A real-world study was conducted to develop a nomogram that predicts the occurrence of anastomotic leakage in patients with esophageal cancer following esophagectomy.

BACKGROUND: The incidence of anastomotic leakage (AL) following esophagectomy is regarded as a noteworthy complication. There is a need for biomarkers to facilitate early diagnosis of AL in high-risk esophageal cancer (EC) patients, thereby minimizing its morbidity and mortality. We assessed the predictive abilities of inflammatory biomarkers for AL in patients after esophagectomy. METHODS: In order to ascertain the predictive efficacy of biomarkers for AL, Receiver Operating Characteristic (ROC) curves were generated. Furthermore, univariate, LASSO, and multivariate logistic regression analyses were conducted to discern the risk factors associated with AL. Based on these identified risk factors, a diagnostic nomogram model was formulated and subsequently assessed for its predictive performance. RESULTS: Among the 438 patients diagnosed with EC, a total of 25 patients encountered AL. Notably, elevated levels of interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and procalcitonin (PCT) were observed in the AL group as compared to the non-AL group, demonstrating statistical significance. Particularly, IL-6 exhibited the highest predictive capacity for early postoperative AL, exhibiting a sensitivity of 92.00% and specificity of 61.02% at a cut-off value of 132.13 pg/ml. Univariate, LASSO, and multivariate logistic regression analyses revealed that fasting blood glucose ≥7.0mmol/L and heightened levels of IL-10, IL-6, CRP, and PCT were associated with an augmented risk of AL. Consequently, a nomogram model was formulated based on the results of multivariate logistic analyses. The diagnostic nomogram model displayed a robust discriminatory ability in predicting AL, as indicated by a C-Index value of 0.940. Moreover, the decision curve analysis provided further evidence supporting the clinical utility of this diagnostic nomogram model. CONCLUSIONS: This predictive instrument can serve as a valuable resource for clinicians, empowering them to make informed clinical judgments aimed at averting the onset of AL.

Bioinformatics analysis and validation of CSRNP1 as a key prognostic gene in non-small cell lung cancer.

Cysteine and serine-rich nuclear protein 1 (CSRNP1) has shown prognostic significance in various cancers, but its role in non-small cell lung cancer (NSCLC) remains elusive. We investigated CSRNP1 expression in NSCLC cases using bioinformatics tools from the GEO public repository and validated our findings through RT-qPCR in tumor and adjacent normal tissues. KEGG and GO enrichment analyses were employed to unveil the significant deregulation in signaling pathways. Additionally, clinical significance of CSRNP1 in NSCLC was determined through receiver operating curve (ROC) analysis, and its impact on survival was assessed using Kaplan-Meier analysis. To explore the functional impact of CSRNP1, we silenced its expression in NSCLC cells and assessed the effects on cell viability, migration, and invasion using MTT, Transwell, and wound-healing assays, respectively. Additionally, we investigated the influence of CSRNP1 silencing on the phosphorylation patterns of critical signaling proteins such as p53, p-Akt, and p-MDM2. Our results demonstrated significantly lower CSRNP1 expression in NSCLC tumor tissues (P < 0.01). ROC analysis indicated that NSCLC patients with high CSRNP1 expression exhibited extended overall survival and disease-free survival. Furthermore, CSRNP1 silencing promoted NSCLC cells viability, migration, and invasion (P < 0.05). Mechanistically, CSRNP1 silencing led to increased phosphorylation of AKT and MDM2, along with a concurrent reduction in p53 protein expression, suggesting its impact on NSCLC through deregulated cell cycle processes. In conclusion, our study underscores the significance of CSRNP1 in NSCLC pathogenesis, offering insights for targeted therapeutic interventions of NSCLC.

Efficacy of Deep Venous Catheterization in the Management of Pneumothorax: A Clinical Study Utilizing Conventional Closed Thoracic Drainage.

