Splenic abscess secondary to COVID-19 acute infection: A case report and literature review.

RATIONALE: Splenic abscess is relatively rare in clinical practice as an invasive disease. However, during the continuous prevalence of coronavirus disease 2019 (COVID-19), the incidence rate of splenic abscess showed an upward trend. However, because the etiology of splenic abscess is not specific, it is easy to be covered by the respiratory symptoms of COVID-19, resulting in omission or delay in diagnosis. If splenic abscesses cannot be treated in a timely manner, the mortality rate can reach 100%. Therefore, it is important to fully understand the correlation between COVID-19 and the development of splenic abscesses. PATIENT CONCERNS: A female patient, 71 years of age, was admitted to our hospital because of cough and sputum for 1 week and fever for 2 days. According to the positive results of novel coronavirus nucleic acid and chest computed tomography, novel coronavirus pneumonia was diagnosed. On the 4th day after treatment, abdominal distension and vomiting were observed. Abdominal ultrasound indicated splenomegaly and mixed echo masses in the spleen and abdominal computed tomography indicated 2 new round low-density lesions were found in the spleen. DIAGNOSES: The patient was diagnosed with secondary splenic abscess after COVID-19 infection. INTERVENTIONS: The patient and her family members refused to undergo ultrasound-guided splenic puncture drainage and splenectomy. In terms of treatment, she was given meropenem combined with vancomycin to continue anti-infection treatment. OUTCOMES: The patient's body temperature and infection indicators gradually increased, and the scope of splenic abscess continued to expand. The infection worsened and progressed to septic shock. The patient abandoned rescue drugs and invasive treatment, and died on the 9th day after admission. LESSONS: This case introduces the clinical characteristics of secondary splenic abscess caused by COVID-19 from the aspects of etiology, disease course, clinical manifestations, auxiliary examinations, and treatment methods. The focus is on improving the understanding of clinical doctors about secondary splenic abscesses caused by COVID-19, providing reference for early diagnosis and timely treatment.

Operationally stable perovskite solar modules enabled by vapor-phase fluoride treatment.

The ever-increasing power conversion efficiency of perovskite solar cells has illuminated the future of the photovoltaic industry, but the development of commercial devices is hampered by their poor stability. In this study, we report a scalable stabilization method using vapor-phase fluoride treatment, which achieves 18.1%-efficient solar modules (228 square centimeters) with accelerated aging-projected T80 lifetimes (time to 80% of efficiency remaining) of 43,000 ± 9000 hours under 1-sun illumination at 30°C. The high stability results from vapor-enabled homogeneous fluorine passivation over large-area perovskite surfaces, suppressing defect formation energy and ion diffusion. The extracted degradation activation energy of 0.61 electron volts for solar modules is comparable to that of most reported stable cells, which indicates that modules are not inherently less stable than cells and closes the cell-to-module stability gap.

DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment.

DARS, encoding for aspartyl-tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ABL1-negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls (P < 0.05). Notably, elevated DARS expression was linked to splenomegaly in MPNs patients. The expression of DARS showed a negative correlation with CD4+ T cells (R = - 0.451, P = 0.0004) and CD4+ T/CD8+ T cell ratio (R = - 0.3758, P = 0.0040), as well as with CD68+ tumor-associated macrophages (R = 0.4037, P = 0.0017). Conversely, it was positively correlated with IL-2 (R = 0.5419, P < 0.001), IL-5 (R = 0.3161, P = 0.0166), IL-6 (R = 0.2992, P = 0.0238), and IFN-γ (R = 0.3873, P = 0.0029). These findings underscore a significant association between DARS expression in MPNs patients and specific clinical characteristics, as well as immune cell composition. Further investigation into the interplay between DARS and the immune microenvironment in MPNs could shed light on the underlying mechanisms of MPNs pathogenesis and immune dysregulation.

ScHGSC-IGDC: Identifying genes with differential correlations of high-grade serous ovarian cancer based on single-cell RNA sequencing analysis.

