Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase.

BACKGROUND: Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. AIM: To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. METHODS: The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. RESULTS: Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. CONCLUSION: Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers.

Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis. Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population. Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population.

Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Identification and analysis of differently expressed transcription factors in aristolochic acid nephropathy.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.

Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

Long-term complete response to anti-programmed-death-1 monotherapy in a patient with relapsed and refractory ovarian adenocarcinoma: A case report.

BACKGROUND: Ovarian cancer is the most common malignant tumor of the female reproductive system, and the survival rate of patients with relapsed and refractory ovarian cancer is very low. CASE SUMMARY: Here, we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy. Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful; however, her tumor relapsed. Subsequent second-line chemotherapy, targeted agents, and other treatments were ineffective, as the tumor continued to recur and metastasize. Anti-programmed cell death-1 (PD-1) monotherapy (tislelizumab) completely alleviated the tumor, and the multiple metastatic tumors disappeared. To date, the patient has used anti-PD-1 for 32 months, experiencing no disease progression and maintaining good health without additional treatment. CONCLUSION: This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors. Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.

SBCNet: Scale and Boundary Context Attention Dual-Branch Network for Liver Tumor Segmentation.

Automated segmentation of liver tumors in CT scans is pivotal for diagnosing and treating liver cancer, offering a valuable alternative to labor-intensive manual processes and ensuring the provision of accurate and reliable clinical assessment. However, the inherent variability of liver tumors, coupled with the challenges posed by blurred boundaries in imaging characteristics, presents a substantial obstacle to achieving their precise segmentation. In this paper, we propose a novel dual-branch liver tumor segmentation model, SBCNet, to address these challenges effectively. Specifically, our proposed method introduces a contextual encoding module, which enables a better identification of tumor variability using an advanced multi-scale adaptive kernel. Moreover, a boundary enhancement module is designed for the counterpart branch to enhance the perception of boundaries by incorporating contour learning with the Sobel operator. Finally, we propose a hybrid multi-task loss function, concurrently concerning tumors' scale and boundary features, to foster interaction across different tasks of dual branches, further improving tumor segmentation. Experimental validation on the publicly available LiTS dataset demonstrates the practical efficacy of each module, with SBCNet yielding competitive results compared to other state-of-the-art methods for liver tumor segmentation.

Integrated Proteogenomic Analysis Reveals Distinct Potentially Actionable Therapeutic Vulnerabilities in Triple-Negative Breast Cancer Subtypes.

Triple-negative breast cancer (TNBC) is characterized by an aggressive clinical presentation and a paucity of clinically actionable genomic alterations. Here, we utilized the Cancer Genome Atlas (TCGA) to explore the proteogenomic landscape of TNBC subtypes to see whether genomic alterations can be inferred from proteomic data. We found only 4% of the protein level changes are explained by mutations, while 21% of the protein and 35% of the transcriptomics changes were determined by copy number alterations (CNAs). We found tighter coupling between proteome and genome in some genes that are predicted to be the targets of drug inhibitors, including CDKs, PI3K, tyrosine kinase (TKI), and mTOR. The validation of our proteogenomic workflow using mass spectrometry Clinical Proteomic Tumor Analysis Consortium (MS-CPTAC) data also demonstrated the highest correlation between protein-RNA-CNA. The integrated proteogenomic approach helps to prioritize potentially actionable targets and may enable the acceleration of personalized cancer treatment.

CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.

Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.

Activation of autophagy promotes the inhibitory effect of curcumin analog EF-24 against MDA-MB-231 cancer cells.

Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.

Diagnostic accuracy of abdominal contrast-enhanced multi-slice spiral CT after oral diluted iodide in a time segment for gastrointestinal fistula in patients with severe acute pancreatitis.

