The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Association between early ambulation exercise and short-term postoperative recovery after open transforaminal lumbar interbody fusion: a single center retrospective analysis.

BACKGROUND: Early ambulation in patients undergoing transforaminal lumbar interbody fusion (TLIF) surgery is recommended, however, the precise time interval after open surgery has never been specified. Current retrospective analysis was conducted aiming to clarify an accurate time interval. METHODS: A retrospective analysis of eligible patients was conducted using the databases of the Bone Surgery Department, Third Affiliated Hospital of Sun Yat-sen University from 2016 to 2021. Data pertaining to postoperative hospital stay length, expenses, incidence of complications were extracted and compared using Pearson's χ2 or Student's t-tests. A multivariate linear regression model was conducted to identify the relationship between length of hospital stay (LOS) and other outcomes of interest. A propensity analysis was conducted to minimize bias and to evaluate the reliability of results. RESULTS: A total of 303 patients met the criteria and were included for the data analysis. Multivariate linear regression results demonstrated that a high ASA grade (p = 0.016), increased blood loss (p = 0.003), cardiac disease (p < 0.001), occurrence of postoperative complications(p < 0.001) and longer ambulatory interval (p < 0.001) was significantly associated with an increased LOS. The cut-off analysis manifested that patients should start mobilization within 3 days after open TLIF surgery (B = 2.843, [1.395-4.292], p = 0.0001). Further comparative analysis indicated that patients who start ambulatory exercise within 3 days have shorter LOS (8.52 ± 3.28d vs 12.24 ± 5.88d, p < 0.001), total expenses ( 9398.12 ± 2790.82vs 10701.03 ± 2994.03 [USD], p = 0.002). Propensity analysis revealed such superiority was stable along with lower incidence of postoperative complications (2/61 vs 8/61, p = 0.0048). CONCLUSIONS: The current analysis suggested that ambulatory exercise within 3 days for patients who underwent open TLIF surgery was significantly associated with reduced LOS, total hospital expenses, and postoperative complications. Further causal relationship would be confirmed by future randomized controlled trials.

Correlation of CT-derived pectoralis muscle status and COVID-19 induced lung injury in elderly patients.

OBJECTIVES: To explore the association between CT-derived pectoralis muscle index (PMI) and COVID-19 induced lung injury. METHODS: We enrolled 116 elderly COVID-19 patients linked to the COVID-19 outbreak in Nanjing Lukou international airport. We extracted three sessions of their CT data, including one upon admission (T1), one during the first 2 weeks when lung injury peaked (T2) and one on day 14 ± 2 (T3). Lung injury was assessed by CT severity score (CTSS) and pulmonary opacity score (POS). Pneumonia evolution was evaluated by changes of CT scores at T2 from T1(Δ). RESULTS: The maximum CT scores in low PMI patients were higher than those of normal PMI patients, including CTSS1 (7, IQR 6-10 vs. 5, IQR 3-6, p < 0.001), CTSS2 (8, IQR 7-11 vs. 5, IQR 4-7, p < 0.001) and POS (2, IQR 1-2.5 vs. 1, IQR 1-2, p < 0.001). Comorbidity (OR = 6.15, p = 0.023) and the presence of low PMI (OR = 5.43, p = 0.001) were predictors of lung injury aggravation with ΔCTSS1 > 4. The presence of low PMI (OR = 5.98, p < 0.001) was the predictor of lung injury aggravation with ΔCTSS2 > 4. Meanwhile, presence of low PMI (OR = 2.82, p = 0.042) and incrementally increasing D-dimer (OR = 0.088, p = 0.024) were predictors of lung injury aggravation with ΔPOS = 2. CONCLUSIONS: PMI can be easily assessed on chest CT images and can potentially be used as one of the markers to predict the severity of lung injury in elderly COVID-19 patients.

DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells.

BACKGROUND: Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. METHODS AND RESULTS: DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. CONCLUSIONS: Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.

OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the Cleavage of Caspases.

Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined. We found that iPSC-MSC grafts led to more cell survival and less infiltration of inflammatory cells in mice. iPSC-MSC transplantation inhibited T cell proliferation, decreased Th1 and Th2 phenotypes and cytokines, upregulated Th17 and Treg subsets. Moreover, iPSC-MSCs inhibited the cleavage of caspases 3 and 8 and inhibition of caspases downregulated Th1, Th2 responses and upregulated Th17, Treg responses. Soluble factors were determined using protein array and TGF-ß1/2/3, IL-10, and MCP-1 were found to be highly expressed in iPSC-MSCs. The administration of the soluble factors decreased Th1/2 response, upregulated Treg response and inhibited the cleavage of caspases. Our results demonstrate that iPSC-MSCs regulate T cell responses as a result of a combined action of the above soluble factors secreted by iPSC-MSCs. These factors suppress T cell responses by inhibiting the cleavage of caspases. These data provide a novel immunomodulatory mechanism for the underlying iPSC-MSC-based immunomodulatory effects on T cell responses. Stem Cells 2017;35:1719-1732.

Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation.

Analytical performance of the Biosino urea reagent kit.

BACKGROUND: Two kinds of analytical system are used to analyze urea concentration, one is the homogeneous ana- lytical system and the other is the heterogeneous analytical system. No matter which analytical systems are used, their performance characteristics must be evaluated. Here, the performance of a heterogeneous analytical system is evaluated. METHODS: The UV urease-glutamate dehydrogenase (GLDH) reference method was reproduced and its accuracy and precision were verified. The performance characteristics of the Biosino urea reagent kit were evaluated ac- cording to the Clinical and Laboratory Standards Institute (CLSI) EP15-A2, EP6-A, and EP9-A2 guidelines. RESULTS: The performance characteristics of the UV urease-GLDH reference method demonstrate that the urea concentrations of the standard reference material (SRM) 909b I and II are within their prescriptive ranges, the within-run CVs are 0.39% and 0.16%, and the within-laboratory CVs are 0.63% and 0.40%, respectively. The performance characteristics of the Biosino urea reagent kit demonstrate that the within-run CVs are 0.84% and 0.78%, the within-laboratory CVs are 2.26% and 0.92%, the ranges of interference are 0-2.84% (0-1 g/L vitamin C), 0 - -2.86% (0-10 g/L intralipid), 0-2.81% (0-10 g/L hemoglobin), 0 - -2.1% (0-0.4 g/L conjugated bilirubin), 0 - -2.1% (0-0.4 g/L unconjugated bilirubin), and the analytical results are linear within the range of 1.8- 35.0 mmol/L. The analytical results of the Biosino urea analytical method and UV urease-GLDH, Olympus and Beckman urea analytical methods are strongly correlated (r > 0.998; p < 0.001), and the predicted biases are con- sidered acceptable at the three medical decision levels for urea. CONCLUSIONS: The Biosino urea reagent kit can provide reliable analytical results and the results are suitable for clinical uses.

Simple Synthesis of [18F] AV-45 and its Clinical Application in the Diagnosis of Alzheimer's Disease.

OBJECTIVE: [18F] AV-45 can be produced in a simple, stable, and repeatable manner on the Tracerlab FXF-N platform using a self-editing synthetic procedure and solid-phase extraction purification method. This technique is applied to positron emission tomography (PET) imaging of Alzheimer's disease (AD) to observe its distribution and characteristics in various brain regions and its diagnostic efficiency for the disease. METHODS: The precursor was subjected to nucleophilic radiofluorination at 120°C in anhydrous dimethyl sulfoxide, followed by acid hydrolysis of the protecting groups. The neutralized reaction mixture was purified by solid phase extraction to obtain a relatively pure [18F] AV-45 product with a high specific activity. A total of 10 participants who were diagnosed with Alzheimer's disease (AD group) and 10 healthy controls (HC group) were included retrospectively. All of them underwent [18F] AV-45 brain PET/CT imaging. The distribution of [18F] AV-45 in the AD group was analyzed visually and semi-quantitatively. RESULTS: Six consecutive radiochemical syntheses were performed in this experiment. The average production time of [18F] AV-45 was 52 minutes, the radiochemical yield was 14.2 % ± 2.7% (n = 6), and the radiochemical purity was greater than 95%. When used with PET/CT imaging, the results of the visual analysis indicated increased [18F] AV-45 radioactivity uptake in the frontal, temporal, and parietal lobes in AD patients. Semiquantitative analysis showed the highest diagnostic efficacy in the posterior cingulate gyrus compared with other brain regions (P < 0.001). CONCLUSION: Intravenous [18F] AV-45 was successfully prepared on the Tracerlab FXF-N platform by solid-phase extraction of crude product and automated radiochemical synthesis. PET/CT imaging can be used to diagnose and evaluate AD patients and provide a more robust basis for clinicians to diagnose AD.

