Efficacy and safety of fondaparinux in preventing venous thromboembolism in Chinese cancer patients: a single-arm, multicenter, retrospective study.

Objective: Fondaparinux is a synthetic anticoagulant for the prevention of venous thromboembolism (VTE), and its administration in Chinese cancer patients is rarely reported. This study aimed to assess the efficacy and safety of fondaparinux in preventing VTE in Chinese cancer patients. Methods: A total of 224 cancer patients who received fondaparinux treatment were reviewed in this single-arm, multicenter, retrospective study. Meanwhile, VTE, bleeding, death, and adverse events of those patients in the hospital and at 1 month after treatment (M1) were retrieved, respectively. Results: The in-hospital VTE rate was 0.45% and there was no (0.00%) VTE occurrence at M1. The in-hospital bleeding rate was 2.68%, among which the major bleeding rate was 2.23% and the minor bleeding rate was 0.45%. Moreover, the bleeding rate at M1 was 0.90%, among which both the major and minor bleeding rates were 0.45%. The in-hospital death rate was 0.45% and the death rate at M1 was 0.90%. Furthermore, the total rate of adverse events was 14.73%, including nausea and vomiting (3.13%), gastrointestinal reactions (2.23%), and reduced white blood cells (1.34%). Conclusion: Fondaparinux could effectively prevent VTE with low bleeding risk and acceptable tolerance in cancer patients.

The regional impact of the COVID-19 lockdown on the air quality in Ji'nan, China.

A number of strict lockdown measures were implemented in the areas most affected by COVID-19 in China, including Ji'nan city, from 24 January to 7 February 2020. Due to these forced restrictions, the pollution levels in cities across the country drastically decreased within just a few days. Since traffic pollution and industrial emissions are important factors affecting regional air quality, congestion has a significant impact on the environment. Therefore, using the aid of air quality data for six pollutants (PM10, PM2.5, SO2, NO2, CO and O3) from 11 monitoring stations (located in urban, suburban and urban-industrial regions) across Ji'nan, we employed the air quality index (AQI) to investigate the spatial pattern of air quality in the pre-COVID-19 (pre-COVID) and COVID-19-related lockdown (COVID lockdown) periods. The results showed that air quality significantly improved during the COVID lockdown period. Among the selected pollutants, compared to the corresponding pre-COVID levels, the greatest reduction was observed for the concentration of NO2 (54.02%), while the smallest reduction was observed for the concentration of SO2 (27.92%). The PM2.5 (38.73%), PM10 (44.92%) and CO (30.60%) levels also decreased during the COVID lockdown period; only the O3 concentration increased (37.42%) during this period. Overall, air quality improved by approximate improvements of 37.33% during the COVID lockdown period. Approximately 35.48%, 37.01% and 43.43% in the AQI were observed in urban, suburban and urban-industrial regions, respectively. Therefore, the AQI exhibited remarkable regional differences in Ji'nan. This study demonstrates the contributions of the transportation sector and local emissions to improving air quality in typical urban areas, and these research results can provide guidance for the further monitoring of air pollution in northern Chinese cities.

microRNA-206 Suppresses Cholangiocarcinoma Cell Growth and Invasion by Targeting Jumonji AT-Rich Interactive Domain 2.

BACKGROUND: The current study set out to elucidate the specific role of microRNA (miR)-206 in cholangiocarcinoma (CCA) cell biological activities by negatively modulating jumonji AT-rich interactive domain 2 (JARID2). METHODS: Firstly, human intrahepatic biliary epithelial cells and CCA cell lines were selected via the analysis of miR-206 and JARID2 expression patterns in CCA by qRT-PCR. Next, the target relation between miR-206 and JARID2 was predicted by Targetscan and validated using dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Subsequently, CCK-8 method, colony formation assay, scratch test, Transwell assay, and western blot analysis were performed to evaluate cancer cell development after the overexpression of miR-206 and/or JARID2, with levels of invasion-related proteins assessed. In addition, xenograft transplantation was also employed to confirm the role of miR-206 in vivo. Lastly, Ki-67 expression pattern was also quantified with immunohistochemistry. RESULTS: It was found that miR-206 was poorly expressed and JARID2 was highly expressed in CCA cell lines. Also, miR-206 overexpression brought about a suppressive effect on cancer cell proliferation, migration, and invasion. Furthermore, miR-206 was observed to target JARID2. Meanwhile, JARID2 overexpression promoted cell growth, while simultaneous overexpression of miR-206 and JARID2 impeded malignant cancer progression, indicating that miR-206 overexpression inhibited cell progression via targeting JARID2. Finally, in vivo experimentation illustrated that miR-206 overexpression suppressed tumor growth and weight, and inhibited the expressions of JARID2 N-cadherin, vimentin, and Ki-67. CONCLUSION: Altogether, our findings clarified that miR-206 inhibited CCA malignancy by negatively regulating JARID2.