Due to the high heterogeneity of ovarian cancer (OC), it occupies the main cause of cancer-related death among women. As the most aggressive and frequent subtype of OC, high-grade serous cancer (HGSC) represents around 70 % of all patients. With the booming progress of single-cell RNA sequencing (scRNA-seq), unique and subtle changes among different cell states have been identified including novel risk genes and pathways. Here, our present study aims to identify differentially correlated core genes between normal and tumor status through HGSC scRNA-seq data analysis. R package high-dimension Weighted Gene Co-expression Network Analysis (hdWGCNA) was implemented for building gene interaction networks based on HGSC scRNA-seq data. DiffCorr was integrated for identifying differentially correlated genes between tumor and their adjacent normal counterparts. Software Cytoscape was implemented for constructing and visualizing biological networks. Real-time qPCR (RT-qPCR) was utilized to confirm expression pattern of new genes. We introduced ScHGSC-IGDC (Identifying Genes with Differential Correlations of HGSC based on scRNA-seq analysis), an in silico framework for identifying core genes in the development of HGSC. We detected thirty-four modules in the network. Scores of new genes with opposite correlations with others such as NDUFS5, TMSB4X, SERPINE2 and ITPR2 were identified. Further survival and literature validation emphasized their great values in the HGSC management. Meanwhile, RT-qPCR verified expression pattern of NDUFS5, TMSB4X, SERPINE2 and ITPR2 in human OC cell lines and tissues. Our research offered novel perspectives on the gene modulatory mechanisms from single cell resolution, guiding network based algorithms in cancer etiology field.

Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling.

Asthma is the most prevalent chronic inflammatory disease of the airways in children. The most prevalent phenotype of asthma is eosinophilic asthma, which is driven by a Th2 immune response and can be effectively managed by inhaled corticosteroid therapy. However, there are phenotypes of asthma with Th17 immune response that are insensitive to corticosteroid therapy and manifest a more severe phenotype. The treatment of this corticosteroid-insensitive asthma is currently immature and requires further attention. The objective of this study is to elucidate the regulation of the Hedgehog signaling pathway in Th17 cell differentiation in asthma. The study demonstrated that both Smo and Gli3, key components of the Hedgehog signaling pathway, were upregulated in Th17 polarization in vitro and in a Th17-dominant asthma model in vivo. Inhibiting Smo with a small molecule inhibitor or genetically knocking down Gli3 was found to suppress Th17 polarization. Smo was found to increase in Th1, Th2, Th17 and Treg polarization, while Gli3 specifically increased in Th17 polarization. ChIP-qPCR analyses indicated that Gli3 can directly interact with IL-6 in T cells, inducing STAT3 phosphorylation and promoting Th17 cell differentiation. Furthermore, the study demonstrated a correlation between elevated Gli3 expression and IL-17A and IL-6 expression in children with asthma. In conclusion, the study demonstrated that the Hedgehog signaling pathway plays an important role in the pathogenesis of asthma, as it regulates the differentiation of Th17 cells through the IL-6/STAT3 signaling. This may provide a potential therapeutic target for corticosteroid-insensitive asthma driven by Th17 cells.

Identification of prognostic risk model based on plasma cell markers in hepatocellular carcinoma through single-cell sequencing analysis.

Hepatocellular carcinoma (HCC) represents a substantial global health burden. Tumorinfiltrating B lymphocytes (TIL-Bs) contribute to tumor progression and significantly impact the efficacy of tumor therapy. However, the characteristics of TIL-Bs in HCC and their effect on HCC therapy remain elusive. Single-cell RNA sequencing (scRNAseq) was applied to investigate the heterogeneity, cellular differentiation and cell-cell communication of TIL-Bs in HCC. Further, the Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC) and liver cancer institutes (LCI) cohorts were applied to construct and validate the plasma cell marker-based prognostic risk model. The relationship between the prognostic risk model and the responsiveness of immunotherapy and chemotherapy in patients with HCC were estimated by OncoPredict and tumor immune dysfunction and exclusion (TIDE) algorithm. Finally, we established nomogram and calibration curves to evaluate the precision of the risk score in predicating survival probability. Our data identified five subtypes of TIL-Bs in HCC, each exhibiting varying levels of infiltration in tumor tissues. The interactions between TIL-Bs and other cell types contributed to shaping distinct tumor microenvironments (TME). Moreover, we found that TIL-Bs subtypes had disparate prognostic values in HCC patients. The prognostic risk model demonstrated exceptional predictive accuracy for overall survival and exhibited varying sensitivities to immunotherapy and chemotherapy among patients with HCC. Our data demonstrated that the risk score stood as an independent prognostic predictor and the nomogram results further affirmed its strong prognostic capability. This study reveals the heterogeneity of TIL-Bs and provides a prognostic risk model based on plasma cell markers in HCC, which could prove valuable in predicting prognosis and guiding the choice of suitable therapies for patients with HCC.