Acute Pancreatitis Complicated by Thrombosis in the Right Brachiocephalic Veins and Superior Vena Cava: A Case Report

BACKGROUND: Acute pancreatitis (AP) is one of the most common digestive emergencies, and vascular complication is one of the primary reasons for death, with splanchnic venous thrombosis being the most common. Although extra-splanchnic venous thrombosis is rare, it carries the risk of life-threatening secondary pulmonary embolism. CASE PRESENTATION: We have, herein, reported a case of AP complicated by rare brachiocephalic vein thrombosis and superior vena cava thrombosis. A 40 years old woman was diagnosed with severe AP for abdominal pain 21 days ago. The patient received symptomatic treatment, including acid suppression, enzyme suppression, lipid-lowering, fluid infusion, anti-infection, and continuous renal replacement therapy. The patient was discharged after symptomatic relief. Recently, the patient was admitted again for middle-upper abdominal pain and discomfort. On admission, her blood platelet, DDimer, fibrin degradation products (FDP), and triglyceride levels have been found to be increased; abdominal enhanced CT showed pancreatic necrosis and an accumulation of peripancreatic necrosis and fluid, while chest enhanced CT suggested thrombosis in the right brachiocephalic vein and superior vena cava. The patient, however, improved and was discharged after anticoagulation combined with insulin and trypsin inhibitors. CONCLUSION: In diagnosing and treating AP, dynamic monitoring of D-dimer levels is necessary for the timely detection of the development of thrombotic complications.

Prediction of viral pneumonia based on machine learning models analyzing pulmonary inflammation index scores.

OBJECT: To obtain Pulmonary Inflammation Index scores from imaging chest CT and combine it with clinical correlates of viral pneumonia to predict the risk and severity of viral pneumonia using a computer learning model. METHODS: All patients with suspected viral pneumonia on CT examination admitted to The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University from December 2022 to March 2023 were retrospectively selected. The respiratory viruses were monitored by RT-PCR and categorized into patients with viral pneumonia and those with non-viral pneumonia. The extent of lung inflammation was quantified according to the Pulmonary Inflammation Index score (PII). Information on patient demographics, comorbidities, laboratory tests, pathogenetic testing, and radiological data were collected. Five machine learning models containing Random Forest(RF), Radial Basis Function Neural Network (RBFNN), Support Vector Machine (SVM), K Nearest Neighbour Algorithm (KNN), and Kernel Ridge Regression (KRR) were used to predict the risk of onset and severity of viral pneumonia based on the clinically relevant factors or PII. RESULTS: Among the five models, the SVM model performed best in ACC (76.75 %), SN (73.99 %), and F1 (72.42 %) and achieved a better area under the receiver operating characteristic curve (ROC) (0.8409) when predicting the risk of developing viral pneumonia. RF had the best overall classification accuracy in predicting the severity of viral pneumonia, especially in predicting pneumonia with a PII classification of grade I, the RF model achieved an accuracy of 98.89%. CONCLUSION: Machine learning models are valuable in assessing the risk of viral pneumonia. Meanwhile, machine learning models confirm the importance in predicting the severity of viral pneumonia through PII. The establishment of machine learning models for predicting the risk and severity of viral pneumonia promotes the further development of machine learning in the medical field.

Self-inflicted intravesical insertion of 83 magnetic balls in a 10-year-old boy: a case report and literature review.

BACKGROUND: A magnetic ball is a toy for children that can cause physical injury when used improperly. The injury of urethra and bladder caused by magnetic ball is rarely reported. CASE: Here we present a case of self-inflicted intravesical insertion of 83 magnetic balls by a 10-year-old boy. Preliminary diagnosis was made by a plain radiograph of the pelvis and ultrasonic examination of bladder and all the magnetic balls were removed under cystoscopy successfully. CONCLUSIONS: For children with recurrent bladder irritation, the possibility of bladder foreign body should be considered. Surgery is an effective method. For patients without serious complications, cystoscopy is the gold standard for diagnosis and treatment.

