LINC00161 upregulated by M2-like tumor-associated macrophages promotes hepatocellular carcinoma progression by methylating HACE1 promoters.

M2-like tumor-associated macrophages (M2-TAM) played an essential part in hepatocellular carcinoma (HCC) progression. Long intergenic noncoding RNA 00161 (LINC00161), is a long non-coding RNA, that was related to HCC development. However, the relationship between LINC00161 and TAM remains indistinct. HCC cells were cocultured with an M2-like conditioned medium (M2-CM). cell counting kit-8 (CCK-8), plate cloning, cell scratch, and transwell assay evaluated cell biological activities of HCC cells. The interactions among molecules were analyzed by chromatin immunoprecipitation (CHIP), dual-luciferase reporter, and RNA immunoprecipitation (RIP). The methylation status of HECT domain and ankyrin repeat-containing, E3 ubiquitin protein ligase 1 (HACE1) was evaluated using methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). The xenograft model was established in vivo using subcutaneous nude mice. Histological analyses were performed using hematoxylin-eosin (HE) staining. The expression of molecules was determined using immunohistochemistry (IHC), western blot and quantitative real-time PCR (qPCR). LINC00161 expression was promoted in HCC. LINC00161 knockdown significantly reduced HCC cell proliferation, migration, and invasion. Additionally, M2-TAM stimulated LINC00161 transcription and expression in HCC cells by secreting hepatocyte growth factor (HGF) to activate the Met/NFκB pathway. LINC00161 suppressed HACE1 expression, and knockdown of LINC00161 decreased the methylation on the HACE1 promoter. Meanwhile, a binding relationship between the enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and HACE1 was observed. LINC00161 overexpression increased the binding of EZH2 on the HACE1 promoter region. Furthermore, LINC00161 knockdown suppressed tumor growth in vivo and induced HACE1 expression by inhibiting its methylation. LINC00161, induced by M2-TAM, played a pivotal role in contributing to HCC development by recruiting EZH2 to promote the methylation of HACE1. This underscores the significant involvement of LINC00161 in mediating the progression of HCC.

Influence of Lacidophilin Vaginal Capsules plus rh-IFN-α2b on Efficacy, Vaginal Microecology, and Safety of Patients with HPV Infection.

Background: Human papillomavirus (HPV) is a self-limiting disease, and there is no specific antiviral drug at present. Purpose: Here, we analyzed the influence of lacidophilin vaginal capsules plus recombinant human interferon α-2b (rh-IFN-α2b) on efficacy, vaginal microecology, and safety of patients with HPV infection. Two hundred cases of HPV infection admitted between January 2019 and December 2020 were retrospectively collected. Of them, 90 cases receiving rh-IFN-α2b intervention were assigned to the control group (CG), and 110 cases given lacidophilin vaginal capsules in addition to rh-IFN-α2b were included in the research group (RG). Baseline data, efficacy, vaginal microecology, microecological restoration recovery, and incidence of adverse events (AEs) were compared between the two groups. Results: The analyses revealed nonsignificant difference in baseline data between RG and CG, indicating comparability. In terms of efficacy, RG showed a statistically higher negative conversion ratio (NCR) than CG (57.27% vs. 47.78%), as well as an obviously higher overall response rate (ORR) (90.90% vs. 72.22%). As far as the vaginal microecology was concerned, the incidence rates of catalase-positive, sialidase-positive, abnormal microbial density, and abnormal microbial diversity of RG were significantly lower compared with CG, but no evident differences were determined in Trichomonas vaginalis-positive and Candida-positive. As for microecological restoration, RG had an obviously higher vaginal microecological recovery rate than CG (90.00% vs. 65.56%), as well as notably lower vaginal secretion pH and Nugent score. On the other hand, RG and CG showed no statistical significance in the incidence of AEs (12.73% vs. 13.33%). Conclusions: The main contributions of this study are as follows: first, it is confirmed that lacidophilin vaginal capsules plus rh-IFN-α2b has better clinical effects than rh-IFN-α2b alone in HPV-infected patients; second, it demonstrates that the combination therapy can significantly improve NCR and ORR, without increasing the incidence of AEs, and is beneficial to improve patients' vaginal microecology and promote its restoration from the multidimensional aspects of efficacy, safety, and vaginal microecology and its recovery. Our findings provide valuable clinical evidence for the drug treatment of HPV-infected patients.

