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"Xia, Quan"
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Construction and validation of prognostic models in critically Ill patients with sepsis-associated acute kidney injury: interpretable machine learning approach
Background
Acute kidney injury (AKI) is a common complication in critically ill patients with sepsis and is often associated with a poor prognosis. We aimed to construct and validate an interpretable prognostic prediction model for patients with sepsis-associated AKI (S-AKI) using machine learning (ML) methods.
Methods
Data on the training cohort were collected from the Medical Information Mart for Intensive Care IV database version 2.2 to build the model, and data of patients were extracted from Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine for external validation of model. Predictors of mortality were identified using Recursive Feature Elimination (RFE). Then, random forest, extreme gradient boosting (XGBoost), multilayer perceptron classifier, support vector classifier, and logistic regression were used to establish a prognosis prediction model for 7, 14, and 28 days after intensive care unit (ICU) admission, respectively. Prediction performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) were used to interpret the ML models.
Results
In total, 2599 patients with S-AKI were included in the analysis. Forty variables were selected for the model development. According to the areas under the ROC curve (AUC) and DCA results for the training cohort, XGBoost model exhibited excellent performance with F1 Score of 0.847, 0.715, 0.765 and AUC (95% CI) of 0.91 (0.90, 0.92), 0.78 (0.76, 0.80), and 0.83 (0.81, 0.85) in 7 days, 14 days and 28 days group, respectively. It also demonstrated excellent discrimination in the external validation cohort. Its AUC (95% CI) was 0.81 (0.79, 0.83), 0.75 (0.73, 0.77), 0.79 (0.77, 0.81) in 7 days, 14 days and 28 days group, respectively. SHAP-based summary plot and force plot were used to interpret the XGBoost model globally and locally.
Conclusions
ML is a reliable tool for predicting the prognosis of patients with S-AKI. SHAP methods were used to explain intrinsic information of the XGBoost model, which may prove clinically useful and help clinicians tailor precise management.
Journal Article
Role of linezolid combination therapy for serious infections: review of the current evidence
As long-standing clinical problems, a series of complicated infections are more difficult to treat due to the development of antibiotic resistance, especially caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). Moreover, the treatment options available to against these infections are also becoming increasingly limited. Linezolid is the first synthetic oxazolidinone antibiotic with a unique mechanism of action, and its efficacy against Gram-positive bacteria has been clearly demonstrated. However, the limitations of linezolid alone for the treatment of these complicated infections have been reported in the recent years. Combination therapy may be a good approach to enhance efficacy and prevent the development of resistance. In this review, the results of multiple linezolid combination therapies from in vitro, animal studies, and clinical cases for the treatment of MRSA, VRE, and multidrug-resistant M. tuberculosis strains will be discussed, and thus provide more relevant information for clinician in clinical practice.
Journal Article
Delivery of germacrone (GER) using macrophages-targeted polymeric nanoparticles and its application in rheumatoid arthritis
Macrophages can transform into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes, which mediate the immune/inflammatory response in rheumatoid arthritis (RA). Activated M1 phenotype macrophages and overexpression of folate (FA) receptors are abundant in inflammatory synovium and joints and promote the progression of RA. Germacrone (GER) can regulate the T helper 1 cell (Th1)/the T helper 2 cell (Th2) balance to delay the progression of arthritis. To deliver GER to inflammatory tissue cells to reverse M1-type proinflammatory cells and reduce inflammation, FA receptor-targeting nanocarriers loaded with GER were developed. In activated macrophages, FA-NPs/DiD showed significantly higher uptake efficiency than NPs/DiD. In vitro experiments confirmed that FA-NPs/GER could promote the transformation of M1 macrophages into M2 macrophages. In adjuvant-induced arthritis (AIA) rats, the biodistribution profiles showed selective accumulation at the inflammatory site of FA-NPs/GER, and significantly reduced the swelling and inflammation infiltration of the rat's foot. The levels of pro-inflammatory cytokines (TNF-α, IL-1β) in the rat's inflammatory tissue were significantly lower than other treatment groups, which indicated a significant therapeutic effect in AIA rats. Taken together, macrophage-targeting nanocarriers loaded with GER are a safe and effective method for the treatment of RA.