Two-year Outcomes after Transurethral Prostate Resection Post-prostatic Artery Embolization Versus Transurethral Prostate Resection Alone For Giant Benign Prostatic Hyperplasia.

PURPOSE: To compare the long-term (two-year) efficacy between transurethral resection of the prostate (TURP) after prostatic artery embolization (PAE) and TURP only for patients with giant (>100 mL) benign prostatic hyperplasia. MATERIALS AND METHODS: We retrospectively analyzed data from 61 and 150 patients with giant benign prostatic hyperplasia treated with PAE+TURP or TURP alone, respectively, from January 2015 to March 2020. We compared index changes before and after surgery. RESULTS: The operative time, intraoperative blood loss, postoperative bladder irrigation time, and catheter retention time in the PAE+TURP group were lower than those of the TURP group, while the speed of resection of the lesion and hospitalization costs were more significant (P < 0.05). International prostate symptom score (IPSS), quality of life (QoL), prostate volume, maximum urinary flow rate, detrusor pressure of maximum urinary flow rate, prostate-specific antigen, and urodynamic obstruction were better in the PAE+TURP group than the TURP group at 24 months (P < 0.05). Regarding IPSS and QoL scores at 24 months postoperatively compared with the preoperative period, the PAE+TURP group was better than the TURP group in terms of the storage period, voiding period, and QoL (P < 0.05). The distribution of postoperative adverse event severity classes was comparable between the groups (P = 0.984). CONCLUSION: In contrast to TURP alone, PAE + TURP is more expensive but provides better postoperative outcomes; there is no significant difference in terms of the severity grade distribution of postoperative complications.

Small nucleolar RNA host gene 25 is a long non-coding RNA helps diagnose and predict outcomes in prostate cancer.

BACKGROUND: The role of a long non-coding RNA called small nucleolar RNA host gene 25 (SNHG25) has been studied in some tumor types but the correlation between SNHG25 and PCA remains unknown. METHODS: The relationship between clinicopathologic characteristics and SNHG25 expression was evaluated using The Cancer Genome Atlas data. The binary classifier value of SNHG25 was calculated using areas under receiver operating characteristic (ROC) curves. Outcomes were evaluated using Kaplan-Meier and Cox regression analyses. Gene set enrichment was performed to identify potential SNHG25 functions. RESULTS: SNHG25 expression was significantly increased in PCA and correlated with age, primary therapy outcome, N stage, Gleason score, and residual tumor (p < 0.05). ROC curves demonstrated the effect of SNHG25 on diagnosis and outcomes (area under the curve = 0.923). Higher SNHG25 expression predicted shorter progression-free interval (PFI) (p < 0.001), and Cox regression showed that SNHG25 expression was an independent risk factor for reduced PFI (p = 0.028). SNHG25 expression was associated with mRNA and protein metabolism. CONCLUSIONS: SNHG25 expression increases significantly in PCA and is negatively associated with PFI. It is a potential diagnostic and prognostic biomarker in PCA.

Pelvic metastatic squamous cell carcinoma of unknown primary site: A case report and brief literature review.

RATIONALE: Cancer with unknown primary site is a kind of disease that is difficult to deal with clinically, accounting for 2% to 9% of all newly diagnosed cancer cases. Here, we report such a case with pelvic metastatic squamous cell carcinoma of an unknown primary site and review the relevant literature. PATIENT CONCERNS DIAGNOSES: A 43-year-old Chinese female patient was referred to our hospital and initially diagnosed as "malignant tumor of right adnexal area?, obstruction of right ureter, secondary hydronephrosis". INTERVENTIONS: Thereafter cytoreductive surgery was performed which included a total hysterectomy, left adnexectomy, partial omentum resection, pelvic lymph node dissection, and para-aortic lymph node dissection. The primary lesion could not be identified by supplementary examination and postoperative pathology. The patient was diagnosed as pelvic metastatic squamous cell carcinoma whose primary site was unknown. To prevent a recurrence, we administered adjuvant chemotherapy for the patient. OUTCOMES: The patient was followed up after treatment, complete remission has been maintained for 72 months, and no recurrence or metastasis has been found. LESSONS: Our case demonstrates that surgery combined with chemotherapy could be helpful for pelvic metastatic squamous cell carcinoma of unknown primary site.

