MiR-371-5p regulates trophoblast cell proliferation, migration, and invasion by directly targeting ZNF516.

Despite its prevalence, preeclampsia (PE) remains unclear as to its etiology. Here, we aimed to investigate the mechanisms regulating differences in the gene expression of zinc-finger protein 516 (ZNF516) in the placenta. The expression of the placental ZNF516 gene and its association with critical clinical markers were verified, and a rigorous correlation analysis was conducted. With a dual-luciferase reporter gene assay, microRNA targeting the ZNF516 gene was predicted and confirmed. Finally, the molecular processes associated with ZNF516 were explored via microarray and bioinformatic analyses. In hypoxic conditions, miR-371-5p expression was reduced, resulting in ZNF516 expression being induced. Moreover, ZNF516 was shown to hinder trophoblast cell migration and invasion while enhancing trophoblast cell death in various in vitro cellular assays, such as cell counting kit-8, colony formation, wound healing, and Transwell assays. Our findings reveal a new regulatory network facilitated by ZNF516. ZNF516 overexpression inhibits trophoblast growth, movement, and penetration, potentially causing problems with placenta formation with the help of miR-371-5p suppression.

Do government policies drive institutional preferences on green investment? Evidence from China.

Through the introduction of green finance policies, governments hope to improve the guiding role of institutional investors in green investment and provide financial support for green enterprises. Using the data in China, the difference-in-difference (DID) analysis explores whether the implementation of policies could change institutional investors' attitude to environmental factors when making investment decisions. Considering the effect of investment horizons, we find that long-term institutional investors have shown symmetric preferences on green investment, while short-term institutions are more affected by green finance policies. Additionally, the mechanism analysis shows that green finance policies can influence the green investment of institutional investors not only by affecting stock price returns but also by increasing the innovation capabilities of green companies and thus improving corporate performance. Besides, heterogeneity and moderating effect analyses find that green finance policies can achieve better policy effects when financial institutions invest in non-state-owned enterprises, enterprises with higher quality of information disclosure and poor external supervision. The finding would extend the studies of green investment in emerging markets and present new evidence about the policy effect on institutions' preferences for green investment.

Successful response to camrelizumab in metastatic bladder cancer: A case report.

BACKGROUND: There has been no report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive programmed death-ligand 1 (PD-L1) expression and high tumor mutational burden (TMB). More effective predictors of bladder cancer immunotherapy have yet to be explored, and the combination of multiple factors may be more predictive than a single factor. CASE SUMMARY: We report the case of a 74-year-old male patient with recurrent metastatic bladder cancer, which demonstrated positive PD-L1 expression and high TMB. The immune checkpoint inhibitor camrelizumab was administered to the patient in combination with gemcitabine and cisplatin. The patient achieved a partial response with a progression-free survival of 11 mo. CONCLUSION: This is the first report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive PD-L1 expression and high TMB.

Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells.

BACKGROUND: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. METHODS: Reverse transcription-polymerase chain reaction and western blot were used to detect PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used to detect cell viability, 5-Ethynyl-2'- deoxyuridine and a soft agar assay were used to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was detected by trans-well assay. Survival rate and tumor size were measured by nude mice transplantation. RESULTS: The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7 cell lines (P<.05). After the PDGF-D gene was silenced, the growth and colony forming abilitys ignificantly decreased (P<.05) together with the induction of apoptosis in MDA-MB-231 cells (P<.05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished aggressive migration and invasion potential compared to other cells (P<.05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth and improved the survival rate of tumor-bearing mice. CONCLUSION: Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation, apoptosis and migration, which indicates that it plays an important role in breast cancer development and progression.

EGFR Thr790Leu as a Potential Resistance Mechanism to First-Generation EGFR Tyrosine Kinase Inhibitor May Respond to Osimertinib in Patients With Lung Adenocarcinoma.

