A nomogram prediction model for sternal incision problems.

Presently, the incidence and mortality rates of sternal incision problems (SIPs) after thoracotomy remain high, and no effective preventive measures are available. The data on 23 182 patients at Xinqiao Hospital, Army Medical University treated with median sternotomy from 1 August 2009 to 31 July 2019 were retrospectively reviewed. A prediction model of SIPs after median thoracotomy was established using R software and then validated using the bootstrap method. Next, the validity and accuracy of the model were tested and evaluated. In total, 15 426 cases met the requirements of the present study, among which 309 cases were diagnosed with SIPs, with an incidence rate of 2%. The body mass index (BMI), intensive care unit (ICU) time, diabetes mellitus, and revision for bleeding were identified as independent risk factors for postoperative SIPs. The nomogram model achieved good discrimination (73.9%) and accuracy (70.2%) in predicting the risk of SIPs after median thoracotomy. Receiver operating characteristic curve analysis showed that the area under curve of the model was 0.705 (95% confidence interval [CI]: 0.746-0.803); the Hosmer-Lemeshow test showed that χ2  = 6.987 and P = 0.538, and the fitting degree of the calibration curve was good. Additionally, the clinical decision curve showed that the net benefit of the model was greater than 0, and the clinical application value was high. The nomogram based on BMI, ICU time, diabetes mellitus, and revision for bleeding can predict the individualised risk of SIPs after median sternotomy, showing good discrimination and accuracy, and has high clinical application value. It also provides significant guidance for screening high-risk populations and developing intervention strategies.

Resection and reconstruction of a giant primitive neuroectodermal tumour of the abdominal wall with an ultra-long lateral circumflex femoral artery musculocutaneous flap: a case report.

BACKGROUND: Primitive neuroectodermal tumours are clinically rare. Here, we report a case of a large peripheral primitive neuroectodermal tumour of the abdominal wall. The defect was reconstructed with the longest lateral circumflex femoral artery musculocutaneous flap reported to date. CASE PRESENTATION: A 15-year-old male suffered rupture and bleeding of an abdominal wall mass with a volume of approximately 23*18*10 cm3, involving the whole layer of the abdominal wall. Pathological examination revealed a peripheral primitive neuroectodermal tumour. The tumour was removed via oncologic resection, and the abdominal wall was reconstructed with a bilateral 44*8 cm2 lateral circumflex femoral artery musculocutaneous flap combined with a titanium polypropylene patch. The patient had smooth recovery postoperative, and the functions of the donor and recipient areas of the flap were not significantly affected. CONCLUSION: In this case report, we describe a rare primitive neuroectodermal tumour of the abdominal wall, which invaded almost the entire abdominal wall due to delay of treatment. After thoroughly removing the tumour, we immediately reconstructed the abdominal wall with an ultra-long lateral circumflex femoral artery musculocutaneous flap and achieved better appearance and function after the operation. This case suggests that we should adopt an integrated scheme of surgery combined with radiotherapy and chemotherapy in the treatment of peripheral primitive neuroectodermal tumours. Under the premise of determining the blood supply, the lateral circumflex femoral artery musculocutaneous flap can be cut to a sufficient length.

Lower serum nicotinamide N-methyltransferase levels in patients with bipolar disorder during acute episodes compared to healthy controls: a cross-sectional study.

BACKGROUND: Nicotinamide N-methyltransferase (NNMT) has been implicated in the pathogenesis of neuropsychiatric diseases. Bipolar disorder (BD) is associated with metabolic abnormalities and NNMT regulates energy metabolism and may also exert a causal role in metabolic disorders. The present study aimed to determine serum NNMT levels in patients with BD and compared the results with that of healthy controls, to explore the correlation between NNMT and clinical and metabolic characteristics. METHODS: The NNMT levels of 80 patients having a manic episode of BD and 65 non-psychiatric control individuals were measured using enzyme-linked immunosorbent assay. Metabolic parameters were evaluated using standard laboratory methods. RESULTS: The serum NNMT levels of bipolar mania patients were significantly lower than that of non-psychiatric controls. Furthermore, the serum levels of NNMT were found to be negatively correlated with Young Mania Rating Scale (YMRS) scores and the duration of the illness. Moreover, lower NNMT serum levels were found in patients with a history of antipsychotic medication and dyslipidemia. Our results also demonstrated the different patterns of correlation that exist between the study groups. Serum NNMT levels were found to be negatively correlated with triglyceride, cholesterol, and apolipoprotein B levels in the BD group, while the same was found to be negatively associated only with high-density lipoprotein cholesterol in the control group. CONCLUSIONS: These findings support the suggestion that lower NNMT serum levels are significantly associated with BD and that serum NNMT has the potential to regulate lipid metabolism in BD patients.

