Anesthesia for extracorporeal membrane oxygenation-assisted thoracoscopic lower lobe subsegmental resection in a patient with a single left lung: A case report.

BACKGROUND: It is difficult and risky for patients with a single lung to undergo thoracoscopic segmental pneumonectomy, and previous reports of related cases are rare. We introduce anesthesia for Extracorporeal membrane oxygenation (ECMO)-assisted thoracoscopic lower lobe subsegmental resection in a patient with a single left lung. CASE SUMMARY: The patient underwent comprehensive treatment for synovial sarcoma of the right lung and nodules in the lower lobe of the left lung. Examination showed pulmonary function that had severe restrictive ventilation disorder, forced expiratory volume in 1 second of 0.72 L (27.8%), forced vital capacity of 1.0 L (33%), and maximal voluntary ventilation of 33.9 L (35.5%). Lung computed tomography showed a nodular shadow in the lower lobe of the left lung, and lung metastasis was considered. After multidisciplinary consultation and adequate preoperative preparation, thoracoscopic left lower lung lobe S9bii+S10bii combined subsegmental resection was performed with the assistance of total intravenous anesthesia and ECMO intraoperative pulmonary protective ventilation. The patient received postoperative ICU supportive care. After surgical treatment, the patient was successfully withdrawn from ECMO on postoperative Day 1. The tracheal tube was removed on postoperative Day 4, and she was discharged from the hospital on postoperative Day 15. CONCLUSION: The multi-disciplinary treatment provided maximum medical optimization for surgical anesthesia and veno-venous ECMO which provided adequate protection for the patient's perioperative treatment.

Deciphering three-dimensional bioanode configuration for augmenting power generation and nitrogen removal in air-cathode microbial fuel cells.

In this study, the engineering-oriented three-dimensional (3D) bioanode concept was applied, demonstrating that spiral-stairs-like/rolled carbon felt (SCF/RCF) configurations achieved good performances in air-cathode microbial fuel cells (ACMFCs). With the 3D anodes, ACMFCs generated significantly higher power densities of 1535 mW/m3 (SCF) and 1800 mW/m3 (RCF), compared with that of a traditional flat carbon felt anode (FCF, 315 mW/m3). The coulombic efficiency of 15.39 % at SCF anode and 14.34 % at RCF anode also is higher than the 7.93 % at FCF anode. The 3D anode ACMFCs exhibited favorable removal of chemical oxygen demand (96 % of SCF and RCF) and total nitrogen (97 % of SCF, 99 % of RCF). Further results show that three-dimensional anode structures could enrich more electrode surface biomass and diversify the biofilm microbial communities for promoting bioelectroactivity, denitrification, and nitrification. These results demonstrate that three-dimensional anodes with active biofilm is a promising strategy for creating scalable MFCs-based wastewater treatment system.

Coupling mixotrophic denitrification and electroactive anodic nitrification by nitrate addition for promoting current generation and nitrogen removal.

Nitrate promotes anodic denitrification and fasts organic matter removal in microbial fuel cells (MFCs). However, it suffers from poor total nitrogen (TN) removal and current recovery. In this study, some novel electroactive nitrifying/denitrifying bacteria (ENDB) were introduced in a single chambered air-cathode MFC to investigate the performance of this device and the microbial community shift by adding nitrate. Results showed a similar disturbance in current output by adding nitrate during a short-term operation. However, a stable and reproducible current increase was achieved in the continuous experiment. A maximum current of 0.76 A m-3 and a maximum TN removal of >99 % were accomplished. The corresponding corrected coulombic efficiency was approximately 18 %. Under repeatable batches, a sharp decrease in chemical oxygen demand (COD) with feeding nitrate confirmed the temporary competition on electron donors through heterotrophic denitrification. The later current increase and nitrite detection occurring without metabolized COD could be considered evidence of electroactive anodic nitrification. The ENDB biofilm successfully coupled mixotrophic denitrification and electroactive anodic nitrification. It eventually promoted TN removal. In the process, genera Pseudoxanthomonas, Thauera, and Pseudomonas were enriched in the anodic ENDB biofilms. Cyclic voltammetry data confirmed the promotion of the electron transfer process by biofilms. The bacterial function predication revealed that the genes related to nitrogen removal and electron transfer were upregulated. Therefore, mixotrophic denitrification and electroactive anodic nitrification processes facilitated power recovery with the high efficiency of pollutant removal, finally ensuring water body security.