Journal Article
Bacteriological concentration of peritoneal drainage fluid could make an early diagnosis of anastomotic leakage following rectal resection
To investigate that the bacteriological concentration and pH value in peritoneal drainage fluid might serve as indicators of early diagnosis of anastomotic leakage following rectal resection. We prospectively analyzed consecutive patients who were treated for rectal diseases with anastomosis at the department of general surgery, the affiliated hospital of Nanjing University Medical School between August 2018 and December 2020. The bacteriological concentration and the pH value in peritoneal drainage fluid were tested on the first, fourth, seventh days postoperatively. A total of 300 consecutive patients underwent rectal resection were tested. 21 patients present with AL and the overall AL rate was 7%. The bacteriological concentration in peritoneal drainage fluid of AL group was significantly higher than that in non-AL group. The AUC value was 0.98 (95% confidence intervals 0.969–1.000) according to the ROC curve. The best cut-off value was 1143/uL. The sensitivity and specificity were 100% and 93.19% respectively. There was no difference of pH value between the AL and non-AL groups. According the results of present study, a high bacteriological concentration in peritoneal drainage fluid is a good marker for predicting and diagnosing AL following rectal resection. However, owing to the limitation of the sample, there was no validation attempt in the study. A large sample study is needed to validate the conclusion.
Journal Article
ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/PI3-kinase/AKT signaling pathway
Chemotherapy is the main treatment method of patients with advanced liver cancer. However, drug resistance is a serious problem in the treatment of hepatocellular carcinoma (HCC). Acid sensing ion channel 1a (ASIC1a) is a H+-gated cation channel; it mediates tumor cell migration and invasion, which suggests that it is involved in the development of malignant tumors. Therefore, we studied the relationship between ASIC1a and drug resistance in human hepatocellular carcinoma. In our study, we found that ASIC1a is highly expressed in human HCC tissue, and that its levels were significantly increased in resistant HCC cells Bel7402/FU and HepG2/ADM. Inhibiting the activity of ASIC1a enhances the chemosensitivity of Bel7402/FU and HepG2/ADM cells. The overexpression of ASIC1a contributed to drug resistance in Bel7402 and HepG2 cells, whereas knockdown of ASIC1a overcame drug resistance in Bel7402/FU and HepG2/ADM cells. We further demonstrated that ASIC1a mediated calcium influx, which resulted in the activation of PI3K/AKT signaling and increased drug resistance. These data suggest that ASIC1a/Ca2+/PI3K/AKT signaling represents a novel pathway that regulates drug resistance, thus offering a potential target for chemotherapy of HCC.
Journal Article
Aidi Injection, a Traditional Chinese Medicine Injection, Could Be Used as an Adjuvant Drug to Improve Quality of Life of Cancer Patients Receiving Chemotherapy: A Propensity Score Matching Analysis
Background: Clinical research has paid increasing attention to quality of life (QoL) in recent years, but the assessment of QoL is difficult, hampered by the subjectivity, complexity, and adherence of patients and physicians. According to previous studies, QoL in cancer patients is related to performance status (PS) and influenced by chemotherapy-related toxicity. Aidi injection, a traditional Chinese medicine injection, is used as an adjuvant drug to enhance effectiveness of chemotherapy. The study aims to investigate whether Aidi injection could improve QoL by improving PS and reducing toxicity caused by chemotherapy. Methods: A retrospective cohort study was performed at the First Affiliated Hospital of Anhui Medicine University. Data of consecutive patients diagnosed with cancers between January 2014 and June 2017 were retrieved from the electronic medical record system. After a 1:1 propensity score match, patients were then divided into 2 groups based on the therapies used, that is, Aidi injection combined with chemotherapy and chemotherapy alone, and the PS, chemotherapy-related toxicity, and combined medication information were compared. The effect of different dosages of Aidi injection on patients was further explored. Results: A total of 3200 patients were included in this study. Aidi injection combined with chemotherapy exhibited significantly benefit in PS (P < .001, odds ratio [OR] 3.4, 95% confidence interval [CI] 2.4-4.8) compared with chemotherapy alone after adjusting for the factors that affect PS. The improvement rate of PS in the Aidi group was significantly higher than in the control group across the stratification of gender, age, tumor type, TNM stage, body mass index, nodal metastasis, prior chemotherapy, chemotherapy regimens, other Chinese tradition medicines, and chemotherapy cycle. Meanwhile, Aidi injection used synchronously with chemotherapeutic drugs could decrease the incident rate of damage to liver and kidney function, myelosuppression, and gastrointestinal reactions caused by chemotherapy. Conclusion: It was indicated that the integrative approach combining chemotherapy with Aidi injection, especially with the conventional dosage of Aidi injection, had significant benefit on QoL in cancer patients.
