Knock-down of IGFBP2 ameliorates lung fibrosis and inflammation in rats with severe pneumonia through STAT3 pathway.

OBJECTIVE: To observe the mechanism of IGFBP2 knock-down in improving lung fibrosis and inflammation through STAT3 pathway in rats with severe pneumonia. MATERIALS AND METHODS: First, SP rat model was established. Then rats were divided into the Control group, the SP group, the SP + Lv-vector shRNA group, the SP + Lv-IGFBP2 shRNA group, the SP + Lv-vector group, and the SP + Lv-IGFBP2 group. The mRNA and protein levels of IGFBP2, NOS, CD206 and Arg 1 were detected by RT-qPCR and Western blot. IHC was used to check the positive expression of IGFBP2 and MCP1. A fully automated blood gas analyzer was used to detected PaCO2, CO2 content, PaO2 and SaO2. HE and Masson staining were performed to observe the lung tissue injury and collagen deposition of rats in each group. ELISA assays were used to calculate the levels of inflammatory factors IL-1ß, IL-6, TNF-α, IL-4, and IL-10. Flow cytometry was conducted to acquire the ratio of M1-type AMs and M2-type AMs. RESULTS: Compared with the Control group, IGFBP2, iNOS, CD206, and Arg1 mRNA and protein expression levels, IGFBP2 and MCP1 positive expressions, PaCO2, p-STAT3/STAT3, p-JAK2/JAK2, IL-1ß, IL-6, and TNF-α levels, the number of AMs and neutrophils, the proportion of M1 type AMs and the expressions of α-SMA, Collagen-I, Collagen III, and Fibronectin were significantly increased in SP rats (p < 0.05), while PaCO2, CO2, and SaO2, IL-4 and IL-10 levels, and the proportion of M2 type AMs decreased (p < 0.05). However, the knockdown of IGFBP2 reversed the above index trends. CONCLUSION: Knock-down of IGFBP2 ameliorated lung injury in SP rats, inhibited inflammation and pulmonary fibrosis, and promoted M2-type transformation of AMs by activating the STAT3 pathway.

Efficacy evaluation of neoadjuvant immunotherapy plus chemotherapy for non-small-cell lung cancer: comparison of PET/CT with postoperative pathology.

OBJECTIVES: To assess the value of positron emission tomography/computed tomography (PET/CT) in the efficacy evaluation of patients undergoing neoadjuvant immunotherapy plus chemotherapy, and to analyze its correlation with postoperative pathology. METHODS: The PET/CT metabolic parameters and CT size were retrospectively analyzed before and after neoadjuvant immunotherapy plus chemotherapy in 67 patients with resectable stage II/IIIA non-small-cell lung cancer (NSCLC). CT assessment based on immune response evaluation criteria in solid tumor criteria ((i)RECIST) was compared with PET/CT assessment based on the response criteria in solid tumors (PERCIST). The correlations between PET/CT metabolic parameters and postoperative pathology were analyzed. The value of PET/CT in the efficacy evaluation was assessed. RESULTS: The PET/CT assessment showed high consistency with postoperative pathological evaluation, yet the CT assessment showed low consistency with postoperative pathological evaluation. The (i)RECIST and PERCIST criteria showed statistically significant differences (p < 0.001). The postoperative pathological response was negatively associated with ΔSUVmax (%) (r = - 0.812, p < 0.001), ΔSUVmean (%) (r = - 0.805, p < 0.001), and ΔSUVpeak (%) (r = - 0.800, p < 0.001). The cut-off values of 75.8 for ΔSUVmax (%), 67.8 for ΔSUVmean (%), and 74.6 for ΔSUVpeak (%) had the highest sensitivity and specificity. CONCLUSION: The PERCIST criteria are more sensitive and accurate than (i)RECIST criteria to identify more responders when evaluating the response of neoadjuvant immunotherapy plus chemotherapy for NSCLC. PET/CT shows high accuracy in predicting postoperative pathological response. Our study shows the important role PET/CT plays in the efficacy evaluation of NSCLC patients undergoing neoadjuvant immunotherapy plus chemotherapy, as well as in predicting the prognosis and guiding postoperative treatment. CLINICAL RELEVANCE STATEMENT: Neoadjuvant immunotherapy plus chemotherapy is highly effective in the treatment of non-small-cell lung cancer. And PET/CT played an important role in the efficacy evaluation following neoadjuvant immunotherapy plus chemotherapy for non-small-cell lung cancer. KEY POINTS: • Neoadjuvant immunotherapy plus chemotherapy is highly effective in the treatment of NSCLC. • The PERCIST criteria are more sensitive and accurate than (i)RECIST criteria to identify more responders when evaluating the response of neoadjuvant immunotherapy plus chemotherapy for NSCLC. • PET/CT played an important role in the efficacy evaluation; ΔSUVmax (%), ΔSUVmean (%), and ΔSUVpeak (%) following neoadjuvant immunotherapy plus chemotherapy for NSCLC had high consistency and strong correlations with postoperative pathology.

