Chlorhexidine gluconate versus povidone-iodine for nasal bacteria decolonization before transsphenoidal surgery in patients with pituitary neuroendocrine tumors: A prospective, randomized, double-blind, non-inferiority trial.

BACKGROUND: This study aimed to compare the nasal decolonization efficacy and comfort between chlorhexidine gluconate (CHG) and povidone-iodine (PVP) to provide an evidence basis for clinical guidance. METHODS: A prospective, randomized, single-blinded, noninferior clinical trial was conducted in 174 patients with pituitary neuroendocrine tumors (PitNETs) who were scheduled to undergo transsphenoidal surgery. The noninferiority margin was δ=-0.1. The primary outcome was the effective rate of disinfection. The secondary outcomes included post-operative inflammatory indicators, the intracranial infection rate, and the proportion of intracranial infection. RESULTS: The effective clearance rate of post-operative nasal bacteria was nonsignificantly different between the CHG and PVP groups (88.64% vs. 82.56%; between-group difference 6.10%; 95% CI [-5.30 to 17.50]). There was no significant difference in the incidence of post-operative central nervous system infections or serum inflammation-related indications between the two groups, but sterilization tended to occur quicker and last longer in the CHG group. CHG seemed to have advantages in terms of comfort, including less nasal irritation, less pungency, and better intranasal coloration. CONCLUSION: CHG and PVP have equal efficacy in nasal decolonization before transsphenoidal surgery, but CHG seems to have comfort-related advantages in terms of less nasal irritation, less pungency, and better intranasal coloration.

MiR-125b targeted regulation of MKNK2 inhibits multiple myeloma proliferation and invasion.

BACKGROUND: An increasing number of studies demonstrate that abnormal miRNA expression contributes to the advancement of many tumors. Nonetheless, the potential role of miR-125b in multiple myeloma (MM) remains unknown. OBJECTIVES: To explore the potential effects and mechanism of miR-125b in MM. METHODS: Real-time quantitative PCR was used to measure the expression levels of miR-125b and MKNK2 in a variety of MM samples. Colony formation and cell counting Kit-8 (CCK-8) assays were used to assess cell proliferation, the transwell assay was used to evaluate the cell invasion capability, and dual luciferase reporter gene assay and Western blot were used to examine the interaction between miR-125b and MKNK2. RESULTS: The levels of miR-125b were higher in MM tissue samples, alongside increased expression of MKNK2. There was a negative correlation between MKNK2 and miR-125b expression in MM tissues. MKNK2 was identified as a direct target gene of miR-125b in MM cells. Overexpression of miR-125b suppressed MM cell growth, colony formation, and invasion. In addition, MKNK2 was found to mediate the effects of miR-125b on cell proliferation, colony formation, and invasion in MM. CONCLUSIONS: miR-125b acts as a suppressive factor in multiple myeloma and can affect the malignant behavior of MM by regulating the expression of MKNK2.

Vonoprazan and amoxicillin dual therapy for 14 days as the first-line treatment of Helicobacter pylori infection: A non-inferiority, randomized clinical trial.

BACKGROUND: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. METHODS: In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. RESULTS: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). CONCLUSION: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.

Association between Pre-operative Body Mass Index and Surgical Infection in Perihilar Cholangiocarcinoma Patients Treated with Curative Resection: A Multi-center Study.

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

Downregulation of tRF-Cys-GCA-029 by hyperglycemia promotes tumorigenesis and glycolysis of diabetic breast cancer through upregulating PRKCG translation.

BACKGROUND: Diabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored. METHODS: tRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM. RESULTS: We identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation. CONCLUSIONS: Hyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM.

Cholesterols Induced Distinctive Entry of the Graphene Nanosheet into the Cell Membrane.

Graphene nanosheets are highly valued in the biomedical field due to their potential applications in drug delivery, biological imaging, and biosensors. Their biological effects on mammalian cells may be influenced by cholesterols, which are crucial components in cell membranes that take part in many vital processes. Therefore, it is particularly important to investigate the effect of cholesterols on the transport mechanism of graphene nanosheets in the cell membrane as well as the final stable configuration of graphene, which may have an impact on cytotoxicity. In this paper, the molecular details of a graphene nanosheet interacting with a 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) membrane with cholesterols were studied using molecular dynamics simulations. Results showed that the structure of the graphene nanosheet transits from the cut-in state in a pure DPPC membrane to being sandwiched between two DPPC leaflets when cholesterols reach a certain concentration. The underlying mechanism showed that cholesterols are preferentially adsorbed on the graphene nanosheet, which causes a larger disturbance to the nearby DPPC tails and thus guides the graphene nanosheet into the core of lipid bilayers to form a sandwiched structure. Our results are helpful for understanding the fundamental interaction mechanism between the graphene nanosheet and cell membrane and to explore the potential applications of the graphene nanosheet in biomedical sciences.