Type 2 Fibroblast Growth Factor Receptor Signaling Preserves Stemness and Prevents Differentiation of Prostate Stem Cells from the Basal Compartment.

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, which include basal, luminal, and neuroendocrine cells. Two types of P-SCs have been identified in both human and mouse adult prostates based on prostasphere or organoid cultures, cell lineage tracing, renal capsule implantation, and expression of luminal- and basal-specific proteins. The sphere-forming P-SCs are from the basal cell compartment that express P63, and are therefore designated as basal P-SCs (P-bSCs). Luminal P-SCs (P-lSCs) express luminal cytokeratins and Nkx3.1. Herein, we report that the type 2 FGF receptor (FGFR2) signaling axis is crucial for preserving stemness and preventing differentiation of P-bSCs. FGFR2 signaling mediated by FGFR substrate 2α (FRS2α) is indispensable for formation and maintenance of prostaspheres derived from P63(+) P-bSCs. Ablation of Fgfr2 in P63(+) cells in vitro causes the disintegration of prostaspheres. Ablation of Fgfr2 in vivo reduces the number of P63-expressing basal cells and enriches luminal cells. This suggests a basal stem cell-to-luminal cell differentiation. In addition, ablation of Fgfr2 in P63(+) cells causes defective postnatal development of the prostate. Therefore, the data indicate that FGFR2 signaling is critical for preserving stemness and preventing differentiation of P-bSCs.

Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment.

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, including basal, luminal, and neuroendocrine cells. Multiple methods have been used to identify P-SCs in adult prostates. These include in vivo renal capsule implantation of a single epithelial cell with urogenital mesenchymal cells, in vitro prostasphere and organoid cultures, and lineage tracing with castration-resistant Nkx3.1 expression (CARN), in conjunction with expression of cell type-specific markers. Both organoid culture and CARN tracing show the existence of P-SCs in the luminal compartment. Although prostasphere cells predominantly express basal cell-specific cytokeratin and P63, the lineage of prostasphere-forming cells in the P-SC hierarchy remains to be determined. Using lineage tracing with P63(CreERT2), we show here that the sphere-forming P-SCs are P63-expressing cells and reside in the basal compartment. Therefore we designate them as basal P-SCs (P-bSCs). P-bSCs are capable of differentiating into AR(+) and CK18(+) organoid cells, but organoid cells cannot form spheres. We also report that prostaspheres contain quiescent stem cells. Therefore, the results show that P-bSCs represent stem cells that are early in the hierarchy of overall prostate tissue stem cells. Understanding the contribution of the two types of P-SCs to prostate development and prostate cancer stem cells and how to manipulate them may open new avenues for control of prostate cancer progression and relapse.

Autophagy defects suggested by low levels of autophagy activator MAP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients.

MAP1S (originally named C19ORF5) is a widely distributed homolog of neuronal-specific MAP1A and MAP1B, and bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. Mitochondrion-associated protein LRPPRC functions as an inhibitor for autophagy initiation to protect mitochondria from autophagy degradation. MAP1S and LRPPRC interact with each other and may collaboratively regulate autophagy although the underlying mechanism is yet unknown. Previously, we have reported that LRPPRC levels serve as a prognosis marker of patients with prostate adenocarcinomas (PCA), and that patients with high LRPPRC levels survive a shorter period after surgery than those with low levels of LRPPRC. MAP1S levels are elevated in diethylnitrosamine-induced hepatocelular carcinomas in wildtype mice and the exposed MAP1S-deficient mice develop more malignant hepatocellular carcinomas. We performed immunochemical analysis to evaluate the co-relationship among the levels of MAP1S, LRPPRC, P62, and γ-H2AX. Samples were collected from wildtype and prostate-specific PTEN-deficient mice, 111 patients with PCA who had been followed up for 10 years and 38 patients with benign prostate hyperplasia enrolled in hospitals in Guangzhou, China. The levels of MAP1S were generally elevated so the MAP1S-mediated autophagy was activated in PCA developed in either PTEN-deficient mice or patients than their respective benign tumors. The MAP1S levels among patients with PCA vary dramatically, and patients with low MAP1S levels survive a shorter period than those with high MAP1S levels. Levels of MAP1S in collaboration with levels of LRPPRC can serve as markers for prognosis of prostate cancer patients.

