Design, synthesis and biological evaluation of novel fluoro-substituted benzimidazole derivatives with anti-hypertension activities.

A series of new fluoro-substituted benzimidazole derivatives were designed, synthesized and pharmacologically evaluated. All the target compounds were characterized by 1HNMR, 13CNMR, mass spectra and elemental analysis. The biological evaluation showed that most of the synthesized compounds displayed nanomolar affinity to the angiotensin II type 1 (AT1) receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. The maximal response of mean blood pressure (MBP) lowered 74.5 ± 3.5 mmHg (1g) and 69.2 ± 0.9 mmHg (2a) at 10 g/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than both losartan and telmisartan. So, compounds 1g and 2a may be considered as potential antihypertension drug candidates.

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study.

Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall survival (OS) and disease free survival (DFS) were significantly higher in the MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p = 0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we conducted a prospective single-arm clinical trial including 188 patients who underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of the MMAC group in the prospective trail (MMAC-P) were similar to the MMAC group in the retrospective study (MMAC-R). This study is the first to demonstrate the superiority of MMAC to MAC in CBT for hematological malignancies.

Synthesis and evaluation of novel angiotensin II receptor 1 antagonists as anti-hypertension drugs.

Three new angiotensin II receptor 1 antagonists, 1, 2 and 3 were designed, synthesized and evaluated. The AT1 receptor-binding assays in vitro showed that all the synthesized compounds had nanomolar affinity for the AT1 receptor. From which compound 3 was found to be the most potent ligands with an IC50 value of 2.67±0.23 nM. Biological evaluation in vivo revealed that all the compounds could cause significant decrease on MBP in a dose dependent manner in spontaneously hypertensive rats, and compound 3 especially showed an efficient and long-lasting effect in reducing blood pressure, whose maximal response lowered 41 mmHg of MBP at 10mg/kg and 62 mmHg at 15 mg/kg after oral administration, the significant anti-hypertensive effect lasted beyond 12 h, which is better than the reference compound losartan. The pharmacokinetic experiments showed that compound 3 could be absorbed efficiently and metabolized smoothly both in blood and in tissues in Wistar rats. The acute toxicity assay suggested that it has low toxicity with the LD50 value of 2974.35 mg/kg. These results demonstrate that compound 3 is a potent angiotensin AT1 receptor antagonist which could be considered as a novel anti-hypertension candidate and deserved for further investigation.

Design, synthesis, and pharmacological evaluation of 5-oxo-1,2,4-oxadiazole derivatives as AT1 antagonists with antihypertension activities.

A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT1 receptor at the same order of magnitude to losartan. The methyl ester with 1, 4-disubsituted indole group, 1 (5.01 ± 1.67 nM) showed high antihypertension activity on spontaneously hypertensive rats (SHRs). Its maximal response lowered 30 mmHg of mean blood pressure (MBP) at 10 mg/kg after oral administration, which was better than irbesartan, and the antihypertensive effect lasted beyond 24 h. These results made 1 deserve further investigation.

Synthesis and pharmacological evaluation of a novel AT1 angiotensin II receptor antagonist with anti-hypertension and anti-tumor effects.

A new compound 2-(4-((2-butyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl) benzamide (1) was designed, synthesized and evaluated as a novel AT1 receptor antagonist. Compound 1 displayed high affinity to AT1 receptor with an IC50 value of 1.65 ± 0.2 nM in radio-ligand binding assays. It had an efficient and long-lasting effect in reducing blood pressure which could last for more than 12 h at the dose of 10 mg/kg in spontaneously hypertensive rats. Acute toxicity tests suggested that compound 1 was safe with the LD50 value of 2519.81 mg/kg. Besides, in vitro and in vivo tests suggested its anti-proliferative and anti-tumor activities, respectively. So compound 1 could be considered as a novel anti-hypertension, anti-tumor candidate and deserved further investigation.

Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities.

