Paeonol alleviates ulcerative colitis by modulating PPAR-γ and nuclear factor-κB activation.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease affecting the gastrointestinal tract. Although paeonol has been used for treating UC due to its anti-inflammatory and antioxidant effects, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of paeonol's action on UC by conducting in-vitro and in-vivo studies using NCM460 cells and RAW264.7 cells, and the DSS-induced mice colitis model. The in vitro studies demonstrate that paeonol exerts inhibitory effects on the activation of the NF-κB signaling pathway through upregulating PPARγ expression, thereby attenuating pro-inflammatory cytokine production, reducing reactive oxygen species levels, and promoting M2 macrophage polarization. These effects are significantly abrogated upon addition of the PPARγ inhibitor GW9662. Moreover, UC mice treated with paeonol showed increased PPARγ expression, which reduced inflammation and apoptosis to maintain intestinal epithelial barrier integrity. In conclusion, our findings suggest that paeonol inhibits the NF-κB signaling pathway by activating PPARγ, reducing inflammation and oxidative stress and improving Dss-induced colitis. This study provides a new insight into the mechanism of treating UC by paeonol.

Iron driven organic carbon capture, pretreatment, recovery and upgrade in wastewater: Process technologies, mechanisms, and implications.

Wastewater treatment plants face significant challenges in transitioning from energy-intensive systems to carbon-neutral, energy-saving systems, and a large amount of chemical energy in wastewater remains untapped. Iron is widely used in modern wastewater treatment. Research shows that leveraging the coupled redox relationship of iron and carbon can redirect this energy (in the form of carbon) towards resource utilization. Therefore, re-examining the application of iron in existing wastewater carbon processes is particularly important. In this review, we investigate the latest research progress on iron for wastewater carbon flow restructuring. During the iron-based chemically enhanced primary treatment (CEPT) process, organic carbon is captured into sludge and its bioavailability is enhanced through iron-based advanced oxidation processes (AOP) pretreatment, further being recovered or upgraded to value-added products in anaerobic biological processes. We discuss the roles and mechanisms of iron in CEPT, AOP, anaerobic biological processes, and biorefining in driving organic carbon conversion. The dosage of iron, as a critical parameter, significantly affects the recovery and utilization of sludge carbon resources, particularly by promoting effective electron transfer. We propose a pathway for beneficial conversion of wastewater organic carbon driven by iron and analyze the benefits of the main products in detail. Through this review, we hope to provide new insights into the application of iron chemicals and current wastewater treatment models.

Learning curve of robotic pancreatoduodenectomy by a single surgeon with extensive laparoscopic pancreatoduodenectomy experience.

With the development of robotic systems, robotic pancreatoduodenectomies (RPDs) have been increasingly performed. However, the number of cases required by surgeons with extensive laparoscopic pancreatoduodenectomy (LPD) experience to overcome the learning curve of RPD remains unclear. Therefore, we aimed to analyze and explore the impact of different phases of the learning curve of RPD on perioperative outcomes. Clinical data were prospectively collected and retrospectively analyzed for 100 consecutive patients who underwent RPD performed by a single surgeon. This surgeon had previous experience with LPD, having performed 127 LPDs with low morbidity. The learning curve for RPD was analyzed using the cumulative sum (CUSUM) method based on operation time, and perioperative outcomes were compared between the learning and proficiency phases. Between April 2020 and November 2022, one hundred patients (56 men, 44 women) were included in this study. Based on the CUSUM curve of operation time, the learning curve for RPD was divided into two phases: phase I was the learning phase (cases 1-33) and phase II was the proficiency phase (cases 34-100). The operation time during the proficiency phase was significantly shorter than that during the learning phase. In the learning phase of RPD, no significant increases were observed in estimated blood loss, conversion to laparotomy, severe complications, postoperative pancreatic hemorrhage, clinical pancreatic fistula, or other perioperative complications compared to the proficiency phases of either RPD or LPD. A surgeon with extensive prior experience in LPD can safely surmount the RPD learning curve without increasing morbidity in the learning phase. The proficiency was significantly improved after accumulating experience of 33 RPD cases.

Lymphocyte-to-Monocyte Ratio Predicts Survival for Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma of the Pancreas: Results from a High-Volume Center.