Type 1 fibroblast growth factor receptor in cranial neural crest cell-derived mesenchyme is required for palatogenesis.

Cleft palate is a common congenital birth defect. The fibroblast growth factor (FGF) family has been shown to be important for palatogenesis, which elicits the regulatory functions by activating the FGF receptor tyrosine kinase. Mutations in Fgf or Fgfr are associated with cleft palate. To date, most mechanistic studies on FGF signaling in palate development have focused on FGFR2 in the epithelium. Although Fgfr1 is expressed in the cranial neural crest (CNC)-derived palate mesenchyme and Fgfr1 mutations are associated with palate defects, how FGFR1 in palate mesenchyme regulates palatogenesis is not well understood. Here, we reported that by using Wnt1(Cre) to delete Fgfr1 in neural crest cells led to cleft palate, cleft lip, and other severe craniofacial defects. Detailed analyses revealed that loss-of-function mutations in Fgfr1 did not abrogate patterning of CNC cells in palate shelves. However, it upset cell signaling in the frontofacial areas, delayed cell proliferation in both epithelial and mesenchymal compartments, prevented palate shelf elevation, and compromised palate shelf fusion. This is the first report revealing how FGF signaling in CNC cells regulates palatogenesis.

Elevated levels of mitochondrion-associated autophagy inhibitor LRPPRC are associated with poor prognosis in patients with prostate cancer.

BACKGROUND: Autophagy has recently been found to play important roles in tumorigenesis and leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) has been identified as an inhibitor that suppresses autophagy and mitophagy and maintains mitochondrial activity. The authors hypothesized that LRPPRC levels can be used as a biomarker for the diagnosis and prognosis of prostate cancer. METHODS: Immunochemistry analysis was performed to evaluate the levels of LRPPRC in 112 samples collected from patients with prostate adenocarcinoma (PCa) and 38 samples from patients with benign prostatic hyperplasia (BPH) who were enrolled in hospitals in Guangzhou City, China and were followed for 10 years. RESULTS: Significantly higher levels of LRPPRC were found in PCa samples compared with BPH samples. Greater than 75% of patients with PCa demonstrated high levels of LRPPRC whereas only 10% of patients with BPH were found to have similar levels of LRPPRC. The levels of LRPPRC were found to be positively correlated with tumor grade, metastasis, and serum prostate-specific antigen level, but were negatively correlated with hormone therapy sensitivity after 2 years of surgery and overall survival. The association between high levels of LRPPRC and late-stage PCa or hormone therapy insensitivity was confirmed in tissue samples collected from prostate-specific phosphatase and tensin homolog (PTEN)(-/-) mice or hormone-dependent and hormone-independent PCa cell lines. CONCLUSIONS: LRPPRC levels may be used as an independent biomarker for patients with PCa at a late stage with poor prognosis.

Abnormal Serum Biochemical Results and Mitochondrial Damage of Lymphocytes in Patients with Schizophrenia and SARS-CoV-2 Infection: A Retrospective Study.

Purpose: In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia. Patients and methods: We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed. Results: The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS). Conclusion: Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.

Postoperative plasma presepsin as a biomarker of postoperative infectious complications in different surgical departments: A meta-analysis and systematic review.