A Modified VATS Procedure for Treating Adult Intralobar Pulmonary Sequestration.

Video-assisted thoracoscopic surgery (VATS) makes it possible to treat intralobar sequestration (ILS) more minimally invasive compared with conventional open surgery. However, this procedure is challenging to expose and isolate the aberrant arteries of ILS and the risk of bleeding is high. Herein, we developed a modified VATS procedure in which the aberrant vessels are treated in the last step of lobectomy, rather than at the beginning. In this way, we can expose the aberrant vessels easier and reduce the risk of massive blood loss, also simplifying the surgical procedure.

LncRNA ANCR Promotes Invasion and Migration of Gastric Cancer by Regulating FoxO1 Expression to Inhibit Macrophage M1 Polarization.

BACKGROUND: Long non-coding RNAs (LncRNAs) are closely related to the occurrence of cancer, but its mechanism in gastric cancer (GC) is still largely unclear. AIMS: This study aimed to reveal the underlying mechanism of LncRNA ANCR in GC. METHODS: The expression of LncRNA ANCR was detected by qRT-PCR. ELISA was used to identify THP-1 cells into macrophage M1 type polarization. After macrophages overexpressing LncRNA ANCR were co-cultured with GC cell HGC-27, the invasion and metastasis of GC were analyzed by Transwell assay. The targeted regulation of FoxO1 by LncRNA ANCR was analyzed by RNA pull-down, RNA immunoprecipitation (RIP), and Western blot. The BALB/c nude mouse model of GC was established to analyze the effect of LncRNA ANCR on tumor growth. RESULTS: LncRNA ANCR was highly expressed in GC. The overexpression of LncRNA ANCR in macrophages reduced the concentrations of M1 macrophage polarized marker molecules IL-1ß and IL-6 in the supernatant of cells, and inhibited the polarization of macrophages to M1, while the knockdown of LncRNA ANCR produced the opposite effect. The co-culture of macrophages overexpressing LncRNA ANCR with GC cells promoted the invasion and migration of cells. LncRNA ANCR targeted FoxO1 and inhibited the expression of FoxO1 in THP-1 cells by promoting FoxO1 ubiquitination degradation. In addition, the overexpression of LncRNA ANCR promoted tumor growth in a BALB/c nude mouse model of GC, while the knockdown of LncRNA ANCR produced the opposite effect. CONCLUSIONS: Based on these results, the overexpression of LncRNA ANCR promoted the invasion and metastasis of GC cells via down-regulating FoxO1 to inhibit macrophage polarization to M1.

Surgical treatment to multiple primary lung cancer patients: a systematic review and meta-analysis.

BACKGROUND: As there is no consensus on the optimal surgery strategy for multiple primary lung cancer (MPLC), we conducted this study to address this issue by comparing the prognosis of MPLC patients underwent different surgical strategies including sublobar resection and the standard resection through a systemic review and meta-analysis. METHODS: Relevant literature was obtained from three databases including PubMed, Embase and Web of Science. Inclusion and exclusion criteria were set for the screening of articles to be selected for further conduction of systemic review and meta-analysis. The HRs of OS of the sublobar group compared with standard resection group were extracted directly or calculated indirectly from included researches. RESULTS: Ten researches published from 2000 to 2017 were included in this study, with 468 and 445 MPLC cases for the standard resection group and sublobar resection group respectively. The result suggested that OS of MPLC patients underwent sublobar resection (segmentectomy or wedge resection for at least one lesion) was comparable with those underwent standard resection approach (lobectomy or pneumonectomy for all lesions), with HR 1.07, 95% CI 0.67-1.71, p = 0.784. Further analysis found no difference in subgroups of synchronous and metachronous (from second metachronous lesion), different population region and dominant sex type. CONCLUSIONS: This study may reveal that sublobar resection is acceptable for patients with MPLC at an early stage, because of the equivalent prognosis to the standard resection and better pulmonary function preservation. Further research is needed to validate these findings.