Different effects of vaccine on VST in critical and non-critical COVID-19 patients: A retrospective study of 363 cases.

Aim: To explore the risk factors of prolonged viral shedding time (VST) in critical/non-critical COVID-19 patients during hospitalization. Methods: In this retrospective study, we enrolled 363 patients with SARS-CoV-2 infection admitted in a designated hospital during the COVID-19 outbreak in Nanjing Lukou International Airport. Patients were divided into critical (n = 54) and non-critical (n = 309) groups. We analyzed the relationship between the VST and demographics, clinical characteristics, medications, and vaccination histories, respectively. Results: The median duration of VST was 24 d (IQR, 20-29) of all patients. The VST of critical cases was longer than non-critical cases (27 d, IQR, 22.0-30.0 vs. 23 d, IQR 20-28, P < 0.05). Cox proportional hazards model showed that ALT (HR = 1.610, 95%CI 1.186-2.184, P = 0.002) and EO% (HR = 1.276, 95%CI 1.042-1.563, P = 0.018) were independent factors of prolonged VST in total cases; HGB (HR = 0.343, 95%CI 0.162-0.728, P = 0.005) and ALP (HR = 0.358, 95%CI 0.133-0.968, P = 0.043) were independent factors of prolonged VST in critical cases, while EO% (HR = 1.251, 95%CI 1.015-1.541, P = 0.036) was the independent factor of prolonged VST in non-critical cases. Vaccinated critical cases showed higher levels of SARS-CoV-2-IgG (1.725 S/CO, IQR 0.3975-28.7925 vs 0.07 S/CO, IQR 0.05-0.16, P < 0.001) and longer VSTs (32.5 d, IQR 20.0-35.25 vs 23 d, IQR 18.0-30.0, P = 0.011) compared with unvaccinated critical patients. Fully vaccinated non-critical cases, however, presented higher levels of SARS-CoV-2-IgG (8.09 S/CO, IQR 1.6975-55.7825 vs 0.13 S/CO IQR 0.06-0.41, P < 0.001) and shorter VSTs (21 d, IQR 19.0-28.0 vs 24 d, IQR 21.0-28.5, P = 0.013) compared with unvaccinated non-critical patients. Conclusions: Our results suggested that risk factors of prolonged VST were different between critical and non-critical COVID-19 patients. Increased level of SARS-CoV-2-IgG and vaccination did not shorten the VST and hospital stay in critical COVID-19 patients.

Interferon-gamma and tumor necrosis factor-alpha synergistically enhance the immunosuppressive capacity of human umbilical-cord-derived mesenchymal stem cells by increasing PD-L1 expression.

BACKGROUND: The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1 (PD-L1), which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases. In MSCs, interferon-gamma (IFN-γ) is a key inducer of PD-L1 expression, which is synergistically enhanced by tumor necrosis factor-alpha (TNF-α); however, the underlying mechanism is unclear. AIM: To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis. METHODS: We assessed PD-L1 expression in human umbilical-cord-derived MSCs (hUC-MSCs) induced by IFN-γ and TNF-α, alone or in combination. Additionally, we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γ alone or in combination with TNF-α induces PD-L1 expression. Moreover, we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters. Finally, we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γ and TNF-α in both an in vitro mixed lymphocyte culture assay, and in vivo in mice with dextran sulfate sodium-induced acute colitis. RESULTS: Our results suggest that IFN-γ induction alone upregulates PD-L1 expression in hUC-MSCs while TNF-α alone does not, and that the co-induction of IFN-γ and TNF-α promotes higher expression of PD-L1. IFN-γ induces hUC-MSCs to express PD-L1, in which IFN-γ activates the JAK/STAT1 signaling pathway, up-regulates the expression of the interferon regulatory factor 1 (IRF1) transcription factor, promotes the binding of IRF1 and the PD-L1 gene promoter, and finally promotes PD-L1 mRNA. Although TNF-α alone did not induce PD-L1 expression in hUC-MSCs, the addition of TNF-α significantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation. TNF-α up-regulated IFN-γ receptor expression through activation of the nuclear factor kappa-B signaling pathway, which significantly enhanced IFN-γ signaling. Finally, co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation, and significantly ameliorate weight loss, mucosal damage, inflammatory cell infiltration, and up-regulation of inflammatory factors in colitis mice. CONCLUSION: Overall, our results suggest that IFN-γ and TNF-α enhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.

