Microglial Activation Imaging Using 18F-DPA-714 PET/MRI for Detecting Autoimmune Encephalitis.

Background Translocator protein (TSPO) PET has been used to visualize microglial activation in neuroinflammation and is a potential imaging tool for detecting autoimmune encephalitis (AIE). Purpose To compare the detection rate between TSPO radioligand fluorine 18 (18F) DPA-714 PET and conventional MRI and assess the relationship between 18F-DPA-714 uptake and clinical features in participants with AIE. Materials and Methods Healthy volunteers and patients with AIE were enrolled in this prospective study between December 2021 and April 2023. All participants underwent hybrid brain 18F-DPA-714 PET/MRI and antibody testing. Modified Rankin scale scoring and AIE-related symptoms were assessed in participants with AIE. Positive findings were defined as intensity of 18F-DPA-714 uptake above a threshold of the mean standardized uptake value ratio (SUVR) plus 2 SD inside the corresponding brain regions of healthy controls. The McNemar test was used to compare the positive detection rate between the two imaging modalities; the independent samples t test was used to compare continuous variables; and correlation with Bonferroni correction was used to assess the relationship between 18F-DPA-714 uptake and clinical features. Results A total of 25 participants with AIE (mean age, 39.24 years ± 19.03 [SD]) and 10 healthy controls (mean age, 28.70 years ± 5.14) were included. The positive detection rate of AIE was 72% (18 of 25) using 18F-DPA-714 PET compared to 44% (11 of 25) using conventional MRI, but the difference was not statistically significant (P = .065). Participants experiencing seizures exhibited significantly higher mean SUVR in the entire cortical region than those without seizures (1.23 ± 0.21 vs 1.15 ± 0.18; P = .003). Of the 13 participants with AIE who underwent follow-up PET/MRI, 11 (85%) demonstrated reduced uptake of 18F-DPA-714 accompanied by relief of symptoms after immunosuppressive treatment. Conclusion 18F-DPA-714 PET has potential value in supplementing MRI for AIE detection. Clinical trial registration no. NCT05293405 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Zaharchuk in this issue.

Comparison of the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer: a prospective study.

PURPOSE: To compare the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer patients. METHODS: Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT within 2 weeks, and surgical treatment was performed within 10 days after PET. RESULTS: Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [18F]FDG and [68 Ga]Ga-FAPI-04 lymph node high metabolism were staged as FIGO IIIC1r, and concurrent chemoradiation therapy (CCRT) was performed. [18F]FDG and [68 Ga]Ga-FAPI-04 had equivalent detection ability on primary tumors, with a positive detection rate of 96.0%. The accuracy of T staging using [18F]FDG and [68 Ga]Ga-FAPI-04 was relatively 50% and 55.0%. Elevated and underrated staging was due to misdiagnosis of either vaginal infiltration or tumor size. In terms of lymph node metastasis detection, the specificity of [68 Ga]Ga-FAPI-04 was 100% (95% CI, 84.6% ~ 100.0%), which was significantly higher than [18F]FDG (59.1% (95% CI, 36.4% ~ 79.3%)) (p = 0.004). CONCLUSION: [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT demonstrated an equivalent detection ability on cervical cancer primary tumors. However, [68 Ga]Ga-FAPI-04 PET/MR's diagnostic value in lymph node metastasis was significantly higher than [18F]FDG PET/CT. [68 Ga]Ga-FAPI-04 PET/MR has the potential for more accurate treatment planning, thus clarifying fertility preservation indications for early-stage young patients.

Multi-modality deep learning-based [68Ga]Ga-DOTA-FAPI-04 PET polar map generation: potential value in detecting reactive fibrosis after myocardial infarction.