Cabergoline possesses a beneficial effect on blood-brain barrier (BBB) integrity against lipopolysaccharide (LPS).

Sepsis is a disease induced by severe systemic inflammation and contributes to multiple acute organic dysfunctions. It is reported that disrupted blood-brain barrier (BBB) integrity is involved in sepsis-associated encephalopathy (SAE), which can be alleviated by repairing the damaged tight junction structure. Cabergoline is a specific dopamine D2 receptor agonist developed to treat Parkinson's disease and hyperprolactinemia and is reported to exert promising anti-inflammatory properties. The present study aimed to explore the beneficial effect of Cabergoline for the treatment of sepsis. In the animal experiments, mice were separated into 4 groups: sham, LPS (5 mg/kg), Cabergoline (0.1 mg/kg/day), and Cabergoline+LPS. We found that the increased neurological deficits, disrupted BBB integrity, elevated production of inflammatory factors, and declined expression level of zonula occludens-1 (ZO-1) were observed in lipopolysaccharide (LPS)-treated mice, all of which were significantly reversed by the administration of Cabergoline. In the in vitro model, human brain microvascular endothelial cells (HBMECs) were challenged with 1 µg/mL LPS in the presence or absence of Cabergoline (10, 20 µM) for 24 hours. The elevated cell permeability Papp value of fluorescein disodium across the HBMECs monolayer and declined trans-endothelial electrical resistance (TEER) in the LPS-treated HBMECs were significantly alleviated by Cabergoline, accompanied by the upregulation of ZO-1. In addition, wnt1 and ß-catenin were found downregulated, which was reversed by Cabergoline. Importantly, the protective benefits of Cabergoline were all abolished by the overexpression of Dickkopf 3 (DKK3). Taken together, our data reveal that Cabergoline possessed a protective effect on BBB integrity against LPS.

Exosomal LINC00161 promotes angiogenesis and metastasis via regulating miR-590-3p/ROCK axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. While exosomal LINC00161 has been identified as a potential biomarker for HCC, its regulatory function and clinical values remain largely unknown. LINC00161 expressions in serum-derived exosomes from HCC patients and HCC cells were determined by qRT-PCR. The ability of proliferation, migration, and angiogenesis in HUVECs was assessed by MTT, Transwell, and tube formation. Luciferase reporter assay and AGO2-RIP assay were conducted to explore the interactions among LINC00161, miR-590-3p, and ROCK2. The level of ROCK signal-related proteins was examined by Western blotting and immunohistochemistry (IHC) assay. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of HCC cells. High levels of LINC00161 were detected in both serum-derived exosomes from HCC patients and the supernatants of HCC cell lines and were significantly associated with poor survival. Functional study demonstrated that exosomal LINC00161 derived from HCC-cells were significantly associated with enhanced proliferation, migration, and angiogenesis in HUVECs in vitro, all of which were effectively inhibited when LINC00161 was sliced with shRNA in HCC-cells. In vivo experiment showed that LINC00161 loss inhibited tumorigenesis and metastasis of HCC. Mechanistic study revealed that exosome-carried LINC00161 directly targeted miR-590-3p and induced its downstream target ROCK2, finally activating growth/metastasis-related signals in HCC. Exosome-carried LINC00161 promotes HCC tumorigenesis through inhibiting miR-590-3p to activate the ROCK2 signaling pathway, suggesting that LINC00161 may be used as potential targets to improve HCC treatment efficiency.

Efficacy of Standardized Rehabilitation in the Treatment of Diastasis Rectus Abdominis in Postpartum Women.