BACKGROUND: High rates of postoperative infection persist after different surgical procedures, encompassing surgical site infections (SSIs), remote infections, sepsis, and septic shock. Our aim was to assess presepsin's diagnostic accuracy for postoperative infections in patients across surgical procedures. METHOD: We conducted a comprehensive search in seven databases, extracting data independently. Using STATA 14.0, we calculated pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and Under the receiver operator curve and 95 â€‹% confidence interval (AUC, 95 â€‹% CI) as primary outcomes, with secondary outcomes involving sensitivity and specificity in subgroup analyses. RESULTS: This meta-analysis of 14 studies (1891 cases) evaluated presepsin's diagnostic value for postoperative infectious complications. Results include sensitivity of 77 â€‹% (70-83), specificity of 81 â€‹% (71-88), DOR of 14 (8-26), AUC of 84 (80-87), PLR of 4 (3-6), and NLR of 0.28 (0.21-0.38). Presepsin exhibits promise as a diagnostic tool for postoperative infections. CONCLUSION: In summary, compared to conventional markers like C-reactive protein (CRP) and procalcitonin (PCT), presepsin demonstrated superior sensitivity and specificity for detecting postoperative infectious complications across various surgical procedures.

GDI2 deletion alleviates neurodegeneration and memory loss in the 5xFAD mice model of Alzheimer's disease.

Accumulation of insoluble deposits of amyloid ß-peptide (Aß), derived from amyloid precursor protein (APP) processing, represents one of the major pathological hallmarks of Alzheimer's disease (AD). Perturbations in APP transport and hydrolysis could lead to increased Aß production. However, the precise mechanisms underlying APP transport remain elusive. The GDP dissociation inhibitor2 (GDI2), a crucial regulator of Rab GTPase activity and intracellular vesicle and membrane trafficking, was investigated for its impact on AD pathogenesis through neuron-specific knockout of GDI2 in 5xFAD mice. Notably, deficiency of GDI2 significantly ameliorated cognitive impairment, prevented neuronal loss in the subiculum and cortical layer V, reduced senile plaques as well as astrocyte activation in 5xFAD mice. Conversely, increased activated microglia and phagocytosis were observed in GDI2 ko mice. Further investigation revealed that GDI2 knockout led to more APP co-localized with the ER rather than the Golgi apparatus and endosomes in SH-SY5Y cells, resulting in decreased Aß production. Collectively, these findings suggest that GDI2 may regulate Aß production by modulating APP intracellular transport and localization dynamics. In summary, our study identifies GDI2 as a pivotal regulator governing APP transport and process implicated in AD pathology; thus highlighting its potential as an attractive pharmacological target for future drug development against AD.

Application of combined preoperative indocyanine green lymphography and ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer.

BACKGROUND: This study aimed to investigate the value of preoperative indocyanine green (ICG) lymphography combined with ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer. METHODS: A total of 29 patients who were admitted to the breast surgery department of our hospital from July 2019 to May 2021 were included in this study. All patients received preoperative reverse lymphography and ultrasonography for low-pressure vein in lymphedema surgery. Three arm circumferences were measured before surgery, 6 months after surgery, and 12 months after surgery for comparison with the healthy limb at the same time. RESULTS: Arm circumference at 12 months after surgery was significantly different from those at the preoperative period and 6 months after surgery (P < 0.05). However, this parameter after surgery was still significantly higher than that of the healthy limb (P < 0.05). CONCLUSIONS: The application of preoperative ICG lymphography combined with ultrasonography for low-pressure vein localization before surgery can greatly shorten operation duration by reducing the number of ineffective incisions and improving the probability of vein-lymphatic vessel matching, while ensuring the postoperative efficacy for patients.

Proteomic profiling of expression of proteasomal subunits from livers of mice treated with diethylnitrosamine.

The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Diethylnitrosamine is metabolized primarily in the liver by cytochrome P-450 and can cause DNA damage. The 26S proteasome is a large proteolytic complex that degrades ubiquitinated proteins, and regulates many physiological processes. We used proteomics-based approaches to examine expressional differences of liver proteasomal subunits from diethylnitrosamine-treated mice. The expression of most proteasomal subunits was observed to be upregulated in the analysis of 2DE and MALDI-TOF MS/MS. Some of these differentially expressed proteasomal subunits were further confirmed by Western blot, RT-PCR, and immunohistochemistry. Our results provided useful information on the relationship between the proteasomal complex and related diseases.

Activation of Liver FGF21 in hepatocarcinogenesis and during hepatic stress.