The design, synthesis, in vitro and in vivo evaluation of 5-nitro benzimidazole with 1,4-disubsituted or 1,5-disubsituted indole derivatives as novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 2-(4-((2-butyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl)benzoic acid, compound 3, displayed a high affinity for the angiotensin II type 1 receptor with IC50 value of 1.03±0.26nM. The biological evaluation on spontaneously hypertensive rats and renal hypertensive rats showed that 3 could cause significant decrease on MBP in a dose dependent manner, whose maximal response lowered 30mmHg of MBP at 5mg/kg and 41mmHg of MBP at 10mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24h, which is better than Losartan. Taken together 3 could be considered as an effective and durable anti-hypertension drug candidate. These encouraging results are deserved of further investigation towards its use for therapeutic benefit.

(Bortezomib plus lenalidomide/thalidomide)- vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma: a meta-analysis of randomized controlled trials.

The aim of the study was to perform a meta-analysis of the efficacy and safety of (bortezomib plus lenalidomide/thalidomide)- vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. We searched electronic and printed sources for relevant articles published. Inclusion criteria was as follows: randomized controlled trials (RCT) of (bortezomib plus lenalidomide/thalidomide) vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. Two reviewers independently assessed potentially eligible studies and extracted relevant data. We retrieved five RCT studies including a total of 1,200 patients. Using the random-effects model to pool the five RCT with a statistically significant heterogeneity (P = 0.03; X² = 10.69; df = 4; I² = 63%), the weighted risk ratios of a complete response (CR) for (bortezomib plus lenalidomide/thalidomide)-containing regimens was 1.81 (P = 0.005; 95% CI: 1.20-2.73). When we excluded the study by Cavo et al. (Lancet 376:2075-2085, 2010), the pooled risk ratio for CR was 1.59 (P < 0.0001, 95% CI: 1.29-1.96) with no statistically significant heterogeneity (P = 0.54; X² = 2.14; df = 3; I² = 0%) among four RCT under the fixed effects mode. The pooled odds ratio for the main grade III/IV adverse events (the peripheral neuropathy, thrombotic events, and infections) were 1.76 (P = 0.32; 95% CI: 0.58-5.31), 0.92 (P = 0.76, 95% CI: 0.52-1.61), and 1.05 (P = 0.82, 95% CI: 0.70-1.57), respectively. Our analysis showed (bortezomib plus lenalidomide/thalidomide)-containing regimens as induction treatment in newly diagnosed multiple myeloma improved CR but did not increase the risk of major adverse events (the peripheral neuropathy, thrombotic events, and infections).

Pre-engraftment syndrome after unrelated donor umbilical cord blood transplantation in patients with hematologic malignancies.

Pre-engraftment syndrome (PES) after umbilical cord blood transplantation (CBT) remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcomes of PES in CBT recipients, who had been treated for hematologic malignancies at our transplantation center. PES was defined as unexplained fever higher than 38.3°C that is not associated with documented infection and unresponsive to antimicrobial manipulations and/or unexplained erythematous skin rash occurring prior to neutrophil engraftment. A total of 81 patients (median 18 yr, range 3-48) received either myeloablative (n=72) or non-myeloablative (n=9) conditioning. Neutrophil engraftment was achieved in 69 of the 81 cases [86.2%, 95% confidence interval (CI)=78.9-94.1%], and the median time to more than 0.5 × 10(9) /L ANC was 19 d (range, 12-39). Fifty-one patients (63.0%) developed PES at a median of 7d (range 3-15) post-transplant: 46 patients had both rash and unexplained fever; one patient had unexplained fever alone; and four patients had rash only. Forty-seven patients (92.2%) received IV methylprednisolone (MP) at a median dose of 1 mg/kg (range 0.4-3). All patients treated with MP responded as evidenced by fever resolution combined with resolution of rash. All patients with PES had high serum levels of C-reactive protein (CRP), which were significantly reduced after effective steroid treatment. Univariate analysis identified myeloablative conditioning and younger age as significant risk factors for developing PES. Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) in the PES+ and PES- groups was 51.5% (95% CI=38.0-70.0%) and 17.0% (95% CI=6.9-41.7%), respectively. In a multivariate analysis, we found significantly increased risk of grade II-IV aGVHD among PES patients (P=0.041). However, PES was not associated with sustained donor engraftment, the day to neutrophil recovery, chronic graft-versus-host disease, transplant-related mortality at day 180, and overall survival. Despite of the inherent limitations of this small retrospective study, PES seemed to be common after CBT and associated with high incidence of aGVHD.

[Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies].

OBJECTIVE: To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies. METHODS: Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23 ± 6) years and the average weight (58 ± 9) kg. Thirty-five (87.5%) patients were high-risk and 15 (37.5%) at the advanced disease status at pre-transplantation. They received 1 (n = 23) or 2 (n = 17) cord blood units. Seventy-five percent of them were transplanted with 1/2-human leukocyte antigen mismatched unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: For the entire group of patients, the average cell doses infused were (4.1 ± 1.1)×107 total nucleated cells/kg and (2.4 ± 1.0)×105 CD34(+) cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count (ANC) ≥ 0.5×109/L was (20 ± 5) days and the average time of platelet ≥ 20×109/L was(38 ± 12) days. Acute GVHD occurred in 23 patients (57.5%) and 4 (10.0%) were of grade III-IV. Chronic GVHD occurred in 22.9% (8/35) evaluable patients. Relapse occurred in 12.5% (5/40) patients. During a median follow-up period of 19.8 (range 4.6 - 55.0) months, the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58.8% and 58.8%, respectively. Two-year OS for patients with advanced or complete remission disease was 48.6% and 63.8%, respectively. CONCLUSIONS: The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.

LncRNA LASTR promote lung cancer progression through the miR-137/TGFA/PI3K/AKT axis through integration analysis.

Background: Long noncoding RNAs (LncRNAs) are widely involved in the physiological and pathophysiological processes of cells. This study sought to identify novel lncRNAs that play key roles in progression of lung cancer. Methods: Cells were purchased from the Cell Bank of Type Culture Collection of the Chinese Academy of Sciences. Public lung cancer data were retrieved from The Cancer Genome Atlas database. Statistical analyses were performed using SPSS, R and GraphPad Prism 8 software. Results: Bioinformatic analysis showed that the lncRNA, LASTR (ENSG00000242147) was significantly upregulated in lung cancer tissues (LUAD and LUSC) compared with the expression level in adjacent normal tissue. Kaplan-Meier survival analysis showed that patients with higher LASTR expression level had a shorter overall survival and worse clinical features relative to patients with low LASTR expression levels. qRT-PCR results showed that LASTR was highly expressed in lung cancer cell lines relative to the expression level in normal lung epithelial cell line. Cell phenotype experiments indicated that knockdown of LASTR significantly inhibited proliferation and metastatic ability of lung cancer cells. Analysis of the downstream mechanism of LASTR demonstrated that LASTR exerts the oncogene effect through the miR-137/TGFA axis. GSEA results indicated that LASTR exhibits its activity by activating the PI3K/AKT signaling pathway, which was validated by western blotting assay. Conclusion: In summary, the results of the present study showed that LASTR promotes lung cancer progression through miR-137/TGFA/PI3K/AKT axis.

Standard-Intensity Induction and Intermediate/High-Dose Cytarabine Consolidation Can Improve Survival for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Cohort Study.

BACKGROUND: There is great uncertainty in the treatment of elderly patients with acute myeloid leukemia (AML), which leads to great challenges in treatment decision. The aim of this study is to find more suitable induction therapy and consolidation therapy for elderly AML patients. METHODS: A total of 149 consecutive newly diagnosed elderly AML patients (aged ≥60 years) who received induction chemotherapy in our medical center from January 2015 to December 2019 were retrospectively analyzed. RESULTS: After the first induction treatment, the complete remission/or complete remission with incomplete hematologic recovery (CR/CRi) rates in the standard-intensity chemotherapy group was significantly higher than that in the low-intensity chemotherapy group (58.2% vs 32.9%, p = 0.003). Compared with the low-intensity chemotherapy, the incidence of severe infection in the standard-intensity chemotherapy was significantly increased (p < 0.001), but the early mortality was comparable. One hundred and seven patients received minimal residual disease (MRD) examination after the first induction treatment; and MRD was negative accounting for 51.9% in the standard-intensity chemotherapy group, while only 32.7% in the low-intensity group (p = 0.05). The 2-year-overall survival (OS) of patients in standard-intensity induction chemotherapy group (37.2%) was slightly higher than that in low-intensity induction chemotherapy group (23.4%) (p = 0.075). Eighty-one CR/CRi patients received intermediate or high dose cytarabine (n = 35) or sequential chemotherapy regimens (n = 46) as consolidation treatment. The 2-year OS and event-free survival (EFS) of patients in the intermediate or high-dose cytarabine group were significantly higher than those in the sequential chemotherapy regimens group (73.0% vs 38.5%, p = 0.002; 54.8% vs 35.0%, p = 0.035). CONCLUSION: Our results showed that standard-intensity induction chemotherapy can significantly improve the CR rate for elderly AML patients, and does not increase the early mortality; consolidation therapy with intermediate or high-dose cytarabine can significantly improve EFS and OS for elderly AML patients achieved CR.