Perioperative complications of arteriovenous tirofiban administration versus oral dual antiplatelet therapy for stent-assisted embolization treated aneurysmal subarachnoid hemorrhage: A retrospective, controlled cohort analysis.

BACKGROUND: Major perioperative complications of stent-assisted embolization treated for aneurysmal subarachnoid hemorrhage patients include the formation of thromboembolic events (TEs) and hemorrhagic events (HEs), for which antiplatelet protocols play a key role. METHODS: We conducted a single-center retrospective analysis to compare the differences between arteriovenous tirofiban administration with traditional oral dual antiplatelet therapy (DAPT). A total of 417 consecutive patients were enrolled. General clinical characteristics, as well as the perioperative ischemic and hemorrhagic events, were retracted in digital documents. Logistic regression was conducted to identify both risk and protective factors of perioperative TEs and HEs. RESULTS: Perioperative TEs occurred in 21 patients, with an overall perioperative TEs rate of approximately 5.04%; among these patients, the incidence of perioperative TEs in the tirofiban group was less than that in the DAPT group. Additionally, 66 patients developed perioperative HEs, with an incidence of approximately 15.83%; among these patients, the incidence of perioperative HEs was less than that in the DAPT group. No significant differences were seen between the two groups in terms of the mRS score at the time of discharge. CONCLUSION: This study indicated that an improved perioperative antiplatelet drug tirofiban was an independent protective factor for perioperative TEs in stent-assisted embolization of ruptured intracranial aneurysms, but it did not impart an elevated risk of perioperative HEs and had no significant effects on the near-term prognosis of the patients.

Monitoring of Perioperative Microcirculation Dysfunction by Near-Infrared Spectroscopy for Neurological Deterioration and Prognosis of Aneurysmal Subarachnoid Hemorrhage: An Observational, Longitudinal Cohort Study.

INTRODUCTION: No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH. METHODS: A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH. RESULTS: Our data suggest that the rSO2 is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4-5, Fisher grade 3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO2 during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators. CONCLUSIONS: The rSO2 concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.

Identifying hormones and other perioperative risk factors for postoperative delirium after endoscope-assisted transsphenoidal pituitary adenoma resection: A retrospective, matched cohort study.

OBJECTIVE: As a complex and acute brain dysfunction, if postoperative delirium (POD) occurs in the postoperative period, it will lead to a prolonged length of stay in the critical care unit, with increased hospitalization costs and higher mortality. A few case reports inspired us to pay close attention to pituitary tumor-associated delirium. We hypothesized that the changes in hormone levels after pituitary tumor resection might be associated with POD occurrence. METHODS: Retrospective analysis was performed on data from a single-center cohort study conducted at Southwest Hospital between January 2018 and May 2022. A total of 360 patients with pituitary tumors who underwent endoscope-assisted transsphenoidal pituitary tumor resection were divided into two groups at a 1:3 ratio, with 36 patients in the POD group and 108 patients in the non-POD group matched by propensity score, age, sex, and tumor size. Basic characteristics, pituitary adenoma features, endocrine levels and other biochemical indicators, and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for postoperative delirium were documented for further analysis. RESULTS: Lower insulin-like growth factor-1 (IGF-1, p = .024) and corticotropin-releasing hormone (CRH, p = .005) levels were closely associated with postoperative delirium and with high levels of blood glucose (GLU, p = .023) after surgery. Subsequent analysis indicated that serum potassium (OR: 0.311, 95% CI 0.103-0.935), sodium (OR: 0.991, 95% CI 0.983-1.000), CRH (OR: 0.964, 95% CI 0.936-0.994), and GLU (OR: 1.654, 95% CI 1.137-2.406) levels in the perioperative period were independent risk factors for delirium. CONCLUSIONS: Our study indicated that lower serum CRH, potassium, sodium, and GLU levels may be associated with the occurrence of POD after endoscopic-assisted transsphenoidal surgery. These data provide preliminary evidence for the management of POD in pituitary adenoma patients after surgery. Further studies are needed to identify pharmacological and nonpharmacological multicomponent treatment strategies.

CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice.

BACKGROUND: Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear. METHODS: Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids. RESULTS: Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway. CONCLUSIONS: CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH.

ST6GAL1 inhibits metastasis of hepatocellular carcinoma via modulating sialylation of MCAM on cell surface.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly because of its high rate of metastasis. Thus, elucidation of the molecular mechanisms underlying HCC metastasis is of great significance. Glycosylation is an important post-translational modification that is closely associated with tumor progression. Altered glycosylation including the altered sialylation resulting from aberrant expression of ß-galactoside α2,6 sialyltransferase 1 (ST6GAL1) has long been considered as an important feature of cancer cells. However, there is limited information on the roles of ST6GAL1 and α2,6 sialylation in HCC metastasis. Here, we found that ST6GAL1 and α2,6 sialylation were negatively correlated with the metastatic potentials of HCC cells. Moreover, ST6GAL1 overexpression inhibited migration and invasion of HCC cells in vitro and suppressed HCC metastasis in vivo. Using a metabolic labeling-based glycoproteomic strategy, we identified a list of sialylated proteins that may be regulated by ST6GAL1. In particular, an increase in α2,6 sialylation of melanoma cell adhesion molecule (MCAM) inhibited its interaction with galectin-3 and decreased its expression on cell surface. In vitro and in vivo analysis showed that ST6GAL1 exerted its function in HCC metastasis by regulating MCAM expression. Finally, we found the relative intensity of sialylated MCAM was negatively correlated with tumor malignancy in HCC patients. Taken together, these results demonstrate that ST6GAL1 may be an HCC metastasis suppressor by affecting sialylation of MCAM on cell surface, which provides a novel insight into the roles of ST6GAL1 in HCC progression and supports the functional complexity of ST6GAL1 in a cancer type- and tissue type-specific manner.

Hsa_circ_0026344 suppresses gastric cancer progression via modulating the miR-1290/FBP2 axis.

BACKGROUND: Circular RNAs (circRNAs) are a novel type of noncoding RNAs and play important roles in tumorigenesis, including gastric cancer (GC). However, the functions of most circRNAs remain poorly understood. In our study, we mainly learn the influence of hsa_circ_0026344 (circ_0026344) in GC progression. METHODS: Circ_0026344, miR-1290 and Fructose-1,6-bisphosphatase 2 (FBP2) expression was determined by quantitative real-time polymerase chain reaction (qRT-PCR). GC cell proliferation, migration, and invasion were detected by colony formation, 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays, respectively. The interaction between circ_0026344 and miR-1290 complex was evaluated by RNA pull-down assay. The interaction of miR-1290 with circ_0026344 or FBP2 was detected using dual-luciferase reporter assay. A xenograft model was established to determine the effect of circ_0026344 on GC tumor growth in vivo. RESULTS: Circ_0026344 expression was dramatically decreased in GC cells and tissues. Circ_0026344 overexpression inhibited GC cell proliferation, migration and invasion. MiR-1290 was predicted as a target of circ_0026344 and miR-1290 overexpression attenuated the anti-tumor effect of circ_0026344 on GC cells. Furthermore, we predicted FBP2 as the target of miR-1290. FBP2 knockdown reversed the effects of circ_0026344 knockdown on GC cell malignant behaviors. Functional analysis showed that circ_0026344 upregulated FBP2 expression via miR-1290. Additionally, in vivo studies demonstrated that circ_0026344 suppressed GC tumor progression. CONCLUSION: In conclusion, circ_0026344 inhibited GC cell proliferation via the miR-1290/FBP2 axis, which might provide a new therapeutic target for GC patients.

Factoring and correlation in sleep, fatigue and mental workload of clinical first-line nurses in the post-pandemic era of COVID-19: A multi-center cross-sectional study.