PURPOSE: To evaluate the diagnostic accuracy of abdominal contrast-enhanced multi-slice spiral CT after oral diluted iodide in a time segment (post-ODI ACE-MSCT) for gastrointestinal fistula (GIF) in severe acute pancreatitis (SAP). MATERIALS AND METHODS: Patients with SAP who underwent both post-ODI ACE-MSCT and endoscopy/surgery from 2017 to 2023 were continuously retrospectively involved. Their demographic information and clinical features were recorded prospectively in an in-hospital database. Using endoscopy/surgery results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of post-ODI ACE-MSCT for diagnosing GIF in SAP were calculated by a four-cell table. The consistency of the two diagnostic methods was evaluated by the Kappa test and McNemar's test. RESULTS: Using endoscopy/surgery as the reference standard, a total of 86 cases were divided into the GIF group (N = 52) and the non-GIF group (N = 34). Among the 52 cases of GIF, 88.5% (46/52) cases had a positive result and 11.5% (5/52) cases had a negative result of post-ODI ACE-MSCT for GIF. Among the 34 cases of non-GIF, 2.9% (1/34) case had a positive result and 97.1% (33/34) cases had a negative result of post-ODI ACE-MSCT for GIF. Post-ODI ACE-MSCT had a sensitivity of 88.5% (95% CI 75.9%-95.2%), a specificity of 97.1% (95% CI 82.9%-99.8%), a positive predictive value of 97.9% (95% CI 87.3%-99.9%), a negative predictive value of 84.6% (95% CI 68.8%-93.6%), and an accuracy of 91.9% (83.4%-96.4%). The kappa value was 0.834, and P < 0.001 by McNemar's test. There were no significant differences in diagnostic test characteristics between the two modalities. CONCLUSION: Post-ODI ACE-MSCT can diagnose GIF in SAP in a simple, noninvasive, and accurate way, and can provide earlier imaging evidence for clinical diagnosis and treatment.

[Single-cell RNA sequencing combined experimental verifies the core genes of dendritic cells in chronic obstructive pulmonary disease].

Objective Single-cell RNA sequencing (scRNA-Seq) and experimental verifies core genes of dendritic cells in chronic obstructive pulmonary disease (COPD). Methods scRNA-seq data GSE173896 and chip data GSE38974 were extracted from the Gene Expression Omnibus (GEO) database. GSE173896 was used to perform quality control, batch correction, dimensionality reduction clustering, cell type annotation and dendritic cell differentially expressed genes (DC-DEGs) identification. DEGs from the analysis of GSE38974 were intersected with DC-DEGs to obtain the common DC-DEGs. The diagnostic efficacy of the common DC-DEGs for COPD and their enrichment analysis were conducted. The correlation of the common DC-DEGs with activated dendritic cell (DCs), plasmacytoid dendritic cell (pDCs) and type 17 T helper(Th17) cells were analyzed. The mRNA expression level of the common DC-DEGs in the lung tissue of emphysema mice was verified. Results From GSE173896, 18 DC-DEGs were obtained between groups and from GSE38974, 646 DEGs were obtained. The intersection of the two resulted in 3 common DC-DEGs, including interleukin 1 receptor antagonist 1 (IL1RN), S100 calcicum-binding protein A8 (S100A8) and S100A9. Their respective area under curve (AUC) values were 0.841, 0.804 and 0.966. The GO and KEGG enrichment analysis mainly concentrated on chronic inflammatory response, collagen-containing extracellular matrix, receptor for advanced glycation end products (RAGE) binding, Toll-like receptor (TLR) binding and interleukin 17 (IL-17) signaling pathway. IL1RN, S100A8 and S100A9 were positively correlated with activated DCs, pDCs and Th17 cells. The results showed that the mRNA relative expression levels of IL1RN, S100A8 and S100A9 were up-regulated in the lung tissue of emphysema mice. Conclusion IL1RN, S100A8 and S100A9 may be the core genes of DCs in the pathogenesis of COPD, which potentially provide targets and a theoretical basis for subsequent COPD immunotherapy.

Adaptive Frequency Learning Network With Anti-Aliasing Complex Convolutions for Colon Diseases Subtypes.