Pre-anesthetic use of butorphanol for the prevention of emergence agitation in thoracic surgery: A multicenter, randomized controlled trial.

Background: Emergence agitation (EA) is common in patients after general anesthesia (GA) and is associated with poor outcomes. Patients with thoracic surgery have a higher incidence of EA compared with other surgery. This study aimed to investigate the impact of pre-anesthetic butorphanol infusion on the incidence of EA in patients undergoing thoracic surgery with GA. Materials and methods: This prospective randomized controlled trial (RCT) was conducted in 20 tertiary hospitals in China. A total of 668 patients undergoing elective video-assisted thoracoscopic lobectomy/segmentectomy for lung cancer were assessed for eligibility, and 620 patients were enrolled. In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. Patients in the intervention group received butorphanol 0.02 mg/kg 15 min before induction of anesthesia. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of EA after 5 min of extubation, and EA was evaluated using the Riker Sedation-Agitation Scale (RSAS). The incidence of EA was determined by the chi-square test, with a significance of P < 0.05. Results: In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. The incidence of EA 5 min after extubation was lower with butorphanol treatment: 9.8% (29 of 296) vs. 24.5% (75 of 306) in the control group (P = 0.0001). Patients who received butorphanol had a lower incidence of drug-related complications (including injecting propofol pain and coughing with sufentanil): 112 of 296 vs. 199 of 306 in the control group (P = 0.001) and 3 of 296 vs. 35 of 306 in the control group (P = 0.0001). Conclusion: The pre-anesthetic administration of butorphanol reduced the incidence of EA after thoracic surgery under GA. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=42684], identifier [ChiCTR1900025705].

Which steroids should we choose for the treatment of adult acute lymphoblastic leukemia?

Corticosteroids are essential and one of the mainstays in the treatment of acute lymphoblastic leukemia (ALL). In vitro assays show that dexamethasone(DXM) is five to six times more cytotoxic to leukemic lymphoblasts than prednisolone (PDN) [1], and the use of DXM as an alternative drug for PDN is an important issue in the treatment of childhood ALL. The current randomized comparisons in childhood ALL indicated a statistically significant and clinically important decrease in rate of isolated central nervous system (CNS) relapses and an increase in event-free survival (EFS) with DXM. However, the data were limited in adult ALL. Recently, Labar et al. [2] reported their first investigation in comparison of the antileukemic activity and toxicity between DXM and PDN for adult patients with ALL and lymphoblastic lymphoma (LBL) through a randomized clinical trial (the ALL-4 trial of the EORTC Leukemia Group), and the author concluded that DXM as a steroid therapy for adult patients with ALL/LBL did not show any benefit compared with PDN, which did not support the experience from several other pediatric studies. In Labar's observation, about 70% of adult patients were high risk (HR) ALL. Most of the patients in pediatric trials were standard risk (SR) ALL. In our study, we also evaluate the role of DXM compared with PDN during induction or subsequent phases of therapy in adult ALL with emphasis on SR group.

CircPVT1 Regulates Cell Proliferation, Apoptosis and Glycolysis in Hepatocellular Carcinoma via miR-377/TRIM23 Axis.