Background: Currently, conventional closed thoracic drainage for pneumothorax involves a painful procedure with a higher risk and wider (1~1.5 cm) incision. Minimally invasive catheterized drainage techniques are urgently needed to address this challenge. Objective: This retrospective study aims to observe the effects of conventional closed thoracic drainage with deep venous catheterization drainage techniques on pneumothorax patients. Design: It was a retrospective study. Setting: This study was conducted at Huaian No.1 People's Hospital, Affiliated with Nanjing Medical University. Participants: A total of 105 pneumothorax patients who underwent conventional closed thoracic drainage (CCTD) or deep venous catheterization drainage technique (DVCDT) procedures at the hospital from 1st February 2020 to 30th October 2022 were selected. Interventions: Patients received either CCTD or DVCDT. Primary Outcome Measures: Included: (1) clinical variables; (2) catheterization procedure-related features; and (3) visual analogue scale (VAS) scores from pneumothorax patients. Results: Both conventional closed thoracic drainage and deep venous catheterization drainage techniques were successfully performed in all 105 (100%) patients, comprising 67 (63.8%) spontaneous pneumothorax, 20 (19%) iatrogenic pneumothorax, and 18 (17.1%) traumatic pneumothorax cases. Significant differences were observed between the enrolled spontaneous pneumothorax and traumatic pneumothorax patients in the two groups (CCTD and DVCDT) (P = .01 and P < .0001). Additionally, 55 (52.4%) patients underwent deep venous catheterization, while 50 (47.6%) patients underwent conventional closed thoracic drainage. The deep venous catheterization insertion procedure had a shorter mean timing (7.51±1.66 min) compared to the conventional closed thoracic drainage procedure (12.44±1.73 min) (P < .0001). Furthermore, VAS scores were significantly lower in pneumothorax patients undergoing deep venous catheterization (2.1±0.99) compared to conventional closed thoracic drainage (5.1±0.81) (P < .0001). Conclusion: Deep venous thoracic drainage technique appears to be safer and more beneficial than conventional closed thoracic drainage procedures for treating pneumothorax. This technique offers advantages such as minimal scarring, lower VAS scores, and shorter insertion time, thereby improving safety and surgical outcomes.

Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy.

Background: Esophageal squamous cell carcinoma (ESCC), characterized by its high invasiveness and malignant potential, has long been a formidable challenge in terms of treatment. Methods: A variety of advanced analytical techniques are employed, including single-cell RNA sequencing (scRNA-seq), cell trajectory inference, transcription factor regulatory network analysis, GSVA enrichment analysis, mutation profile construction, and the inference of potential immunotherapeutic drugs. The purpose is to conduct a more comprehensive exploration of the heterogeneity among malignant squamous epithelial cell subgroups within the ESCC microenvironment and establish a model for predicting the prognosis and immunotherapy outcomes of ESCC patients. Results: An analysis was conducted through scRNA-seq, and three Cluster of malignant epithelial cells were identified using the infer CNV method. Cluster 0 was found to exhibit high invasiveness, whereas Cluster 1 displayed prominent characteristics associated with epithelial-mesenchymal transition. Confirmation of these findings was provided through cell trajectory analysis, which positioned Cluster 0 at the initiation stage of development and Cluster 1 at the final developmental stage. The abundance of Cluster 0-2 groups in TCGA-LUAD samples was assessed using ssGSEA and subsequently categorized into high and low-expression groups. Notably, it was observed that Cluster 0-1 had a significant impact on survival (p<0.05). Furthermore, GSVA enrichment analysis demonstrated heightened activity in hallmark pathways for Cluster 0, whereas Cluster 1 exhibited notable enrichment in pathways related to cell proliferation. It is noteworthy that a prognostic model was established utilizing feature genes from Cluster 0-1, employing the Lasso and stepwise regression methods. The results revealed that in TCGA and GSE53624 cohorts, the low-risk group demonstrated significantly higher overall survival and increased levels of immune infiltration. An examination of four external immunotherapy cohorts unveiled that the low-risk group exhibited improved immunotherapeutic efficacy. Additionally, more meaningful treatment options were identified for the low-risk group. Conclusion: The findings revealed distinct interactions between malignant epithelial cells of ESCC and subgroups within the tumor microenvironment. Two cell clusters, strongly linked to survival, were pinpointed, and a signature was formulated. This signature is expected to play a crucial role in identifying and advancing precision medicine approaches for the treatment of ESCC.