PURPOSE: Generating polar map (PM) from [68Ga]Ga-DOTA-FAPI-04 PET images is challenging and inaccurate using existing automatic methods that rely on the myocardial anatomical integrity in PET images. This study aims to enhance the accuracy of PM generated from [68Ga]Ga-DOTA-FAPI-04 PET images and explore the potential value of PM in detecting reactive fibrosis after myocardial infarction and assessing its relationship with cardiac function. METHODS: We proposed a deep-learning-based method that fuses multi-modality images to compensate for the cardiac structural information lost in [68Ga]Ga-DOTA-FAPI-04 PET images and accurately generated PMs. We collected 133 pairs of [68Ga]Ga-DOTA-FAPI-04 PET/MR images from 87 ST-segment elevated myocardial infarction patients for training and evaluation purposes. Twenty-six patients were selected for longitudinal analysis, further examining the clinical value of PM-related imaging parameters. RESULTS: The quantitative comparison demonstrated that our method was comparable with the manual method and surpassed the commercially available software-PMOD in terms of accuracy in generating PMs for [68Ga]Ga-DOTA-FAPI-04 PET images. Clinical analysis revealed the effectiveness of [68Ga]Ga-DOTA-FAPI-04 PET PM in detecting reactive myocardial fibrosis. Significant correlations were demonstrated between the difference of baseline PM FAPI% and PM LGE%, and the change in cardiac function parameters (all p < 0.001), including LVESV% (r = 0.697), LVEDV% (r = 0.621) and LVEF% (r = -0.607). CONCLUSION: The [68Ga]Ga-DOTA-FAPI-04 PET PMs generated by our method are comparable to manually generated and sufficient for clinical use. The PMs generated by our method have potential value in detecting reactive fibrosis after myocardial infarction and were associated with cardiac function, suggesting the possibility of enhancing clinical diagnostic practices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04723953). Registered 26 January 2021.

Transformation of A1/A2 Astrocytes Participates in Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning via Inhibiting NDRG2.

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia-reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10+/GFAP+ cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10+/GFAP+ cells yet increased C3d expression and the number of C3d+/GFAP+ cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d+/GFAP+ cells increased, while S100A10 expression and the number of S100A10+/GFAP+ cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression.

CircANKRD17 promotes glycolysis by inhibiting miR-143 in breast cancer cells.

Glucose metabolic reprogramming, known as the Warburg effect, is one of the metabolic hallmarks of tumor cells. Cancer cells preferentially metabolize glucose by glycolysis rather than mitochondrial oxidative phosphorylation regardless of oxygen availability, but the regulatory mechanism underlying this switch has been incompletely understood. Here, we report that the circular RNA circ ankyrin repeat domain 17 (ANKRD17) functions as a key regulator for glycolysis to promote cell growth, migration, invasion, and cell-cycle progression in breast cancer (BC) cells. We further show that circANKRD17 acts to accelerate glycolysis in BC cells by acting as a sponge for miR-143 and in turn overrides the repressive effect of miR-143, a well-documented glycolytic repressor, on hexokinase 2 in BC cells, thus resulting in enhanced glycolysis in BC cells. These data suggest the circANKRD17-miR-143 cascade as a novel mechanism in controlling glucose metabolic reprogramming in BC cells and suggest circANKRD17 as a promising therapeutic target to interrupt cancerous glycolysis.

Pseudomonas aeruginosa isolation is an important predictor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a multicenter cohort study.

BACKGROUND: Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown. METHODS: A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence. RESULTS: A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3-53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25-3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13-2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29-3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09-1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688-0.769]. CONCLUSIONS: Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.

A comparative study of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in the diagnostic accuracy and resectability prediction of ovarian cancer.

