Clinicopathological factors correlated with lymph node metastasis in gastric cancer: A retrospective cohort study involving 5606 patients.

BACKGROUND: The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment program. METHODS: 5606 gastric cancer patients with comprehensive clinicopathological data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be utilized for further analysis. Subsequently, univariate and multivariate logistic regression analyses were conducted to identified the risk factors. RESULTS: The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6% respectively. Female [odds ratio (OR)=1.559, P=0.032], lower tumor location (OR=1.773, P=0.023), tumor size >2cm (OR=2.007, P<0.001), mixed (OR=2.371, P=0.001) and undifferentiated histological types (OR=2.952, P<0.001), T1b stage (OR=2.041, P<0.001), presence of ulceration (OR=1.758, P=0.027), and lymphovascular invasion (LVI) (OR=5.722, P<0.001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in EGC cases. CONCLUSIONS: This study identified the clinicopathological factors associated with LNM in EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing EGC patients.

Risk factors associated with lymph node metastasis in early-stage distal gastric cancer.

OBJECTS: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. METHODS: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. RESULTS: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. CONCLUSIONS: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.

Iron retardation in lysosome protects senescent cells from ferroptosis.

Ferroptosis, an iron-triggered modality of cellular death, has been reported to closely relate to human aging progression and aging-related diseases. However, the involvement of ferroptosis in the development and maintenance of senescent cells still remains elusive. Here, we established a doxorubicin-induced senescent HSkM cell model and found that both iron accumulation and lipid peroxidation increase in senescent cells. Moreover, such iron overload in senescent cells has changed the expression panel of the ferroptosis-response proteins. Interestingly, the iron accumulation and lipid peroxidation does not trigger ferroptosis-induced cell death. Oppositely, senescent cells manifest resistance to the ferroptosis inducers, compared to the proliferating cells. To further investigate the mechanism of ferroptosis-resistance for senescent cells, we traced the iron flux in cell and found iron arrested in lysosome. Moreover, disruption of lysosome functions by chloroquine and LLOMe dramatically triggered the senescent cell death. Besides, the ferroitinophagy-related proteins FTH1/FTL and NCOA4 knockdown also increases the senescent cell death. Thus, we speculated that iron retardation in lysosome of senescent cells is the key mechanism for ferroptosis resistance. And the lysosome is a promising target for senolytic drugs to selectively clear senescent cells and alleviate the aging related diseases.

Identification of predictors for short-term recurrence: comprehensive analysis of 296 retroperitoneal liposarcoma cases.

BACKGROUND: The short-term (≤ 1 year) recurrence (STR) is the primary determinant impacting both the life quality and survival duration in patients who have undergone surgical resection for retroperitoneal liposarcoma (RPLS), a condition with intricate and ambiguous pathogenesis. The purpose of this study was to analyze the risk factors associated with STR in cases of RPLS and primary retroperitoneal liposarcoma (PRPLS). METHODS: For this retrospective observational study, a total of 296 RPLS cases were selected as research subjects, who experienced tumor recurrence during the follow-up period. The Local recurrence-free survival (LRFS) rates were estimated using the Kaplan-Meier method and subsequently compared between groups utilizing the log-rank test. The subsequent analyses involved univariate and multivariate logistic regression to identify predictors of STR in RPLS cases. Additionally, a logistic regression model was constructed for PRPLS. RESULTS: The 1-, 3-, and 5-year LRFS rates of the 296 RPLS cases were 51.7%, 16.9%, and 7.1%, respectively. In the univariate analysis, several factors were found to be associated with STR, including preoperative neutrophil/lymphocyte ratio (NLR), smoking history, surgical frequency, combined organ excision, operative time, intraoperative bleeding, transfer to the intensive care unit (ICU), multiple primary tumors, tumor shape and capsule characteristics, histological subtype, and presence of tumor necrosis. The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, and tumor necrosis were identified as independent risk factors for STR in surgically resected RPLS. Conversely, diabetes, intact tumor capsule, and well-differentiated histological subtype appeared to be independent protective factors. Analysis for PRPLS revealed that tumor capsule and tumor necrosis were independent predictors of STR. CONCLUSIONS: The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, tumor necrosis, and tumor capsule were expected to serve as predictive factors of STR for surgical resected RPLS and PRPLS.