Comparative efficacy of five approved Janus kinase inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis: a systematic review and network meta-analysis of randomized controlled trials.

Background: The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis. Methods: The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics. Results: This study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference. Conclusion: This NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.

Spatiotemporal pattern of coastal water pollution and its driving factors: implications for improving water environment along Hainan Island, China.

In the context of human activities and climate change, the gradual degradation of coastal water quality seriously threatens the balance of coastal and marine ecosystems. However, the spatiotemporal patterns of coastal water quality and its driving factors were still not well understood. Based on 31 water quality parameters from 2015 to 2020, a new approach of optimizing water quality index (WQI) model was proposed to quantitatively assess the spatial and temporal water quality along tropical Hainan Island, China. In addition, pollution sources were further identified by factor analysis and the effects of pollution source on water quality was finally quantitatively in our study. The results showed that the average water quality was moderate. Water quality at 86.36% of the monitoring stations was good while 13.53% of the monitoring stations has bad or very bad water quality. Besides, the coastal water quality had spatial and seasonal variation, along Hainan Island, China. The water quality at "bad" level was mainly appeared in the coastal waters along large cities (Haikou and Sanya) and some aquaculture regions. Seasonally, the average water quality in March, October and November was worse than in other months. Factor analysis revealed that water quality in this region was mostly affected by urbanization, planting and breeding factor, industrial factor, and they played the different role in different coastal zones. Waters at 10.23% of monitoring stations were at the greatest risk of deterioration due to severe pressure from environmental factors. Our study has significant important references for improving water quality and managing coastal water environment.

In-Situ Cross-linked F- and P-Containing Solid Polymer Electrolyte for Long-Cycling and High-Safety Lithium Metal Batteries with Various Cathode Materials.

The practical application of lithium metal batteries (LMBs) has been hindered by limited cycle-life and safety concerns. To solve these problems, we develop a novel fluorinated phosphate cross-linker for gel polymer electrolyte in high-voltage LMBs, achieving superior electrochemical performance and high safety simultaneously. The fluorinated phosphate cross-linked gel polymer electrolyte (FP-GPE) by in-situ polymerization method not only demonstrates high oxidation stability but also exhibits excellent compatibility with lithium metal anode. LMBs utilizing FP-GPE realize stable cycling even at a high cut-off voltage of 4.6 V (vs Li/Li+) with various high-voltage cathode materials. The LiNi0.6Co0.2Mn0.2O2|FP-GPE|Li battery exhibits an ultralong cycle-life of 1200 cycles with an impressive capacity retention of 80.1 %. Furthermore, the FP-GPE-based batteries display excellent electrochemical performance even at practical conditions, such as high cathode mass loading (20.84 mg cm-2), ultrathin Li (20 µm), and a wide temperature range of -25 to 80 °C. Moreover, the first reported solid-state 18650 cylindrical LMBs have been successfully fabricated and demonstrate exceptional safety under mechanical abuse. Additionally, the industry-level 18650 cylindrical LiMn2O4|FP-GPE|Li4Ti5O12 cells demonstrate a remarkable cycle-life of 1400 cycles. Therefore, the impressive electrochemical performance and high safety in practical batteries demonstrate a substantial potential of well-designed FP-GPE for large-scale industrial applications.

Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer.

Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.

Long-cycling and High-voltage Solid State Lithium Metal Batteries Enabled by Fluorinated and Crosslinked Polyether Electrolytes.

Solid-state lithium metal batteries (LMBs), constructed through the in situ fabrication of polymer electrolytes, are considered a critical strategy for the next-generation battery systems with high energy density and enhanced safety. However, the constrained oxidation stability of polymers, such as the extensively utilized polyethers, limits their applications in high-voltage batteries and further energy density improvements. Herein, an in situ fabricated fluorinated and crosslinked polyether-based gel polymer electrolyte, FGPE, is presented, exhibiting a high oxidation potential (5.1 V). The fluorinated polyether significantly improves compatibility with both lithium metal and high-voltage cathode, attributed to the electron-withdrawing -CF3 group and the generated LiF-rich electrolyte/electrode interphase. Consequently, the solid-state Li||LiNi0.6Co0.2Mn0.2O2 batteries employing FGPE demonstrate exceptional cycling performances of 1000 cycles with 78 % retention, representing one of the best results ever reported for polymer electrolytes. Moreover, FGPE enables batteries to operate at 4.7 V, realizing the highest operating voltage of polyether-based batteries to date. Notably, our designed in situ FGPE provides the solid-state batteries with exceptional cycling stability even at practical conditions, including high cathode loading (21 mg cm-2) and industry-level 18650-type cylindrical cells (1.3 Ah, 500 cycles). This work provides critical insights into the development of oxidation-stable polymer electrolytes and the advancement of practical high-voltage LMBs.

Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials.

Objective: To systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference, and body weight. Methods: A search formula was written using search terms such as "tirzepatide," "overweight," and "obesity." A comprehensive search was conducted on databases such as PubMed, Cochrane Library, Embase, and Web of Science using a computer. Random controlled trial (RCT) literature was selected based on inclusion and exclusion criteria. After extracting the data, literature bias risk assessment and meta-analysis were conducted using RevMan 5.4 software. The search deadline is from the establishment of each database to May 2023. Results: A total of 12 randomized controlled trials were included, with a total of 11,758 patients. Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = -1.71, 95% CI (-2.46, -0.95), p < 0.00001], [MD = -3.99, 95% CI (-3.69, -2.45), p < 0.00001], [MD = -4.02, 95% CI (-4.72, -3.31), p < 00.00001]. In terms of decreasing waist circumference, tirzepatide has a more significant advantage [MD = -4.08, 95% CI (-5.77, -2.39), p < 0.00001], [MD = -7.71, 95% CI (-10.17, -5.25), p < 0.00001], [MD = -9.15, 95% CI (-10.02, -8.29), p < 0.00001]. In the analysis of body weight, tirzepatide showed a more significant reduction effect compared to the control group [MD = -5.65, 95% CI (-7.47, -3.82), p < 0.001], [MD = -10.06, 95% CI (-12.86, -7.25), p < 0.001], [MD = -10.63, 95% CI (-12.42, -8.84), p < 0.001]. In comparison with placebo, tirzepatide had a prominent advantage in weight loss ≥20% and ≥25% [RR = 30.43, 95% CI (19.56, 47.33), p < 0.00001], [RR = 37.25, 95% CI (26.03, 53.30), p < 0.00001]. Subgroup analysis showed a dose-dependent therapeutic effect. In terms of safety, compared with the placebo and insulin groups, the incidence of gastrointestinal adverse reactions was markedly higher in the tirzepatide group, slightly higher to the GLP-1 RAs group. The hypoglycemic (<70 mg/dL) risk of tirzepatide was slightly higher to that of placebo and GLP-1 RAs, but significantly lower than that of the insulin group [RR = 0.46, 95% CI (0.36, 0.58), p < 0.001]. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events-4, hypersensitivity reactions, and neoplasms did not show significant statistical differences compared to the control group (p > 0.05). Conclusion: Tirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.

Double counting heart rate - Littmann sign in electrocardiogram.

This report highlights necessity of correctly and quickly identifying Littmann sign. Littmann sign is not common in clinical practice, which is easily overlooked by most physicians, leading to delays in the treatment of hyperkalemia. A 68 year old patient with hyperkalemia was found to have inconsistent heart rate displayed on electrocardiogram monitoring with cardiac auscultation and synchronous electrocardiogram in the early stages of onset. Hyperkalemia was highly suspected by the Littmann sign. After completing arterial blood gas analysis, hyperkalemia was identified and active potassium lowering treatment was immediately initiated. The Littmann syndrome disappeared, and the patient eventually recovered.

Convolutional neural network-based measurement of crown-implant ratio for implant-supported prostheses.

STATEMENT OF PROBLEM: Research has revealed that the crown-implant ratio (CIR) is a critical variable influencing the long-term stability of implant-supported prostheses in the oral cavity. Nevertheless, inefficient manual measurement and varied measurement methods have caused significant inconvenience in both clinical and scientific work. PURPOSE: This study aimed to develop an automated system for detecting the CIR of implant-supported prostheses from radiographs, with the objective of enhancing the efficiency of radiograph interpretation for dentists. MATERIAL AND METHODS: The method for measuring the CIR of implant-supported prostheses was based on convolutional neural networks (CNNs) and was designed to recognize implant-supported prostheses and identify key points around it. The experiment used the You Only Look Once version 4 (Yolov4) to locate the implant-supported prosthesis using a rectangular frame. Subsequently, two CNNs were used to identify key points. The first CNN determined the general position of the feature points, while the second CNN finetuned the output of the first network to precisely locate the key points. The network underwent testing on a self-built dataset, and the anatomic CIR and clinical CIR were obtained simultaneously through the vertical distance method. Key point accuracy was validated through Normalized Error (NE) values, and a set of data was selected to compare machine and manual measurement results. For statistical analysis, the paired t test was applied (α=.05). RESULTS: A dataset comprising 1106 images was constructed. The integration of multiple networks demonstrated satisfactory recognition of implant-supported prostheses and their surrounding key points. The average NE value for key points indicated a high level of accuracy. Statistical studies confirmed no significant difference in the crown-implant ratio between machine and manual measurement results (P>.05). CONCLUSIONS: Machine learning proved effective in identifying implant-supported prostheses and detecting their crown-implant ratios. If applied as a clinical tool for analyzing radiographs, this research can assist dentists in efficiently and accurately obtaining crown-implant ratio results.