INTRODUCTION: Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV. METHODS: From 2015 to 2021, patients with pathologically confirmed IPMN who underwent surgical resection at Peking Union Medical College Hospital were enrolled. The clinical, radiological, and pathological data of the enrolled patients were collected and analyzed. Preoperative systemic inflammatory parameters were calculated as previously reported. RESULTS: Eighty-six patients with IPMN-INV met the inclusion criteria. The lymphocyte-to-monocyte ratio (LMR) was the only systemic inflammatory parameter independently associated with the cancer-specific survival (CSS). An LMR higher than 3.5 was significantly associated with a favorable CSS in univariate (hazard ratio [HR] 0.305, p = 0.003) and multivariate analyses (HR 0.221, p = 0.001). Other independently prognostic factors included the presence of clinical symptoms, cyst size, N stage, and tumor differentiation. Additionally, a model including LMR was established for the prognosis prediction of IPMN-INV and had a C-index of 0.809. CONCLUSIONS: Preoperative LMR could serve as a feasible prognostic biomarker for IPMN-INV. A decreased LMR (cutoff value of 3.5) was an independent predictor of poor survival for IPMN-INV.

YTHDF1 regulates immune cell infiltration in gastric cancer via interaction with p53.

The N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) has been assessed in several tumor types and holds significance in the tumor microenvironment (TME). Furthermore, p53, an important tumor suppressor, is closely associated with the TME. The present study evaluated the roles of YTHDF1 and p53 in regulating the TME in gastric cancer (GC). Genetic alterations in the YTH domain family were analyzed using the cBioPortal database. Expression of YTHDF1 in GC cells and tissues was assessed using the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer data analysis portal and Tumor-Immune System Interactions and Drug Bank (TISIDB) databases, along with reverse-transcription-quantitative PCR and western blotting in GC. The prognostic value of multiple tumors was determined using Kaplan-Meier analysis. Correlation analyses were performed using the TIMER, TISIDB and GEPIA databases. Protein-protein interactions of YTHDF1 were predicted using GeneMANIA and HitPredict, and confirmed using co-immunoprecipitation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the YTHDF1 functional network in GC were performed using LinkedOmics. Genetic alterations revealed that, among the YTH domain family members, YTHDF1 had the highest alteration in GC and was associated with a shorter survival. Additionally, YTHDF1 was significantly negatively associated with the level of CD8+ T cells, B cells, macrophages, dendritic cells (DCs) and neutrophils in GC. Furthermore, tumor associate macrophage-related and DC markers were significantly negatively correlated with YTHDF1 expression, whilst regulatory T cells and T cell exhaustion markers were significantly negatively associated with YTHDF1 expression. In addition, compared with that in p53-nonmutant GC cells, YTHDF1 expression was significantly higher in p53-mutated GC cells, indicating a potential association between YTHDF1 and p53. Analyses using the GeneMANIA and HitPredict databases, and co-immunoprecipitation, demonstrated that YTHDF1 interacted with p53. In conclusion, the findings of the present study indicate that YTHDF1 is associated with a poor prognosis and serves an important role in the TME of GC. We hypothesize, for the first time to the best of our knowledge, that YTHDF1 regulates immune cell infiltration by interacting with p53 in GC, which provides a promising direction for future research.

The significance of an immunohistochemical marker-based panel in assisting the diagnosis of parathyroid carcinoma.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. However, the diagnosis of PC is still a difficult problem. A model with immunohistochemical (IHC) staining of 5 biomarkers has been reported from limited samples for the differential diagnosis of PC. In the present study, a series of IHC markers was applied in relatively large samples to optimize the diagnostic model for PC. METHODS: In this study, 44 patients with PC, 6 patients with atypical parathyroid tumors and 57 patients with parathyroid adenomas were included. IHC staining for parafibromin, Ki-67, galectin-3, protein-encoding gene product 9.5 (PGP9.5), E-cadherin, and enhancer of zeste homolog 2 (EZH2) was performed on formalin-fixed, paraffin-embedded tissue samples. The effects of clinical characteristics, surgical procedure, and IHC staining results of tumor tissues on the diagnosis and prognosis of PC were evaluated retrospectively. RESULTS: A logistic regression model with IHC results of parafibromin, Ki-67, and E-cadherin was created to differentiate PC with an area under the curve of 0.843. Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio: 3.26, 95% confidence interval: 1.28-8.34, P = 0.013) was related to the recurrence of PC. CONCLUSION: An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish PC from parathyroid neoplasms. Among the 6 IHC markers and clinical features examined, the risk factor related to PC recurrence was parafibromin staining loss.

Modulating ferroptosis sensitivity: environmental and cellular targets within the tumor microenvironment.