PURPOSE: The incidence of diastasis rectus abdominis (DRA) in parturients is continuously increasing, which may cause uncomfortable and affect the quality of life. The present study aims to retrospectively summarize the experience and efficacy in the treatment of DRA via standardized rehabilitation procedures in Eastern China. METHODS: This retrospective study included the parturients with DRA admitted to the Xishan People's Hospital of Wuxi between January 2017 and May 2021. Patients were separated into standardized rehabilitation group (SR) and non-standardized rehabilitation group (non-SR). The outcomes were the change in rectus abdominis separation and Physical Functioning Scale (PFS). Measurement data were compared between the two groups, and multivariate linear regression was used to analyze the factors associated with the standardized rehabilitation process. P values < 0.05 were considered statistically significant. RESULTS: Among a total of 294 patients with DRA who were included in the study, 171 patients were treated with SR (SR), and the other 123 patients were treated without SR process (non-SR). Compared with non-SR, the separation of the rectus abdominis was significantly reduced in SR after standardized rehabilitation treatment (p value < 0.0001). The multiple linear regression model analysis results suggested that standardized rehabilitation was an independent factor influencing the prognosis of DRA in parturients (p < 0.0001). In addition, the quality of life of the study group was significantly improved (p < 0.0001). CONCLUSION: Standardized rehabilitation method revealed high efficiency in treating DRA in postpartum women and could improve the quality of life of parturients.

Prevalence of the methylenetetrahydrofolate reductase 677C>T polymorphism in the pregnant women of Yunnan Province, China.

Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene can result in a reduced ability to utilize folic acid. The MTHFR 677C>T polymorphism in particular has been linked to both birth defects and pregnancy-associated diseases. This study aimed to evaluate the prevalence of the MTHFR 677C>T mutation among pregnant women in Yunnan Province so as to collect baseline data that may be utilized to guide folic acid supplementation efforts and to support related disease prevention programs. We retrospectively reviewed 3387 pregnant women from Yunnan Province. The MTHFR 677C>T polymorphism was identified using polymerase chain reaction (PCR) and DNA sequencing. In total, 1350 (39.9%) subjects were homozygous for the C allele (CC), 1540 (45.4%) subjects were heterozygous (CT), and 497 (14.7%) subjects were homozygous for the T allele (TT). The MTHFR 677C>T polymorphism was found to be present within the studied population, with ∼60% of these patients being either heterozygous or homozygous for the mutant allele and with an overall T allele frequency of 0.37. The frequency of the T allele was significantly higher among pregnant women with complications relative to women with healthy pregnancies, particularly among women <30 years old. As such, the maternal MTHFR 677C>T polymorphism may be a genetic risk factor associated with pregnancy complications and may help identify pregnant women at a high risk of such complications.

S-1 for treatment of advanced hepatocellular carcinoma: a systematic review of the literature.

Hepatocellular carcinoma (HCC) is the most common liver neoplasm worldwide. Based on its potent inhibition of dihydropyrimidine dehydrogenase (DPD), S-1 is expected to be more active than other fluoropyrimidines against HCC with DPD activity. This systematic review was aimed to assess the efficacy and safety of S-1 for treatment of advanced HCC. PubMed, the Cochrane Library, EMBA-SE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and ''S-1''. Outcomes of main interest included overall survival (OS) and toxicities. We identified four studies of S-1 treatment alone from 1059 references, including a total of 272 patients. There were two original articles and two conference abstracts. The percentage of male patients ranged from 88 to 91.3% and median age ranged from 59 to 70 years. Median OS ranged from 8.6 to 16.5 months. The incidences of toxicity of more than 50% were thrombocytopaenia and fatigue. According to the original description, toxicities were acceptable. The current evidence from the available clinical studies suggests that S-1 may be an effective and tolerable treatment for advanced HCC. Further clinical studies are warranted to further investigate this treatment option.

Metronomic S-1 chemotherapy plus transcatheter arterial chemoembolization (TACE): a promising treatment of hepatocellular carcinoma refractory to TACE.