[Study on the chemical constituents of Pithecellobium clypearia].

OBJECTIVE: To study the chemical constituents of Pithecellobium clypearia. METHODS: Silica gel column chromatography and Sephadex LH-20 were used to separate and purify compounds from the EtOAc soluble fraction of Pithecellobium clypearia. 9 compounds were elucidated on the basis of physicochemical properties and spectrascopic analysis. RESULTS: They were identified as beta-Sitosterol (1), tritriacontane (2), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (3), oleanolic acid (4), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (5), alpha-amyrin (6), luteolin (7), ursolic acid (8), luteoloside (9). CONCLUSION: Compounds 3 and 5 are isolated from this plant for the first time.

[Polymorphism in BP1 binding site upstream of ß-globin gene in Chinese Han population].

This study was aimed to analyze the BP1 binding site sequence upstream of ß-globin gene in Chinese Han population, and to investigate polymorphism in the BP1 binding site upstream of ß-globin gene, so as to provide the basis for exploration of relation between polymorphisms in the BP1 binding site and ß-globin expression. Genomic DNA was extracted from peripheral leukocytes of 110 healthy individuals in Chinese Han population. Sequence of the BP1 binding site upstream of ß-globin gene was amplified by polymerase chain reaction, the polymorphic variation in the BP1 binding site was determined by DNA sequencing. The results indicated that 2 polymorphism loci were found in the BP1 binding site upstream of ß-globin gene, they were C/T at the -551 bp region and (AC)(n)(AT)(x)T(y) at the -530 bp region in Chinese Han population. Frequencies of C and T were 60.4% and 39.6% at position -551. Analysis of the (AC)(n)(AT)(x)T(y) polymorphism revealed 9 different genotypes: (AC)(2)(AT)(9)T(5), (AC)(2)(AT)(8)T(5), (AC)(2)(AT)(7)T(7), (AC)(3)(AT)(7)T(5), (AC)(2)(AT)(8)T(9), (AC)(3)(AT)(8)T(5), (AC)(2)(AT)(10)T(3), (AC)(2)(AT)(11)T(3), and (AC)(2)(AT)(7)T(5) at position -530. Frequencies of 9 (AC)(n)(AT)(x)T(y) polymorphisms were 33.2%, 29.1%, 24.1%, 5.4%, 3.2%, 1.8%, 1.4%, 0.9%, and 0.9% respectively. It is concluded that rich (AC)(n)(AT)(x)T(y) polymorphisms at the -530 bp region in the BP1 binding site upstream of ß-globin gene are found in Chinese Han population. (AC)(2)(AT)(9)T(5), (AC)(2)(AT)(8)T(5), and (AC)(2)(AT)(7)T(7) are 3 major polymorphisms among Chinese Han population, and (AC)(3)(AT)(8)T(5) is a novel polymorphism at the -530 bp region. More studies should be done to explore relation between (AC)(n)(AT)(x)T(y) polymorphisms and ß-globin expression.

Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by δ-elemene.

  Î´-Elemene, an antitumor component, is a chemical compound isolated from Curcuma wenyujin, a Chinese traditional herb. We examined whether δ-elemene could inhibit cell growth and cell cycle progression and induce apoptosis in human leukemia HL-60 cells. The results demonstrated that δ-elemene induces significant apoptosis of HL-60 cells, as shown by MTT assay, annexin V (AnV) binding of externalized phosphatidylserine (PS), and the mitochondrial probe JC-1 using flow cytometry. HL-60 cells treated with δ-elemene showed high percentages in the early apoptotic and late apoptoctic/necrotic stages, as well as caspase-3 activation of HL-60 cells. By monitoring the changes in cell cycle profiles, we confirmed that δ-elemene could interfere with the cell cycle in the G2/M phase and induce apoptosis in HL-60 cells in a time-dependent manner. Caspase-3 plays a direct role in proteolytic cleavage of the cellular proteins responsible for progression to apoptosis. Therefore we examined apoptosis in HL-60 cells after exposure to δ-elemene and measured caspase-3 activities with or without Z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk, a broad-spectrum caspase inhibitor) pretreatment using flow cytometric analysis. The results showed that δ-elemene could induce caspase-3 activation as detected by the decrease in δ-elemene-induced caspase-3 activities after treatment with z-VAD-fmk. In the present study, δ-elemene activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an inhibitory effect of z-VAD-fmk on this cell death. During δ-elemene-induced apoptosis, cytochrome c and apoptosis-inducing factor were released into the cytosol and BAX was translocated from the cytosol to mitochondria. However, these were not prevented by z-VAD-fmk. In conclusion, our study demonstrated that δ-elemene could induce G2/M cell cycle transition and trigger apoptosis through a caspase-3-dependent pathway.