Ferroptosis, a novel form of cell death triggered by iron-dependent phospholipid peroxidation, presents significant therapeutic potential across diverse cancer types. Central to cellular metabolism, the metabolic pathways associated with ferroptosis are discernible in both cancerous and immune cells. This review begins by delving into the intricate reciprocal regulation of ferroptosis between cancer and immune cells. It subsequently details how factors within the tumor microenvironment (TME) such as nutrient scarcity, hypoxia, and cellular density modulate ferroptosis sensitivity. We conclude by offering a comprehensive examination of distinct immunophenotypes and environmental and metabolic targets geared towards enhancing ferroptosis responsiveness within the TME. In sum, tailoring precise ferroptosis interventions and combination strategies to suit the unique TME of specific cancers may herald improved patient outcomes.

Advanced insights on tumor-associated macrophages revealed by single-cell RNA sequencing: The intratumor heterogeneity, functional phenotypes, and cellular interactions.

Single-cell RNA sequencing (scRNA-seq) is an emerging technology used for cellular transcriptome analysis. The application of scRNA-seq has led to profoundly advanced oncology research, continuously optimizing novel therapeutic strategies. Intratumor heterogeneity extensively consists of all tumor components, contributing to different tumor behaviors and treatment responses. Tumor-associated macrophages (TAMs), the core immune cells linking innate and adaptive immunity, play significant roles in tumor progression and resistance to therapies. Moreover, dynamic changes occur in TAM phenotypes and functions subject to the regulation of the tumor microenvironment. The heterogeneity of TAMs corresponding to the state of the tumor microenvironment has been comprehensively recognized using scRNA-seq. Herein, we reviewed recent research and summarized variations in TAM phenotypes and functions from a developmental perspective to better understand the significance of TAMs in the tumor microenvironment.

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

Identification of potential therapeutic drugs targeting core genes for systemic lupus erythematosus (SLE) and coexisting COVID-19: Insights from bioinformatic analyses.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at risk during the COVID-19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID-19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. METHODS: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein-protein interaction (PPI) network analysis, regulatory network construction, and gene-drug interaction construction. RESULTS: A total of 50 common DEGs were found between COVID-19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab-CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene-drug interaction. CONCLUSION: Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE.

A new prognostic model for glioblastoma multiforme based on coagulation-related genes.

Background: Glioblastoma multiforme (GBM) is the most aggressive, common, and lethal type of primary brain tumor. Multiple cancers have been associated with abnormalities in the coagulation system that facilitate tumor invasion and metastasis. In GBM, the prognostic value and underlying mechanism of coagulation-related genes (CRGs) have not been explored. Methods: RNA sequencing (RNA-seq) and clinical information on GBM were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), respectively. Following the identification of differentially expressed CRGs (DECRGs) between GBM and control samples, the survival-related DECRGs were selected via univariate and multivariate Cox regression analyses to establish a prognostic signature. The prognostic performance and clinical utility of the prognostic signature were assessed by the Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC) curve analysis, and a nomogram was constructed. The signature genes-related underlying mechanisms were analyzed according to gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-cell analysis. Finally, the difference in immune cell infiltration, stromal score, immune score, and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) score were compared between different risk groups. Results: A 5-gene prognostic signature (PLAUR, GP6, C5AR1, SERPINA5, F2RL2) was established for overall survival (OS) prediction of GBM patients. The predicted efficiency of the prognostic signature was confirmed in TGGA-GBM dataset and validated in the CGGA-GBM dataset, revealing that it could differentiate GBM patients from controls well, and high risk score was accompanied with poor prognosis. Moreover, biological process (BP) and signaling pathway analyses showed that signature genes were mainly enriched in the functions of blood coagulation and tumor invasion and metastasis. Moreover, high-risk patients exhibited higher levels of immune cell infiltration, stromal score, immune score, and ESTIMATE score than that of low-risk patients. Conclusions: An analysis of coagulation-related prognostic signatures was conducted in this study, as well as how signature genes may affect GBM progress, providing information that might provide new ideas for the development of GBM-related molecular targeted therapies.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm.

Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.