BACKGROUND: Recent studies reported that circular RNAs (circRNAs) exert essential functions in hepatocellular carcinoma (HCC) progression. However, the expression profile and function of circular RNA PVT1 (circPVT1) in HCC are not fully addressed. Thus, we aimed to probe into the function of circPVT1 in HCC development. METHODS: The levels of circPVT1, microRNA-377 (miR-377) and transcripts encoding tripartite motif containing 23 (TRIM23) were determined by qRT-PCR. The stability and localization of circPVT1 were examined by RNase R digestion assay and subcellular fraction assay, respectively. Cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The relationship between miR-377 and circPVT1 or TRIM23 was determined by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). The protein expression of TRIM23 was measured by Western blot. The glycolysis level was assessed by specific kits and Seahorse Extracellular Flux Analyzer XF96. The function of circPVT1 in vivo was investigated in a murine xenograft model. RESULTS: CircPVT1 and TRIM23 levels were elevated, while miR-377 was decreased in HCC. CircPVT1 knockdown restrained proliferation and glycolysis, but enhanced apoptosis in HCC cells. CircPVT1 could bind to miR-377 and inhibition of miR-377 restored circPVT1 knockdown-mediated effect on HCC cells. TRIM23 was certified as a target of miR-377, and TRIM23 upregulation overturned the influence of miR-377 upregulation or circPVT1 silence on HCC progression. Moreover, circPVT1 knockdown restrained tumor growth in HCC in vivo. CONCLUSION: CircPVT1 aggravated the progression of HCC by upregulating TRIM23 via sponging miR-377.

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma].

OBJECTIVE: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). METHODS: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL). The phenotypes of cell products were detected, and the disease statuse was evaluated in 7 patients during or after infusion. The changes of TAA-CTL amount in the PBMNC of patients were measured by using IFN-γ ELISpot assay. RESULTS: TAA-CTL products were generated comprising CD3+ T cells (mean 82.98%) with a mixture of CD4+ (mean 42.09%) and CD8+ (mean 25.32%) T cells. Among them, 70% expressed effectors memory markers (CD45RO+CD62L-CCR7-). Each patient received TAA-CTL infusions for 1-4 times, and none of them showed obvious adverse reactions. The clinical symptoms and laboratory or imaging examination of 5 patients achieved positive effects. After cell therapy, the spot-forming cells (SFC) levels of most patients gradually increased and the peak often appeared about 2-3 weeks after the infusion. CONCLUSION: TAA-CTLs preliminarily show its safety and efficacy in MM and NHL patients, however, a larger population sample is needed to explore its clinical application value.

Short-Term Efficacy of Different First-Line Chemotherapy Regimens for Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis.

This study intends to compare short-term efficacy of 12 chemotherapy regimens in treatment of advanced non-small cell lung cancer (NSCLC) by a network meta-analysis (NMA). PubMed, Cochrane Library, and Embase were searched from the inception of each database to June 2018. Randomized controlled trials (RCTs) of the 12 chemotherapy regimens for advanced NSCLC were included. Direct and indirect evidence were combined by NMA to evaluate the odds ratio and the surface under the cumulative ranking curves (SUCRA) of the 12 chemotherapy regimens. Nineteen RCTs that met our inclusion criteria were collected in this study. For partial response (PR), gemcitabine exhibited relatively poor efficacy compared with cisplatin + gemcitabine, carboplatin + gemcitabine, carboplatin + paclitaxel, paclitaxel + gemcitabine, and cisplatin + gemcitabine + vinorelbine. For overall response rate (ORR), gemcitabine had poorer efficacy than cisplatin + gemcitabine and paclitaxel + gemcitabine. For disease control rate (DCR), compared with carboplatin + gemcitabine and gemcitabine, paclitaxel + gemcitabine had a better efficacy. Gemcitabine had the lowest SUCRA values in terms of complete response, PR, ORR, stable disease, and DCR; whereas paclitaxel + gemcitabine ranked the highest in ORR, progressive disease, and DCR. The cluster analysis revealed that cisplatin + gemcitabine, paclitaxel + gemcitabine, and cisplatin + gemcitabine + vinorelbine had better short-term efficacy for advanced NSCLC. Collectively, short-term efficacy of multidrug combination chemotherapy regimens was superior to that of single-drug chemotherapy regimens for advanced NSCLC. Cisplatin + gemcitabine, paclitaxel + gemcitabine, and cisplatin + gemcitabine + vinorelbine may have particularly prominent short-term efficacy for advanced NSCLC.