Surgical outcomes after reoperation for patients with recurrent presacral tumors: a retrospective study.

BACKGROUND: Relevant reports on the surgical resection and prognosis of recurrent presacral tumors are limited. The objective of this study was to explore the outcomes associated with surgical resection of recurrent presacral tumors. METHODS: The data of patients with recurrent presacral tumors who received surgical resection in our hospital between June 2009 and November 2018 were retrospectively analyzed. RESULTS: Thirty-one patients, comprising 22 females and 9 males, with recurrent presacral lesions were included in our study. A posterior approach was utilized in 27 patients, an anterior approach in 1 patient, and a combined approach in 3 patients. Intraoperative complications occurred in 13 patients (41.9%), while postoperative complications occurred in 6 patients (19.4%). The length of hospital stay was significantly shorter in patients who underwent the posterior approach compared to those who underwent the anterior and combined approaches (P = 0.002). The operative time for the posterior approach was significantly shorter compared to both the anterior and combined approaches (P = 0.006). Temporary tamponade was performed for hemostasis in 4 patients, while staged resection was performed in 2 patients during the surgical treatment process. After a median follow-up period of 115.5 months, 5 patients with recurrent malignant presacral tumors succumbed to tumor recurrence after reoperation in our hospital. CONCLUSIONS: Surgical resection remains the mainstream treatment for recurrent presacral tumors. The outcomes for recurrent benign presacral tumors after surgery demonstrate favorable results, whereas further enhancements are required to improve the outcomes for recurrent malignant presacral tumors after surgery.

Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study.

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

Gastrointestinal Fistula in Radical Distal Gastrectomy: Case-Control Study from a High-Volume Hospital.

Background: Postoperative gastrointestinal fistula (PGF) is one of the main causes of abdominal infection and perioperative death. This study was designed to investigate the risk factors of PGF, anastomotic fistula (AF), and duodenal stump fistula (DSF) for patients who underwent radical distal gastrectomy. Materials and Methods: In this retrospective observational study, 2652 gastric cancer cases who received radical distal gastrectomy from 2010 to 2020 were selected as research subjects. Subsequently, we adopted the univariate and multivariate logistic regression analysis as statistical method to screen the risk factors for PGF, AF, and DSF, respectively. Results: In univariate analysis, gender (P = .022), operative time (P = .013), intraoperative blood loss (P < .001), tumor diameter (P = .002), and tumor stage (P < .001) were related to PGF. Multivariate logistic regression analysis identified the male (odds ratio [OR] = 2.691, P = .042), massive intraoperative hemorrhage (OR = 1.002, P = .008), and advanced tumor (OR = 2.522, P = .019) as independent predictors for PGF. Moreover, diabetes (OR = 4.497, P = .008) and massive intraoperative hemorrhage (OR = 1.003, P = .010) were proved to be associated with AF, while massive intraoperative hemorrhage (OR = 1.001, P = .050) and advanced tumor (OR = 6.485, P = .005) were independent risk factors of DSF. Conclusions: The gender, intraoperative hemorrhage, tumor stage, and diabetes were expected to be used as predictors of PGF for radical distal gastrectomy.

TNF is a critical cytokine in age-related dry eye disease.

Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1ß, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), IFN-γ, IL-12p40, IL-17, and IL-10 proteins in tears of aged mice. Moreover, genetic loss of the Tnf-/- in mice decreased goblet cell loss and the development of ectopic lymphoid structures in the lacrimal gland compared to wild-type mice. This was accompanied by a decrease in cytokine production. Treatment of mice at an early stage of aging (12-14-month-old) with TNF inhibitor tanfanercept eye drops for eight consecutive weeks decreased cytokine levels in tears, improved goblet cell density, and decreased the marginal zone B cell frequency in the lacrimal gland compared to vehicle-treated animals. Our studies indicate that modulation of TNF during aging could be a novel strategy for age-related dry eye disease.