Local resection for solid pseudopapillary neoplasms of the pancreas shows improved postoperative gastrointestinal function and reduced mental stress: a multiquestionnaire survey from a large cohort.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant pancreatic tumor with a highly favorable prognosis. Most SPN patients are young and middle-aged women. The main controversial topic for SPN is local resection (LR) versus radical resection (RR). Theoretically, LR could lead to better gastrointestinal function (GIF) and less mental stress. However, no data is available to support this hypothesis. METHODS: All SPN patients undergoing surgical treatment in Peking Union Medical College Hospital from 2001 to 2021 were included in the study. A cross-sectional online multiquestionnaire survey containing 110 questions was sent to them (Clinicaltrial.org, NCT05604716). This online multiquestionnaire survey focused on GIF and mental stress and consisted of eight questionnaires. Multiple linear regression analysis was conducted to identify independent factors impacting GIF and mental stress. RESULTS: A total of 183 cases provided valid results. Among them, 46 patients (25.1%) underwent LR, and 137 (74.9%) underwent RR. Ninety-four cases (51.4%) underwent minimally invasive surgery (MIS), while 89 (48.6%) underwent open surgery. The average GSRS score of the patients was 1.9±0.7, indicating that most suffered from mild gastrointestinal dysfunction. The scores of PHQ-9 and GAD-7 in 16 patients (8.7%) and 27 (14.8%) patients, respectively, were beyond 10.0, which indicated clinical depression and anxiety. Additionally, 19 (10.4%) patients reported poor ability to work, and 31(16.9%) patients had significant body image concerns. Compared to other clinicopathological characteristics, LR (LR vs. RR: PHQ-9 score, P =0.018; WAI average score, P =0.010; EORTC QLQ-C30, nine subdomains, P <0.05; GSRS average score, P =0.006) and MIS (MIS vs. open surgery: EORTC QLQ-C30, three subdomains, P <0.05; GSRS average score, P =0.006) were the most significant factors predicting improved GIF and reduced mental stress. CONCLUSIONS: This study systematically presents postoperative GIF and mental stress of SPN patients using validated multiquestionnaires for the first time. It provides solid evidence that LR and MIS can improve GIF and reduce mental stress after surgery for SPN patients, which could be helpful for the surgeons to make more personalized surgical plans for their patients.

miR-3133 inhibits gastrointestinal cancer progression through activation of Hippo and p53 signalling pathways via multi-targets.

BACKGROUND: Malignant cell growth and chemoresistance, the main obstacles in treating gastrointestinal cancer (GIC), rely on the Hippo and p53 signalling pathways. However, the upstream regulatory mechanisms of these pathways remain complex and poorly understood. METHODS: Immunohistochemistry (IHC), western blot and RT-qPCR were used to analyse the expression of RNF146, miR-3133 and key components of Hippo and p53 pathway. CCK-8, colony formation, drug sensitivity assays and murine xenograft models were used to investigate the effect of RNF146 and miR-3133 in GIC. Further exploration of the upstream regulatory mechanism was performed using bioinformatics analysis, dual-luciferase reporter gene, immunoprecipitation assays and bisulfite sequencing PCR (BSP). RESULTS: Clinical samples, in vitro and in vivo experiments demonstrated that RNF146 exerts oncogenic effects in GIC by regulating the Hippo pathway. Bioinformatics analysis identified a novel miRNA, miR-3133, as an upstream regulatory factor of RNF146. fluorescence in situ hybridization and RT-qPCR assays revealed that miR-3133 was less expressed in gastrointestinal tumour tissues and was associated with adverse pathological features. Functional assays and animal models showed that miR-3133 promoted the proliferation and chemotherapy sensitivity of GIC cells. miR-3133 affected YAP1 protein expression by targeting RNF146, AGK and CUL4A, thus activating the Hippo pathway. miR-3133 inhibited p53 protein degradation and extended p53's half-life by targeting USP15, SPIN1. BSP experiments confirmed that miR-3133 promoter methylation is an important reason for its low expression. CONCLUSION: miR-3133 inhibits GIC progression by activating the Hippo and p53 signalling pathways via multi-targets, including RNF146, thereby providing prognostic factors and valuable potential therapeutic targets for GIC.

Can we skip technetium-99 m sestamibi scintigraphy in pediatric primary hyperparathyroidism patients with positive neck ultrasound results?