A purified membrane protein from Akkermansia muciniphila blunted the sepsis-induced acute lung injury by modulation of gut microbiota in rats.

The gut microbiota has been implicated in the pathogenesis and progression of sepsis. Akkermansia muciniphila is considered to be a promising probiotic with reduced abundance in cecal ligation and puncture (CLP)-induced sepsis model, and its specific outer membrane protein (Amuc_1100) can partially recapitulate the probiotic function of Akkermansia muciniphila. However, its role in sepsis is unclear. This study aimed to investigate the effect of Amuc_1100 on the gut microbiota of septic rats, thereby improving the prognosis of septic acute lung injury (ALI). A total of 42 adult Sprague-Dawley (SD) rats were randomly divided into three groups: the sham control (SC group), the septic ALI induced by CLP method (CLP group), and administered Amuc_1100 by oral gavage (3 µg/d) for 7 d before the CLP procedure (AMUC group). The survival of the three groups was recorded and the feces and lung tissues of rats were collected 24 h after treatment for 16S rRNA sequencing and histopathological evaluation. Oral administration of Amuc_1100 improved the survival rate and alleviated lung histopathological damage induced by sepsis. Serum levels of pro-inflammatory cytokines and chemokines were substantially attenuated. Amuc_1100 significantly increased the abundance of some beneficial bacteria in septic rats. Additionally, the Firmicutes/Bacteroidetes ratio was low in septic rats, which was partially corrected by increasing Firmicutes and decreasing Bacteroidetes after oral administration of Amuc_1100 (p < 0.05). In addition, Escherichia-Shigella, Bacteroides, and Parabacteroides were relatively enriched in septic rats, while in the AMUC group, their abundance was restored to levels similar to that of the healthy group. Amuc_1100 protects against sepsis by enhancing beneficial bacteria and reducing potential pathogenic bacteria. These findings indicate that Amuc_1100 can blunt CLP-induced ALI through the modulation of gut microbiota, thereby providing a new promising therapeutic target in sepsis.

Clinical application value of metagenomic next-generation sequencing in the diagnosis of central nervous system infections.

Objectives: The purpose of this study is to evaluate the clinical application value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infections. Methods: Both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with CNS infections retrospectively analyzed the efficacy of mNGS in this cohort and were ultimately compared with a clinical diagnosis. Results: A total of 94 cases consistent with CNS infections were included in the analysis. The positive rate for mNGS is 60.6% (57/94), which is significantly higher than 20.2% (19/94; p < 0.01) detected using conventional methods. mNGS detected 21 pathogenic strains that could not be detected by routine testing. Routine tests were positive for two pathogens but negative for mNGS. The sensitivity and specificity of mNGS in the diagnosis of central nervous system infections were 89.5% and 44%, respectively, when compared with traditional tests. At discharge, 20 (21.3%) patients were cured, 55 (58.5%) patients showed improvements, five (5.3%) patients did not recover, and two (2.1%) patients died. Conclusion: mNGS has unique advantages in the diagnosis of central nervous system infections. mNGS tests can be performed when patients are clinically suspected of having a central nervous system infection but no pathogenic evidence.

Clinical Characteristics and Prognosis Analysis of Acinetobacter baumannii Bloodstream Infection Based on Propensity Matching.

Purpose: In view of the fact that Acinetobacter baumannii bloodstream infection(BSI) is a great threat to human survival, early identification of the risk factors affecting prognosis will be of great benefit to the clinic. Patients and Methods: A propensity score matching method was used to collect patients identified with Acinetobacter baumannii BSI from 2016 to 2020 from a reputable hospital in China. Results: A total of 398 patients were considered. According to the 28-day prognosis, they were divided into the survival group 150 (37.7%) and the death group 248 (62.3%), and the prognosis was analyzed. Subsequently, Propensity score matching was adjusted for variables with p-values

Adjunctive sepsis therapy with aminophylline (STAP): a randomized controlled trial.