Predictive factors and a novel nomogram for recurrence of primary retroperitoneal liposarcoma: Comprehensive analysis of 128 cases.

Since primary retroperitoneal liposarcoma (PRPLS) is rare in the clinic, related clinical studies are lacking. The present study was designed to investigate the predictive factors of short-term (≤1 year) recurrence (STR) and construct a novel nomogram of local recurrence-free survival (LRFS) for surgically resected PRPLS. A total of 128 PRPLS cases who underwent radical surgery were retrospectively analyzed. Based on the interval from the operation to tumor recurrence, the predictors of STR were screened using univariate and multivariate logistic regression analyses. Cox proportional hazard regression models were applied to identify the predictors of LRFS. Furthermore, the independent predictors acquired from multivariate analyses were used to construct a nomogram. Multivariate logistic regression analysis revealed that age ≥55 years [odds ratio (OR)=5.607, P=0.010], operative time ≥260 min (OR=9.716, P=0.005) and tumor necrosis (OR=3.781, P=0.037) were independent risk factors of STR for PRPLS. In the Cox regression analysis, clinical symptoms [hazard ratio (HR)=1.746, P=0.017], resection method (OR=0.370, P=0.021) and de-differentiated histological subtype (HR=1.975, P=0.048) were identified as independent predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram for LRFS. Age, operative time, tumor necrosis, clinical symptoms, resection method and histological subtype were related to recurrence for surgically resected PRPLS and a novel nomogram was constructed based on the above predictors.

Multidisciplinary treatment for locally advanced gastric cancer: A systematic review and network meta-analysis.

Introduction: This study aimed to evaluate the efficacy of multidisciplinary treatment for patients with locally advanced gastric cancer (LAGC) who underwent radical gastrectomy. Patients and Methods: Randomised controlled trials (RCTs) comparing the effectiveness of surgery alone, adjuvant chemotherapy (CT), adjuvant radiotherapy (RT), adjuvant chemoradiotherapy (CRT), neoadjuvant CT, neoadjuvant RT, neoadjuvant CRT, perioperative CT and hyperthermic intraperitoneal chemotherapy (HIPEC) for LAGC were searched. Overall survival (OS), disease-free survival (DFS), recurrence and metastasis, long-term mortality, adverse events (grade ≥3), operative complications and R0 resection rate were used as outcome indicators for meta-analysis. Results: Forty-five RCTs with 10077 participants were finally analysed. Adjuvant CT had higher OS (hazard ratio [HR] = 0.74, 95% credible interval [CI] = 0.66-0.82) and DFS (HR = 0.67, 95% CI = 0.60-0.74) than surgery-alone group. Perioperative CT (odds ratio [OR] = 2.56, 95% CI = 1.19-5.50) and adjuvant CT (OR = 0.48, 95% CI = 0.27-0.86) both had more recurrence and metastasis than HIPEC + adjuvant CT, while adjuvant CRT tended to have less recurrence and metastasis than adjuvant CT (OR = 1.76, 95% CI = 1.29-2.42) and even adjuvant RT (OR = 1.83, 95% CI = 0.98-3.40). Moreover, the incidence of mortality in HIPEC + adjuvant CT was lower than that in adjuvant RT (OR = 0.28, 95% CI = 0.11-0.72), adjuvant CT (OR = 0.45, 95% CI = 0.23-0.86) and perioperative CT (OR = 2.39, 95% CI = 1.05-5.41). Analysis of adverse events (grade ≥3) showed no statistically significant difference between any two adjuvant therapy groups. Conclusion: A combination of HIPEC with adjuvant CT seems to be the most effective adjuvant therapy, which contributes to reducing tumour recurrence, metastasis and mortality - without increasing surgical complications and adverse events related to toxicity. Compared with CT or RT alone, CRT can reduce recurrence, metastasis and mortality but increase adverse events. Moreover, neoadjuvant therapy can effectively improve the radical resection rate, but neoadjuvant CT tends to increase surgical complications.

