[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

[Clinical effects of flaps or myocutaneous flaps transplantation after titanium mesh-retaining debridement in repairing the wounds with exposed titanium mesh after cranioplasty].

Objective: To explore the clinical effects of flaps or myocutaneous flaps transplantation after debridement to repair the wounds with exposed titanium mesh after cranioplasty on the premise of retaining the titanium mesh. Methods: This study was a retrospective observational study. From February 2017 to October 2022, 22 patients with titanium mesh exposure after cranioplasty who met the inclusion criteria were admitted to the Department of Plastic, Aesthetic & Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University, including 15 males and 7 females, aged from 19 to 68 years. After admission, treatments such as bacterial culture of wound exudate sample, anti-infection, and dressing change were carried out. Thorough surgical debridement was performed when the wound improved, and the wound area was 3.0 cm×2.0 cm to 11.0 cm×8.0 cm after debridement. The wound was repaired with local flaps, expanded flaps, or free latissimus dorsi myocutaneous flaps according to the size, location, severity of infection, and surrounding tissue condition of the wounds, and the areas of flaps or myocutaneous flaps were 5.5 cm×4.0 cm to 18.0 cm×15.0 cm. The donor areas of flaps were sutured directly or repaired by split-thickness skin grafts from head. The wound repair method was recorded. The survivals of flaps or myocutaneous flaps after surgery and wound healing in 2 weeks after surgery were recorded. During postoperative follow-up, recurrence of infection or titanium mesh exposure in the implanted area of titanium mesh was observed; the head shapes of patients, scar formation of the operative incision, and baldness were observed. At the last follow-up, the satisfaction of patients with the treatment effect (dividing into three levels: satisfied, basically satisfied, and dissatisfied) was evaluated. The total treatment costs of patients during their hospitalization were calculated. Results: The wounds in 11 cases were repaired with local flaps, the wounds in 5 cases were repaired with expanded flaps, and the wounds in 6 cases were repaired with free latissimus dorsi myocutaneous flaps. All flaps or myocutaneous flaps survived completely after surgery, and all wounds healed well in 2 weeks after surgery. Follow up for 6 to 48 months after operation, only one patient with local flap grafting experienced a recurrence of infection in the titanium mesh implanted area at more than one month after surgery, and the titanium mesh was removed because of ineffective treatment. Except for one patient who had a local depression in the head after removing the titanium mesh, the rest of the patients had a full head shape. Except for myocutaneous flap grafting areas in 6 cases and skin grafting area in 1 case with local flaps grafting had no hair growth, the other patients had no baldness. All the scars in surgical incision were concealed. At the last follow-up, 19 cases were satisfied with the treatment effects, 2 cases were basically satisfied, and 1 case was dissatisfied. The total treatment cost for patients in this group during hospitalization was 11 764-36 452 (22 304±6 955) yuan. Conclusions: For patients with titanium mesh exposure after cranioplasty, on the premise of adequate preoperative preparation and thorough debridement, the wound can be repaired with appropriate flaps or myocutaneous flaps according to the wound condition. The surgery can preserve all or part of the titanium mesh. The postoperative wound healing is good and the recurrence of infection or titanium mesh exposure in the titanium mesh implanted area is reduced, leading to good head shape, reduced surgical frequency, and decreased treatment costs.

High-flow nasal cannula therapy for pediatric obstructive sleep apnea: a systematic review and meta-analysis.

OBJECTIVE: Heated and humidified high-flow nasal cannula (HFNC) therapy has been used to manage different respiratory conditions in pediatric patients. However, no review has summarized its efficacy for the management of pediatric obstructive sleep apnea (OSA). MATERIALS AND METHODS: PubMed, Embase, CENTRAL, and Google Scholar were searched for all types of studies assessing the efficacy of HFNC for pediatric OSA. We compared pre-treatment and post-treatment obstructive apnea-hypopnea index (OAHI), obstructive hypopnea index (OHI), obstructive apnea index (OAI), SPO2 nadir and SPO2 mean values in a random-effect meta-analysis model. RESULTS: Six studies reporting data of 67 pediatric patients treated with HFNC were included. Most of the data were from one-time titration. Meta-analysis revealed a statistically significant reduction in OAHI with HFNC therapy (MD: 15.58 95% CI: 8.30, 22.86 I2=77% p=0.001). Similarly, pooled analysis revealed that both OHI (MD: 12.35 95% CI: 0.78, 23.92 I2=98% p=0.04) and OAI (MD: 7.54 95% CI: 2.10, 12.98 I2=79% p=0.007) were significantly reduced with HFNC treatment. Also, HFNC led to statistically significant improvement in SPO2 nadir values (MD: -8.17 95% CI: -10.40, -5.94 I2=21% p<0.00001) but it did not change the mean SPO2 values before and after treatment (MD: -0.85 95% CI: -1.94, 0.25 I2=52% p=0.13). CONCLUSIONS: Evidence from a limited number of heterogeneous and uncontrolled titration studies indicates that HFNC improves OAHI and minimum oxygen saturation in pediatric patients with OSA. However, further research is required on the long-term efficacy and compliance of HFNC therapy with a focus on different pediatric age groups.