BACKGROUND: Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis. METHODS: We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days. RESULTS: From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P  = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P  = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. CONCLUSIONS: Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR1800019173.

Case Report: Diagnostic Value of Metagenomics Next Generation Sequencing in Intracranial Infection Caused by Mucor.

mNGS(metagenomics Next Generation Sequencing), as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. At present, there have been many case reports about the use of mNGS to assist in the diagnosis of bacterial, fungal, viral and parasitic infections and to guide clinicians to determine appropriate treatment. However, the clinical understanding of this technique is not comprehensive, and the experience of using it is relatively limited. We reported a 53-year-old man who was admitted to hospital with a high fever and headache. His inflammatory biomarkers were markedly elevated. Based on the clinical presentation, He was initially diagnosed as having an intracranial infection of unknown etiology and received empirical antibiotics and systemic supportive treatment. But these did not relieve his symptoms. Both the blood and CSF specimens were examined using traditional culture, serological testing, and mNGS. Traditional culture and serological testing produced negative results, while the mNGS revealed the presence of a potential pathogen, mucor, in the CSF specimen. Then targeted antifungal treatment was selected quickly and his temperature gradually returned to normal. Thus, we report the case in which mNGS was an auxiliary method to diagnose mucormycosis, and discuss this case in combination with relevant literature, in order to improve the clinical cognition of this technology.

Homologous Escherichia coli Identified in Cerebrospinal Fluid and Bloodstream.

Background: Escherichia coli is an opportunistic bacterium that causes a wide range of diseases, such as bloodstream infection and central nervous system infection. The traditional culture-based method to detect E. coli usually takes more than 2 days. The object of this study is to explore the value of metagenomic next-generation sequencing (mNGS) in identifying E. coli from human cerebrospinal fluid. In addition, we investigated the infection source of E. coli through whole genome sequencing and phylogenetic analysis. Methods: We combined a clinical example to analyze the function of mNGS in pathogen detection from cerebrospinal fluid. NextSeq 550Dx platform was applied for mNGS. Next, whole genome sequencing was performed to obtain the genomic characterization of E. coli. Furthermore, we screened 20 E. coli strains from the National Center for Biotechnology Information and conducted a phylogenetic analysis. Results: A middle-aged patient who attended our hospital was diagnosed with craniopharyngioma and received surgery. The patient had recurrent fever and persistent lethargy after surgery. Cerebrospinal fluid culture firstly failed to grow the bacteria. Next the cerebrospinal fluid sample was detected by mNGS and the sequence readings of E. coli were identified. Later, E. coli was reported via the second cerebrospinal fluid culture, certifying the result of mNGS. Moreover, we also cultured carbapenem-resistant E. coli from the patient's bloodstream. Through whole genome sequencing and phylogenetic analysis, we found that the E. coli isolated from cerebrospinal fluid and the bloodstream was 100% homologous, indicating the E. coli central nervous system infection was originated from the bloodstream. Conclusion: Metagenomic next-generation sequencing is a valuable tool to identify the pathogens from cerebrospinal fluid, and seeking the infection source is of great significance in clinical diagnosis and treatment. Furthermore, carbapenem-resistant E. coli is a serious problem as the cause of bloodstream infection and central nervous system infection, and effective and adequate measures to prevent and control the present circumstance are urgent.

Overexpression of mm9_circ_013935 alleviates renal inflammation and fibrosis in diabetic nephropathy via the miR-153-3p/NFIC axis.