INTRODUCTION: It has been well established that EGFR Thr790Met is one of the major resistance mechanisms to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, whether EGFR Thr790Leu (T790L), which shares the mutation site of Thr790 with EGFR Thr790Met, mediates resistance to EGFR TKIs remains elusive. The treatment options for patients harboring this rare mutation have not been reported. METHODS: Capture-based targeted ultradeep sequencing was performed on tumor and plasma samples collected at various treatment milestones from three patients with advanced lung adenocarcinoma undergoing targeted therapy. RESULTS: Needle biopsy of lymph node metastasis from patient 1 revealed EGFR T790L at disease progression on first-line treatment of gefitinib. Patient 2 had EGFR T790L identified from needle biopsy of lung tissue at disease progression on icotinib treatment. This patient was subsequently treated with osimertinib and achieved stable disease with a progression-free survival of 9 months. For patient 3, at disease recurrence after surgery, resected lung tumor tissue was retrieved for molecular profiling and revealed EGFR exon 19 deletion and EGFR T790L. The patient subsequently received osimertinib treatment and continued to benefit for 16 months and counting. She has maintained stable disease at the time of submission of this manuscript. CONCLUSIONS: We revealed for the first time that EGFR T790L may serve as a potential resistance mechanism to first-generation EGFR TKIs. We also report the first clinical evidence of efficacy generated by osimertinib in patients with lung adenocarcinoma harboring primary or acquired EGFR T790L, shedding light on treatment options for this subset of patients.

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. METHODS: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. RESULTS: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. CONCLUSIONS: MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

MicroRNAs and long non-coding RNAs in liver surgery: Diagnostic and therapeutic merits.

BACKGROUND: Hepatectomy and liver transplantation (LT) are the two most commonly performed surgical procedures for various hepatic lesions. microRNA (miRNA) and long non-coding RNA (lncRNA) have been gradually unveiled their roles as either biomarkers for early diagnosis or potentially therapeutic tools to manipulate gene expression in many disease entities. This review aimed to discuss the effects of miRNA or lncRNA in the hepatectomy and LT fields. DATA SOURCES: We did a literature search from 1990 through January 2018 to summarize the currently available evidence with respect to the effects of miRNA and lncRNA in liver regeneration after partial hepatectomy, as well as their involvement in several key issues related to LT, including ischemia-reperfusion injury, allograft rejection, tolerance, recurrence of original hepatic malignancies, etc. RESULTS: Certain miRNAs and lncRNAs are actively involved in the regulation of various aspects of liver resection and transplantation. During the process of liver regeneration after hepatectomy, the expression of miRNAs and lncRNAs shows dynamic changes. CONCLUSIONS: It is now clear that miRNAs and lncRNAs orchestrate in various aspects of the pathophysiological process of LT and hepatectomy. Better understanding of the underlying mechanism and future clinical trials may strengthen their positions as either biomarkers or potential therapeutic targets in the management of complications after liver surgery.

Core stability training on an unstable surface better improves ambulation and static balance after thoracolumbar fracture with incomplete spinal cord injury / 中华物理医学与康复杂志

Objective:To explore the effect of conducting core stability training (CST) on an unstable supporting surface using thoracolumbar fracture patients with an incomplete spinal cord injury.Methods:Forty thoracolumbar fracture patients with incomplete spinal cord injury were randomly divided into an experiment group and a control group, each of twenty. Both groups received 30 minutes of CST five times per week for 8 weeks. The patients in the control group were trained on a stable supporting surface while those in the experiment group used an unstable surface. Evaluations were conducted before and after the 8-week intervention. Gait and static balance data were collected and analyzed using 3D motion analysis software and an EAB-100 active balancer.Results:After the intervention, the average stride length and comfortable walking speed of the experimental group were both significantly better than the control group′s averages. Moreover, the path length, circumferential area, rectangular area and effective value area of the Romberg rate were all significantly better, on average, in the experiment group, as was the average displacement of the deflection center with the eyes closed in static balance.Conclusions:An unstable supporting surface is superior to a stable one for conducting CST after thoracolumbar fracture with incomplete spinal cord injury. The effect may be due to improved nonvisual postural control.

Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice.