[CD44 regulates biological behavior and Ras signaling pathway in nasopharyngeal carcinoma stem cells].

Objective: To study the biological behavior of nasopharyngeal carcinoma stem cells and to explore the activation of Ras signaling pathway regulated by CD44. Methods: CNE2-SC and 5-8F-SC were nasopharyngeal carcinoma stem cells and obtained by serum-free suspension culture. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, cell adhesion array were used to investigate the growth, proliferation, migration and adhesion of nasopharyngeal carcinoma stem cells. Western blot test was used to detect the expressions of Ras signaling pathway related proteins and siRNA-mediated interference was used to determine the activation of Ras signaling pathway regulated by CD44. Results: The growth rates of CNE2-SC and 5-8F-SC cells were significantly lower than those of nasopharyngeal carcinoma cells at 24, 48 and 72 hours after inoculation (P<0.05). After 14 days of implantation, the colony formation rates of CNE2-SC (44.5±1.9)% and 5-8F-SC (47.4±1.8)% were higher than those of CNE2 (34.9±1.5)% and 5-8F (37.2±1.7)%, respectively(P<0.01). The migration cell number of CNE2-SC was (87.6±7.8), 3.97 times higher than that of CNE2 (P<0.01). The migration cell number of 5-8F-SC was (67.2±5.7), 3.07 times higher than 5-8F (P<0.01). The adhesion rates of CNE2-SC and CNE2 cells were (42.1±7.6)% and (8.9±2.0)%, respectively at 3 hours after inoculation and were (82.4±5.0)% and (12.1±2.2)% at 6 hours after inoculation, respectively. The adhesion rate of CNE2-SC cells was higher than that of CNE2 cells (all P<0.01). The adhesion rates of 5-8F-SC and 5-8F cells were (53.6±6.1)% and (7.3±1.5)% at 3 hours after inoculation, and (90.7±3.6)% and (11.0±1.2)% at 6 hours after inoculation, respectively. The adhesion rate of 5-8F-SC cells was higher than that of 5-8F cells (P<0.01). The expression levels of CD44, Ras and N-cadherin were significantly higher, while phosphatase and tensin homolog deleted on chromosome 10 (PTEN), E-cadherin in nasopharyngeal carcinoma stem cells were lower than those of the nasopharyngeal carcinoma cells. Furthermore, the levels of phosphorylated mitogen extracellular kinase1/2 (p-MEK1/2) and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2)were significantly increased in nasopharyngeal carcinoma stem cells (P<0.01). Correlation analysis showed that the protein expression levels of CD44 was highly positively correlated with RAS in nasopharyngeal carcinoma stem cells(r=0.985, P=0.002; r=0.962, P=0.038). Deletion of CD44 in CNE2-SC decreased the expression levels of HER-2, Ras and p-ERK1/2, p-Akt and phosphorylated protein kinase C-δ(p-PKCδ) (P<0.01). Conclusions: Despite compare to the nasopharyngeal carcinoma cell, nasopharyngeal carcinoma stem cells grows at a relatively slow rate, the capacities of clone formation, migration, adhesion are promoted. This may be related to the CD44-regulated abnormal activation of Ras signaling pathway.

LncRNA TMPO-AS1 promotes proliferation and migration in bladder cancer.

OBJECTIVE: This study aims to uncover the in vitro influences of lncRNA TMPO-AS1 on the progression of bladder cancer (BLCA) and the underlying mechanism. PATIENTS AND METHODS: Expression levels of TMPO-AS1 in BLCA tissues and normal bladder tissues were analyzed in The Cancer Genome Atlas (TCGA) database. Differential expressions of TMPO-AS1 in BLCA tissues and normal bladder epithelial tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Potential influence of TMPO-AS1 on prognosis of BLCA patients was assessed. In vitro influences of TMPO-AS1 on proliferative and migratory abilities in T24 and UMUC-3 cells were evaluated by Cell Counting Kit-8 (CCK-8), transwell, and wound healing assay, respectively. Finally, the correlation between TMPO-AS1 and its sense RNA TMPO was assessed by analyzing TCGA database, clinical samples, and BLCA cell lines. RESULTS: By analyzing TCGA database and clinical samples, it was found that TMPO-AS1 was upregulated in BLCA tissues compared with that in normal bladder tissues. Worse survival was observed in BLCA patients with high expression of TMPO-AS1. TMPO-AS1 level was correlated to muscle invasiveness and TNM stage of BLCA patients. In T24 and UMUC-3 cells, the knockdown of TMPO-AS1 suppressed proliferative and migratory abilities. TMPO-AS1 level was positively correlated to that of its sense RNA TMPO. Moreover, the knockdown of TMPO-AS1 downregulated mRNA and protein levels of TMPO in BLCA cells. CONCLUSIONS: TMPO-AS1 is upregulated in BLCA tissue and closely linked to poor prognosis of BLCA patients.