Circ-RBM4 (mm9_circ_013935) has been revealed to have low expression in the renal tissues of diabetic nephropathy (DN) mice, and its underlying regulatory mechanism remains unexplored. The high glucose (HG) - treated mouse podocytes were used to establish DN cell models. A cell counting kit-8 assay was used to examine the viability of mouse podocytes. The expression of proteins related to fibrosis (collagen I, collagen III, fibronectin) was detected using Western blot. The concentration of inflammation cytokines (tumor necrosis factor α, interleukin 1ß (IL-1ß), IL-8) in mouse podocytes was assessed by ELISA. The interaction between genes was explored by luciferase reporter assays. HG treatment decreased the viability and elevated the expression of fibrosis and inflammation factors in mouse podocytes. Circ-RBM4 expression was downregulated in HG-treated mouse podocytes. Circ-RBM4 overexpression reversed HG-induced increase in levels of proteins related to fibrosis and the concentration of inflammation factors. The miR-153-3p was revealed to bind with circ-RBM4 and directly targeted nuclear factor I/C (NFIC) in mouse podocytes. Rescue assays indicated that circ-RBM4 attenuated HG-induced fibrosis and inflammation response in mouse podocytes by inhibiting miR-153-3p expression or upregulating NFIC expression. Circ-RBM4 alleviated the renal inflammation and renal fibrosis in DN by targeting the miR-153-3p/NFIC axis.

Case Report: Metagenomics Next-Generation Sequencing Can Help Define the Best Therapeutic Strategy for Brain Abscesses Caused by Oral Pathogens.

Brain abscesses are associated with an increased long-term risk of new seizures and increased mortality within several years after infection. Common microorganisms that cause brain abscesses include bacteria, fungi, and mycoplasma. We report a 75-year-old man with a brain abscess caused by Prevotella denticola, an oral pathogen. Based on the clinical condition, we suspected that the patient had a blood-borne brain abscess, and he received antibiotics and systemic supportive treatment. The patient developed shock for the second time after negative Gram-staining results. Metagenomics next-generation sequencing showed one strain from the oral microbiome, confirming our hypothesis, and targeted antibiotic treatment was administered quickly. Thus, we report a case in which genomic analysis was the critical factor in determining the best antimicrobial therapy for administration.

CircZNF609 aggravates neuropathic pain via miR-22-3p/ENO1 axis in CCI rat models.

Neuropathic pain is caused by damage or disease happened to somatosensory nerve system. Due to the high prevalence and inefficient clinic intervention, neuropathic pain has brought considerable burden for world health care system. It is urgent to find novel targets for neuropathic pain basic research and clinical management. In this study, we found that miR-22-3p was decreased in Chronic Constriction Injury （CCI）rats and involved in neuropathic pain progression. Furthermore, it was found that ENO1 was a downstream target of miR-22-3p using bioinformatics analysis and luciferase reporter assays. MiR-22-3p downregulation promoted neuropathic pain via regulating inflammation factors expression by targeting ENO1. Then, we explored the upstream regulator of miR-22-3p using Miranda database. It was found that circular RNA ZNF609 sponged miR-22-3p by biotinylated RNA pull-down, AGO2-RIP, and luciferase reporter assays. Collectively, our study revealed that circZNF609 promoted inflammation factors expression to aggravate neuropathic pain progression via miR-22-3p/ENO1 axis in CCI rat models. Our study might provide a new direction for neuropathic pain basic research.