[Effects of shikonin on the proliferation and apoptosis of HL-60 cells].

OBJECTIVE: To explore the mechanism of shikonin for inducing the apoptosis of human promyelocytic leukemia cell HL-60. METHODS: The effects of shikonin on the HL-60 cell proliferation were detected using MTT. The apoptosis rate was analyzed by Annexin-V/PI double staining. The expression level of the bcl-2 gene was detected using semi-quantitative reverse transcriptase PCR (RT-PCR), thus analyzing the correlation between the bcl-2 expression level and the apoptosis of HL-60. RESULTS: Shikonin could inhibit the proliferation of HL-60 cells with the concentration range of 1-8 microg/mL in a time- and concentration-dependent manner. Two microg/mL shikonin could induce the apoptosis of HL-60 cells in a time-dependent manner. The expression level of bcl-2 was obviously down-regulated at 2 microg/mL shikonin. CONCLUSIONS: Shikonin could induce the apoptosis of HL-60 cells. Its mechanism was correlated with down-regulation of the expression level of bcl-2.

Immunoglobulin G4-Related Spinal Intramedullary Inflammatory Pseudotumor: A Case Report and Literature Review.

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disease that affects several organs. An inflammatory pseudotumor is a histologically proven benign tumor-like lesion that most commonly involves the lung and orbit. It is rare in the central nervous system, but rarest in the spinal canal. In this report, we present a case of IgG4-related intramedullary spinal inflammatory pseudotumor, along with a literature review. A 29-year-old male was transferred to the Department of Neurosurgery of Lanzhou University Second Hospital with progressive quadriparesis after numbness and weakness in both lower limbs for 50 days. Enhanced magnetic resonance imaging (MRI) of the spine revealed an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images from an enhanced mass located at the thoracic vertebrae region, for which a schwannoma was highly suspected. Then, a posterior median approach was adopted. The lesion was resected. The patient received further glucocorticoid after the diagnosis of an IgG4-related inflammatory pseudotumor was established, and the patient's symptoms improved, such as quadriparesis and lower limb weakness. This case highlights the importance of considering IgG4-related inflammatory pseudotumor as a differential diagnosis in patients with lesions involving the spinal intramedullary compartment and lower limb weakness when other more threatening causes have been excluded. IgG4-related inflammatory pseudotumor is etiologically unclear and prognostically unpredictable, and imaging may not help establish the diagnosis of IgG4-related inflammatory pseudotumor due to its resemblance to malignant tumors, and total resection might not be warranted. Glucocorticoid and surgery are usually the first-line treatments used.

A dynamic bidirectional coupling model for watershed water environment simulation based on the multi-grid technique.

Water pollution is a critical issue of global importance. Water environment modeling is an important tool for studying water pollution in basins. Based on a review of existing water environment models, a dynamic bidirectional coupling model for the water environment (E-DBCM), consisting of an upland watershed module (UWSM) and a 2D downstream waterbody module (DWBM), was developed using the multi-grid technique. The computational domain was discretized with grids of different sizes, and different time steps were adopted in regions with different grid sizes. The UWSM was applied to describe the generation and transport of pollutants on coarse grids to improve the computational efficiency, while the DWBM was capable of simulating the hydrodynamic and pollutant transport processes on fine grids to obtain a high accuracy. These two modules were spatially connected by a moving coupling boundary. Two test cases were used to validate the performance of the proposed model, and the results indicated that the E-DBCM had satisfactory computing efficiency while maintaining acceptable numerical accuracy. The water environment of the Yanqi River Basin was evaluated using the proposed E-DBCM. The maximum percent bias was 10.31 %, which indicates that the E-DBCM is reliable and that the numerical accuracy satisfies the engineering demand. The computational efficiency dramatically increased by 90 % when the watershed was discretized using the multi-grid technique. It was found that water pollution problems in this basin were serious, especially during the flood season. Various measures should be taken to improve the water environment treatment and strengthen protection measures in the Yanqi River Basin.