Comparative efficacy and safety of lock solutions for the prevention of catheter-related complications including infectious and bleeding events in adult haemodialysis patients: a systematic review and network meta-analysis.

BACKGROUND: Central venous catheters are used extensively as temporary or permanent vascular access for haemodialysis patients. Catheter-related bloodstream infections are the main complication of central venous catheters and increase morbidity and mortality in haemodialysis patients. OBJECTIVES: The aim was to assess the most appropriate lock solution for central venous catheters to prevent catheter-related bloodstream infections and other complications. DATA SOURCES: Medline, Embase and the Cochrane Central Register of Controlled Trials from the date of their inception to August 2018 were used as data sources. The reference lists of eligible studies and relevant reviews were also checked. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Randomized controlled trials (RCTs) comparing different lock solutions for the prevention of central venous catheter-related infectious and bleeding complications for adult dialysis patients were included. INTERVENTIONS: Interventions were lock solutions for haemodialysis catheters. METHODS: The primary outcomes were catheter-related bloodstream infections and bleeding events. The secondary outcomes were catheter malfunction, exit-site infection, and all-cause mortality. We estimated summary risk ratios (RRs) using pairwise and network meta-analysis. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool. RESULTS: Forty-nine trials (7020 patients) were included for this study. Compared with heparin 5000 U/mL, antibiotic locks (antibiotics with trisodium citrate (TSC), ethylenediamine tetraacetic acid (EDTA), heparin 5000 U/mL, low-dose heparin or urokinase) and ethanol locks were more effective in preventing catheter-related bloodstream infections. Antimicrobial agents plus low-dose heparin (500-2500 U/mL), TSC and low-dose heparin locks had lower risk of bleeding events than heparin 5000 U/mL. None of the lock solutions reduced rates of catheter malfunction and all-cause mortality compared with heparin 5000 U/mL. In summary, antibiotics plus low-dose heparin was ranked as the best lock solution. The overall results were not materially changed in sensitivity analyses. CONCLUSIONS: Taking into account both efficacy and safety, antibiotics plus low-dose heparin (500-2500 U/mL) may be the preferred lock solution.

[Survey on the quadrivalent influenza vaccine intention and related factors of health care workers in the Pearl River Delta region from 2015 to 2017].

Objective: To analyze the quadrivalent influenza vaccine intention of 718 health care workers (HCWs) in the Pearl River Delta region from 2015 to 2017. Method: In May 2018, 718 HCWs from the department related to the diagnosis and treatment of influenza in 17 hospitals (6 tertiary hospitals, 5 secondary hospitals and 6 primary hospitals) from Guangzhou, Jiangmen, Zhuhai and Dongguan were selected by using stratified sampling method. Questionnaire survey and face-to-face interview were used to collect the information of influenza vaccination, the intention of the quadrivalent influenza vaccine, the acceptance of free and required vaccination policies, and recommendations for increasing influenza vaccination intentions from 2015 to 2017. The multivariate logistic regression was used to analyze factors associated with the vaccination intention. Results: A total of 718 HCWs were surveyed and 147 of them were interviewed face to face. Among them, the vaccination rate of primary hospitals [17.39%(40/230)] was higher than that of other hospitals (χ(2)=15.80, P<0.05). If the vaccine could be free, 84.82% (609/718) of HCWs would like to be vaccinated. The multivariate logistic regression showed that the factors, HCWs who were aged ≥50 years (OR=3.44, 95%CI:1.43-8.28), worked in department of prevention and health care (OR=2.35, 95%CI:1.16-4.75), learned about the quadrivalent influenza vaccine (OR=2.94, 95%CI:2.08-4.18), knowed that HCWs are priority (OR=2.33, 95%CI:1.56-3.48), and had a history of trivalent influenza vaccination from 2015 to 2017 (OR=4.70, 95%CI:3.08-7.15), were associated with the vaccination intention. Conclusion: HCWs in the Pearl River Delta region had weak inclination of getting quadrivalent influenza vaccine. HCWs who were age (≥50 years old), worked in department of prevention and health care, learned about the quadrivalent influenza vaccine, knowed that HCWs are priority, and had a history of trivalent influenza vaccination from 2015 to 2017 were factors positively associated with the vaccination intention.