The association between serum adipocyte fatty acid-binding protein and 3-month disability outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Adipocyte fatty acid-binding protein (FABP4) is an adipokine that plays an important role in development of cardiovascular and metabolic diseases. The aim of this study was to assess the 3-month prognostic value of serum levels of FABP4 in Chinese patients with aneurysmal subarachnoid hemorrhage (aSAH) on hospital admission. METHODS: This was a prospective observational study from a stroke treatment center in Zhengzhou, China. From October 2016 to May 2018, patients with aSAH who were hospitalized within 24 h were included. In addition, 202 age- and gender-matched healthy volunteers were assigned to the healthy control group. At admission, serum levels of FABP4 were measured, and patients' characteristics, Hunt-Hess grade, and modified Fisher grade evaluated. At 3-month follow-up, functional outcome (Glasgow Outcome Scale score; dichotomized as poor [score 1-3] or good [score 4-5]) and all-cause mortality were recorded. Univariate and multivariate logistic regression models were used to investigate the association of FABP4 with the two endpoints. RESULTS: A total of 418 patients with aSAH were included in this study. The median age was 58 years (interquartile range, 49-66 years), and 57.9% were women. FABP4 serum levels were related to Hunt-Hess score (r[Spearman] = 0.381; P < 0.001). Patients with a poor outcome and non-survivors had significantly increased serum FABP4 levels on admission (P < 0.001 for all). In multivariate logistic regression analysis, FABP4 was an independent predictor of poor outcome and mortality, with increased risks of 7% (odds ratios 1.07, 95% confidence interval [CI] 1.02-1.13; P = 0.001) and 5% (odds ratio 1.05, 95% CI, 1.01-1.12; P = 0.003), respectively. Receiver operating characteristics to predict functional outcome and mortality were significantly different between conventional risk factors (difference area under the curve 0.024, 95% CI 0.018-0.032) and FABP4 plus conventional risk factors (area under the curve 0.015, 95%CI 0.011-0.020). After FABP4 was added to the existing risk factors, mortality was better reclassified and was associated with the net reclassification improvement statistic (P = 0.009), while poor outcome was better reclassified and associated with both the integrated discrimination improvement and net reclassification improvement statistics (P < 0.05 for all). CONCLUSIONS: Elevated serum FABP4 levels were related to poor outcome and mortality in a cohort of patients with aSAH.

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients.

The mycophenolate mofetil (MMF) dose management for optimization of post-transplant treatment especially the early postoperative phase has been well recognized. MMF is a pro-drug of mycophenolic acid (MPA) and is widely used in Chinese renal transplant patients. Until now, the pharmacokinetic (PK) characteristics and model for the area under the concentration-time curve for the 12-h (h) of exposure (AUC0-12h) of MPA (MPA-AUC0-12h) estimation were lacking for the new formulation of MMF dispersible tablet in renal transplant patients. The aims of the study were to investigate the PK characteristics of MMF dispersible tablet by detecting the active metabolite of MPA and to establish an accuracy and precision equation for calculating MPA-AUC0-12h by limited sampling strategy (LSS) in Chinese kidney transplant patients. A total of 60 postoperative kidney transplant recipients were given a multiple-dose of MMF dispersible tablet twice daily combination with tacrolimus (Tac) and steroids. On the 5th day post-transplantation, blood specimens were collected before drug administration and up to 12 h after MMF dispersible tablet administration. Non-compartmental PK analysis was used to determine the data obtained from individual patients. Multivariate stepwise regression analysis was used to develop models for predicting MPA-AUC0-12h. The 3- and 4-point sampling models using 2 h, 4 h, 8 h and 1 h, 2 h, 4 h and 8 h, respectively, allowed accurate estimation of MPA-AUC0-12h. PK parameters of MMF dispersible tablet were obtained and the 4-point LSS is the best model for accurate and precise estimation of MPA-AUC0-12h.

Pharmacokinetic Comparison of Two Mycophenolate Mofetil Formulations in Kidney Transplant Recipients.

BACKGROUND: The aim of this study was to investigate and compare the pharmacokinetic (PK) characteristics of mycophenolate mofetil (MMF) capsule and MMF dispersible tablet by detecting the active metabolite of mycophenolic acid (MPA) in Chinese kidney transplant recipients. METHODS: In the prospective, randomized, open-label study, the renal transplant patients were given a multiple dose of either the MMF capsule or MMF dispersible tablet combination with tacrolimus (Tac). For each patient, 11 serial blood samples were collected over 12 hours (h). Parameters including predose concentration (C0), postdose minimum and maximum concentration (Cmin and Cmax), time to Cmax (Tmax), total body clearance (CL), and area under the concentration-time curve for the 12-hour exposure (AUC0-12h) were determined. Patient interviews were conducted to assess the occurrence of adverse events. RESULTS: Baseline characteristics were comparable between both groups. The C0, Cmin, Cmax, Tmax, CL, and AUC0-12h values were not significantly different after multiple doses of MMF capsule or MMF dispersible tablet (P > 0.05). The median values of AUC0-12h were 43.98 and 41.95 mcg·h/mL for MMF capsule and MMF dispersible tablet, respectively. Interindividual variability in Cmax, Cmin, and C0 were considerable in both groups. No serious adverse events were reported by patients or found on analysis of laboratory tests. CONCLUSIONS: PK parameters of the 2 MPA drugs were comparable in early renal transplant patients in this study. The 2 formulations were well tolerated in Chinese kidney transplant patients.

Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer.

Breast cancer (BRCA) is the second leading cause of cancer-related death among female worldwide. Recent studies have revealed that LACTB was frequently repressed and functioned as a bona fide new tumor suppressor in a series of cancers, including BRCA. However, the molecular mechanisms underlying LACTB dysregulation in BRCA have not been reported. In the present study, we find that LACTB is repressed in BRCA and associated with poor prognosis by BRCA tissue microarray (TMA) analysis. Moreover, we confirm that LACTB is a direct target of miR-374a, which is significantly overexpressed and associated with malignancies in BRCA. Mechanistically, applying loss-of-function and gain-of-function approaches in a series of in vitro and in vivo experiments show that miR-374a knockdown suppresses the cell proliferative and colony formation activity, as well as migration and invasion capacity, but LACTB silencing in these cells reverses this change. Furthermore, we find that miR-374a silencing markedly reduces the tumor growth in xenograft mouse models. In summary, our findings suggest the miR-374a/LACTB axis plays a critical role in the tumorigenicity and progression of BRCA. miR-374a/LACTB axis may be a potential target in the development of therapeutic strategies for BRCA patients.

[Efficacy and safety of nalbuphine on analgesia of patients in intensive care unit].

OBJECTIVE: To analyze the efficacy and safety of nalbuphine in patients with sedative analgesia in intensive care unit (ICU). METHODS: A prospective observation was conducted. The adult patients with mild and moderate analgesia in general ICU of the First Affiliated Hospital of Zhengzhou University from January to November in 2017 were enrolled, and they were divided into nalbuphine group and sufentanil group in proper order. The nabobrown group was given 40 mg nabobrown, the sufentanil group was given 0.1 mg sufentanil, both of which were injected with 50 mL normal saline for continuous intravenous infusion in micro-pump. Infusion speed was checked according to pain level. The analgesic target was critical-care pain observation tool (CPOT) score < 2. The change in hemodynamics of patients in both groups were observed, and CPOT score and Richmond agitation-sedation scale (RASS) score were recorded before and l, 3, 5, 12, 24 hours after administration. The analgesic and sedative effects of two drugs were evaluated. RESULTS: A total of 141 patients were enrolled, including 71 patients in nalbuphine group and 70 in sufentanil group. There was no significant difference in general data including gender, age, body weight, acute physiology and chronic health evaluation II (APACHE II) or pain source, as well as baseline hemodynamics parameter between the two groups. At 1 hour and 3 hours after administration, nalbuphine had no effect on blood pressure, but the heart rate was decreased slightly, while the heart rate and blood pressure of the sufentanil group were decreased obviously. The two drugs could make the heart rate and blood pressure fluctuate obviously with the time of medication, but there was no statistical difference between the two drugs. The two drugs had no significant effect on pulse oxygen saturation (SpO2) during analgesia. The average dosage of nalbuphine was 0.03 (0.02, 0.05) mg×kg-1×h-1 in the nalbuphine group, and the patient was satisfied with the analgesic effect until 3 hours after the use of the drug, and CPOT score was significantly decreased as compared with that before administration [1.0 (1.0, 2.0) vs. 3.0 (2.0, 4.0), P < 0.01], and the sedative effect was increased, RASS score was significantly lower than that before administration [0 (0, 1.0) vs. 1.0 (1.0, 2.0), P < 0.01]. No patients in naporphine group were treated with sufentanil due to unsatisfactory analgesia. The average dosage was 0.11 (0.06, 0.14) µg×kg-1×h-1 in the sufentanil group, the patient was satisfied with the analgesic effect until 5 hours after administration, and the CPOT score was significantly lower than that before administration [1.0 (1.0, 2.0) vs. 4.0 (3.0, 6.0), P < 0.01], and the sedative effect was significantly increased, RASS score was significantly lower than that before administration [0 (-1.0, 0) vs. 2.0 (1.0, 2.0), P < 0.01]. The scores of CPOT and RASS in the sufentanil group were significantly higher than those of the naporphine group before use, so the decrease in the CPOT and RASS scores of the two drugs was further analyzed, which indicated the decrease in CPOT score of naporphine group was significantly lower than that in sufentanil group from 3 hours on [1.0 (0, 2.0) vs. 2.0 (1.0, 3.0), P < 0.05], and the decrease in RASS score of naporphine group was significantly lower than that in sufentanil group from 1 hour on [0 (0, 1.0) vs. 1.0 (0, 2.0), P < 0.01]. It suggested that naporphine could achieve sustained and stable analgesic effect and avoid excessive sedation caused by sufentanil. CONCLUSIONS: Naporphine had a sustained and stable analgesic effect on patients with mild and moderate ICU analgesia. The onset time of naporphine was equivalent to sufentanil, and it had a certain sedative effect and less influence on hemodynamics.