Hyperthermic Intraperitoneal Chemotherapy May Damage Renal Function and Cause Serum Electrolyte Disturbance: A Retrospective Observational Study.

OBJECTIVE: The objective of this study was to evaluate the efficacy of postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) on bone marrow hematopoiesis, liver and kidney function, and serum electrolytes for patients who underwent open radical gastrectomy, and investigate the variation tendency of above indicators. MATERIALS AND METHODS: The clinical data of 153 patients who underwent open radical gastrectomy were retrospectively analyzed and were divided into HIPEC group (n=83) and control group (n=70). Repeated analysis of variance was used to analyze the variation tendency of bone marrow hematopoiesis, liver and kidney function, and serum electrolytes in the HIPEC and control group, respectively, and then made a comparison between the 2 groups. RESULTS: There were statistical differences in alanine aminotransferase ( P =0.034), phosphorus ( P+ ) ( P <0.05), potassium (K + ) ( P =0.023), sodium (Na + ) ( P <0.001), and chloride (Cl - ) ( P =0.008) between HIPEC and control group. All outcome indicators changed significantly over time ( P <0.05). No significant difference was found in hemoglobin, white blood cell, platelet, aspartate aminotransferase, total bilirubin, or uric acid between the 2 treatment groups at each time point. On the next day after HIPEC treatment, the levels of blood urea nitrogen, creatinine, and P+ were higher in the HIPEC group, whereas the calcium (Ca + ), magnesium (Mg + ), and K + levels of HIPEC group tended to be lower. However, the effects of HIPEC on alanine aminotransferase, Na + , and Cl - levels needed to be further explored. CONCLUSIONS: HIPEC treatment after open radical gastrectomy has no significant effect on hematopoietic bone marrow and liver function but may damage renal function; reduce Ca + , Mg + , K + levels; and increase P+ level.

Risk Factor Analysis of Gastroparesis Syndrome in 2652 Patients with Radical Distal Gastrectomy.

OBJECTIVE: The aim of this study is to investigate the risk factors of postoperative gastroparesis syndrome (PGS) in patients with gastric cancer who underwent radical distal gastrectomy. METHODS: The clinical data of 2652 patients with gastric cancer who underwent radical distal gastrectomy in the past 10 years were retrospectively analyzed. Furthermore, the incidence of PGS was set as the dependent variable, and the risk factors for PGS were screened using univariate and multivariate logistic regression analyses. Risk factor analysis for the different digestive tract reconstruction methods was also performed. RESULTS: Univariate analysis revealed that preoperative pyloric obstruction (p = 0.001), digestive tract reconstruction (p = 0.001), jejunum nutrition tube application (p = 0.001), intraperitoneal chemotherapy drug application (p = 0.002), age (≥ 66 years or < 66 years) (p = 0.042), operative time (≥ 184.5 min or < 184.5 min) (p = 0.049), and postoperative indwelling catheter time (≥ 4.5 days or < 4.5 days) (p = 0.045) were related to PGS. Multivariate logistic regression analysis showed that preoperative pyloric obstruction (odds ratio (OR) = 2.830, p = 0.004), application of a jejunum nutrition tube (OR = 3.309, p = 0.011), intraperitoneal chemotherapy (OR = 0.482, p = 0.010), and digestive tract reconstruction were independent risk factors for PGS. CONCLUSION: This study identified risk factors associated with PGS, which could be further applied in clinical practice.

Correlation Analysis Between Demographic, Surgical, and Pathological Characteristics with Local Recurrence-Free Survival for Surgical Resected Retroperitoneal Liposarcoma.