miR-130b regulates B cell proliferation via CYLD-mediated NF-κB signaling.

Previous studies have revealed that B cell activation is regulated by various microRNAs(miRNAs). However, the role of microRNA-130b regulating B cell activation and apoptosis is still unclear. In the present study, we first found that the expression of miR-130b was the lowest in Pro/Pre-B cells and the highest in immature B cells. Besides, the expression of miR-130b decreased after activation in B cells. Through the immuno-phenotypic analysis of miR-130b transgenic and knockout mice, we found that miR-130b mainly promoted the proliferation of B cells and inhibited B cell apoptosis. Furthermore, we identified that Cyld, a tumor suppressor gene was the target gene of miR-130b in B cells. Besides, the Cyld-mediated NF-κB signaling was increased in miR-130b overexpressed B cells, which further explains the enhanced proliferation of B cells. In conclusion, we propose that miR-130b promotes B cell proliferation via Cyld-mediated NF-κB signaling, which provides a new theoretical basis for the molecular regulation of B cell activation.

Prognostic value of PD­L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer.

The programmed death receptor 1/programmed death receptor ligand 1 axis (PD-1/PD-L1) is involved in tumor immune escape and is a potential prognostic biomarker and anti-tumor immunotherapy target in patients with gastric cancer (GC). However, the results of studies obtained in recent years have been inconsistent. The present study aimed to determine the possible predictive significance of PD-L1 in conjunction with three proteins linked with PD-L1 regulation in patients with primary GC. In the present study, the PD-L1, human epidermal growth factor receptor 2 (HER2), cluster of differentiation (CD)133 and microphage-associated CD68 expression levels were identified by multiplexed immunohistochemistry and assessed by automated pathological analysis system in 93 GC tumors and neighboring normal tissues arrayed on the same tissue microarray. All four proteins were statistically analyzed in relation to the clinicopathological characteristics. The expression levels of HER2, CD133 and CD68 were considerably higher in cancer tissues compared with neighboring normal tissues (P<0.05), however, the reverse trend was detected for PD-L1 expression (P=0.0577), particularly in tumor nest (TN; P<0.05). There was no significant correlation between the HER2 and CD133 expression levels and clinicopathological factors. However, significant relationships were found between PD-L1 expression and the TNM stage, pathological differentiation and survival status of patients (P<0.05). Moreover, survival time was prolonged in individuals with elevated PD-L1 expression in TN and GC tissues, but no significant correlation was identified (P=0.0881). The CD68 expression level in tumor stroma, but not in TN, was significantly correlated with poor pathological differentiation in patients with GC (P<0.05). However, PD-L1+CD68+ macrophages were strongly related to lower tumor size (diameter <5 cm), early TNM stage (stage I+II), good pathological differentiation and overall survival in TN (P<0.05). In conclusion, PD-L1+CD68+ macrophage infiltration in TN might be a potential indicator of prognosis in patients with primary GC and merits further investigation.