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer.

Hepatitis B virus (HBV) infection has been reported to be associated with gastric cancer (GC). Nonetheless, no study has revealed the role of HBV infection in the survival of patients with GC, and the mutation profiles of HBV-infected patients with GC have never been documented. Here, we performed an updated meta-analysis and found a significantly increased risk of GC in HBV-infected individuals (sOR, 1.29; 95% CI, 1.22-1.37). Furthermore, we observed that in the Anhui area, the rate of serum HBsAg positivity (OR, 1.62; 95% CI, 1.03-2.55) was significantly higher in GC patients than in controls. Moreover, our results showed that HBV-positive patients had significantly worse disease-free survival (HR, 1.98; 95% CI, 1.39-2.82) and overall survival (HR, 1.84; 95% CI, 1.19-2.85) than HBV-negative patients. The results of Cox proportional hazards regression proved that HBV infection was an independent adverse prognostic factor in GC. Furthermore, by performing targeted-NGS, we found unique mutation profiles in HBV-infected GC samples, including five frequently mutated protein-coding genes (KMT2B, KMT2D, SOX1, FGF12, and TUBB2B). Expression and survival analyses of these genes identified three novel candidate genes that may have potential roles in GC development. Gene Ontology enrichment analysis showed that the recurrent mutations in HBV-positive GC samples were related to cell proliferation, cell migration, and transcription. Taking together, our study proved that HBV infection is an independent prognostic factor in GC patients. The unique mutation profiles of HBV-infected patients with GC open a new research direction toward the underling mechanism between HBV infection and GC.

Efficacy and safety of intermittent versus continuous dose apatinib plus docetaxel as second-line therapy in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma: a randomized controlled study.

Background: Previous studies of the second-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJAC) had reported that apatinib combined with chemotherapy improved the treatment outcomes. However, the benefits were sometimes limited due to the tolerance of continuous dose regimen. This randomized controlled study aimed to investigate the efficacy and safety of intermittent or continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Methods: Advanced GC/GEJAC patients who failed first-line chemotherapy were recruited (enrollment time: from September 15, 2017 to July 21, 2019), and randomly assigned to either the intermittent dose group (IG group) or the continuous dose group (CG group) (1:1 ratio) using the block randomization method. In the IG group, patients received apatinib 500 mg/d for 5 consecutive days then held for 2 days plus docetaxel 60 mg/m2 q3w, in a 3-week cycle. In the CG group, patients received apatinib 500 mg daily plus docetaxel 60 mg/m2 q3w, in a 3-week cycle. The progression free survival (PFS) was evaluated every two cycles and follow-ups were performed monthly. The primary endpoint was PFS, and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: In total, 76 eligible patients were enrolled and randomly assigned (1:1 ratio). The IG group exhibited similar PFS compared to the CG group [median PFS: 3.88 (95% CI: 1.72-6.03) months vs. 3.98 (95% CI: 1.06-6.90) months, P=0.546] and OS [median OS: 9.00 (95% CI: 5.31-12.70) months vs. 9.40 (95% CI: 5.20-13.59) months, P=0.310]. ORR (21.1% vs. 18.4%, P=0.773) and DCR (60.5% vs. 60.5%, P=1.000) were of not statistically different between the IG and CG groups. As for safety, the IG group exhibited less frequent hypoproteinemia (31.6% vs. 55.3%, P=0.037) and lactate dehydrogenase increased (18.4% vs. 44.7%, P=0.014), while no differences in other adverse events were observed between the two groups. Conclusions: Intermittent dose apatinib plus docetaxel was equally effective and more tolerable than continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Trial Registration: ClinicalTrials.gov NCT03334591.

Prognostic Significance of Platelet (PLT) and Platelet to Mean Platelet Volume (PLT/MPV) Ratio During Apatinib Second-Line or Late-Line Treatment in Advanced Esophageal Squamous Cell Carcinoma Patients.