BACKGROUND: FGF21 is a promising intervention therapy for metabolic diseases as fatty liver, obesity and diabetes. Recent results suggest that FGF21 is highly expressed in hepatocytes under metabolic stress caused by starvation, hepatosteatosis, obesity and diabetes. Hepatic FGF21 elicits metabolic benefits by targeting adipocytes of the peripheral adipose tissue through the transmembrane FGFR1-KLB complex. Ablation of adipose FGFR1 resulted in increased hepatosteatosis under starvation conditions and abrogation of the anti-obesogenic action of FGF21. These results indicate that FGF21 may be a stress responsive hepatokine that targets adipocytes and adipose tissue for alleviating the damaging effects of stress on the liver. However, it is unclear whether hepatic induction of FGF21 is limited to only metabolic stress, or to a more general hepatic stress resulting from liver pathogenesis and injury. METHODS: In this survey-based study, we examine the nature of hepatic FGF21 activation in liver tissues and tissue sections from several mouse liver disease models and human patients, by quantitative PCR, immunohistochemistry, protein chemistry, and reporter and CHIP assays. The liver diseases include genetic and chemical-induced HCC, liver injury and regeneration, cirrhosis, and other types of liver diseases. RESULTS: We found that mouse FGF21 is induced in response to chemical (DEN treatment) and genetic-induced hepatocarcinogenesis (disruptions in LKB1, p53, MST1/2, SAV1 and PTEN). It is also induced in response to loss of liver mass due to partial hepatectomy followed by regeneration. The induction of FGF21 expression is potentially under the control of stress responsive transcription factors p53 and STAT3. Serum FGF21 levels correlate with FGF21 expression in hepatocytes. In patients with hepatitis, fatty degeneration, cirrhosis and liver tumors, FGF21 levels in hepatocytes or phenotypically normal hepatocytes are invariably elevated compared to normal health subjects. CONCLUSION: FGF21 is an inducible hepatokine and could be a biomarker for normal hepatocyte function. Activation of its expression is a response of functional hepatocytes to a broad spectrum of pathological changes that impose both cellular and metabolic stress on the liver. Taken together with our recent data, we suggest that hepatic FGF21 is a general stress responsive factor that targets adipose tissue for normalizing local and systemic metabolic parameters while alleviating the overload and damaging effects imposed by the pathogenic stress on the liver. This study therefore provides a rationale for clinical biomarker studies in humans.

Death-related factors of systemic lupus erythematosus patients associated with the course of disease in Chinese populations: multicenter and retrospective study of 1,958 inpatients.

Despite the improved survival rate among systemic lupus erythematosus (SLE) patients, there are many factors associated with the mortality of SLE. In the current study, death-related factors of patients associated with course of disease were surveyed. Retrospective study was used. Mortalities among these three groups (group A, B and C, the course of disease was ≤ 5 years, 5-10 years and > 10 years, respectively) were calculated and compared. Various factors related to mortality were analyzed. Male SLE patients died relatively more than female patients. The total mortality was 8.5 %. The mortalities were significant difference in group A, B and C which were 9.4, 4.8 and 8.9 %, respectively. The mortalities of group A and group C were significantly higher than that of group B, but there was no significant difference between mortalities of group A and group C. The most common death-related factor was infection, followed by involved disorders in renal, brain, multisystem, heart, etc. The mortalities resulted from neuropsychiatric systemic lupus erythematosus (NPSLE), pulmonary infection, involved digestive system and hematological system were significantly different between three groups. There was no difference between mortalities of group A and group C associated with pulmonary infection and NPSLE. Patients in group C died more than in group A from involved renal, heart, multisystem, etc, while group A had more patients than group C who died of pulmonary infection, involved hematological system. In conclusion, Male SLE patients have worse outcome than female patients. Infection and active SLE are not only contributors to the death of early stage patients, but also to that of later stage patients.

REEP1 Preserves Motor Function in SOD1G93A Mice by Improving Mitochondrial Function via Interaction with NDUFA4.

A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.

Mice with the Rab10 T73V mutation exhibit anxiety-like behavior and alteration of neuronal functions in the striatum.