BACKGROUND: Parathyroidectomy is the only curative treatment for primary hyperparathyroidism (PHPT). Ultrasound (US) and technetium-99 m sestamibi (99mTc-MIBI) scintigraphy are recommended as the first-line localization imaging modalities for PHPT in adults, but the value of preoperative imaging in pediatric patients has not been reported. OBJECTIVE: To evaluate the added value of 99mTc-MIBI scintigraphy in pediatric PHPT patients with positive ultrasound results. MATERIALS AND METHODS: Pediatric patients (≤18 years old) who were diagnosed with PHPT and underwent surgical treatment in Peking Union Medical College Hospital between January 2003 and January 2021 were included in this study. Demographic and clinical characteristics, preoperative localization US, 99mTc-MIBI scintigraphy and pathology results were collected. Preoperative localization results were evaluated by comparison with surgical and pathological findings. RESULTS: There were 32 pediatric PHPT patients with median age of 14.7 ± 2.5 years who all proved to have single-gland disease without ectopic lesions. The median lesion size was 2.85 cm (range 1.0-5.8 cm). All patients underwent US and 99mTc-MIBI scintigraphy. Neck US demonstrated 100% sensitivity. Of 32 patients with a positive US, 99mTc-MIBI scintigraphy was concordant in 30 (93.8%). In 2 patients (6.3%), US reported suspected multigland disease, which was correctly diagnosed by 99mTc-MIBI scintigraphy as single lesions. CONCLUSION: In pediatric PHPT patients, US achieved high sensitivity for preoperative localization. 99mTc-MIBI scintigraphy for pediatric patients with positive US results would not increase the sensitivity. Implementation of 99mTc-MIBI scintigraphy could increase the specificity in pediatric patients with multigland disease suspected by US.

Acute inflammatory reaction during anti-angiogenesis therapy combined with immunotherapy as a possible indicator of the therapeutic effect: Three case reports and literature review.

The posterior line treatment of unresectable advanced or metastatic gastrointestinal (GI) tumors has always been a challenging point. In particular, for patients with microsatellite stable (MSS)/mismatch repair proficient (pMMR) 0GI tumors, the difficulty of treatment is exacerbated due to their insensitivity to immune drugs. Accordingly, finding a new comprehensive therapy to improve the treatment effect is urgent. In this study, we report the treatment histories of three patients with MSS/pMMR GI tumors who achieved satisfactory effects by using a comprehensive treatment regimen of apatinib combined with camrelizumab and TAS-102 after the failure of first- or second-line regimens. The specific contents of the treatment plan were as follows: apatinib (500 mg/d) was administered orally for 10 days, followed by camrelizumab (200 mg, ivgtt, day 1, 14 days/cycle) and TAS-102 (20 mg, oral, days 1-21, 28 days/cycle). Apatinib (500 mg/d) was maintained during treatment. Subsequently, we discuss the possible mechanism of this combination and review the relevant literature, and introduce clinical trials on anti-angiogenesis therapy combined with immunotherapy.

[Epidemiological Analysis of Carbapenem-Resistant Enterobacteriaceae Strains in the Clinical Specimens of a Hospital].

Objective: To analyze the detection rate, in vitro susceptibility to antibiotics, and carbapenemase types of carbapenem-resistant Enterobacteriaceae (CRE) strains in the clinical samples of a hospital and to provide support for the prevention, control and treatment of CRE-related infections. Methods: Clinical specimens were examined according to the operating procedures of bacteriological tests. Species identification and in vitro drug susceptibility testing were performed on the isolated strains. Carbapenemase inhibitor enhancement testing, which combined the use of 3-aminobenzeneboronic acid and ethylenediaminetetraacetic acid, was conducted to identify the types of carbapenemase in the CRE strains. Results: In 2021, 2215 CRE strains were isolated from 157196 clinical samples collected in this hospital, presenting a detection rate of 1.4% (2215/157196). A total of 1134 non-repetitive strains of CRE were isolated from 903 patients. The main sources of samples were respiratory tract (494/1134, 43.6%), secretion (191/1134, 16.8%) and blood (173/1134, 15.3%) samples. The cases with the same CRE strain isolated from the samples of two, three and four sites accounted for 12.5%, 4.9%, and 1.1%, respectively. The most common species was Klebsiella pneumoniae (883/1134, 77.9%), followed by Enterobacter cloacae complex (107/1134, 9.4%) and Escherichia coli (96/1134, 8.5%). The rates of resistance to polymyxin B and tigecycline of different species of CRE strains were not significantly different ( P<0.05). Serine carbapenemase-producing strains, metallo-ß-lactamase-producing strains, and those producing both enzymes accounted for 82.6% (809/979), 17.2% (168/979), and 0.2% (2/979), respectively. Conclusion: CRE strains are frequently isolated from samples collected from the respiratory tract, secretion, and blood. The most common strain is serine carbapenemase-producing K. pneumoniae, which has a high resistance rate to various antimicrobial drugs, and risk factors of its associated infections deserve more attention.