Serum potassium levels and prognosis in HBV-associated decompensated cirrhosis.

BACKGROUND: Serum potassium disorders are commonly seen in patients with advanced cirrhosis and have a detrimental effect on clinical outcome, but its role in HBV-related decompensated cirrhosis (DeCi) is remained to be illustrated. We aim to assess the effects of serum potassium on outcomes in HBV-DeCi patients. METHODS: Retrospective study included 155 subjects. Multivariate analysis was used to determine the independent prognostic factor. Predictive ability of mortality for variables was determined using the receiver operating characteristics curves. RESULTS: The 30-day in-hospital mortality was 12.9%. Serum potassium levels differed markedly between survivors and non-survivors. On multivariate analysis, Model for End-Stage Liver Disease (MELD) score and serum potassium level were identified as independent predictors of outcomes in HBV-DeCi patients. The combination of serum potassium and MELD score could improve prognostic accuracy in these patients. CONCLUSIONS: Our findings suggest that serum potassium is an effective predictor for poor outcomes in HBV-DeCi patients.

Laparoscopic versus Conventional Surgery for Acute Cholangitis of Severe Type: A Systematic Review of Randomized Controlled Trials.

Objective: Currently, the choice between laparoscopic surgery and conventional laparotomy in the surgical treatment of acute cholangitis of severe type (ACST) is debatable. This study compared the clinical efficacy of these two surgical methods through a meta-analysis based on relevant clinical randomized controlled trials (RCT) on ACST. Methods: We systematically searched several databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and WangFang) for RCT on the surgical treatment of ACST between 2010 and 2022. Relevant data were extracted, and a meta-analysis was performed using the statistical software Stata 16.0. Results: From initial 1089 studies retrieved, 15 studies (n = 1247 patients) were eligible. The total number of patients was 1247, of whom 635 were classified in the treatment group (laparoscopic surgery) and 612 patients in the control group (conventional laparotomy). This meta-analysis showed that compared with conventional laparotomy, laparoscopic surgery was associated with higher effective rate (OR = 3.808, 95% CI [2.383, 6.085], P < 0.001), lower incidence rate of complications (OR = 0.192, 95% CI [0.139, 0.265], P < 0.001), shorter operation duration (SMD = -3.274, 95% CI [-4.503, -2.045], P < 0.001), and shorter postoperative hospital stay (SMD = -2.432, 95% CI [-2.988, -1.877], P < 0.001). Further, the indicators of symptomatic relief (anus exhaust time, jaundice relief time, gastrointestinal function recovery time, and abdominal pain relief time) and inflammatory levels (white blood cell count, alanine aminotransferase, total bilirubin level, and high-sensitivity C-reactive protein level) in the treatment group were better than those in the control group. Conclusion: Laparoscopic surgery was associated with significant improvement in treatment efficiency, reduced risk of complications, and better treatment outcomes in patients with ACST.

Analysis of Omics Data Reveals Nucleotide Excision Repair-Related Genes Signature in Highly-Grade Serous Ovarian Cancer to Predict Prognosis.