Background: A better understanding of the factors and their correlation with clinical first-line nurses' sleep, fatigue and mental workload is of great significance to personnel scheduling strategies and rapid responses to anti-pandemic tasks in the post-COVID-19 pandemic era. Objective: This multicenter and cross-sectional study aimed to investigate the nurses' sleep, fatigue and mental workload and contributing factors to each, and to determine the correlation among them. Methods: A total of 1,004 eligible nurses (46 males, 958 females) from three tertiary hospitals participated in this cluster sampling survey. The Questionnaire Star online tool was used to collect the sociodemographic and study target data: Sleep quality, fatigue, and mental workload. Multi-statistical methods were used for data analysis using SPSS 25.0 and Amos 21.0. Results: The average sleep quality score was 10.545 ± 3.399 (insomnia prevalence: 80.2%); the average fatigue score was 55.81 ± 10.405 (fatigue prevalence: 100%); and the weighted mental workload score was 56.772 ± 17.26. Poor sleep was associated with mental workload (r = 0.303, P < 0.05) and fatigue (r = 0.727, P < 0.01). Fatigue was associated with mental workload (r = 0.321, P < 0.05). COVID-19 has caused both fatigue and mental workload. As 49% of nurses claimed their mental workload has been severely affected by COVID-19, while it has done slight harm to 68.9% of nurses' sleep quality. Conclusion: In the post-COVID-19 pandemic era, the high prevalence of sleep disorders and fatigue emphasizes the importance of paying enough attention to the mental health of nurses in first-class tertiary hospitals. Efficient nursing strategies should focus on the interaction of sleep, fatigue and mental workload in clinical nurses. In that case, further research on solutions to the phenomenon stated above proves to be of great significance and necessity. Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR2100053133].

Effect of hypophosphatemia on prognosis after spontaneous intracerebral hemorrhage: a retrospective study.

OBJECTIVE: Hypophosphatemia often occurs after spontaneous intracerebral hemorrhage, but the effect of hypophosphatemia on its prognosis is under debate. METHODS: Clinical data of patients with spontaneous intracerebral hemorrhage admitted to our neurosurgery department from January 2018 to June 2020 were retrospectively analyzed. The patients were divided into the hypophosphatemia group and the nonhypophosphatemia group according to the serum phosphorus test values obtained three times within 1 week after admission. The incidence of complications during hospitalization, 28-day mortality, and 6-month mRS score were compared between the two groups. The influence of low phosphorus in patients with hypophosphatemia on the 6-month mRS score was explored. RESULTS: A total of 133 patients were included, of which 85 had hypophosphatemia. Forty-two patients (21 in the hypophosphatemia group and 21 in the nonhypophosphatemia group) were enrolled after propensity score matching. There were no statistically significant differences in the incidence of complications during hospitalization, 28-day mortality, and 6-month mRS score between the two groups (P > 0.05). In 85 patients with hypophosphatemia, the minimum serum phosphorus was associated with the 6-month mRS score (B = - 3.153, 95% CI: - 5.842 ~ - 0.463, P = 0.022). The cutoff value of serumphosphorus for predicting 6-month mRS score was 0.505 mmol/l. CONCLUSION: Whether hypophosphatemia occurred during hospitalization in patients with spontaneous intracerebral hemorrhage showed no effect on the incidence of complications, 28-day mortality, and 6-month mRS score. A significant decrease in serum phosphorus during hospitalization (≤ 0.505 mmol/l) might correlate with a poor 6-month mRS score. Maintaining serum phosphorus stability after spontaneous intracerebral hemorrhage may improve prognosis.

Intrathoracic infections in Hodgkin lymphoma (HL) patients may cooperate with HL to trigger hemophagocytic lymphohistiocytosis: A retrospective study.

Hodgkin lymphoma (HL)-related hemophagocytic lymphohistiocytosis (HLH) has been reported in the literature; however, there is almost no literature on the factors related to HL triggering HLH. One hundred forty patients with HL were retrospectively analyzed. The incidence of HL-related HLH (we call HL-related HLH as HL-HLH). And all HL-HLH patients in our cohort had HLH as the first manifestation and its clinical characteristics and the role of intrathoracic infection (ITI) in triggering HLH are discussed. The 140 patients with HL mainly included mixed-cellularity classic HL (MCCHL) in 81 (57.9%), nodular sclerosis classic HL (NSCHL) in 36 (25.7%), and lymphacyte-rich classic HL in 14 (10.0%) patients. Of the 137 patients who underwent chest computed tomography scans on admission, 44 had ITI, and most of these ITI were mildly ill and had no respiratory symptoms. Among 140 HL patients, 8 patients from MCCHL were diagnosed as HL-HLH. Among 81 MCCHL patients, 26 patients with ITI had a significantly higher incidence of HL-HLH than those without ITI (26.9% vs 1.8%, P = .002). The median survival time of 8 cases of HL-HLH was only 2 months. When HL patients were first admitted to the hospital, 5.7% had HLH as the first manifestation, and 32.1% had ITI. These ITI can cooperate with HL to trigger HLH, despite their mild illness. The prognosis of HL-HLH was poor.