[Application of Rapid Detection Method Based on NG-Test® CARBA 5 in Bloodstream Infections Associated With Carbapenem-Resistant Enterobacterales].

Objective: To compare the consistency and accuracy of a rapid test method and a traditional test method for pathogen identification, antimicrobial susceptibility and carbapenemase type identification of positive blood culture samples. Methods: A total of 51 positive blood culture samples of bloodstream infection (BSI) were collected between March 2022 and May 2022. All samples were found to be "positive for Gram-negative bacilli" according to the blood smear results. The rapid method was adopted to perform rapid antimicrobial susceptibility test (RAST) and analysis of the positive blood culture samples. According to the RAST result interpretation standards, NG-Test® CARBA 5 was used for rapid carbapenemase detection of the imipenem-resistant strains and the results were confirmed by PCR. In addition, mass spectrometry, VITEK 2 Compact drug sensitivity analysis, and carbapenemase type identification were performed with the colonies cultured with positive samples according to the traditional method. Results: In the identification of bacteria, the rapid method and the traditional method had 100% consistency rate in the identification results of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. In the antimicrobial susceptibility test, the consistency rate between the results of the two methods was high and the consistency rate for results for susceptibility to imipenem was 100%. In the identification of carbapenemase type, 18 serinase-producing strains and 3 metal-ß-lactamase-producing strains of Enterobacterales were detected by the traditional method. With the rapid method, 18 Klebsiella pneumoniae carbapenemase (KPC)-producing strains, 2 New Delhi metallo-betalactamase (NDM)-producing strains, and 1 imipenem enzyme (IMP)-producing strain were identified in the blood culture samples by using a testing kit. Compared with the PCR results, the sensitivity and specificity of the rapid test for determining carbapenemase types were 100%. In this study, we investigated a rapid method for bacteria and carbapenemase type identification of positive blood culture specimens and found that the turnaround time (TAT) of the rapid method was reduced by 1.94 days on average in comparison with the TAT of the traditional method. Conclusion: The rapid method established in the study can effectively shorten the TAT for pathogenic microorganism identification and antimicrobial susceptibility test of blood culture samples, and the joint report of colloidal gold carbapenemase type identification results can provide a reference for clinicians to use antibiotics appropriately and accurately manage multi-drug resistant bacterial infections.

Qualitative and quantitative superb vascular imaging in the diagnosis of thyroid nodules ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4).

Background: To compare qualitative and quantitative superb microvascular imaging (SMI) and determine the value of SMI in the diagnosis of thyroid nodules (TNs) ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4). Methods: From October 2020 to June 2022, 106 patients with 109 C-TIRADS 4 (C-TR4) TNs (81 malignant, 28 benign) at the Peking Union Medical College Hospital were included. Qualitative SMI reflected the vascular pattern of the TNs and quantitative SMI was recorded by the vascular index (VI) of the nodules. Results: The VI was significantly higher in malignant nodules versus benign nodules both in the longitudinal (19.9±11.4 vs. 13.8±10.6, P=0.01) and transverse (20.2±12.1 vs. 11.3±8.7, P=0.001) sections. The area under the curve (AUC) of qualitative and quantitative SMI did not show a statistical difference in the longitudinal {0.657 [95% confidence interval (CI): 0.560-0.745] vs. 0.646 (95% CI: 0.549-0.735), P=0.79} and transverse [0.696 (95% CI: 0.600-0.780) vs. 0.725 (95% CI: 0.632-0.806), P=0.51] sections. Next, we combined qualitative and quantitative SMI to upgrade and downgrade the C-TIRADS classification. If a C-TR4B nodule had VIsum >12.2 or intra-nodular vascularity, the original C-TIRADS was upgraded to C-TR4C. If a C-TR4C or C-TR4B nodule manifested VIsum ≤12.2 and no intra-nodular vascularity, the original C-TIRADS was downgraded to C-TR4A. As a result, 18 C-TR4C nodules were downgraded to C-TR4A and 14 C-TR4B nodules were upgraded to C-TR4C. The new model of SMI + C-TIRADS showed high sensitivity (93.8%) and accuracy (79.8%). Conclusions: There is no statistical difference between qualitative and quantitative SMI in the diagnosis of C-TR4 TNs. The combination of qualitative and quantitative SMI may have the potential to manage diagnosis of C-TR4 nodules.