Effect of Abdominal Compression on Total Single-Balloon Enteroscopy Rate: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether abdominal compression significantly increased the total enteroscopy rate in single-balloon enteroscopy (SBE). METHODS: Consecutive patients who underwent SBE at 2 hospitals were prospectively included between June 1, 2020, and September 30, 2021. They were randomly divided into an abdominal compression group and a non-abdominal compression group with use of sealed envelopes generated by a computer. Total enteroscopy rates were compared between the groups. RESULTS: The study included 200 patients. The total enteroscopy rates were 73% and 16% in the abdominal compression and non-abdominal compression groups, respectively (relative risk, 13.55; 95% CI, 6.79 to 27.00; P<.001). The total enteroscopy rate was higher in the 70 patients who were identified to have undergone no previous abdominal surgery or small intestinal stenosis than in the 32 patients who had undergone such procedures in the abdominal compression group (84% vs 47%; relative risk, 6.08; 95% CI, 2.36 to 15.67; P<.001). Relevant positive findings were not significantly different between the groups (58% vs 45%; P=.07). Binary logistic regression analysis found abdominal compression to be associated with a better total enteroscopy rate (odds ratio, 16.68; 95% CI, 7.92 to 35.15; P<.001), and the presence of previous abdominal surgery or small intestinal stenosis was associated with difficulty in completing the total enteroscopy procedure (odds ratio, 0.26; 95% CI, 0.12 to 0.58; P<.01). CONCLUSION: Abdominal compression significantly increased the total enteroscopy rate in SBE. Complete total enteroscopy may be challenging in patients with a history of abdominal surgery or small intestinal stenosis.

Cytokine levels in patients with non-M3 myeloid leukemia are key indicators of how well the disease responds to chemotherapy.

Acute myeloid leukemia (AML) is a malignant hematological neoplastic disease. Autocrine or paracrine cytokines released by leukemic cells regulate the proliferation of AML cells. It is uncertain whether cytokines can indicate whether patients with AML are in remission with chemotherapy. The goal of this study was to evaluate the levels of Th1/Th2/Th17 cytokines in AML patients before and after chemotherapy to determine whether the cytokine levels could predict disease remission after chemotherapy. It was found that the levels of IL-5, IL-6, IL-8, IL-10, TNF-α, TNF-ß, IL-17F, and IL-22 were significantly increased at the time of AML diagnosis in patients who achieved remission after two chemotherapy treatments (P < 0.05). After chemotherapy, the cytokine levels were reduced in patients with remission, while the levels of IL-6 and IL-8 were raised in patients without remission (P < 0.05). A comparison of cytokine levels before and after chemotherapy in patients who achieved remission showed areas under the curve (AUCs) of 0.69 for both IL-6 and IL-8. In addition, a comparison of the remission and non-remission groups after chemotherapy showed an AUC of 0.77 for IL-6. We then calculated the cutoff value using receiver operating characteristic curves. Values of IL-6 < 9.99 and IL-8 < 8.46 at the time of diagnosis were predictive of chemotherapy success and remission, while IL-6 > 14.89 at diagnosis suggested that chemotherapy would not be successful and remission would not be achieved. Multifactorial analysis showed that age, Neu, IL-6, and IL-8 were independent risk factors for AML prognosis, and IL-6 (OR = 5.48, P = 0.0038) was superior to age (OR = 3.36, P = 0.0379), Neu (OR = 0.28, P = 0.0308), IL-8 (OR = 0.0421, P = 0.0421). In conclusion, IL-6 levels were found to be predictive of the likelihood of remission.

Comparative analysis of the biological characteristics and mechanisms of azole resistance of clinical Aspergillus fumigatus strains.

Aspergillus fumigatus is a common causative pathogen of aspergillosis. At present, triazole resistance of A. fumigatus poses an important challenge to human health globally. In this study, the biological characteristics and mechanisms of azole resistance of five A. fumigatus strains (AF1, AF2, AF4, AF5, and AF8) were explored. There were notable differences in the sporulation and biofilm formation abilities of the five test strains as compared to the standard strain AF293. The ability of strain AF1 to avoid phagocytosis by MH-S cells was significantly decreased as compared to strain AF293, while that of strains AF2, AF4, and AF5 were significantly increased. Fungal burden analysis with Galleria mellonella larvae revealed differences in pathogenicity among the five strains. Moreover, the broth microdilution and E-test assays confirmed that strains AF1 and AF2 were resistant to itraconazole and isaconazole, while strains AF4, AF5, and AF8 were resistant to voriconazole and isaconazole. Strains AF1 and AF2 carried the cyp51A mutations TR34/L98H/V242I/S297T/F495I combined with the hmg1 mutation S541G, whereas strains AF4 and AF8 carried the cyp51A mutation TR46/Y121F/V242I/T289A, while strain AF5 had no cyp51A mutation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed differences in the expression levels of genes associated with ergosterol synthesis and efflux pumps among the five strains. In addition, transcriptomics, RT-qPCR, and the NAD+/NADH ratio demonstrated that the mechanism of voriconazole resistance of strain AF5 was related to overexpression of genes associated with energy production and efflux pumps. These findings will help to further elucidate the triazole resistance mechanism in A. fumigatus.