PURPOSE: To provide a theory for guiding clinical treatment by comparing the clinical application value of [18F]fluorodeoxyglucose ([18F]FDG) PET/CT and [68Ga]Ga-FAPI (fibroblast activating protein inhibitor) PET/MR in the diagnosis and evaluation of resectability of ovarian cancer. METHODS: Thirty patients with high clinical suspicion of ovarian malignancies were enrolled from July 2021 to October 2022 and underwent [18F]FDG PET/CT and [68Ga]Ga-FAPI-04 PET/MR within 5 days. Twenty patients underwent [18F]FDG PET/MR at once completing [18F]FDG PET/CT for consistency checking. Images were analysed for comparing SUVs and for judging incomplete resectability according to the peritoneal cancer index (PCI) and SUIDAN scoring system. The expression of FAP, HK2 and Ki67 was analysed by immunohistochemistry staining. RESULTS: There was no significant difference between PET/MR and PET/CT in SUVs-FDG at different locations (p > 0.05), and their diagnostic accuracies were similar. The diagnostic accuracy of [68Ga]Ga-FAPI-04 PET/MR had advantages for peritoneal metastasis since SUVsFAPI were higher (p < 0.01). The sensitivity of [68Ga]Ga-FAPI-04 PET/MR in the diagnosis of peridiaghragmatic metastases was higher because SUVmax in the liver was decreased (p < 0.001). [68Ga]Ga-FAPI-04 PET/MR might have advantages in diagnosing gastrointestinal invasion. In PCI score analysis, [68Ga]Ga-FAPI-04 PET/MR could partially correct missing or underestimated scores by [18F]FDG PET/CT, but the matching probability between left peri-intestinal metastasis scores was low and easy to overestimate. Interestingly, diaphragmatic metastasis detected by [68Ga]Ga-FAPI-04 PET/MR had the greatest correlation with the prediction of incomplete resectability (logistic regression p = 0.02). Through immunohistochemistry, the expression of FAP had a strong correlation with SUVmax-FAPI (p < 0.001), while the expression of HK2 was correlated with SUVmax-FDG (p < 0.01). In addition, SUVmax-FDG with Ki67 ≥ 20% was significantly higher than that with Ki67 < 20% (p < 0.05). CONCLUSIONS: [68Ga]Ga-FAPI-04 PET/MR had obvious advantages for metastases diagnosis and could more accurately assess tumour load and predict incomplete resectability. SUVmax-FDG was conducive to evaluating the degree of tumour malignancy.

Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats.

Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP.

Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Inhibit the TGF-ß1 Pathway in Hepatic Fibrosis Rats Through a Paracrine Regulation Process.

BACKGROUND: The aim is to verify the therapeutic effect and possible mechanism of human umbilical cord Wharton's jelly-derived transplantation of mesenchymal stem cells (UMSCs) on CCl4-induced hepatic fibrosis rats through in vivo studies and to explore the regulatory mechanism of UMSCs on fibrosis of hepatic stellate cells (HSCs) through in vitro experiments. METHODS: In vivo experiment: Rats were randomly divided into blank control group and hepatic fibrosis group. During the entire trial, the blank control group received subcutaneous injection of normal saline, while in the hepatic fibrosis group received injections of 50% CCl4-olive oil subcutaneously for 10 weeks to establish the rat model of liver fibrosis. Hepatic fibrosis rats were then randomly and evenly divided into umbilical cord mesenchymal stem cell (UMSC) group, bone marrow mesenchymal stem cell (BMSC) group, UMSC-culture medium (CM) group, and control group. Rats in each group were infused with the following substances through the caudal vein as follows: 1 mL UMSCs (2 × 106/mL) in UMSC group, 1 mL BMSCs (2 × 106/mL) in BMSC group, 1 mL UMSCs-CM in CM group, and 1 mL saline in control group. Rats of each group were closely observed (weight, hair condition, activity, appetite, diarrhea, etc.), venous blood samples were collected, the number of white blood cells and lymphocytes were measured, and liver function indicators (ALT, AST, TBIL, ALB) were determined. Three weeks later, rat liver specimens were taken, HE stained, pathological changes were examined and quantified. In vitro experiments: HSCs were seeded in 6-well plates at 1.0 × 105/mL, with a serum-free medium for 24 hours. Then, 2 mL of UMSCs-CM was added in the study group, while an equal amount of complete medium was added to the control group. RT-PCR was used to detect TGF-ß1, Collagen-I, TIMP-2 mRNA expression in HSCs, and western blot was used to detect TGF-ß1 protein expression in HSCs. RESULTS: In vivo experiment: Compared with the control group, after the transplantation, the activity status (weight, spirit, appetite, movement, hair, diarrhea, etc.) of rats in the UMSC group, BMSC group, and CM group were improved. The liver function indexes of these groups, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly decreased (p < 0.05), while albumin (ALB) levels were mildly but not significantly increased (p > 0.05). The Knodell score (reflecting the degree of liver inflammation) and Chevallier score (reflecting the degree of liver fibrosis) of liver specimens in pathological examination were also significantly reduced, and the difference in the quantitative scores of those indexes was statistically significant (p < 0.05). There was no statistically significant difference in the number of venous white blood cells and lymphocytes, liver function indexes (ALT, AST, TBIL, ALB), Knodell score, and Chevallier score of liver samples among the UMSC group, BMSC group, and CM group. In vitro experiments: After treatment with UMSCs-CM, the expression of TGF-ß1, Collagen-I, and TIMP-2 mRNA in HSCs was significantly down-regulated compared with that of the control group (treated with complete medium), and it gradually decreased with the extension of the treatment time. Compared with the control group, the expression of TGF-ß1 protein in the HSCs of the experimental group was down-regulated, and this effect was time-dependent, specifically, the control group (2.49 ± 0.43) > the experimental group at 48 hours (1.98 ± 0.26) > the experimental group at 72 hours (1.62 ± 0.20) (F = 7.796, p < 0.05). CONCLUSIONS: In rats with liver fibrosis, transplantation of UMSCs can improve liver function and reduce the inflammatory activity and fibrosis of the liver, possibly through the paracrine mechanism. UMSCs inhibit HSCs fibrosis through a paracrine mechanism, which is time-dependent, possibly by targeting TGF-ß1 and its downstream gene products.