BACKGROUND: Pancreatic cancer (PC) represents one of the most aggressive forms of cancer. The role of long non-coding RNAs (lncRNAs) has been highlighted in various malignancies including PC. The aim of the present study was to investigate the effects associated with actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on the progression of PC and the underlying mechanism. METHODS: Microarray-based gene expression profiling of PC was performed to identify PC-related lncRNAs, after which the expression of AFAP1-AS1 and cancer stem cell (CSC) markers in PC tissues and cells were determined accordingly. The potential microRNA-384 (miR-384) capable of binding to AFAP1-AS1, in addition to its ability to regulate activin receptor A type I (ACVR1) were analyzed. In order to investigate the effect of the AFAP1-AS1/miR-384/ACVR1 axis on self-renewal ability, tumorigenicity, invasion, migration and stemness of PC cells, shRNA-AFAP1-AS1, miR-384 mimic and inhibitor were cloned into cells. RESULTS: High expression of AFAP1-AS1 and ACVR1 with low expression of miR-384 were detected in PC tissues. ACVR1 was determined to be down-regulated when miR-384 was overexpressed, while the inhibition of AFAP1-AS1 decreased its ability to binding competitively to miR-384, resulting in the down-regulation of ACVR1 and enhancing miR-384 expression, ultimately inhibiting the progression of PC. The knockdown of AFAP1-AS1 or overexpression of miR-384 was confirmed to impair PC cell self-renewal ability, tumorigenicity, invasion, migration and stemness. CONCLUSIONS: Taken together, AFAP1-AS1 functions as an endogenous RNA by competitively binding to miR-384 to regulate ACVR1, thus conferring inhibitory effects on PC cell stemness and tumorigenicity.

The study of duration of indwelling ureteral stent after the ureteroscopic lithotripsy / 中华泌尿外科杂志

Objective To investigate the duration of indwelling ureteral stent after the ureteroscopic lithotripsy.Methods 300 cases of patients were retrospectively analyzed from June 2015 to June 2017,including 168 with renal calculi and 132 with non-incarcerated upper ureteral calculi.The size of stone is ＜2 cm in diameter.According to the length of time for indwelling ureteral stent,all patients were divided into two groups-150 cases in 14-day group (Group A) and 150 in the 28-day group (Group B) for comparing the complication and outcome,and then received modular flexible ureteroscopic lithotripsy combined with holmium laser.Lastly,6F ureteral stent was indwelling postoperatively.Results Complications happened in both two groups after stenting.There were 140 cases (93.3％) complained of bladder irritation symptoms (LUTS) in Group A,while 107 (71.3％) in Group B;85 cases (56.7％) suffered from flank or abdominal pain in Group A and 36 (24％) in Group B;gross hematuria happened in 133 cases (88.7％) of Group A and 60 cases (40％) of Group B.As the duration of indwelling ureteral stent extended,the incidence of complications increased,significantly (P ＜ 0.05).CT scan showed there was no statistical difference in stone-free rate (diameter ＜ 3 mm) of two groups [A group:91.3 ％ (137/150) vs.B group:89.3 ％ (134/150),respectively].Conclusion With high stone-free rate and low complication incidence,2-week indwelling ureteral stent is safe for patients suffered from renal calculi or non-incarcerated upper ureteral calculi (diameter ＜ 2 cm).

Primary tracheal schwannoma treated by surgical resection: a case report.

The rarity and non-specific symptoms of benign primary tracheal tumors always leaded to misdiagnosis and delayed treatment, and also undefined the optimal treatment. In this case, a 45-year-old woman had a history of progressive shortness of breath and dry cough for several years, CT scan revealed an intra-luminal tracheal mass invaded the left side of tracheal wall. After being located by bronchoscope preoperatively, the tumor was removed by surgical resection. The tumor was 1.5 cm in diameter with intact capsule. The pathological result confirmed the diagnosis of schwannoma.

Synthesis, Fungicidal Activity, and Structure Activity Relationship of ß-Acylaminocycloalkylsulfonamides against Botrytis cinerea.

