The risk of patient infection inevitably increases with the use of more invasive operations in the intensive care unit(ICU),including endotracheal tubes,indwelling catheter,central venous catheter,etc.The preparation of antibacterial coatings is an effective way to solve such infections.Antibacterial coatings,such as silver nanoparticles coating,zinc oxide coating,methyl blue coating,antimicrobial peptides coating,and nano titanium dioxide(TiO2)coating,can effectively prevent the formation of biofilms on the surface of implant materials.As a photocatalyst,TiO2 has excellent photocatalytic and antibacterial activity,non-toxic and biocompatible properties,strong physical and chemical stability,and long-lasting antibacterial properties,which makes it high value for research.This review summarizes the bactericidal mechanism and clinical application of TiO2,offering valuable reference for clinical practice.

Humans ; Asthma/drug therapy* ; Biological Therapy

Photohardening therapy, also known as photodesensitization therapy, refers to the phototherapy and photochemotherapy of idiopathic actinic dermatoses, and its goal is to improve the patients′ tolerance to sunlight and prevent disease flares. Its mechanisms of action involve a variety of cellular and inflammatory factors. This therapy is suitable for all idiopathic actinic dermatoses, with definite efficacy and good safety. However, the treatment specificity usually leads to poor compliance. The development of UVA1 rush hardening and home phototherapy is expected to solve this problem.

Objective:To investigate serum lipidomic profiles in patients with chronic actinic dermatitis (CAD), and to search for biomarkers of CAD.Methods:A retrospective analysis was conducted. Serum samples were collected from 46 patients with CAD and 16 age- and gender-matched healthy controls in the Guangzhou Institute of Dermatology from April 2011 to December 2021. Changes in serum lipid composition and expression were assessed by liquid chromatography-mass spectrometry. Principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis were performed to screen differential biomarkers, and receiver operating characteristic (ROC) curve analysis was conducted to screen diagnostic markers. Comparisons of the age and gender distribution between groups were performed using t test and chi-square test, respectively. Results:The 46 CAD patients were aged from 30 to 84 (60.39 ± 10.52) years, including 41 males and 5 females; the 16 healthy controls were aged from 50 to 89 (59.81 ± 10.72) years, including 14 males and 2 females; there were no significant differences in the age or gender distribution between the two groups (age: t = 0.19, P = 0.853; gender: χ2 = 0.03, P = 0.859). Totally, 4 136 lipid molecules belonging to 40 subclasses were identified in the serum samples from CAD patients as well as healthy controls. Twenty-two differential lipid molecules were identified between the CAD patients and healthy controls, belonging to 9 subclasses (triglycerides, sphingomyelin, phosphatidylserine, phosphatidylethanolamine, monofatty acid glycerides, lysophosphatidylcholine, hexose ceramide, diglycerides, and cardiolipin). When the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, or those of phosphatidylserine (18.0_18.1) and H served as diagnostic markers separately, the areas under the ROC curve (AUCs) were all > 0.8, and the AUCs of 16 differential lipid molecules were all > 0.7. Conclusion:The serum lipid composition differed between healthy controls and CAD patients, and the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, and those of phosphatidylserine (18.0_18.1) and H may be promising biomarkers for the diagnosis of CAD.