Combination treatment with hENT1 and miR-143 reverses gemcitabine resistance in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and is susceptible to develop gemcitabine (GEM) resistance. Decreased expression of human equilibrative nucleoside transporter 1 (hENT1) accompanied by compensatory increase of glycolysis is strongly associated with GEM resistance in TNBC. In this study, we investigated the treatment feasibility of combined hENT1 upregulation and miR-143-mediated inhibition of glycolysis for reversing GEM resistance in TNBC. METHODS: Experiments were performed in vitro and in vivo to compare the efficacy of GEM therapies. In this study, we established stable drug-resistant cell line, GEM-R cells, from parental cells (MDA-MB-231) through exposure to GEM following a stepwise incremental dosing strategy. Then GEM-R cells were transfected by lentiviral plasmids and GEM-R cells overexpressing hENT1 (GEM-R-hENT1) were established. The viability and apoptosis of wild-type (MDA-MB-231), GEM-R, and GEM-R-hENT1 cells treated with GEM or GEM + miR-143 were analyzed by CCK8 assay and flow cytometry. The RNA expression and protein expression were measured by RT-PCR and western blotting respectively. GEM uptake was determined by multiple reaction monitoring (MRM) analysis. Glycolysis was measured by glucose assay and 18F-FDG uptake. The antitumor effect was assessed in vivo in a tumor xenograft model by evaluating toxicity, tumor volume, and maximum standardized uptake value in 18F-FDG PET. Immunohistochemistry and fluorescence photography were taken in tumor samples. Pairwise comparisons were performed using Student's t-test. RESULTS: Our results represented that overexpression of hENT1 reversed GEM resistance in GEM-R cells by showing lower IC50 and higher rate of apoptosis. MiR-143 suppressed glycolysis in GEM-R cells and enhanced the effect of reversing GEM resistance in GEM-R-hENT1 cells. The therapeutic efficacy was validated using a xenograft mouse model. Combination treatment decreased tumor growth rate and maximum standardized uptake value in 18F-FDG PET more effectively. CONCLUSIONS: Combined therapy of exogenous upregulation of hENT1 expression and miR-143 mimic administration was effective in reversing GEM resistance, providing a promising strategy for treating GEM-resistant TNBC.