LDHA is a direct target of miR-30d-5p and contributes to aggressive progression of gallbladder carcinoma.

Gallbladder cancer (GBC) is the most general biliary tract malignancy, with poor prognosis due to rapid tumor progression and lack of specific symptoms. Lactate dehydrogenase-A (LDHA) can promote Warburg effect to produce lactate and Adenosine Triphosphate (ATP) in aerobic condition, which contributes to oncogenesis metastasis and drug resistance in various cancers. However, the expression and functional role of LDHA in GBC are largely unknown. We determined that LDHA was over-expressed in GBC tumor tissues compared with normal tissues, which was also an independent prognostic factor for the overall survival of GBC patients by tissue microarrays analysis. In addition, RNAi-mediated LDHA silencing could suppress the GBC cell proliferation, invasion, colony formation and glycolysis while promoting cell apoptosis in vitro. Similar results were observed in GBC cells treated with LDHA specific inhibitor FX11. Moreover, we confirmed that knockdown of LDHA could inhibit tumor growth in vivo. Additionally, we found that the 3'-untranslated region (3'-UTR) of LDHA mRNA was the direct target of microRNA-30d-5p (miR-30d-5p), which was low expressed in GBC tissues and associated with poor prognosis of GBC patients. Our findings disclose a novel role for miR-30d-5p/LDHA axis contribute to aggressive progression by reprogramming the metabolic process in GBC cells, and suggest a potential application of miR-30d-5p/LDHA axis in prognosis prediction and GBC treatment.

Upregulation of ALDH1B1 promotes tumor progression in osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. The mechanism underlying tumorigenesis and development of OS is largely unknown. ALDH1B1 has been reported to involve in many kinds of human cancers and functions as an oncogene, but the role of ALDH1B1 in OS has not been investigated comprehensively. In the present study, we aimed to examine clinical value and biological function of ALDH1B1 in OS. Firstly, we investigated the roles of ALDH1B1 on an OS tissue microarray (TMA) as well as two OS cohorts from GEO database. We found that ALDH1B1 was significantly up-regulated in OS tissues and was independently associated with poor prognosis. Moreover, ALDH1B1 silencing could suppress the proliferation, migration, invasion in vitro and inhibit the growth of xenograft tumor and of OS cells in vivo. Additional, ALDH1B1 knockdown increased the apoptosis rate and lead to cell cycle arrest in G1 stage of OS cell in vitro. More importantly, the inhibition of ALDH1B1 expression could increase the sensitivity of OS cells to chemotherapy, which suggested that ALDH1B1 might be served as a therapeutic target to reverse drug resistance in chemotherapy in OS patients. Taken together, our founding suggested that ALDH1B1 contributes to OS tumor progression and drug resistance, which may represent a novel prognostic marker and potential therapeutic target for OS patients.