Objective:To evaluate the effect of metformin on ultraviolet A (UVA) -induced photoaging of an immortalized human keratinocytes cell line (HaCaT), and to explore its potential mechanisms.Methods:Cell counting kit 8 (CCK8) assay was performed to evaluate the effect of metformin at different concentrations (0 - 100 mmol/L) on the viability of HaCaT cells, and 10 mmol/L metformin was selected for subsequent experiments. Cultured HaCaT cells were divided into a blank control group (conventional culture), a metformin group (treated with culture medium containing 10 mmol/L metformin), a UVA irradiation group (conventional culture for 24 hours followed by 10 J/cm 2 UVA irradiation) and a metformin + UVA group (treated with culture medium containing 10 mmol/L metformin for 24 hours followed by 10 J/cm 2 UVA irradiation) ; UVA irradiation was performed at a dose of 10 J/cm 2 once a day for 3 consecutive days. After 4-day treatment, cells were collected, the β-galactosidase assay was performed to determine the proportion of senescent cells in each group, 2′, 7′-dichlorodihydrofluorescein diacetate assay to detect levels of intracellular reactive oxygen species (ROS), and the comet assay to detect DNA damage levels. Additionally, some HaCaT cells were divided into the blank control group, metformin group, 1.25 μmol/L dorsomorphin (an adenosine monophosphate-activated protein kinase [AMPK] inhibitor) + metformin group, and 2.5 μmol/L dorsomorphin + metformin group, and cells in the latter two groups were treated with 1.25 and 2.5 μmol/L dorsomorphin respectively for 2 hours, followed by the treatment with 10 mmol/L metformin for 24 hours. Western blot analysis was performed to determine the cellular localization and phosphorylation levels of nuclear factor-erythroid 2-related factor 2 (Nrf2). By using the small-interfering RNA (siRNA) -mediated silencing method, siRNA-Nrf2 was transfected into HaCaT cells to knock down Nrf2 expression (siRNA-Nrf2 group) ; 2.5 μmol/L dorsomorphin-treated HaCaT cells or Nrf2-knockdown HaCaT cells were treated with metformin and UVA irradiation (dorsomorphin + metformin + UVA group, siRNA-Nrf2 + metformin + UVA group, respectively), and the proportions of senescent cells were further calculated in each group. Statistical analysis was carried out by using one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Treatment with different concentrations of metformin for 24 hours could affect the viability of HaCaT cells to varying degrees ( F = 5 206.31, P < 0.001) ; there were no significant differences in the relative survival rates of HaCaT cells between the 10 - 20 mmol/L metformin groups and the control group (0 mmol/L metformin group, all P > 0.05), while the relative cell survival rates were significantly lower in the 25 - 100 mmol/L metformin groups than in the control group (all P < 0.05). After UVA irradiation, HaCaT cells shrank significantly and became narrow and elongated, and the intercellular spaces increased; the relative cell survival rate was significantly lower in the UVA irradiation group (76.13% ± 1.03%) than in the blank control group (100.00% ± 1.24%, LSD- t = 14.86, P < 0.001), but significantly higher in the metformin + UVA group (106.69% ± 2.45%) than in the UVA irradiation group (LSD- t = 11.55, P < 0.001). Moreover, the UVA irradiation group showed significantly increased proportions of senescent cells (45.14% ± 4.98%), intracellular ROS levels (144.61% ± 4.91%), and percentages of DNA in the tail (75.33% ± 1.77%) compared with the blank control group (23.84% ± 1.89%, 55.49% ± 1.57%, 1.88% ± 0.29%, respectively, all P < 0.001), while the metformin + UVA group showed significantly decreased proportions of senescent cells (24.26% ± 1.34%), intracellular ROS levels (58.62% ± 2.17%), percentages of DNA in the tail (15.83% ± 1.23%) compared with the UVA irradiation group (all P < 0.001). Western blot analysis showed that the Nrf2 expression in the cytoplasm was lower in the 10 mmol/L metformin group than in the blank control group, while the phosphorylated Nrf2 expression in the nuclei was higher in the 10 mmol/L metformin group than in the blank control group, suggesting that metformin could effectively induce the phosphorylation of Nrf2 and its nuclear translocation; both the pretreatment with 1.25 and 2.5 μmol/L dorsomorphin could significantly reduce the phosphorylation levels of AMPKα and Nrf2 induced by 10 mmol/L metformin. The proportions of senescent cells in the dorsomorphin + metformin + UVA group and the siRNA-Nrf2 + metformin + UVA group were 67.84% ± 2.74% and 65.94% ± 1.33%, respectively, which were significantly higher than those in the metformin + UVA group (37.76% ± 1.64%, t = 14.45, 13.34, respectively, both P < 0.001) . Conclusion:Metformin may inhibit UVA-induced photoaging of HaCaT cells by activating the AMPK/Nrf2 signaling pathway, scavenging ROS and reducing DNA damage.