[Network Meta-analysis of Chinese medicine injections in treatment of rheumatoid arthritis].

This study aims to systematically evaluate the efficacy and safety of Chinese medicine injections in the treatment of rheumatoid arthritis. Specifically, randomized controlled trial(RCT) in the treatment of rheumatoid arthritis with Chinese medicine injections was retrieved from PubMed, EMbase, Cochrane Library, Web of Science, Wanfang, CNKI, VIP, and SinoMed(from inception to February 16, 2022). RevMan 5.3 and Stata 15.0 were employed for data analysis. Finally, 53 RCTs, involving 4 280 patients were included. The experimental groups involved the following injections: including Danshen Chuanxiongqin Injection, Tanshinone Ⅱ_A Sodium Sulfonate Injection, Danhong Injection, Dengzhan Xixin Injection, Gugua Extract Injection, Honghua Injection, Lugua Polypeptide Injection, Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection, Shuxuetong Injection, Zhengqing Fengtongning Injection, Compound Danshen Injection, and Xuebijing Injection. The network Meta-analysis showcased the following trends.(1) As for improving total clinical effective rate, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional treatment of western medicine combined with Xuebijing Injection > combined with Gugua Extract Injection > combined with Compound Danshen Injection > combined with Danshen Chuanxiongqin Injection > combined with Honghua Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection > combined with Lugua Polypeptide Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Dengzhan Xixin Injection.(2) As for improving erythrocyte sedimentation rate(ESR), SUCRA followed the order of conventional treatment of western medicine combined with Xuebijing Injection > combined with Shuxuetong Injection > combined with Honghua Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Gugua Extract Injection > combined with Danhong Injection > combined with Lugua Polypeptide Injection > combined with Dengzhan Xixin Injection > combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Danshen Chuanxiongqin Injection > combined with Zhengqing Fengtongning Injection.(3) As for improving rheumatoid factor(RF), SUCRA followed the order of conventional treatment of western medicine combined with Lugua Polypeptide Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Gugua Extract Injection > combined with Danshen Chuanxiongqin Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection > combined with Dengzhan Xixin Injection.(4) As for improving C-reactive protein(CRP), SUCRA followed the order of conventional treatment of western medicine combined with Xuebijing Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Honghua Injection > combined with Danshen Chuanxiongqin Injection > combined with Dengzhan Xixin Injection > combined with Gugua Extract Injection > combined with Lugua Polypeptide Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection.(5) As for alleviating morning stiffness, SUCRA followed the order of conventional treatment of western medicine combined with Shuxuetong Injection > combined with Lugua Polypeptide Injection > combined with Dengzhan Xixin Injection > combined with Xuebijing Injection > combined with Gugua Extract Injection > combined with Zhengqing Fengtongning Injection > combined with Danhong Injection > combined with Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Honghua Injection.(6) As for improving disease activity score(DAS28), SUCRA followed the order of conventional treatment of western medicine combined with Lugua Polypeptide Injection + Tanshinone Ⅱ_A Sodium Sulfonate Injection > combined with Lugua Polypeptide Injection > combined with Zhengqing Fengtongning Injection > combined with Honghua Injection > combined with Gugua Extract Injection > combined with Dengzhan Xixin Injection. The experimental groups had lower incidence of adverse reactions than the control group. The results of network Meta-analysis suggest that on the combination of conventional treatment of western medicine with Chinese medicine injections can improve the efficacy on rheumatoid arthritis. However, in view of the great differences in the quality and number of studies included for different therapies, the SUCRA of Chinese medicine injections need to be further verified with high-quality multi-center, large-sample, randomized double-blind trials.

Comparing EQ-5D-3L and EQ-5D-5L performance in common cancers: suggestions for instrument choosing.