[Analysis of GJB2 gene coding sequence in patients with nonsyndromic hearing loss].

OBJECTIVE: To analyze the coding sequence of GJB2 gene in six pedigrees with nonsyndromic hearing loss in order to find deafness-causing mutations in the GJB2 gene, and to explore the inherent pattern of deafness-causing mutations in the GJB2 gene. METHODS: Genomic DNA was extracted from peripheral blood for the probands and their family members. Coding sequence of the GJB2 gene was amplified by polymerase chain reaction, sequence variations were determined by DNA sequencing. Amplified fragments with overlapping peaks on sequencing chromatogram were sequenced by TA cloning in order to determine whether the mutations originated from the same allele. RESULTS: Mutations in the GJB2 gene were found in 4 out of the 6 pedigrees with nonsyndromic hearing loss. Four types of mutations were detected in the GJB2 gene, which were 235delC, 299-300delAT, 79G>A+341A>G, and 109G>A. Compound heterozygous polymorphisms 79G>A and 341A>G, and mutations 109G>A and 235delC had deafness-causing effects. CONCLUSION: Heterogeneous mutations of the GJB2 gene are frequently seen in patients with nonsyndromic hearing loss. Sometimes, polymorphisms may cause deafness when they are combined. Environmental factors and other genes may contribute to hearing loss caused by the GJB2 gene mutations.

Cell apoptosis induced by delta-elemene in colorectal adenocarcinoma cells via a mitochondrial-mediated pathway.

The chemical compound delta-elemene, isolated from the Chinese herbal medicine plant Curcuma Wenyujin, has been known to exert antitumor activity. In this study we demonstrated that apoptotic cell death induced by delta-elemene in DLD-1 cells was concentration-and time-dependent, and had little inhibition of the normal human liver cell line WRL-68. Apoptosis was further confirmed and quantified by DNA fragmentation ELISA, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. The rapid increase in intracellular reactive oxygen species (ROS) levels was involved in the mechanism of cell death. Western blot analysis demonstrated that delta-elemene activated the caspase-signaling pathway, leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and the subsequent cleavage of the caspase substrate PARP. In the process of the induction of apoptotic cell death, Bax translocated into mitochondria, a reduction in Deltapsim was observed and a release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria into the cytosol occurred, indicating that cell death induced by delta-elemene was through a mitochondrial-mediated pathway.

[Novel double heterozygous mutations on Met306Val and Thr181Asn related to a hereditary coagulation factor VII deficiency].

OBJECTIVE: To identify the genetic defect of coagulation factor VII in a Chinese family with hereditary FVII deficiency. METHODS: Peripheral blood samples were collected from the proband of hereditary FVII deficiency, female, aged 15, 4 members of her family, and 100 healthy persons. Genomic DNA was isolated. All the exons and exon-intron boundaries of FVII gene were amplified by PCR, then the PCR products were sequenced by direct sequencing. Restrictive endonuclease analysis was performed in all of the family members and the 100 healthy donors to exclude gene polymorphism. Biostructural analysis of the mutated FVII was completed by molecular modeling. RESULTS: Double heterozygous mutations in the proband were identified: A-->G mutation at position 10833 and C-->A mutation at position 9643, resulting in Met306Val and Thr181Asn substitution respectively. Heterozygosity for Met306Val was confirmed in the proband's mother and her elder sister; heterozygosity for Thr181Asn was confirmed in the proband's father. It was found by computer simulated molecular model that the Met306Val replacement, which was located on the surface of the FVII molecule, might cause steric hindrance and change the configuration and function of FVII protein. CONCLUSION: Double heterozygous mutations for Met306Val and Thr181Asn in FVII gene have been found in a proband with hereditary FVII deficiency. The Met306Val substitution in FVII gene is a novel mutation in hereditary FVII deficiency. The heterozygous mutation of FVII gene may change the configuration of FVII protein and result in FVII dysfunction.