BACKGROUND: As the leading cause of mortality for retroperitoneal liposarcoma (RPLS) cases, postoperative recurrence has complicated and unclear risk factors. This study was conducted to explore the correlations between demographic, surgical, and pathological characteristics with local recurrence-free survival (LRFS) for surgical resected RPLS. METHODS: RPLS cases that underwent radical operation were considered to be included in this analysis. LRFS rates were estimated based on the Kaplan-Meier method and were compared between groups by the log-rank test. Cox proportional hazard regression models were constructed to identified the predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram. RESULTS: 348 RPLS cases who underwent radical operation were included. Of the 348 cases, 333 had tumor recurrence or with a follow-up period ≥5 years. Thus, 296 (88.9%) of the 333 cases had recurrent disease, and the median LRFS duration of 296 recurrence cases was 17.0 (95% confidence interval (CI) 13.2-20.8) months. Multivariate analysis identified the preoperative neutrophil/lymphocyte ratio (NLR), surgical frequency, operative time, tumor shape, histological subtype, and tumor necrosis as independent predictors of LRFS. Based on above independent predictors, a nomogram was constructed to predict the 1-, 3-, and 5-year LRFS of surgical resected RPLS. CONCLUSION: Elevated preoperative NLR, ≥2nd time surgical frequency, extended operation time, irregular tumor shape, no well-differentiated histological subtype, and tumor necrosis could be used as predictors of LRFS for surgical resected RPLS.

Astrocyte-Derived Exosomes Contribute to Pathologies of Neuromyelitis Optica Spectrum Disorder in Rodent Model.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that leads to severe disability. A large proportion of NMOSD patients are seropositive for aquaporin-4 autoantibodies (AQP4-IgG, named as NMO-IgG) targeting AQP4, which is selectively expressed on astrocytes in the central nervous system. This study tests the hypothesis that in response to NMO-IgG, the pathogenic astrocyte-derived exosomes are released and injure the neighboring cells. METHODS: IgG purified from serum of either NMOSD patients or healthy controls was used to generate astrocyte-derived exosomes (AST-ExosNMO vs AST-ExosCON ) in cultured rat astrocytes. The exosomes were respectively delivered to cultured rat oligodendrocytes in vitro, tissue culture of rat optic nerve ex vivo, and rat optic nerve in vivo to evaluate the pathogenic roles of AST-ExosNMO . The microRNA (miRNA) sequencing of AST-Exos and verification were performed to identify the key pathogenic miRNA. The custom-designed adeno-associated virus (AAV) antagonizing the key miRNA was evaluated for its therapeutic effects in vivo. Moreover, the serum levels of the key exosomal miRNA were measured between NMOSD patients and healthy controls. RESULTS: AST-ExosNMO led to notable demyelination in both cultured oligodendrocytes and optic nerve tissue. Exosomal miR-129-2-3p was identified as the key miRNA mediating the demyelinating pathogenesis via downstream target gene SMAD3. AAV antagonizing miR-129-2-3p protected against demyelination in an NMOSD rodent model. The serum exosomal miR-129-2-3p level was significantly elevated in NMOSD patients and correlated with disease severity. INTERPRETATION: Astrocytes targeted by NMO-IgG release pathogenic exosomes that could potentially be used as therapeutic targets or disease monitoring biomarkers in NMOSD. ANN NEUROL 2023;94:163-181.

Non-small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment.