PURPOSE: To compare the performance of three-level EuroQol five-dimensions (EQ-5D-3L) and five-level EuroQol five-dimensions (EQ-5D-5L) among common cancer patients in urban China. METHODS: A hospital-based cross-sectional survey was conducted in three provinces from 2016 to 2018 in urban China. Patients with breast cancer, colorectal cancer, or lung cancer were recruited to complete the EQ-5D-3L and EQ-5D-5L questionnaires. Response distribution, discriminatory power (indicator: Shannon index [H'] and Shannon evenness index [J']), ceiling effect (the proportion of full health state), convergent validity, and health-related quality of life (HRQoL) were compared between the two instruments. RESULTS: A total of 1802 cancer patients (breast cancer: 601, colorectal cancer: 601, lung cancer: 600) were included, with the mean age of 55.6 years. The average inconsistency rate was 4.4%. Compared with EQ-5D-3L (average: H' = 1.100, J' = 0.696), an improved discriminatory power was observed in EQ-5D-5L (H' = 1.473, J' = 0.932), especially contributing to anxiety/depression dimensions. The ceiling effect was diminished in EQ-5D-5L (26.5%) in comparison with EQ-5D-3L (34.5%) (p < 0.001), mainly reflected in the pain/discomfort and anxiety/depression dimensions. The overall utility score was 0.790 (95% CI 0.778-0.801) for EQ-5D-3L and 0.803 (0.790-0.816) for EQ-5D-5L (p < 0.001). A similar pattern was also observed in the detailed cancer-specific analysis. CONCLUSIONS: With greater discriminatory power, convergent validity and lower ceiling, EQ-5D-5L may be preferable to EQ-5D-3L for the assessment of HRQoL among cancer patients. However, higher utility scores derived form EQ-5D-5L may also lead to lower QALY gains than those of 3L potentially in cost-utility studies and underestimation in the burden of disease.

Does Hepatitis B Virus Affect the Coagulation Parameters for HBV-Related Decompensated Cirrhosis?

BACKGROUND: To evaluate the effect of the hepatitis B virus (HBV) on the coagulation parameters in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). METHODS: A retrospective analysis was conducted on the medical records of 112 patients with HBV-DeCi. Baseline clinical and laboratory characteristics were retrieved. Subjects were subdivided into 3 groups. Group I: 22 cases of hepatitis B were HBsAg, HBeAg, and HbcAb positive; Group II: 67 patients were HBsAg, HBeAb, and HbcAb positive; Group III: 23 patients were HBsAb, HBeAb and HbcAb positive. The coagulation indicators, such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and international normalized ratio (INR, a method to standardize reporting of the PT, using the formula, INR = (PTpatient/PTcontrol)ISI) of each groups were analyzed, The correlation between the characteristics of coagulation function and the type of hepatitis infection were studied. RESULTS: The FIB values of Group I and II were lower than those of Group III, and Group I had significantly longer TT compared to Group III. CONCLUSIONS: In patients with HBV-DeCi, hepatitis B virus has an effect on coagulation parameters; therefore, antiviral treatment must be carried out as soon as possible.

Clinical Treatment Experience in Severe and Critical COVID-19.

Compared with other deadly diseases, the coronavirus disease 2019 (COVID-19) is highly infectious with a relatively low mortality rate. Although critical cases account for only 5% of cases, the mortality rate for the same is nearly 50%. Therefore, the key to the COVID-19 treatment is to effectively treat severe patients and reduce the transition from severe to critical cases. A retrospective study was carried out to evaluate outcomes of treatment in patients with severe and critical COVID-19 admitted to a COVID-19 special hospital in Wuhan, China. A total of 75 severe and critical COVID-19 patients were admitted and treated with immunomodulation as the main strategy combined with anti-inflammatory therapy and appropriate anticoagulation. Leukocyte levels in patients with 7-14 days of onset to diagnosis were significantly lower than in those with >14 days. Higher levels of globulin and D-dimer and lower lymphocyte levels were found in the older age group (>65 years) than in the middle-aged group (50-64 years). Patients with comorbidity had higher levels of inflammatory indicators. After treatment, 65 (86.67%) patients were cured, 7 (9.33%) had improved, and 3 (4.00%) had died. Median hospitalization duration was 23 days. Fatal cases showed continuously increased levels of globulin, dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), D-dimer, and cytokines during treatment. Time from onset to diagnosis, age, and comorbidity are important influencing factors on treatment effects. The occurrence of immunosuppression, "cytokine storm," and thrombosis may be an important cause of death in severely infected cases. In conclusion, high cure rate and low mortality suggested that immunomodulation combined with anti-inflammatory therapy and appropriate anticoagulant therapy is a good strategy for treatment of patients with severe and critical COVID-19.