MicroRNA-181a-3p as a Diagnostic and Prognostic Biomarker for Acute Myeloid Leukemia.

BACKGROUND: Micro (mi) RNAs play an important role in the pathogenesis and development of acute myeloid leukemia (AML), and their abnormal expression may be sufficient to predict the prognosis and outcomes in AML patients. We evaluated the clinical diagnostic value of miRNA-181a-3p in predicting prognosis and outcomes in patients with AML. METHODS: A total of 119 newly diagnosed adult patients with AML and 60 healthy controls were recruited. Blood specimens were obtained from all AML patients at diagnosis, and 10 blood specimens were obtained on day 28 after induction chemotherapy. The controls also provided blood samples. Relative gene expression was quantified by PCR and determined using the comparative Ct method. Publicly available clinical data and gene expressions for 188 patients with AML were downloaded from TCGA data portal. RESULTS: Compared with healthy controls, the expression of miRNA-181a-3p was significantly increased in patients with AML. MiR-181a-3p expression could be used to discriminate AML patients from controls, with up-regulated expression correlating with favorable prognosis. Moreover, miRNA-181a-3p expression was significantly decreased in patients who achieved a complete response after induction chemotherapy. The multivariate Cox analysis highlighted the prognostic value of miR-181a-3p for patients with AML. Finally, we found that miR-181a-3p expression was negatively correlated with the expression of the NF-κB essential modulator (NEMO/IKBKG). CONCLUSIONS: MiR-181a-3p may be clinically useful as a disease marker for AML, and enhanced the prediction of patient outcomes to chemotherapy.

Pulmonary Langerhans cell histiocytosis in adults: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease of unknown aetiology. While it may affect any organ of the body, few cases of solitary lung involvement are published in the literature. Here, we report a rare case of pulmonary LCH (PLCH) in an adult. CASE SUMMARY: A 52-year-old male presented to hospital in July 2018 with complaints of progressively worsening cough with sputum, breathlessness, easy fatigability, and loss of appetite since 2016, and a 32-year history of heavy cigarette smoking (average 30 cigarettes/d). Physical examination showed only weakened breathing sounds and wheezing during lung auscultation. Chest computed tomography (CT) showed irregular micronodules and multiple thin-walled small holes. Respiratory function tests showed a slight decrease. Ultrasonic cardiogram showed mild tricuspid regurgitation and no pulmonary hypertension. Fibreoptic bronchoscopy was performed with transbronchial biopsies from the basal segment of right lower lobe. LCH was confirmed by immunohistochemistry. The final diagnosis was PLCH without extra-pulmonary involvement. We suggested smoking cessation treatment. A 3-mo follow-up chest CT scan showed clear absorption of the nodule and thin-walled small holes. The symptoms of cough and phlegm had improved markedly and appetite had improved. There was no obvious dyspnoea. CONCLUSION: Imaging manifestations of nodules, cavitating nodules, and thick-walled or thin-walled cysts prompted suspicion of PLCH and lung biopsy for diagnosis.

Fabrication of Concentric Carbon Nanotube Rings and Their Application on Regulating Cell Growth.

The carbon nanotube (CNT) pattern plays an important role in various electronic devices and biological fields for its superior conductivity and biocompatibility. Herein, we fabricated regularly arranged concentric multiwalled carbon nanotube (MWCNT) rings in a Petri dish by evaporation-driven self-assembly technology. By adjusting the dispersion ratio, heating temperature, and solution volume, various MWCNT rings with different shapes and morphologies were obtained. The variation law of ring radius, formation range, and ring numbers was processed with statistical analysis. With fine adjustment of parameters, the control of desired MWCNT rings can be achieved for further scientific researches. By culturing L929 cells with these rings, oriented cell growth along the rings was achieved, which is of significance for cell regulation, tissue repairing, and related biological applications.

Design, Synthesis, and Biological Evaluation of 6-Benzoxazole Benzimidazole Derivatives with Antihypertension Activities.

A series of new angiotensin II receptor 1 antagonists were prepared. They displayed nanomolar affinity to AT1 receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. Among them, compounds 1b and 2b could reduce the blood pressure with more or equal potency compared to Losartan. So, compounds 1b and 2b could be considered as potential antihypertension drug candidates.