyle (χ²=35.379,P<0.001),the strongest contrast between articular disc and surrounding soft tissue (χ²=27.324,P<0.001),and the clearest movement of articular disc (χ²=44.655,P<0.001).SSFSE and FIESTA sequences showed higher proportion of disc displacement and reduction than SPGR sequence (all P<0.001).The CNR (χ²=21.400,P<0.001),SNR (χ²=34.880,P<0.001),and condyle signal intensity (F=337.151,P<0.001) demonstrated differences among SSFSE,FIESTA,and SPGR sequences.The CNR of SSFSE sequence was higher than that of FIESTA sequence (P<0.001),while it had no significant difference between SSFSE and SPGR sequences (P=0.472).In addition,the SSFSE sequence had higher SNR and signal intensity than FIESTA and SPGR sequences (all P<0.001). Conclusion The best image quality can be observed from SSFSE sequence where both the structure and movement of temporomandibular joint are well displayed.Therefore,SSFSE is preferred for the examination of temporomandibular joint movement.
Humans ; Temporomandibular Joint/diagnostic imaging* ; Motion ; Plastic Surgery Procedures

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; B7-H1 Antigen/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Tomography, X-Ray Computed ; Immunotherapy

Objective:To investigate the effect of T-lymphocyte and subpopulation counts on the prognosis of severe acute pancreatitis (SAP) patients.Methods:The clinical data of 90 patients with SAP diagnosed at the Shanghai General Hospital between January 2019 and June 2022 were retrospectively analyzed, and the patients were divided into good prognosis and poor prognosis group according to whether they were diagnosed for 28 d. The general information of the patients was recorded, including blood-related immunological indicators within 24 h of diagnosis, including leukocytes, neutrophils, lymphocytes, monocytes, CD 3+ , CD 4+ , CD 8+ T-lymphocyte count and CD 4+ /CD 8+ T-lymphocyte ratio, IgG4 level; blood inflammation index procalcitonin, albumin level and APACHEⅡ score at admission; survival and complication status of patients at 28 d of diagnosis. Non-parametric Mann-Whitney U test was used to analyze the correlation between each index and the prognosis of the patients. The subject operating characteristic curve (ROC) of patients was plotted, and area under curve (AUC) was calculated to assess the value of CD 3+ and CD 4+ T-lymphocytes in predicting the prognosis of SAP. Results:The majority of SAP patients were male (65.6%). The main cause of SAP was gallstone (56.7%), followed by hyperlipidemia (35.6%). At 28 days after diagnosis, 85(94.4%) patients survived, and 39 of them were cured and included in the good prognosis group. Forty-six cases were complicated with infection, multiple organ dysfunction syndrome (MODS) and local pancreatic complications, and 5 cases (5.56%) died; and a total of 51 cases were included in the poor prognosis group. Compared with the good prognosis group, the number of CD 3+ T-lymphocytes [366(268, 498) cells /μl vs 709(578, 999) cells /μl], CD 4+ T-lymphocytes [209(120, 298) cells /μl vs 486(303, 548) cells /μl] and albumin level (33.9 g/L vs 35.9 g/L) within 24 hours in the poor prognosis group were significantly lower, while the level of procalcitonin (1.02 ng/ml vs 0.43 ng/ml) and APACHEⅡ score [7(4, 10) vs 5(3, 8)] were significantly increased, and all the differences were statistically significant (all P value <0.05). ROC curve analysis showed that the AUC values for CD 3+ and CD 4+ T-lymphocyte counts within 24 hours for predicting poor prognosis of SAP were 0.857 (95% CI 0.696-1.000) and 0.867 (95% CI 0.708-1.000), respectively. The cut-off values were 524 cells /μl and 301 cells /μl, the sensitivity were both 85.7%, and the specificity were 78.6% and 85.7%, respectively. Conclusions:The significant decrease of peripheral blood CD 3+ and CD 4+ T-lymphocyte count within 24 h of SAP diagnosis has a certain predictive value for the prognosis of patients with SAP.

Objective:To analyse the clinical efficacy and outcome of early abdominal paracentesis drainage (APD) in the treatment of severe acute pancreatitis (SAP).Methods:The clinical data of 107 SAP patients with massive abdominal fluid in Shanghai General People Hospital from May 2017 to December 2021 were collected and analyzed. Patients were divided into APD group ( n=56) and NO-APD group ( n=51) according to whether they underwent APD or not within 3 days after admission. The APD group was then divided into abdominal compartment syndrome (ACS) subgroup ( n=29) and NO-ACS subgroup ( n=27) according to whether ACS had occurred or not at the time of puncture. Patients' general data, the duration of systemic inflammatory response (SIRS), length of ICU stay, the trends of intra-abdominal pressure and inflammatory indicators (white blood cell count and the content of C-reactive protein) within 1-3 days after admission, incidence of infection complication, step-up therapy, discharge or death were recorded. Results:The intra-abdominal pressure were 18.6±5.6mmHg , 13.7±4.2mmHg (1 mmHg=0.133 kpa) in APD group and NO-APD group, respectively. The intra-abdominal pressure of APD group was significantly higher than that of NO-APD group, and the difference was statistically significant ( P=0.000). Compared with NO-APD group, the duration of SIRS was significantly shortened in APD group [3(2, 4) days vs 4(3, 6) days, P=0.029]. On day 1, 2 and 3 after admission, the intra-abdominal pressure was 18.6±5.6 mmHg, 16.4±4.7 mmHg and 13.5±3.9 mmHg in APD group, and was 13.7±4.2 mmHg, 12.3±3.6 mmHg and 11.0±2.6 mmHg in NO-APD group, respectively. The intra-abdominal pressure of the APD group dropped faster than the NO-APD group ( P=0.004). The white blood cell count was (14.8±4.8), (10.5±4.5) and (9.0±3.8)×10 9/L in APD group, and was (14.2±5.4), (12.3±7.3), (11.7±5.3)×10 9/L in NO-APD group, respectively. Compared with the NO-APD group, the decrease rate of white blood cell count was faster in APD group ( P=0.006). The C-reactive protein content was (153.6±47.1), (150.4±10.5) and (108.8±49.4)mg/L in APD group, and were (174.8±31.1), (191.6±29.4) and (186.8±45.5)mg/L in NO-APD group . The content of C-reactive protein in APD group decreased significantly, while that in NO-APD group did not decrease. There was a significant difference between the two groups ( P=0.009). In the subgroup comparisons, the duration of SIRS in the ACS subgroup was significant longer than that in the NO-ACS subgroup [4(3, 5) days vs 2(1, 3)days, P=0.000]. Compared between the two groups and two subgroups respectively, there were no statistically significant differences on length of ICU stay, infection complication rate, advanced treatment rate and mortality. Conclusions:For SAP patients with abdominal fluid, APD in the early stage could shorten the duration of SIRS, decrease intra-abdominal pressure rapidly, improve inflammatory indicators, but could not improve the clinical outcome.

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4⁺ and CD8⁺ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4⁺ and CD8⁺ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.
Humans ; Anemia, Aplastic ; CD8-Positive T-Lymphocytes ; Melatonin ; Blood Cell Count