In order to discover new antifungal agrochemicals that could have highly active and novel motifs, thirty-six new 2-acylaminocycloalkylsulfonamides (IV) were synthesized. Their structures were characterized and confirmed by 1H NMR, 13C NMR, IR, MS, elemental analysis and X-ray single crystal diffraction. In vitro and in vivo activities against various Botrytis cinerea strains were evaluated. Bioassay results revealed that most of the title compounds exhibited excellent in vitro fungicidal activity, in which compound IV-26 showed the highest activity against sensitive, low-resistant, moderate-resistant and high-resistant strains of B. cinerea compared with the positive fungicide procymidone. Meanwhile in vivo fungicidal activity of compound IV-31 was better than the commercial fungicides procymidone and chesulfamide in greenhouse trial. The structure activity relationship (SAR) was also discussed and the results were of importance to the structural optimization and development of more potent sulfonamides antifungal agents.

Non-fastidous antibiotic-resistance bacteria pollution in tap water / 军事医学

Objective To study the non-fastidous antibiotic-resistance bacteria pollution in tap water from a neighborhood in Tianjin.Methods Tap water samples were collected and bacteria were isolated by R2A agar,and 16S rRNA gene sequence for the identification of bacteria isolates was used.Antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method.Results Among the 39 non-fastidous bacteria isolates,the resistance rate of antibioticresistance bacteria was 79.49％,including Enterococcus,Staphylococcus,Acinetobacter and Pseudomonas.Some bacteria (28.21％) showed resistance against only one antibiotic.The others (51.28％) were multiple resistant bacteria.Trimethoprim/sulfamethoxazole resistance was most prevalent (53.85％),and sulfamethoxazole resistance was also widely distributed (28.21％).Conclusion Tap water from this neighborhood is heavily polluted by non-fastidous antibioticresistantance bacteria,which deserves more attention.

Self-made optical puncture needle combined with ureteral access sheath for renal calculi treatment / 实用医学杂志

Objective To evaluate the clinical value of a new optic puncture needle designed by our department for renal calculi treatment. Methods There were 8 patients undergoing micro-PCNL with the new device from June 2016 to February 2017. Values of basic demographic data ,operation time ,pain score ,drop in hemoglobin and complications were recorded. Results The mean stone size,operation time,pain score,drop in hemoglobin,and in-hospital time was(21.9 ± 7.3)mm,(43.6 ± 13.6)min,2.8 ± 1.3,7.0 g/L[(133.2 ± 10.3 g/L vs.(123.2 ± 13.9)g/L,P>0.05]and(3.1 ± 1.0)d,respectively. No patient required blood transfusion. Stone-free rate at 1 and 3 months post-operation were 87.5%(7/8)and 100%(8/8),respectively. One suffered urinary tract infections( ClavienⅠ)and was treated with antibiotics. There were no major complications. Conclusion The new device for treatment of renal calculi is feasible and effective.

Self-made optical puncture needle combined with ureteral access sheath for renal calculi treatment / 实用医学杂志

Objective To evaluate the clinical value of a new optic puncture needle designed by our department for renal calculi treatment. Methods There were 8 patients undergoing micro-PCNL with the new device from June 2016 to February 2017. Values of basic demographic data ,operation time ,pain score ,drop in hemoglobin and complications were recorded. Results The mean stone size,operation time,pain score,drop in hemoglobin,and in-hospital time was(21.9 ± 7.3)mm,(43.6 ± 13.6)min,2.8 ± 1.3,7.0 g/L[(133.2 ± 10.3 g/L vs.(123.2 ± 13.9)g/L,P>0.05]and(3.1 ± 1.0)d,respectively. No patient required blood transfusion. Stone-free rate at 1 and 3 months post-operation were 87.5%(7/8)and 100%(8/8),respectively. One suffered urinary tract infections( ClavienⅠ)and was treated with antibiotics. There were no major complications. Conclusion The new device for treatment of renal calculi is feasible and effective.

Comparison of community structures of Candidatus Methylomirabilis oxyfera-like bacteria of NC10 phylum in different freshwater habitats.