Objective:To investigate the effect of pterostilbene on the growth, apoptosis and autophagy of a human papillomavirus type 16 (HPV-16) -immortalized cervical epithelial cell line H8.Methods:H8 cells were treated with pterostilbene at different concentrations of 0 (control group) , 25, 50, 75, 100 μmol/L for 24 and 48 hours. Cell counting kit-8 (CCK8) assay was performed to evaluate the cellular proliferative activity, flow cytometry was conducted to detect apoptosis and cell cycle, monodansylcadaverine (MDC) staining and fluorescence microscopy were performed to detect autophagy, and Western blot analysis was conducted to determine the expression of the cell cycle-related protein cyclinD1, apoptosis-related proteins caspase-3 and caspase-9, autophagy-related proteins Beclin1, microtubule-associated protein 1 light chain 3 (LC3) -Ⅱ/Ⅰ, ATG5 and P62, as well as HPV oncoproteins E6 and E7. Statistical analysis was carried out by using one-way analysis of variance, repeated measures analysis of variance and least significant difference- t test. Results:After 48-hour treatment with pterostilbene at different concentrations of 0, 25, 50, 75, 100 μmol/L, the relative cellular proliferation rate significantly differed among the groups (100.00% ± 1.56%, 99.02% ± 4.97%, 93.59% ± 2.01%, 81.28% ± 4.90%, 69.17% ± 7.56%, respectively; F = 77.22, P < 0.05) , and gradually decreased along with the increase in the concentration of pterostilbene; compared with the control group, the pterostilbene groups all showed significantly decreased cellular proliferation rate (all P < 0.05) . After 24-hour treatment with pterostilbene, the proportions of H8 cells at G1, G2 and S phases significantly differed among the above groups ( F = 7 845.00, 51.14, 266.50, respectively, all P < 0.05) ; compared with the control group, the pterostilbene groups showed significantly increased proportions of H8 cells at G1 and G2 phases (all P < 0.05) , but significantly decreased proportions of H8 cells at S phase ( P < 0.05) . After 48-hour treatment with pterostilbene, the apoptosis rate was significantly higher in the 25-, 50-, 75- and 100-μmol/L pterostilbene groups (14.66% ± 0.22%, 13.50% ± 0.49%, 14.56% ± 0.19%, 15.30% ± 0.76%, respectively) than in the control group (11.58% ± 0.50%, all P < 0.05) . After 24-hour treatment with pterostilbene, MDC staining showed only a small number of H8 cells with bright dot-like fluorescence in the control group, but increased number of autophagosome-positive H8 cells with bright dot-like fluorescence in the pterostilbene groups. Western blot analysis revealed that there were significant differences in the protein expression of cyclin D1, caspase-3, caspase-9, Beclin1, LC3-Ⅱ/Ⅰ, ATG5, P62, E6 and E7 among the control and pterostilbene groups after 24- and 48-hour treatment with pterostilbene (all P < 0.05) . The treatment with pterostilbene could down-regulate the expression of cyclin D1, E6 and E7, and up-regulate the expression of caspase-3, caspase-9, Beclin1, LC3-Ⅱ/Ⅰ, ATG5 and P62, with significant differences between the control group and most pterostilbene groups in expression of the above proteins (all P < 0.05) . Conclusion:Pterostilbene can inhibit the proliferation of H8 cells, promote their apoptosis and autophagy, and down-regulate the expression of oncogenes E6 and E7.

Background: Visceral hypersensitivity is considered as a key pathophysiological mechanism involved in functional gastrointestinal disorders (FGIDs). Visceral nociception and hyperalgesia is existed extensively following exposure to post-traumatic stress disorder (PTSD), however, its molecular mechanism in intestinal tract is unclear. Aims: To explore the potential role of N-Myc downstream-regulated gene 2 (NDRG2) in intestinal tract for mediating visceral hypersensitivity following exposure to PTSD. Methods: PTSD model was established by single prolonged stress (SPS). SD rats were divided into normal control group, CTX group, PTSD group and PTSD+CTX group. Mice were divided into normal control group, PTSD group, NDRG2

BACKGROUND: Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase (RTK) inhibitor that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of anlotinib-bronchial fistula (BF) during the treatment of lung cancer patients and summarize the possible causes. METHODS: We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and PubMed for medical literature published between 2018 and 2020 using the following search terms: "anlotinib," "lung cancer," and "fistula." RESULTS: Our literature search produced two case reports (three patients) which, in addition to our three patients. We collated the patients' clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced age, male, concurrent infection symptoms, diabetes mellitus (DM), advanced squamous cell and small cell lung cancers, centrally located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophago-tracheobronchial fistula. Six patients all died within 6 months. CONCLUSIONS Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close observation of high-risk patients.