Hyperphosphorylated Rab10 has been implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. However, the neurophysiological function of the evolutionarily conserved Thr73 phosphorylation of Rab10 remains poorly understood. Here, we generated a novel mouse model expressing the non-phosphorylatable T73V mutation of Rab10 and performed a comprehensive series of neurological analyses, including behavioral tests, synaptic evaluations, neuronal and glial staining, assessments of neurite arborization and spine morphogenesis. The Rab10 T73V mutantmice exhibited a characteristic anxiety-like phenotype with other behavioral modules relatively unaffected. Moreover, Rab10 T73V mutant mice displayed striatum-specific synaptic dysfunction, as indicated by aberrantly increased expression levels of synaptic proteins and impaired frequencies of miniature inhibitory postsynaptic currents. The genetic deletion of Rab10 phosphorylation enhanced neurite arborization and accelerated spine maturation in striatal medium spiny neurons. Our findings emphasize the specific role of intrinsic phospho-Rab10 in the regulation of the striatal circuitry and its related behaviors.

Diagnostic Accuracy of Procalcitonin for Infection After Adult Liver Transplantation: A Meta-Analysis and Systematic Review.

Background: Post-operative infection remains a major cause of morbidity and mortality in adults early after liver transplantation (LT). Procalcitonin (PCT) may be a good test method for early diagnosis of post-operative infection and determining its severity. This study was performed to assess the diagnostic accuracy of PCT as a biomarker for infection after LT. Patients and Methods: A meta-analysis and systematic review was conducted for studies reporting diagnostic performance of PCT for infection in adults after LT. Observational studies were evaluated for their reporting of diagnostic accuracy, relevance, and quality. Results: Ten eligible studies assessing 730 patients were included in this meta-analysis and systematic review summarizing the diagnostic value of PCT for post-operative infection in adult liver transplantation. Pooled sensitivity and specificity with corresponding 95% confidence interval were 69% (95% confidence interval [CI], 54-81; heterogeneity I2 = 82.4%) and 88% (95% CI, 82-92; I2 = 52.7%), respectively. The diagnostic odd ratio (DOR) was 16 (95% CI, 10-25; I2 = 76.4%). The summary receiver operator characteristic (SROC) of PCT for post-operative infection was 0.88. There was a wide range of variability in the cutoff values, ranging from 0.22 to 42.80 ng/mL. Heterogeneity was reduced by excluding studies that focused on pediatric LT recipients. Conclusions: Procalcitonin is a moderately accurate diagnostic marker for post-operative infection in adult LT. Additionally, the diagnostic performance can be improved by combining it with other inflammatory biomarkers. This article provides the research direction for post-operative infection control.

Highly tumoricidal efficiency of non-oxidized MXene-Ti3C2Tx quantum dots on human uveal melanoma.

Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti3C2Tx quantum dots (NMQDs-Ti3C2Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti3C2Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti3C2Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti3C2Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti3C2Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.

Discovering Innate Driver Variants for Risk Assessment of Early Colorectal Cancer Metastasis.

Metastasis is the main fatal cause of colorectal cancer (CRC). Although enormous efforts have been made to date to identify biomarkers associated with metastasis, there is still a huge gap to translate these efforts into effective clinical applications due to the poor consistency of biomarkers in dealing with the genetic heterogeneity of CRCs. In this study, a small cohort of eight CRC patients was recruited, from whom we collected cancer, paracancer, and normal tissues simultaneously and performed whole-exome sequencing. Given the exomes, a novel statistical parameter LIP was introduced to quantitatively measure the local invasion power for every somatic and germline mutation, whereby we affirmed that the innate germline mutations instead of somatic mutations might serve as the major driving force in promoting local invasion. Furthermore, via bioinformatic analyses of big data derived from the public zone, we identified ten potential driver variants that likely urged the local invasion of tumor cells into nearby tissue. Of them, six corresponding genes were new to CRC metastasis. In addition, a metastasis resister variant was also identified. Based on these eleven variants, we constructed a logistic regression model for rapid risk assessment of early metastasis, which was also deployed as an online server, AmetaRisk (http://www.bio-add.org/AmetaRisk). In summary, we made a valuable attempt in this study to exome-wide explore the genetic driving force to local invasion, which provides new insights into the mechanistic understanding of metastasis. Furthermore, the risk assessment model can assist in prioritizing therapeutic regimens in clinics and discovering new drug targets, and thus substantially increase the survival rate of CRC patients.