Downregulation of MTAP promotes Tumor Growth and Metastasis by regulating ODC Activity in Breast Cancer.

5'-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway and has been reported to suppress tumorigenesis. The MTAP gene is located at 9p21, a chromosome region often deleted in breast cancer (BC). However, the clinical and biological significance of MTAP in BC is still unclear. Here, we reported that MTAP was frequently downregulated in 41% (35/85) of primary BCs and 89% (8/9) of BC cell lines. Low expression of MTAP was significantly correlated with a poor survival of BC patients (P=0.0334). Functional studies showed that MTAP was able to suppress both in vitro and in vivo tumorigenic ability of BC cells, including migration, invasion, angiogenesis, tumor growth and metastasis in nude mice with orthotopic xenograft tumor of BC. Mechanistically, we found that downregulation of MTAP could increase the polyamine levels by activating ornithine decarboxylase (ODC). By treating the MTAP-repressing BC cells with specific ODC inhibitor Difluoromethylornithine (DFMO) or treating the MTAP-overexpressing BC cells with additional putrescine, metastasis-promoting or -suppressing phenotype of these MTAP-manipulated cells was significantly reversed, respectively. Taken together, our data suggested that MTAP has a critical metastasis-suppressive role by tightly regulating ODC activity in BC cells, which may serve as a prominent novel therapeutic target for advanced breast cancer treatment.

MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine-cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein-protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

P300 Inhibition Improves Cell Apoptosis and Cognition Impairment Induced by Sevoflurane Through Regulating IL-17A Activation.

BACKGROUND: Sevoflurane (Sev) is a rapidly acting, potent inhalation anesthetic with rapid uptake and elimination. But many studies have shown that Sev could result in cognition dysfunction in adolescent or aging patients. Now, therapeutic targeting with IL-17A antibody has shown a promising effect on Sev-induced cognition impairment. In the study we report that P300 inhibition could act as an alternative approach to decrease IL-17A activity. METHODS: SHSY5Y cells were treated with Sev and cell apoptosis was evaluated by Annexin V-FITC/PI staining. The expression of P300 and IL-17A were assessed by Western blotting. Water maze tests were conducted in order to assess the cognitive function. RESULTS: We found that P300 and IL-17A were activated in SHSY5Y cells treated with Sev. P300 inhibitor C646 could reduce the apoptosis induced by Sev through decreasing IL-17A avtivity. Furthermore, IL-17A expression was upregulated after neurons were transfected with P300 expression plasmid and IL-17A expression was downregulated after neurons were incubated with P300 inhibitor C646. P300 overexpression could upregulate the promoter activity of IL-17A. Finally, in a rat model treated with Sev, we also found C646 to significantly improve the cognition impairment through the IL-17A pathway. CONCLUSIONS: These data show that P300 will potentially be a new drug target for the therapy of cognition impairment caused by Sev.

Intrapleural infections in patients with subcutaneous panniculitis-like T-cell lymphoma are susceptible to hemophagocytic lymphohistiocytosis.

Patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) are prone to the development of hemophagocytic lymphohistiocytosis (HLH). It is not known whether small infections in SPTCL patients can trigger the development of HLH. The clinical data were collected from 21 SPTCL patients admitted to our hospital from January 2006 to October 2019. Among 21 cases of SPTCL, six cases had HLH as the first manifestation (SPTCL/HLH), seven cases had intrathoracic infection (ITI), five cases were SPTCL/HLH, 13 cases had no ITI or HLH (SPTCL/no HLH). Two patients with SPTCL/noHLH healed spontaneously. We found that 28.6% of the SPTCL patients had HLH as the first presentation. ITI may cooperate with SPTCL to trigger HLH and a small number of SPTCL/noHLH can fully recover without treatment.