Objective:APOBEC3B (A3B) is an important member of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family. The study aims to investigate the relationship between A3B expression and prognosis as well as resistance to cisplatin in non-small cell lung cancer (NSCLC).Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to analysis the A3B mRNA expression in 40 NSCLC tissues; Kaplan Meier plotter was used to analyse the correlation between A3B expression and clinical prognosis; in addition, the knock-down A3B expression cell line in human lung adenocarcinoma cell A549 was constructed; MTS and plate cloning experiment were performed to observe the changes in cell cisplatin sensitivity, and γ-H2AX immunofluorescence was used to quantitate the DNA damage.Results:Compared with adjacent tissues, A3B was highly expressed in NSCLC tissues (27/40). Kaplan Meier plotter analysis showed that A3B expression was positively correlated with NSCLC overall survival (OS) [adenocarcinoma: HR=0.64(0.47-0.86), P=0.002 6; squamous cell carcinoma: HR=0.77(0.59-1.01), P=0.006]. Cell-based studies showed that the knock-down A3B expression contributed to sensitivity to cisplatin in A549 cells. Conclusions:A3B mediates the sensitivity of lung cancer to cisplatin. This effect may partly explain why NSCLC patients with high A3B expression have a better prognosis.

Objective To evaluate the protective effect of pterostilbene against ultraviolet B (UVB)-induced acute damage in HaCaT cells,and to explore related mechanisms.Methods The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazo1ium (MTS) assay and flow cytometry were performed to estimate the proliferative activity and the apoptosis and necrosis rate of HaCaT cells treated with different concentrations of pterostilbene respectively,so as to screen the non-toxic concentration of pterostilbene.HaCaT cells were randomly divided into several groups:normal control group receiving no treatment,UVB group irradiated with 57 mJ/cm2 UVB,3 pterostilbene groups treated with 2.44,4.88 and 9.75 μmol/L pterostilbene respectively for 24 hours,3 pterostilbene + UVB groups treated with 2.44,4.88 and 9.75 μmol/L pterostilbene respectively for 24 hours followed by UVB radiation.Western blot analysis was conducted to detect changes of the transcription factor NF-E2-related factor 2 (Nrf2) expression in cell nuclei and cytoplasm before and after the treatment with pterostilbene and UVB,quantitative PCR to determine the mRNA expression of catalase and superoxide dismutase in the HaCaT cells,and enzyme-linked immunosorbent assay (ELISA) to evaluate the activity of catalase and superoxide dismutase.Results MTS assay and flow cytometry showed that 2.44,4.88 and 9.75 μmol/L pterostilbene had non-toxic effect on HaCaT cells.The protein expression of Nrf2 in the nuclei and cytoplasm in the normal control group was 1.03 ± 0.08 and 1.04 ± 0.11 respectively.Compared with the normal control group,the protein expression of Nrf2 in the nuclei and cytoplasm experienced no significant changes in the 2.44-,4.88-and 9.75-μmol/L pterostilbene groups,and the UVB group showed similar protein expression of Nrf2 in the cytoplasm,but significantly increased protein expression of Nrf2 in the nuclei (1.77 ± 0.08,q =17.24,P ＜ 0.01).Compared with the normal control group and UVB group,the 2.44-,4.88-and 9.75-μmol/L pterostilbene + UVB groups all showed significantly lower protein expression of Nrf2 in the cytoplasm (0.86 ± 0.10,0.87 ± 0.11 and 0.46 ± 0.11 respectively,all P ＜ 0.05),but significantly higher protein expression of Nrf2 in the nuclei (2.38 ± 0.11,2.57 ± 0.11 and 2.07 ± 0.13,all P ＜ 0.01).As qPCR showed,UVB radiation could significantly inhibit the mRNA expression of CAT (P ＜ 0.05),but had no obvious effect on the mRNA expression of SOD (P ＞ 0.05).The mRNA expression of CAT and SOD experienced no significant changes in the 2.44-,4.88-and 9.75-μmol/L pterostilbene groups compared with the normal control group (P ＞ 0.05).However,2.44,4.88 and 9.75 μmol/L pterostilbene could significantly reduce the inhibitory effect of UVB radiation on the mRNA expression of CAT (P ＜ 0.05) and up-regulate the mRNA expression of SOD in the pterostilbene + UVB groups (P ＜ 0.05).ELISA revealed that UVB radiation could inhibit the activity of CAT and SOD in the HaCaT cells (both P ＜ 0.001),while 2.44,4.88 and 9.75 μmol/L pterostilbene could reduce the inhibitory effect of UVB radiation on the activity of CAT and SOD (all P ＜ 0.05).However,the activity of CAT and SOD were still lower in the 2.44-,4.88-and 9.75-μmol/L pterostilbene + UVB groups than in the normal control group (P ＜ 0.05).Conclusion Pterostilbene can prevent UVB-induced acute damage in HaCaT cells by activating the Nrf2 pathway and up-regulating the expression of the downstream antioxidant enzymes CAT and SOD.