Journal Article
Genome analysis and signature discovery for diving and sensory properties of the endangered Chinese alligator
Crocodilians are diving reptiles that can hold their breath under water for long periods of time and are crepuscular animals with excellent sensory abilities. They comprise a sister lineage of birds and have no sex chromosome. Here we report the genome sequence of the endangered Chinese alligator （Alligator sinensis） and describe its unique features. The next-generation sequencing generated 314 Gb of raw sequence, yielding a genome size of 2.3 Gb. A total of 22 200 genes were predicted in Alligator sinensis using a de novo, homology- and RNA-based combined model. The genetic basis of long-diving behavior includes duplication of the bicarbonate-binding hemoglobin gene, co-function- ing of routine phosphate-binding and special bicarbonate-binding oxygen transport, and positively selected energy metabolism, ammonium bicarbonate excretion and cardiac muscle contraction. Further, we elucidated the robust Alligator sinensis sensory system, including a significantly expanded olfactory receptor repertoire, rapidly evolving nerve-related cellular components and visual perception, and positive selection of the night vision-related opsin and sound detection-associated otopetrin. We also discovered a well-developed immune system with a considerable num- ber of lineage-specific antigen-presentation genes for adaptive immunity as well as expansion of the tripartite motif- containing C-type lectin and butyrophilin genes for innate immunity and expression of antibacterial peptides. Mul- tifluorescence in situ hybridization showed that alligator chromosome 3, which encodes DMRT1, exhibits significant synteny with chicken chromosome Z. Finally, population history analysis indicated population admixture 0.60-1.05 million years ago, when the Qinghai-Tibetan Plateau was uplifted.
Journal Article
Emerging Roles for NLRC5 in Immune Diseases
Innate immunity activates the corresponding immune response relying on multiple pattern recognition receptors (PRRs) that includes pattern recognition receptors (PRRs), like NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and C-type lectin receptors (CLRs), which could accurately recognize invasive pathogens. In particular, NLRs belong to a large protein family of pattern recognition receptors in the cytoplasm, where they are highly correlated with activation of inflammatory response system followed by rapid clearance of invasive pathogens. Among the NLRs family, NLRC5, also known as NOD4 or NOD27, accounts for a large proportion and involves in immune responses far and wide. Notably, in the above response case of inflammation, the expression of NLRC5 remarkably increased in immune cells and immune-related tissues. However, the evidence for higher expression of NLRC5 in immune disease still remains controversial. It is noted that the growing evidence further accounts for the participation of NLRC5 in the innate immune response and inflammatory diseases. Moreover, NLRC5 has also been confirmed to exert a critical role in the control of regulatory diverse signaling pathways. Together with its broad participation in the occurrence and development of immune diseases, NLRC5 can be consequently treated as a potential therapeutic target. Nevertheless, the paucity of absolute understanding of intrinsic characteristics and underlying mechanisms of NLRC5 still make it hard to develop targeting drugs. Therefore, current summary about NLRC5 information is indispensable. Herein, current knowledge of NLRC5 is summarized, and research advances in terms of NLRC5 in characteristics, biological function, and regulatory mechanisms are reviewed.
Journal Article
Safety and effectiveness of tigecycline combination therapy in renal transplant patients with infection due to carbapenem-resistant gram-negative bacteria
Carbapenem-resistant gram-negative bacterial (CRGNB) infections are increasing among kidney transplant recipients, and effective therapeutic options are limited. This study aimed to investigate the efficacy and adverse events associated with combination therapy tigecycline in renal transplant patients with CRGNB infections.
This study retrospectively analyzed 40 Chinese patients with confirmed or suspected CRGNB infections who received tigecycline therapy. The patients' case features and clinical and microbiological data were analyzed.
A total of 40 renal transplant recipients received tigecycline therapy for a median duration of 9 (range, 3-25) days. CRGNB isolates were obtained from the organ preservation solution of the donor kidney in 28 patients, with confirmed transmission in 4 patients. Infections were detected in the bloodstream, urinary tract, sputum, and wound. The most prevalent isolates were
(75%, 30/40),
(15%, 6/40), and
(10%, 4/40). A clinical response was observed in 32 (80%) patients. The 28-day all-cause mortality rate was 7.5% (3/40), while the one-year all-cause mortality rate was 2.5% (1/40). While one patient died owing to severe pancreatitis, no serious adverse events related to tigecycline therapy were reported. However, multiple indices of liver function and pancreatitis precursors increased after treatment with tigecycline compared to before treatment.
Tigecycline therapy appears to be well tolerated in renal transplant recipients with multidrug-resistant bacterial infections. Nevertheless, attention should be paid to adverse reactions related to tigecycline therapy, especially gastrointestinal reactions, and the related laboratory tests should be closely monitored.
Journal Article