Molecular Dynamics Study of Binary Nanodroplet Evaporation on a Heated Homogeneous Substrate.

The evaporation mechanism of miscible binary nanodroplets from heated homogeneous surfaces was studied by molecular dynamics simulations, which has never been studied before. The binary droplets contain a hydrophilic component (type-2 particles) and a hydrophobic component (type-3 particles). It is shown that liquid-liquid interaction strength (ε23) and hydrophilic particle number fraction (φ) have great influence on the surface tension, wetting characteristics, evaporation patterns, evaporation rate, and local mass flux. It is observed that when ε23 ≥ 1, or φ ≈ 0.5, the evaporation mode is the constant-contact-angle mode. Otherwise, it is the mixed mode. We found that the evaporation rate becomes faster when φ and ε23 increase. The droplets become more hydrophilic when φ increases, which promotes heat transfer efficiency between the liquid-solid interface. Besides, a larger ε23 promotes the heat transfer inside the droplet. The mass transfer to the vapor phase occurs preferentially in the vicinity of TPCL (three phase contact line) in the hydrophilic systems (θ < θc), where θc is the critical contact angle, while in most hydrophobic systems (θ > θc), the mass flux close to the TPCL is suppressed. We found that θc ∈ (102°-106°), which is different from the theoretical one, θc = 90°. The discrepancy is attributed to the existence of the adsorption layer near the TPCL.

A novel putative betapartitivirus isolated from the plant-pathogenic fungus Rhizoctonia solani.

In this study, we describe the genome sequence of a novel double-stranded RNA (dsRNA) mycovirus, designated as "Rhizoctonia solani partitivirus 15" (RsPV15), from the phytopathogenic fungus Rhizoctonia solani. RsPV15 consists of two genomic double-stranded RNA segments, dsRNA-1 and dsRNA-2, which are 2433 bp and 2350 bp long, respectively. Each of the dsRNA segments contains a single open reading frame, encoding the putative RNA-dependent RNA polymerase and coat protein, respectively. Homology searches and phylogenetic analysis suggested that RsPV15 is a new member of the genus Betapartitivirus within the family Partitiviridae.

Discovery of novel glyceraldehyde-3-phosphate dehydrogenase inhibitor via docking-based virtual screening.

Glycolysis is enhanced in cancer cells. Cancer cells utilize glycolysis as their primary energy source, even under aerobic conditions. This is known as the Warburg effect. Thus, effective inhibition of the glycolytic pathway is a crucial component of cancer therapy. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an important enzyme in glycolysis and overexpresses in cancers. Therefore, targeting GAPDH to inhibit its role in glycolysis is important for GAPDH functional studies and the treatment of cancers. However, only a few GAPDH inhibitors have been reported. In our current study, we identified a GAPDH inhibitor, DC-5163, using docking-based virtual screening and biochemical and biophysical analysis. DC-5163 is a small molecule compound that inhibits GAPDH enzyme activity and cancer cell proliferation (normal cells were tolerant to it). It can inhibit glycolysis pathway partially, which was manifested by decreased glucose uptake and lactic acid production. And it also leaded to cell death through apoptotic pathways. This study reflects the pivotal role of GAPDH in cancer cells and demonstrates that DC-5163 is a useful inhibitor and can be of value in studying the role of GAPDH and the development of new clinical cancer treatments.