Design of back-streaming white neutron beam line at CSNS.

A white neutron beam line using back-streaming neutrons from the spallation target is under construction at China Spallation Neutron Source (CSNS). Different spectrometers, to be installed in the so-called Back-n beam line for nuclear data measurements, are also being developed in phases. The physical design of the beam line is carried out with the help of a complicated collimation system and a sophisticated neutron dump, taking the overview of the neutron beam characteristics into account. This includes energy spectrum, flux and time structure, the optimizations of neutron beam spots and in-hall background. The wide neutron energy range of 1eV-100MeV is excellent for supporting different applications, especially nuclear data measurements. At Endstation#2, which is about 80m away from the target, the main properties of the beam line include neutron flux of 106n/cm2/s, time resolution of a few per mille over nearly the entire energy range, and in-hall background of about 0.01/cm2/s for both neutron and gamma. With its first commission in late 2017, Back-n will not only be the first high-performance white neutron source in China, but also one of the best white neutron sources in the world.

Nutritional effects on the mycelial growth and enzymatic activity of Isaria farinosa, and Hepialus larvae growth.

AIMS: To investigate the nutritional requirements of the mycelial growth and pathogenesis-related enzymatic activity on Isaria farinosa and the nutritional effect of fungus on its host Hepialus larvae. METHODS AND RESULTS: Sixteen carbon sources, 16 nitrogen sources and 9 vitamin combinations were tested. The nutritional conditions that significantly prevented I. farinosa pathogenesis were selected as feed additives for rearing Hepialus larvae. Citric acid significantly inhibited the growth of I. farinosa and the activity of three enzymes. l-histidine and l-aspartic acid significantly reduced the dry weights of mycelia and their protease and lipase activities. Vitamin combination that lacked VB 1 significantly increased the growth of I. farinosa and enhanced its chitinase and lipase activities. l-aspartic acid, VB 1 or a combination of them were beneficial for maintaining the larvae survival rate and decreasing the disease rate. The result provides new insight to develop a nutrition-based strategy to control fungal epidemics during insect rearing. CONCLUSIONS: The ability of some specific nutrients to inhibit mycelial growth and enzymatic activity can prevent epidemics of fungal disease. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will aid in the development of nutrition-based strategies to control entomopathogenic fungal epidemics during the large-scale rearing of insects.

Lack of an association between the XRCC1 Arg399Gln polymorphism and gastric cancer based on a meta-analysis.

Association between the XRCC1 Arg399Gln polymorphism and susceptibility to gastric cancer has been investigated; overall, the results have been inconclusive. We made a meta-analysis of 13 case-control studies, including 3278 cases and 6243 controls. Crude odds ratios (OR) with 95% confidence intervals (95%CI) were used to assess this possible association. We found no evidence of a significant association between the XRCC1 Arg399Gln polymorphism and gastric cancer risk (in the additive inheritance model, OR = 0.986, 95%CI = 0.831-1.156, in the dominant inheritance model, OR = 1.044, 95%CI = 0.890-1.224 and in the recessive inheritance model, OR = 0.975, 95%CI = 0.894-1.063). We conclude that the XRCC1 Arg399Gln polymorphism is not a risk factor for developing gastric cancer.

Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinoma.

Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca(2+) current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca(2+) current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.

Submicrostructure and typing of female genital condylomata.

Thirty biopsies from female genital condylomata were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to study structural characteristics and typing of condylomata. It was found that cytoplasmic clearing was marked in acuminate condylomata, diffuse interstitial and epithelial proliferation in nodular condylomata (flat condylomata), and invagination of the lesions into the interstitial tissue or glandular ducts in endophytic condylomata. In nodular condylomata, SEM also showed some structural features similar to those of intra-epithelial neoplasia. Microridges on the surface of squamous cells had villiform of granular changes. On the surface of a percentage of squamous or columnar cells, there were holes with a diameter of about 3 to 5 microns. A number of giant cells were seen among other cells. The cervical squamatization zone contained groups of special cells covered with dense microvilli. TEM of nodular condylomata revealed some pictures resembling active proliferation of tumor cells, such as enlarged or irregular nuclei (large N/C ratio), evaginated or invaginated nuclear membranes, condensed chromatin attached to the inner part of the nuclear membrane, transparent nucleoplasm, and frequent nucleosomes and karyokinesis. Virus particles with the morphological characteristics of HPV (naked hexagon-like particles with an average diameter of 45-50 nm) were seen in some nuclei with markedly condensed chromatin. It is suggested that HPV-induced genital condylomata, especially nodular one (flat condylomata), entail a potential progression to malignancy.