Background: Apatinib has a certain efficacy for advanced esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the prognostic significance of platelet (PLT) and platelet to mean platelet volume (PLT/MPV) ratio for advanced ESCC patients with apatinib second-line or late-line treatment. Methods: A retrospective study included 80 patients with advanced ESCC who received Apatinib ≥ 2 lines targeted therapy. We collected baseline clinical characteristics and blood parameters from the patients. Kaplan-Meier plots and univariate and multivariate analysis were used to find the factors related to progression-free survival (PFS). Results: The optimal cut-off values of PLT and PLT/MPV ratio were determined by X-tile software. Kaplan-Meier analysis demonstrated that patients in the high PLT group had better PFS than those in the low PLT group (156 d vs 80 d, P <.001), and patients in the high PLT/MPV ratio group had better PFS than those in low PLT/MPV ratio group (157 d vs 85 d, P <.001). Univariate analysis revealed pretreatment PLT and PLT/MPV ratio were significantly correlated with PFS. Multivariate analysis revealed high levels of pretreatment PLT/MPV ratio was an independent predictor of longer PFS (HR: 0.257, 95% CI: 0.089-0.743, P = .012). Conclusion: High levels of baseline PLT and PLT/MPV may indicate a better prognosis in apatinib ≥ 2 lines treatment for advanced ESCC patients.

Knockdown of CENPK inhibits cell growth and facilitates apoptosis via PTEN-PI3K-AKT signalling pathway in gastric cancer.

Previous studies have indicated that centromere protein K (CENPK) is upregulated in several cancers and related to tumorigenesis. Nevertheless, the potential function of CENPK in gastric cancer (GC) remains unknown. Here, we investigated the function of CENPK on oncogenicity and explored its underlying mechanisms in GC. Our results showed that CENPK was dramatically overexpressed in GC and was associated with poor prognosis through bioinformatics analysis. We demonstrated that CENPK is upregulated in GC tissues and cell lines. Moreover, knockdown of CENPK significantly inhibited proliferation in vitro and attenuated the growth of implanted GCs in vivo. In addition, CENPK silencing induced G1 phase cell cycle arrest and facilitated apoptosis of GC cells. KEGG pathway analysis indicated that the PI3K-AKT signalling pathway was considerably enriched. Knockdown of CENPK decreased the expression of PI3K, p-Akt (Ser437) and p-GSK3ß (Ser9) in GC cells, and increased the expression of PTEN. In conclusion, this study indicated that CENPK was overexpressed in GC and may promote gastric carcinogenesis through the PTEN-PI3K-AKT signalling pathway. Thus, CENPK may be a potential target for cancer therapeutics in GC.

Integrated simultaneous nitrification/denitrification and comammox consortia as efficient biocatalysts enhance treatment of domestic wastewater in different up-flow bioelectrochemical reactors.

Simultaneous nitrification/denitrification (SND) can efficiently deplete NH4+ by using air-exposed biocathode (AEB) in bioelectrochemical reactors. However, the fluctuation of wastewater adversely affects the functional biofilms and therefore the performance. In this work, four up-flow bioelectrochemical reactors (UBERs) with some novel inocula were investigated to improve domestic wastewater treatment. The UBERs exhibited favorable removal of chemical oxygen demand (COD, 95%), NH4+-N (99%), and total nitrogen (TN, 99%). The maximum of current (2.7 A/m3), power density (136 mW/m3) and coulombic efficiency (20.5%) were obtained. Cyclic voltammetry analysis showed all the electrodes were of diversified catalytic reactions. Illumina pyrosequencing showed the predominant Ignavibacterium, Thauera, Nitrosomonas, Geminicoccus and Nitrospira were in all electrodes, contributing functional biofilms performing SND, comammox, and bioelectrochemical reactions. FAPROTAX analysis confirmed twenty-one functional groups with obvious changes related to chemoheterotrophy, respiration/oxidation/denitrification of nitrite and nitrate. Comfortingly, such novel diversified consortia in UBERs enhance the microbial metabolisms to treat domestic wastewater.

Comparative evaluation of simultaneous nitritation/denitritation and energy recovery in air-cathode microbial fuel cells (ACMFCs) treating low C/N ratio wastewater.