Virology and Serological Characteristics of Chronic Hepatitis B Patients with the Co-existence of HBsAg and Anti-HBs Antibodies.

BACKGROUND: To investigate the virological and serological characteristics of chronic hepatitis B patients concurrently positive for HBsAg and anti-HBs. METHODS: Chronic hepatitis B patients with coexistence of HBsAg and anti-HBs were screened by electrochemiluminescence immunoassay (ECLIA). The serum biomarkers such as HBV markers, HBV DNA load, AFP, and liver function were detected, and the virological and serological features were analyzed. RESULTS: The simultaneous seropositivity for hepatitis-B surface antigen and anti-HBS antibodies was 3.867%. There was no significant difference in the detection rate between men and women (p > 0.05). The HBV DNA detection rate, HBV DNA load, and liver function index of the high HBsAg titer group were significantly higher than those of the low titer group. There was no significant difference in HBV DNA load, AFP, and liver function between different levels of anti-HBs (p > 0.05). CONCLUSIONS: In chronic hepatitis B patients, there is a certain proportion of patients with coexistence of HBsAg and anti-HBs. The emergence of anti-HBs does not mean that HBsAg can be completely and effectively eliminated. HBV DNA load can be replicated continuously with the presence of anti-HBs, and its follow-up is worthy of clinical attention.

Pinning-Depinning Mechanism of the Contact Line during Evaporation of Nanodroplets on Heated Heterogeneous Surfaces: A Molecular Dynamics Simulation.

Droplet evaporation on heterogeneous or patterned surfaces has numerous potential applications, for example, inkjet printing. The effect of surface heterogeneities on the evaporation of a nanometer-sized cylindrical droplet on a solid surface is studied using molecular dynamics simulations of Lennard-Jones particles. Different heterogeneities of the surface were achieved through alternating stripes of equal width but two chemical types, which lead to different contact angles. The evaporation induced by the heated substrate instead of the isothermal evaporation is investigated. It is found that the whole evaporation process is generally dominated by the nonuniform evaporation effect. However, at the initial moment, the volume expansion and local evaporation effects play important roles. From the nanoscale point of view, the slow movement of the contact line during the pinning process is observed, which is different from the macroscopic stationary pinning. Particularly, we found that the speed of the contact line may be not only affected by the intrinsic energy barrier between the two adjacent stripes ( u) but also relevant to the evaporation rate. Generally speaking, the larger the intrinsic energy barrier, the slower the movement of the contact line. At the specified temperature, when u is less than a critical energy barrier ( u*), the speed of the contact line would increase with the evaporate rate. When u > u*, the speed of the contact line is determined only by u and no longer affected by the evaporation rate at different stages (the first stick and the second stick).

Rapid and visual detection of dengue virus using recombinase polymerase amplification method combined with lateral flow dipstick.

Dengue virus (DENV), a member of the genus Flavivirus within the family Flaviviridae, is one of the most significant mosquito-borne viruses that causing dengue fever in human. A rapid diagnostic would be helpful to detect DENV infection in a timely manner. In the last decade, recombinase polymerase amplification (RPA) technique has been experiencing rapid development and widely employed to detect various other pathogens. In present study, a reverse transcription RPA (RT-RPA) assay combined with lateral flow dipstick (LFD) was established for rapid detection of DENV. The assay could detect DENV-1, -2, -3 and -4. The minimal detection limit of the RT-RPA-LFD assay was 10 copies RNA molecules. The assay was DENV-specific since it had no non-specific reactions with other common human pathogens. The clinical performance of the RT-RPA assay was validated using 120 clinical samples. The coincidence rate between RT-RPA-LFD and qRT-PCR for the clinical samples was 100%, indicating the RT-RPA-LFD assay had good diagnostic performance on clinical samples. The RT-RPA-LFD assay required no sophisticated instrument, providing a possible solution for DENV diagnosis in recourse-limited settings where DENV infection is epidemic.