Non-small cell lung cancer (NSCLC) is the most common tumor that metastasizes to the brain. It is now accepted that the successful colonization and growth of tumor cells are determined by the interaction between tumor cells and the tumor microenvironment (TME). Microglia, brain innate immune cells, have been reported to play a vital role in the establishment of brain metastases. As essential mediators of intercellular communications, tumor-derived exosomes have an important role in the pathogenesis and progression of cancer by transferring their cargos to specific recipient cells. The crosstalk between microglia and tumor-derived exosomes has been extensively described. However, it is still unclear whether metastatic NSCLC cells secret exosomes to microglia and regulate the microglial functions. Here, our results showed that microglia aggregated in the brain metastatic sites. Meanwhile, microglia could take up the exosomes derived from NSCLC cells, leading to alterations of microglial morphology and increased proliferation, phagocytosis, and release of inflammatory cytokines including interleukin-6, interleukin-8, and CXCL1. Further investigation indicated that miR1246 was the most enriched microRNA in NSCLC-derived exosomes and mediated the partial effects of exosomes on microglia. Notably, miR1246 was also upregulated in the plasmatic exosomes of NSCLC patients. These results offer a new insight into the impact of NSCLC-derived exosomes on microglia and provide a new potential biomarker for diagnosing NSCLC.

A, B, C's of Trk Receptors and Their Ligands in Ocular Repair.

Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in glaucoma, retina, and neuroscience. Recently, neurotrophin analogs with panTrk activity and TrkC selectivity have shown promise as novel drugs for treating dry eye disease. In this review, we discuss the biology of the neurotrophin family, its role in corneal homeostasis, and its use in treating ocular surface diseases. There is an unmet need to investigate parenteral neurotrophins and its analogs that activate TrkB and TrkC selectively.

Common Core Genes Play Vital Roles in Gastric Cancer With Different Stages.

Background : Owing to complex molecular mechanisms in gastric cancer (GC) oncogenesis and progression, existing biomarkers and therapeutic targets could not significantly improve diagnosis and prognosis. This study aims to identify the key genes and signaling pathways related to GC oncogenesis and progression using bioinformatics and meta-analysis methods. Methods: Eligible microarray datasets were downloaded and integrated using the meta-analysis method. According to the tumor stage, GC gene chips were classified into three groups. Thereafter, the three groups' differentially expressed genes (DEGs) were identified by comparing the gene data of the tumor groups with those of matched normal specimens. Enrichment analyses were conducted based on common DEGs among the three groups. Then protein-protein interaction (PPI) networks were constructed to identify relevant hub genes and subnetworks. The effects of significant DEGs and hub genes were verified and explored in other datasets. In addition, the analysis of mutated genes was also conducted using gene data from The Cancer Genome Atlas database. Results: After integration of six microarray datasets, 1,229 common DEGs consisting of 1,065 upregulated and 164 downregulated genes were identified. Alpha-2 collagen type I (COL1A2), tissue inhibitor matrix metalloproteinase 1 (TIMP1), thymus cell antigen 1 (THY1), and biglycan (BGN) were selected as significant DEGs throughout GC development. The low expression of ghrelin (GHRL) is associated with a high lymph node ratio (LNR) and poor survival outcomes. Thereafter, we constructed a PPI network of all identified DEGs and gained 39 subnetworks and the top 20 hub genes. Enrichment analyses were performed for common DEGs, the most related subnetwork, and the top 20 hub genes. We also selected 61 metabolic DEGs to construct PPI networks and acquired the relevant hub genes. Centrosomal protein 55 (CEP55) and POLR1A were identified as hub genes associated with survival outcomes. Conclusion: The DEGs, hub genes, and enrichment analysis for GC with different stages were comprehensively investigated, which contribute to exploring the new biomarkers and therapeutic targets.

Therapeutic Effects of 4 Surgical Approaches for Small Gastrointestinal Stromal Tumors: A Network Meta-analysis.

This study aims to systematically evaluate the efficacy of endoscopic resection (ER), laparoscopic resection (LR), laparoscopic endoscopic cooperative surgery (LECS), and open surgery (OpS) for gastrointestinal stromal tumors with small diameters (≤5 cm). Relevant studies were collected through Pubmed, Cochrane Library, and Embase databases. Operative time, hospital stays, time to liquid diet, intraoperative bleeding, and complications were used as outcome indicators for meta-analysis. Twenty-four retrospective cohort studies with 2406 participants were analyzed. LR and OpS groups had longer operating time than the ER group. ER, LECS, and LR groups had decreased lengths of hospital stay than the OpS group. Moreover, patients in LR and LECS groups had fewer complications than those in the OpS group. Endoscopic operation for small gastrointestinal stromal tumors contributes to shortened lengths of surgery and hospital stay. This reduces intraoperative blood loss and promotes gastroenteric functional recovery without increasing the risk of complications or tumor recurrence.