Most of the high-grade serous ovarian cancers (HGSOC) are accompanied by P53 mutations, which are related to the nucleotide excision repair (NER) pathway. This study aims to construct a risk signature based on NER-related genes that could effectively predict the prognosis for advanced patients with HGSOC. In our study, we found that two clusters of HGSOC with significantly different overall survival (OS) were identified by consensus clustering and principal component analysis (PCA). Then, a 7-gene risk signature (DDB2, POLR2D, CCNH, XPC, ERCC2, ERCC4, and RPA2) for OS prediction was developed subsequently based on TCGA cohort, and the risk score-based signature was identified as an independent prognostic indicator for HGSOC. According to the risk score, HGSOC patients were divided into high-risk group and low-risk group, in which the distinct OS and the predictive power were also successfully verified in the GEO validation sets. Then we constructed a nomogram, including the risk signature and clinical-related risk factors (age and treatment response) that predicted an individual's risk of OS, which can be validated by assessing calibration curves. Furthermore, GSEA showed that the genes in the high-risk group were significantly enriched in cancer-related pathways, such as "MAPK signaling pathway", "mTOR signaling pathway", "VEGF signaling pathway" and so on. In conclusion, our study has developed a robust NER-related genes-based molecular signature for prognosis prediction, and the nomogram could be used as a convenient tool for OS evaluation and guidance of therapeutic strategies in advanced patients with HGSOC.

18F-FDG PET/CT Image Analysis of Penicilliosis Marneffei in an Immunocompetent Child Patient.

ABSTRACT: Penicilliosis marneffei is an extremely rare fungal infectious disease that often occurs in hosts with immunodeficiency or immune dysfunction. Penicilliosis marneffei has been seldom reported in children with multiple infiltrations throughout the body. We report a case of a boy with normal immune function who had multiple infiltrations of penicilliosis marneffei and was misdiagnosed with lymphoma by PET/CT.

Clinical Characteristics, Risk Factors, and Outcomes of Patients with Polymicrobial Klebsiella pneumoniae Bloodstream Infections.

BACKGROUND: Polymicrobial Klebsiella pneumoniae bloodstream infection (KP-BSI) has been reported to account for more than 10% of all KP-BSI, but few studies have characterized polymicrobial KP-BSI. Our study investigated the clinical characteristics, risk factors, and outcomes of polymicrobial KP-BSI by comparing with monomicrobial KP-BSI. METHODS: We conducted a single-center retrospective cohort study of patients with KP-BSI from 1 January 2013 to 31 December 2018 and collected the clinical data by reviewing electronic medical records. RESULTS: Of the 818 patients with KP-BSI recruited, 13.9% (114/818) were polymicrobial KP-BSI. The severity of illness in polymicrobial and monomicrobial KP-BSI was similar, while the rate of resistance to carbapenems was obviously higher in polymicrobial KP-BSI (78.1% vs. 65.6%, p = 0.009). On multivariate analysis, hospitalization in burn ward (odds ratio (OR) 6.13, 95% confidence interval (CI) 2.00-18.76, p = 0.001) and intensive care unit (OR 2.39, 95% CI 1.05-5.43, p = 0.038) was independently associated with polymicrobial KP-BSI. Gram-negative bacteria accounted for the highest proportion (68.9%) among copathogens of polymicrobial KP-BSI, whereas gram-positive bacteria (22.9%) and Candida (8.2%) ranked the second and the third, respectively, with Acinetobacter baumannii being the most common (23.0%). Patients with polymicrobial KP-BSI had longer hospital days after BSI onset and total hospital days than patients with monomicrobial KP-BSI (median (interquartile range (IQR)), 19 (5, 39) vs. 12 (6, 25), 37 (21, 67) vs. 29 (16, 53), respectively, p < 0.05). The mortality did not differ between polymicrobial KP-BSI and monomicrobial KP-BSI (all p > 0.05). CONCLUSIONS: It was observed that polymicrobial KP-BSI accounted for a significant proportion among all KP-BSI in the current study. Hospitalization in burn ward and intensive care unit was an independent risk factor for the development of polymicrobial KP-BSI. The patients with polymicrobial KP-BSI had a higher rate of carbapenem-resistant K. pneumoniae and might have poor outcomes compared to monomicrobial KP-BSI.