The automatic and dependable identification of colonic disease subtypes by colonoscopy is crucial. Once successful, it will facilitate clinically more in-depth disease staging analysis and the formulation of more tailored treatment plans. However, inter-class confusion and brightness imbalance are major obstacles to colon disease subtyping. Notably, the Fourier-based image spectrum, with its distinctive frequency features and brightness insensitivity, offers a potential solution. To effectively leverage its advantages to address the existing challenges, this article proposes a framework capable of thorough learning in the frequency domain based on four core designs: the position consistency module, the high-frequency self-supervised module, the complex number arithmetic model, and the feature anti-aliasing module. The position consistency module enables the generation of spectra that preserve local and positional information while compressing the spectral data range to improve training stability. Through band masking and supervision, the high-frequency autoencoder module guides the network to learn useful frequency features selectively. The proposed complex number arithmetic model allows direct spectral training while avoiding the loss of phase information caused by current general-purpose real-valued operations. The feature anti-aliasing module embeds filters in the model to prevent spectral aliasing caused by down-sampling and improve performance. Experiments are performed on the collected five-class dataset, which contains 4591 colorectal endoscopic images. The outcomes show that our proposed method produces state-of-the-art results with an accuracy rate of 89.82%.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

Spatial transcriptomics: recent developments and insights in respiratory research.

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

Impact of immunosuppression level on liver allograft fibrosis after pediatric liver transplantation: a retrospective cohort study.

BACKGROUND: Liver allograft fibrosis (LAF) is prevalent among children with long-term survival after liver transplantation (LT). The authors aimed to identify clinical risk factors, with a focus on the impact of immunosuppression (IS) level in the early post-transplant period on LAF. METHODS: A retrospective study was conducted on pediatric LT recipients with at least 1-year of follow-up. Cox regression models were used to analyze risk factors associated with LAF, and landmark analysis was used to evaluate the impact of IS level on LAF. Longitudinal analysis was also conducted in patients with paired biopsies. RESULTS: A total of 139 patients involving 174 liver biopsies were included. With 2.3 to 5.9 years of follow-up, LAF was detected in 91.4% of patients (7.9% were significant), up to 88.2% of whom showed normal liver function. Episodes of acute rejection, biliary complications, cytomegalovirus infection, and prolonged cold ischemia time were independent risk factors. Besides, the risk of LAF in patients with relatively low IS levels at postoperative 1-3, 3-6, 6-12, and 12-36 months was higher than the counterparts. Especially, in patients with relatively high IS levels (mean tacrolimus trough concentration ≥5.1 ng/ml) during postoperative 12-36 months, the risk of LAF was 67% lower in the short future ( P =0.006). In paired analysis, patients with increased IS levels were more likely to achieve fibrosis-reduction (HR=7.53, P =0.025). CONCLUSIONS: Mild to moderate LAF is common among pediatric LT recipients and can appear early and silently. Maintaining adequate levels of IS during 1-3 years after LT seems crucial to ensure protection against LAF.

The Spectrum of Tigecycline-Induced Pancreatitis in Clinical Characteristics, Diagnosis, and Management.

Introduction: Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP. Methods: Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis. Results: Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9-87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5-61) versus 57.5 years (range 9-87) (P=0.03). The median time of symptom onset was 7 days (range 2-29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1-43), and the median time to relieve symptoms was 4 days (range 1-12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia. Conclusion: Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients.

Air pollution, EGFR mutation, and cancer initiation.

Swanton et al.1 find that PM2.5 exposure is associated with EGFR/KRAS-driven lung cancer incidence. PM2.5 increases EGFR pre-mutated alveolar type II cell progenitor function and tumorigenic activity through interstitial macrophage-secreted IL-1ß, providing potential prevention approaches to inhibit cancer initiation.

[Latest Findings on the Role of CD47 in Tumor Immune Evasion and Related Targeted Therapies].

CD47 is an immunoglobulin that is overexpressed on the surface of a variety of cancer cells. CD47 forms a signaling complex with signal regulatory protein alpha (SIRPα), prompting the escape of cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed in many types of solid tumors and is associated with poor prognosis in patients. More and more studies have shown that inhibition of the CD47-SIRPα signaling pathway can promote adaptive immune responses and enhance the phagocytosis of tumor cells by macrophages. Humanized anti-CD47 IgG4 monoclonal antibody has been studied in clinical trials for the treatment of a variety of advanced solid tumors and lymphomas, demonstrating a sound safety profile and achieving partial remission in some patients. In this review we discuss the structure and function of CD47 and the mechanism of CD47 regulation in tumors, summarize the research progress in therapeutic antibody drugs targeting CD47 and a bottleneck in research that targeted drugs are more prone to result in serious adverse effects, and evaluated the potential of the applying CD47-SIRPα signaling pathway in anti-cancer therapy.