Serum Trimethylamine N-oxide and the Diversity of the Intestinal Microbial Flora in Type 2 Diabetes Complicated by Diabetic Kidney Disease.

BACKGROUND: Trimethylamine N-oxide (TMAO) serves as a metabolite of intestinal bacteria as well as a urotoxin influencing the prognosis of chronic kidney disease (CKD), which has become a research hotspot in the field of kidney disease. This study preliminarily explored the alternations of the microbial flora and serum TMAO in patients with type 2 diabetes mellitus (T2DM) complicated with diabetic kidney disease (DKD). METHODS: Seventeen T2DM patients at the Affiliated Hospital of Zunyi Medical University between September 2018 and February 2019 were included. Among these patients, 8 patients had T2DM complicated with DKD. Eight healthy volunteers constituted the control group. Fresh stool was collected for Illumina sequencing. Based on the sequencing outcomes, the flora diversity and species differences were analyzed. Serum TMAO, cystatin C, urinary albumin/urine creatinine ratios (ACRs), and routine biochemical outcomes were also compared. RESULTS: The DKD group exhibited a significantly higher TMAO level than the remaining groups. The high-TMAO group had a significantly increased ACR level compared with the low-TMAO group. TMAO positively correlated with the ACR. Compared with the control group, the DKD group exhibited a decreased flora diversity. At the genus level, both the T2DM group and the DKD group showed decreased numbers of Alloprevotella and Megasphaera compared with the control group. The difference in Megasphaera between the DKD group and the control group was significant. CONCLUSIONS: The alternation of the intestinal microbial flora may participate in the development of DKD, and TMAO and chronic inflammation might be important factors for DKD development.

The association of serum magnesium and chronic kidney disease: a two-sample mendelian randomization study of European descent.

BACKGROUND: Previous observational studies focused on the association of serum magnesium (SMg) and chronic kidney disease (CKD), but the conclusion was inconsistent. To investigate the causal relationship of SMg and CKD, we performed a two-sample mendelian randomization (TSMR) analysis using publicly datasets. METHOD: In mendelian randomization (MR) analysis, we used single nucleotide polymorphisms (SNPs) which had genetic statistical significance with SMg but not associated with kidney function and confounding factors as instrumental variable (IV). To select SNPs, we used publicly database of Genome Wide Association Study (GWAS) and Chronic Kidney Disease Genetics (CKDGen) Confirms. We used inverse-variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode approaches in TSMR analysis. RESULTS: We selected 4 SNPs (rs4072037, rs7965584, rs11144134 and rs448378) as IV. In IVW approach, the result of MR analysis for CKD was OR = 0.55, 95% CI: 0.06, 4.75, P = 0.58; for estimated glomerular filtration rate from creatinine (eGFR)crea was ß = -0.06, 95% CI: -1.08, 0.07, P = 0.39; for estimated glomerular filtration rate from cystatin C (eGFR)cys was ß = -0.03, 95% CI: -0.43, 0.36, P = 0.86, respectively per SD increase in SMg. When subgroup by diabetes mellitus (DM), the results for DM-eGFRcrea was ß = -0.33, 95% CI: -0.85, 0.19, P = 0.21; and for non-DM-eGFRcrea was ß = -0.03, 95% CI: -0.16, 0.11, P = 0.71. The results of other four MR approaches were consistent with IVW approach (all P > 0.05). CONCLUSION: Our TSMR analysis showed that SMg had no causal effect on kidney function and progress CKD in European descent. As for the results about overall population, the verified study is needed in future study.