Air-cathode microbial fuel cells (ACMFCs) can extract available electrons from the low C/N ratio wastewater (LCNW) for pollutant degradation and power generation. However, the multiple effects of operating parameters and their relationship between the performances and parameters are still lacking. In this study, several ACMFCs for simultaneous nitritation/denitritation (SND) and energy recovery were constructed and evaluated in terms of chemical oxygen demand (COD), NH4+-N, C/N ratio, phosphate buffer solution (PBS), and external resistance (Rext), and several derived parameters (e.g., organic loading rate (OLR), nitrogen loading rate (NLR)). Results indicated that ACMFCs could be used to treat LCNW successfully with high pollutant removal rates and sustainable current generation. Maximum removal efficiencies of 94% COD, 92% NH4+-N, and 92% total nitrogen (TN) were achieved. A maximum power density of 1400 mW m-2 and columbic efficiency of 69.2% were also obtained at a low C/N ratio of 1.7-2.6. Low C/N ratios promoted SND by balancing nitritation and denitritation. The microbial community and their predicated function results showed considerable nitrifiers and denitrificans were enriched in the ACMFCs, contributing to SND and power recovery. Further analyses showed that the NH4+-N could inhibit SND, but PBS and Rext had no obvious effects on this outcome. Co-occurrence network analysis demonstrated that power is positively correlated with COD and Rext; strong correlations between organic removal and COD, and between nitrogen removal and ammonia, conductivity, and C/N ratio were also noted. Overall, the appropriate control of such parameters is necessary to achieve efficient SND in ACMFCs for LCNW treatment.

Substrate salinity: A critical factor regulating the performance of microbial fuel cells, a review.

Substrate salinity is a critical factor influencing microbial fuel cells (MFCs) performance and various studies have suggested that increasing substrate salinity first improves MFC performance. However, a further increase in salinity that exceeds the salinity tolerance of exoelectrogens shows negative effects because of inhibited bacterial activity and increased activation losses. In this review, electricity generation and contaminant removal from saline substrates using MFCs are summarized, and results show different optimal salinities for obtaining maximum performance. Then, electroactive bacteria capable of tolerating saline environments and strategies for improving salinity tolerance are discussed. In addition to ohmic resistance and bacterial activity, membrane resistance and catalyst performance will also be affected by substrate salinity, all of which jointly contribute the final overall MFC performance. Therefore, the combined effect of salinity is analyzed to illustrate how the MFC performance changes with increasing salinity. Finally, the challenges and perspectives of MFCs operated in saline environments are discussed.

Limb-bud and heart as a novel biomarker for gastric intestinal type adenocarcinoma.

The present study compared the expression levels of limb-bud and heart (LBH) between gastric intestinal-type adenocarcinoma (GITA) and healthy gastric tissues; with the aim of investigating the possible effect of LBH on the prognosis of patients with GITA and to analyze the associated signaling pathways in GITA. Three Oncomine gastric datasets were utilized for the preliminary prediction of the expression levels of LBH mRNA in GITA and healthy gastric tissues. Gene expression and corresponding clinical data of 163 patients with GITA were downloaded from The Cancer Genome Atlas. Wilcoxon signed rank-sum test was used to distinguish the clinical value of LBH expression in the various clinicopathological features. Subsequently, Kaplan-Meier univariate and Cox multivariate survival analyses were performed to determine the prognostic significance of LBH expression in patients with GITA. Function enrichment analysis was conducted for the co-expression gene of LBH, defined as correlation coefficient r>0.06 and P<0.05 using Pearson's χ2 test. Bioinformatics data demonstrated that compared with that in the normal gastric mucosa, LBH mRNA expression was dramatically higher in GITA tissues (P<0.05). There were significant relationships between the differential expression levels of LBH and clinicopathological parameters in GITA patients (all p<0.05), including pathological stage T (T3-4 vs. T1-2), lymph node metastasis (no vs. yes), distant metastasis (no vs. yes), histological grade (grade 3 vs. grades 1-2) and tumor stage (stages 3-4 vs. stages 1-2). Additionally, the overall survival and disease-free survival (DFS) of patients in the high expression group were poorer compared with those in the low expression group (P<0.05). Cox multivariate survival analysis indicated that increased LBH expression was an independent predictor of poor DFS prognosis in patients with GITA (P=0.045). In summary, LBH is highly expressed in GITA, which can be used as an independent predictor of poor prognosis in patients with GITA. LBH co-expressed genes are closely associated with GITA tumor migration and metastasis.

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca2+/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes.