PURPOSE: To assess the efficacy and safety of metronomic S-1 chemotherapy combination with transcatheter arterial chemoembolization (TACE) for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) refractory to TACE. METHODS: Twenty six patients met the eligibility criteria and were enrolled. TACE was performed on day 1, and metronomic S-1 chemotherapy on days 2-15. Tumor assessment was performed one month later. The primary endpoints were time to progression (TTP) and adverse events (AE). RESULTS: Twenty six patients in total received 176 TACE interventions. There were 101 TACE interventions in 15 patients of metronomic S-1 chemotherapy plus TACE (TS) and 75 in 11 patients of TACE monotherapy (TM). Fifteen TS patients received a total of 55 cycles of treatment with S-1, with a median of 4 cycles (range 2-6). The total dose of S-1 was 6165 mg per day in 15 patients (average 120 mg, range 100-125). Median TTP and overall survival (OS) of TS group were 6 months (95% CI, 4.7-7.3) and 17 months (95% CI, 15.6-18.4), respectively, while for the TM group were 4 months (95% CI, 2.4-5.6) and 15 months (95% CI, 9.2-20.8), respectively. Though there were higher tumor response rate (RR) and disease control rates (DCRs) in patients with TS, no significant differences were detected. Both treatment approaches were tolerable with low grade AE. CONCLUSIONS: In the present study, metronomic S-1 chemotherapy plus TACE in the present study was tolerable and associated with a better but not statistically significant TTP, RR and OS. It showed that metronomic S-1 chemotherapy plus TACE may be a promising treatment of BCLC Stage B HCC refractory to TACE.

Transcatheter arterial chemoembolisation (TACE) plus S-1 for the treatment of BCLC stage B hepatocellular carcinoma refractory to TACE.

AIM OF THE STUDY: To assess the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus S-1 for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B HCC refractory to TACE. MATERIAL AND METHODS: 26 patients meeting the eligibility criteria were enrolled. TACE was given on day 1, and S-1 on days 2-15. Tumor assessment was performed one month later according to mRECIST. The primary endpoints were TTP and OS. RESULTS: Twenty-six patients received 176 TACE interventions in all. Fifteen patients of TACE plus S-1 received a total of 55 cycles of treatment of S-1, with a median of 4 cycles (range, 2-6). The total dose of S-1 was 6165 mg per day, while average was 120 mg (range, 100-125 mg) for 15 patients of TACE plus S-1. Median TTP and OS of TACE plus S-1 were 6 months (95% CI: 4.7-7.3) and 18 months (95% CI: 15.3-24.7), respectively, while TACE monotherapy was 4 months (95% CI: 2.4-5.6) and 13 months (95% CI: 9.8-16.2), respectively, and significant differences were detected. Though there were higher DCRs in patients of TACE plus S-1, no significant differences were detected. A total of 612 adverse events occurred during the course of the treatment, 367 in TACE plus S-1 and 245 in TACE mono-therapy. There were significant differences to anorexia and nausea, but they were tolerable. CONCLUSIONS: TACE plus S-1 in the present analysis was tolerable and associated with an interesting TTP and OS. TACE plus S-1 may be used as a new treatment method to BCLC Stage B HCC refractory to TACE.

S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma.

PURPOSE: To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma (HCC). METHODS: PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and "S-1" and "Sorafenib" or "Nexavar". Outcomes of main interest included overall survival (OS) and toxicities. RESULTS: We identified 2 studies of S"1 plus sorafenib from 77 references that included a total of 65 patients. The percentage of male patients ranged from 70.0 to 89.5%. Median age was 59.2 years and ranged from 48.0 to 65.5 years. The percentage of hepatitis B virus ranged from 23.1 to 90.0%. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m2/day and 800 mg/day, respectively and treatment was administered orally on days 1-14 and days 1-21, respectively. Median OS were 10.4 and 10.5 months, respectively. The incidence of all-grade toxicities of more than 30% were hand"foot syndrome (HFS) and rash. The incidence of grade 3/4 toxicities more than 5% were thrombocytopenia, elevated AST/ALT and hyperbilirubinemia. CONCLUSION: This systematic review suggests that S-1 plus sorafenib showed modest clinical efficacy and tolerable toxicity profile in patients with advanced HCC. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m2/day and 800 mg/day, respectively.

[Simultaneous determination of residues of six zeranols in eggs by high performance liquid chromatography with immunoaffinity cleanup column].