Methane oxidation coupled to nitrite reduction is mediated by 'Candidatus Methylomirabilis oxyfera' (M. oxyfera), which belongs to the NC10 phylum. In this study, the community composition and diversity of M. oxyfera-like bacteria of NC10 phylum were examined and compared in four different freshwater habitats, including reservoir sediments (RS), pond sediments (PS), wetland sediments (WS) and paddy soils (PAS), by using Illumina-based 16S rRNA gene sequencing. The recovered NC10-related sequences accounted for 0.4-2.5% of the 16S rRNA pool in the examined habitats, and the highest percentage was found in WS. The diversity of NC10 bacteria were the highest in RS, medium in WS, and lowest in PS and PAS. The observed number of OTUs (operational taxonomic unit; at 3% cut-off) were 97, 46, 61 and 40, respectively, in RS, PS, WS and PAS. A heterogeneous distribution of NC10 bacterial communities was observed in the examined habitats, though group B members were the dominant bacteria in each habitat. The copy numbers of NC10 bacterial 16S rRNA genes ranged between 5.8 × 10(6) and 3.2 × 10(7) copies g(-1) sediment/soil in the examined habitats. These results are helpful for a systematic understanding of NC10 bacterial communities in different types of freshwater habitats.

Evidence for anaerobic ammonium oxidation process in freshwater sediments of aquaculture ponds.

The anaerobic ammonium oxidation (anammox) process, which can simultaneously remove ammonium and nitrite, both toxic to aquatic animals, can be very important to the aquaculture industry. Here, the presence and activity of anammox bacteria in the sediments of four different freshwater aquaculture ponds were investigated by using Illumina-based 16S rRNA gene sequencing, quantitative PCR assays and (15)N stable isotope measurements. Different genera of anammox bacteria were detected in the examined pond sediments, including Candidatus Brocadia, Candidatus Kuenenia and Candidatus Anammoxoglobus, with Candidatus Brocadia being the dominant anammox genus. Quantitative PCR of hydrazine synthase genes showed that the abundance of anammox bacteria ranged from 5.6 × 10(4) to 2.1 × 10(5) copies g(-1) sediment in the examined ponds. The potential anammox rates ranged between 3.7 and 19.4 nmol N2 g(-1) sediment day(-1), and the potential denitrification rates varied from 107.1 to 300.3 nmol N2 g(-1) sediment day(-1). The anammox process contributed 1.2-15.3% to sediment dinitrogen gas production, while the remainder would be due to denitrification. It is estimated that a total loss of 2.1-10.9 g N m(-2) per year could be attributed to the anammox process in the examined ponds, suggesting that this process could contribute to nitrogen removal in freshwater aquaculture ponds.

Distribution and activity of anaerobic ammonium-oxidising bacteria in natural freshwater wetland soils.

Anaerobic ammonium oxidation (anammox) process plays a significant role in the marine nitrogen cycle. However, the quantitative importance of this process in nitrogen removal in wetland systems, particularly in natural freshwater wetlands, is still not determined. In the present study, we provided the evidence of the distribution and activity of anammox bacteria in a natural freshwater wetland, located in southeastern China, by using (15)N stable isotope measurements, quantitative PCR assays and 16S rRNA gene clone library analysis. The potential anammox rates measured in this wetland system ranged between 2.5 and 25.5 nmol N2 g(-1) soil day(-1), and up to 20% soil dinitrogen gas production could be attributed to the anammox process. Phylogenetic analysis of 16S rRNA genes showed that anammox bacteria related to Candidatus Brocadia, Candidatus Kuenenia, Candidatus Anammoxoglobus and two novel anammox clusters coexisted in the collected soil cores, with Candidatus Brocadia and Candidatus Kuenenia being the dominant anammox genera. Quantitative PCR of hydrazine synthase genes showed that the abundance of anammox bacteria varied from 2.3 × 10(5) to 2.2 × 10(6) copies g(-1) soil in the examined soil cores. Correlation analyses suggested that the soil ammonium concentration had significant influence on the activity of anammox bacteria. On the basis of (15)N tracing technology, it is estimated that a total loss of 31.1 g N m(-2) per year could be linked the anammox process in the examined wetland.