Ca2+/calmodulin-dependent protein kinase II (CaMKII), regulated by inhibitor 1 of protein phosphatase 1 (I1PP1), is vital for maintaining cardiovascular homeostasis. However, the role and mechanism of I1PP1 against hypoxia-reoxygenation (H/R) injury in cardiomyocytes remain a question. In our study, after I1PP1 overexpression by adenovirus infection in the neonatal cardiomyocytes followed by hypoxia for 4 h and reoxygenation for 12 h, the CaMKIIδ alternative splicing subtype, ATP content, and lactate dehydrogenase (LDH) release were determined. CaMKII activity was evaluated by phosphoprotein phosphorylation at Thr17 (p-PLB Thr17), CaMKII phosphorylation (p-CaMKII), and CaMKII oxidation (ox-CaMKII). Reactive oxygen species (ROS), mitochondrial membrane potential, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expressions were assessed. Our study verified that I1PP1 overexpression attenuated the CaMKIIδ alternative splicing disorder; suppressed PLB phosphorylation at Thr17, p-CaMKII, and ox-CaMKII; decreased cell LDH release; increased ATP content; attenuated ROS production; increased mitochondrial membrane potential; and decreased DRP1 expression but increased OPA1 expression in the cardiomyocytes after H/R. Contrarily, CaMKIIδ alternative splicing disorder, LDH release, ATP reduction, and ROS accumulation were aggravated after H/R injury with the I1PP1 knockdown. Collectively, I1PP1 overexpression corrected disorders of CaMKIIδ alternative splicing, inhibited CaMKII phosphorylation, repressed CaMKII oxidation, suppressed ROS production, and attenuated cardiomyocyte H/R injury.

Cytoplasmic ERß1 expression is associated with survival of patients with Stage IV lung adenocarcinoma and an EGFR mutation at exon 21 L858R subsequent to treatment with EGFR-TKIs.

The present study assessed whether estrogen receptor (ER)ß1 is associated with the survival of patients with advanced lung adenocarcinoma, with or without mutations of the epidermal growth factor receptor (EGFR) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). Pathologically confirmed stage IV lung adenocarcinomas were assessed for EGFR mutations and ERß1 expression. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and the log-rank test. A total of 122 out of the 201 (60.7%) patients had EGFR mutations, 64 (31.8%) of which were EGFR Del19 and 58 mutations (28.9%) were EGFR exon 21 L858R mutation. The presence of EGFR mutations was significantly increased in female patients compared with male patients (P<0.001) and in non-smokers compared with smokers (P<0.001). Patients with EGFR mutations had a significantly improved PFS and OS compared with patients without EGFR mutations treated with EGFR-TKIs. Furthermore, ERß1 expression was significantly increased in patients with EGFR mutations compared with patients without EGFR mutations (P=0.001). However, the median PFS (P=0.005) and OS (P=0.002) of patients carrying the EGFR exon 21 L858R mutation was significantly decreased in patients with tumors where ERß1 cytoplasmic expression was high. The multivariate analysis demonstrated that ERß1 expression was the only independent predictor of PFS (P=0.002) and OS (P=0.003) in patients carrying the EGFR exon 21 L858R mutation. The data demonstrated that ERß1 expression may predict outcomes of patients with lung adenocarcinoma treated with EGFR-TKI.

Ca2+/Calmodulin-Dependent Protein Kinase II Regulation by Inhibitor 1 of Protein Phosphatase 1 Protects Against Myocardial Ischemia-Reperfusion Injury.

Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) plays a vital role in cardiovascular system. However, the potential protective role of inhibitor 1 of protein phosphatase 1 (I1PP1), which can regulate CaMKII, on myocardial ischemia-reperfusion (I/R) injury remains unknown. In the present study, expression of CaMKIIδ variants was detected by quantitative real-time polymerase chain reaction. I1PP1 was overexpressed by pericardial injection of recombinant adenovirus. Two weeks later, rats were subjected to left anterior descending ligation for 30 minutes followed by reperfusion. Myocardial infarct size was assessed by Evans blue/triphenyl tetrazolium chloride staining. Serum creatine kinase (CK) and lactate dehydrogenase (LDH) activity as well as myocardial pathological structure were detected. CaMKII activity was evaluated by phosphorylation of phospholamban (PLB) and oxidation of CaMKII. Expression of dynamin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) in the mitochondria was measured by Western blot. We found that CaMKIIδA and CaMKIIδB expression decreased, while the expression of CaMKIIδC increased after myocardial I/R. Moreover, after 30-minute ischemia followed by 6 hours of reperfusion, I1PP1 overexpression reduced myocardial infarct size, decreased serum CK and LDH activity, ameliorated myocardial pathological structure, inhibited PLB phosphorylation at Thr17, suppressed CaMKII oxidation, elevated CaMKIIδA and CaMKIIδB variants but reduced CaMKIIδC variants, attenuated myocardial oxidative stress, improved myocardial mitochondrial ultrastructure, increased mitochondrial number and mitochondrial DNA copy number, and decreased DRP1 but increased OPA1 protein expression from the mitochondria in rats. Thus, I1PP1 regulated CaMKII, protected mitochondrial function, reduced oxidative stress, and attenuated myocardial I/R injury.