An immunoaffinity cleanup-high performance liquid chromatography (IAC-HPLC) method was established for the simultaneous determination of residues of six zeranols (alphazeranol, beta-zeranol, alpha-zearalenol, beta-zearalenol, zearalanone and zearalenone) in eggs. The enzymolyzed samples were extracted with methyl tert-butyl ether, and subsequently reextracted with a sodium hydroxide solution. After the pH value was adjusted to 7, the extract was cleaned up on an immunoaffinity column. The chromatographic separation was performed on an Agilent Eclipse XDB-C18 column (150 mm x 4.6 mm, 3.5 microm) using methanol-acetonitrile-water (50:15:35, v/v/v) as the mobile phase at a flow rate of 1.0 mL/min and ultraviolet (UV) detection at 270 nm. The six zeranols had good linear relationships in the range of 0.01-0.2 mg/L with the correlation coefficients not less than 0.999 8; the recoveries of six target compounds at different spiked levels ranged from 73.2% to 95.7% and the relative standard deviations were less than 8%. The limit of detection (S/N > or = 3) was 1.0 microg/kg for each zeranol. The method is stable, reliable and accurate, and can be used for the determination of trace residues of the six zeranols in eggs.

Analysis of a high PM(10) episode observed at a coastal site nearby Shanghai, China.

A high PM(10) episode observed at a coastal site nearby Shanghai during 18-19 January 2007 was analyzed in this study. The maximum hourly averaged PM(10) concentrations for the 2 days were 0.58 and 0.62 mg/m(3), respectively. The meteorological condition during the episode was favorable for air pollution with large-scale stagnation. There was no dispersing effect by high wind, no scavenging function by precipitation, and no diluting process by clean marine air during the episode. The trajectories for 16-19 January all came from the northern region and kept in low levels, and during the episode peak time, from the morning of 18 to the morning of 19 January, trajectories all came from the northern inland areas and had passed over the coastal region of Jiangsu province before arriving at the site. The variation of the air pollution indexes (APIs) in the cities located in the upwind direction of the site during the episode days clearly shows a process of large-scale air pollution from north to south. The liner correlation coefficient for PM(10) and SO(2) concentrations is 0.774 during the episode, while for PM(10) and CO, it even reaches 0.995, which indicated that the high PM(10) was mainly emitted from the coal burning for domestic heating in winter. Therefore, the observed episode was caused by the transport of domestic heating pollutants accumulated in the boundary layer from northern continental areas.

[Photo-catalytic degradation of gas phase benzene and toluene over multi-composite TiO2 catalyst].

Photo-catalytic degradation of gas-phase benzene and toluene were studied in the condition of no catalyst, pure anatase catalyst, pure rutile catalyst and multi-composite catalyst. The influences of initial concentration of reactants and the catalysts of different composite on photo-catalytic degradation rate of gas-phase benzene and toluene were investigated. The results show that the degradation efficiency of benzene and toluene is improved a lot on anatase catalyst, but improved a little on rutile catalyst in relation to the crystal-structure of anatase and rutile catalyst. In the condition of no catalyst and pure rutile catalyst, toluene is easier to be degradated than benzene, and on anatase catalyst benzene is easier to be done than toluene. The initial concentration of reactant has an effect on the photo-catalytic degradation process. The degradation rates of benzene and toluene are faster in low concentration than in high concentration. A certain amount of rutile doped in anatase catalyst could improve the photo-catalytic activity. The catalyst with 80% anatase and 20% rutile shows the best photo-catalytic activity to benzene, and the catalyst with 90% anatase and 10% rutile gives the best photo-catalytic activity to toluene.

[Characteristics of atmospheric ozone in the urban area of Ji'nan].

Based on the observational data of near surface O3 in the urban area of Ji'nan during the latest two years, the O3 concentrations and their temporal variation characteristics were analyzed. The results showed that O3 concentrations fluctuated periodically,and the photochemical pollution in Ji'nan was serious. Diurnal variations of ozone concentrations exhibited with the characteristic of a single peak, and showed the maximum in the afternoon and minimum in the early morning before sunrise. Ozone concentrations in spring and summer were higher than autumn and winter, while the varying scopes of ozone concentrations in summer and autumn were broader than spring and winter. Variations of ozone concentrations in weekend days were different from weekdays, which caused by the temporal regulation of human activities.