Ca2+/calmodulin-dependent protein kinase II regulation by inhibitor 1 of protein phosphatase 1 alleviates necroptosis in high glucose-induced cardiomyocytes injury.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays an important role in the cardiovascular system. However, the potential protective role of inhibitor 1 of protein phosphatase 1 (I1PP1), which is able to regulate CaMKII, in high glucose-induced cardiomyocytes injury remains unknown. In the present study, cardiomyocytes were transfected with I1PP1 adenovirus to inhibit protein phosphatase 1 (PP1) expression. After the cardiomyocytes were subjected to high glucose stimulation for 48 h, quantitative real-time PCR was used to detect CaMKIIδ alternative splicing. Lactate dehydrogenase (LDH) release and adenosine triphosphate (ATP) level were measured to assess cell damage and energy metabolism respectively. CaMKII activity was represented as phospholamban (PLB) phosphorylation, CaMKII phosphorylation (p-CaMKII) and oxidation (ox-CaMKII). Dihydroethidium (DHE), MitoSOX and JC-1 staining were used to assess oxidative stress and mitochondrial membrane potential. Necroptosis was evaluated by receptor interacting protein kinase 3 (RIPK3) expression, TUNEL and cleaved-caspase 3 levels. RIPK3, mixed lineage kinase domain like protein (MLKL) and dynamin-related protein 1 (DRP1) expressions were also detected. We found that high glucose disordered CaMKIIδ alternative splicing. I1PP1 over-expression suppressed PLB phosphorylation, ox-CaMKII, DRP1, RIPK3 and cleaved-caspase 3 proteins expression, decreased LDH release, attenuated necroptosis, increased ATP level, inhibited oxidative stress, and elevated mitochondrial membrane potential in high glucose-stimulated cardiomyocytes. However, there was no effect on phosphorylation of MLKL (p-MLKL), p-CaMKII, and receptor interacting protein kinase 1 (RIPK1) expression. Altogether, I1PP1 over-expression alleviated CaMKIIδ alternative splicing disorder, suppressed CaMKII oxidation, reduced reactive oxygen species (ROS) accumulation and inhibited necroptosis to attenuate high glucose-induced cardiomyocytes injury.

Effect of Apatinib on Serum CD4+CD25+ T cells, NK Cells, and T Cells Subgroup in Malignant Tumor.

OBJECTIVE: The immune makers including CD4+CD25+ T cells, natural killer cells, and T cells subgroup were retrospectively analyzed to find the relationship between apatinib and the immune system in the patients treated with apatinib. METHOD: Forty-two patients with advanced malignant tumors orally took apatinib as treatment and 16 patients with the same situation did not take apatinib as a control group. These patients were all included in the study, and they orally received apatinib 500 mg daily as monotherapy or combination. The treatment was continued until disease progression or intolerable toxicity. CD4+CD25+ T cells, natural killer cells, and T cells subgroup were detected before and 1 month after therapy for all the patients. The relationship between the changing number of immune cells and progression-free survival was analyzed in this study. RESULT: For the apatinib group, the rate of CD4+CD25+ T cells significantly increased (P = .048). The median progression-free survival was 3.25 months for the 42 patients. The median progression-free survival in the patients with the rate of CD4+CD25+ T cells increased and decreased was 5.8 months and 2.9 months, respectively (P = .012). Multivariate analysis found the increased rate of CD4+CD25+ T cells was an independent prognostic factor for a longer progression-free survival. The rate of natural killer cells and T cells subgroup did not change much after apatinib therapy, and they were not independent prognostic factors for progression-free survival. CONCLUSION: The rate of CD4+CD25+ T cells is very important in patients with apatinib treatment. The changing number of CD4+CD25+ T cells may be a good indicator for apatinib prognosis. Natural killer cells and T cells subgroup did not change much after apatinib, and they were not independent prognostic factors for progression-free survival.

The role of prostaglandin E receptor 2 and epidermal growth factor receptor in esophageal squamous cell carcinoma patients with (pN+) regional lymph node metastasis.

BACKGROUND: To find the relationship between prostaglandin E receptor 2 (EP2) and epidermal growth factor receptor (EGFR) in esophageal squamous cell carcinoma (ESCC) patients with regional lymph nodes metastasis (pN+) who had undergone curative resection, and to analyze them in the role of judging prognosis. METHODS: Sixty-three patients with ESCC who underwent attempted curative esophagectomy with lymph node metastasis were collected. Immunohistochemistry (IHC) was used to analyse the expression of EP2 and EGFR in tumor tissues. We analyzed the relationship between the two markers. Furthermore, we analyzed the role of EP2 and EGFR in disease-free survival (DFS) and overall survival (OS). RESULTS: The expression rate of EP2 and EGFR in this study were 73.0%, 85.7%, respectively. And the EP2 status was closely related with the expression of EGFR in tumor tissues (χ2=0.260, P=0.011). The patients with EP2 or EGFR positive expression had a shorter DFS and OS than the negative group. Further analysis found EGFR is an important prognostic factor for DFS and OS (P<0.001), the expression of EP2 was related with PFS (P=0.048), but it was not an independent influencing factors for OS (P>0.05). CONCLUSIONS: The expression of EP2 and EGFR were high in tumor tissues of (pN+) ESCC, and they are playing a key role in the prognosis of ESCC patients with local lymph node metastases.

Effects of Human Interleukin-10 on Ventilator-Associated Lung Injury in Rats.

Ventilator-induced lung injury (VILI) is one of the most serious complications of mechanical ventilation (MV) and can increase the mortality of patients with acute respiratory distress syndrome (ARDS). This work aimed to test the hypothesis that the anti-inflammatory properties of human interleukin-10 (hIL-10) can reduce VILI. Thirty-six healthy male Sprague-Dawley rats were randomly assigned into three groups (n = 12) as follows: a control group, a VILI group, and a hIL-10 group. Lung function was evaluated by oxygenation index and pulmonary edema, and morphological changes associated with lung injury were assessed by HE staining and quantitative histological lung injury score. Malondialdehyde (MDA) and Superoxide dismutase (SOD) were measured, and the levels of various inflammatory cytokines were assessed in BALF and plasma. The oxygenation index in the VILI group decreased significantly relative to the control group and improved substantially in the hIL-10 group (P < 0.01). Compared to the control group, MDA production was stimulated (P < 0.01), and SOD activity rapidly declined (P < 0.01) in the VILI group. After hIL-10, MDA content was lower than that seen in the VILI group (P < 0.01), and SOD activity was enhanced (P < 0.01). The VILI group had the highest cytokine levels, compared to either the hIL-10 group or the control group (P < 0.05). High tidal volume MV can induce VILI. hIL-10 may regulate the inflammatory response in the lung tissue, improve lung tissue oxygenation, and inhibit oxidative stress, therefore reducing VILI in rats. These experiments reveal a potential new treatment option for VILI.

Recent Update on the Pharmacological Effects and Mechanisms of Dihydromyricetin.

As the most abundant natural flavonoid in rattan tea, dihydromyricetin (DMY) has shown a wide range of pharmacological effects. In addition to the general characteristics of flavonoids, DMY has the effects of cardioprotection, anti-diabetes, hepatoprotection, neuroprotection, anti-tumor, and dermatoprotection. DMY was also applied for the treatment of bacterial infection, osteoporosis, asthma, kidney injury, nephrotoxicity and so on. These effects to some extent enrich the understanding about the role of DMY in disease prevention and therapy. However, to date, we still have no outlined knowledge about the detailed mechanism of DMY, which might be related to anti-oxidation and anti-inflammation. And the detailed mechanisms may be associated with several different molecules involved in cellular apoptosis, oxidative stress, and inflammation, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), protein kinase B (Akt), nuclear factor-κB (NF-κB), nuclear factor E2-related factor 2 (Nrf2), ATP-binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-γ (PPARγ) and so on. Here, we summarized the current pharmacological developments of DMY as well as possible mechanisms, aiming to push the understanding about the protective role of DMY as well as its preclinical assessment of novel application.