Histopathological characteristics analysis of giant melanocytic naevi in children.

BACKGROUND: The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin, pathogenesis, and GCMN progression are not yet completely clear. Unlike other medium or small superficial lesions, histomorphological evaluation is significant for GCMN pathological classification, malignant transformation assessment, and early detection of prognosis. AIMS: This study aimed to investigate the pathological features of GCMN, including its satellite lesions. PATIENTS/METHODS: Twenty-three giant naevi and seventeen "satellite lesions" were collected from children aged 1 to 10 in Shanghai Ninth People's Hospital from 2018 to 2020. A histological study was conducted to evaluate their histological appearance. All the data observed and recorded data were statistically analyzed. RESULTS: In 23 cases of GCMN primary nevus, nevus cells were mainly distributed in the dermal region, with melanocyte proliferation and the presence of nevus nests at the dermal-epidermal junction. However, in satellite nevus, a junctional growth pattern was noted. Additionally, other histopathologic features, including epidermal contour, cell morphology, and architecture disorder also showed significant differences between primary nevus and satellite nevus. CONCLUSIONS: We demonstrated that the congenital pattern of the main nevus is more obvious than one of the satellite nevus, suggesting that the satellite nevus and the main nevus may occur slightly later than the main nevus. "Satellite nevus" happens as a result of a separate genetic event.

Single-cell RNA sequencing reveals distinct tumor microenvironment of ground glass nodules and solid nodules in lung adenocarcinoma.

Introduction: Lung adenocarcinoma (LUAD) is the most prevalent lung cancer. LUAD presents as ground glass nodules (GGN) and solid nodules (SN) in imaging studies. GGN is an early type of LUAD with good prognosis. However, SN exhibits a more malignant behavior than GGN, including worse pathological staging and tumor prognosis. The mechanism leading to the different malignancy levels of GGN and SN remains elusive. Methods: Three patients with GGN and three patients with SN diagnosed with early LUAD were enrolled. The tumor samples were digested to a single-cell suspension and analyzed using 10× Genomic Single-cell ribonucleic acid sequences (scRNA-seq) techniques. Results: A total of 15,902 cells were obtained and classified into nine major types. The tumor microenvironment (TME) was subsequently described in detail. ScRNA-seq revealed that ribosome-related pathways and cell adhesion played similar but distinct roles in the two groups. SN also had more active cell proliferation, enriched cell cycle regulatory pathways, and severe inflammatory responses. Conclusion: We observed changes in the cellular composition and transcriptomic profile of GGN and SN. The study improved the understanding of the underlying mechanisms of lung carcinogenesis and contributed to lung cancer prevention and treatment.

Comprehensive management for complex complications after periumbilical fat implantation into the upper eyelid.

BACKGROUND: Recently, periumbilical fat (PF) mass, an autologous material with a high survival rate, has been transplanted to treat sunken or dissatisfactory double eyelids. However, the intricate complications of PF grafts and associated reconstructive strategies are infrequently discussed. METHODS: During 3 years, 20 patients (33 eyes) with eyelid malformations caused by PF grafts into the orbital septum or on the surface of the levator aponeurosis underwent corrective blepharoplasty. We recorded patients' subjective feelings and identified deformities from crease abnormalities, bloated appearance, and problems with the eyelid's height. Then, we categorize them into three types based on their complexity: type I, swollen appearance; type II, obvious adhesion; type III, severe comprehensive damage. The relevant management included removing fat implants, releasing the adhesion, and rebuilding the physical structure according to the anatomic damage mechanism. The improvement effect was assessed with a satisfaction survey from patients and doctors at 6 months of follow-up. RESULTS: The swollen appearance was observed in 26 eyes (78.8%), an unsmooth double-eyelid line was in 23 eyes (69.7%), and the incidence of adhesion was in 22 eyes (66.7%). Following a comprehensive evaluation, 15 eyes (45.5%) and 13 (39.4%) were classified as type I and type II respectively. After the 6-month follow-up, 22 eyes (66.7%) showed exceptional aesthetic results, whereas only 2 eyes as type III had a poor outcome. CONCLUSIONS: The deformities emerging from periumbilical fat into the upper eyelid are associated with the shape of the fat and the adhesion in tissues. Graft removal, adhesion release, and restoration of the natural anatomic structure can have positive outcomes.

Neutrophil-to-Lymphocyte ratio on admission predicts gastrointestinal bleeding in acute basal ganglia hemorrhage.

BACKGROUND: Gastrointestinal bleeding (GIB) is a potential contributing factor for poor prognosis of spontaneous basal ganglia hemorrhage (BGH). This study aimed to investigate the predictive value of new inflammatory biomarkers including neutrophil to lymphocytes (NLR) on admission and construct a nomogram for rapidly predicting GIB in acute BGH. METHODS: The retrospective study included all patients with acute BGH admitted from the emergency department in Huashan Hospital from July 2017 to January 2019. Multivariate analysis was conducted to evaluate the correlation between factors within 24 h and the occurrence of GIB within 7 days after BGH. The receiver operating characteristic (ROC) curve was performed to estimate the prediction ability of inflammatory biomarkers. A nomogram based on significant predictors was validated by ROC curve and calibration curve. RESULTS: A total of 122 patients were enrolled in this study, and the incidence of GIB was 23.0%. Patients with GIB had larger hematoma volume (≥30 ml), lower Glasgow Coma Scale (GCS) score (≤8) and increased inflammatory biomarkers on admission. ROC curve revealed that NLR had a high predictive value to the complication (area under the curve = 0.87). According to multivariate analysis, NLR, GCS score, and hematoma volume were main factors for nomogram, with good calibration and discrimination. CONCLUSIONS: Neutrophil-to-lymphocyte ratio and GCS score within 24 h after the onset of acute BGH are the independent risk factors for GIB. The nomogram developed by these predictors may assist surgeons in rapidly assessing and preventing of GIB for BGH patients in earlier stage.

Application of three-dimensional reconstruction technology combined with three-dimensional printing in the treatment of pectus excavatum.

OBJECTIVES: To explore the clinical value of three-dimensional (3D) reconstruction technology combined with 3D printing in the treatment of pectus excavatum (PE). METHODS: The clinical data of 10 patients with PE in our department from June 2018 to December 2020 were analyzed retrospectively. All patients underwent thin-layer computed tomography examination before the operation, and then 3D reconstruction was performed with Mimics 20.0 software. The radian and curvature of the pectus bar were designed according to the reconstructed images. Afterward, the images were imported into the light-curing 3D printer in STL format for slice printing. Hence that the personalized operation scheme, including the size of the pectus bar and the surgical approach, can be made according to the 3D printed model. The thoracoscopic-assisted Nuss operation was completed by bilateral incisions. The operation time, intraoperative blood loss, and postoperative hospitalization were counted and analyzed. The satisfaction of the surgery was evaluated according to the Haller index and the most posterior sternal compression sternovertebral distance. RESULTS: The surgeries were successfully completed in 10 patients without a transfer to open procedure. The average operation time was (56 ± 8.76) min, the intraoperative blood loss was (23.5 ± 11.07) mL, and the postoperative hospitalization was (7.2 ± 0.92) d. There were no serious complications or death during the perioperative period. Compared with the data before the operation, the most posterior sternal compression sternovertebral distance was larger, and the Haller index was lower, the differences were statistically significant (P < 0.05). CONCLUSIONS: 3D reconstruction technology combined with 3D printing, which can be used before operation, contributes to the operator performing thoracoscopic-assisted Nuss operation safely and effectively, which has productive clinical application value for the treatment of pectus excavatum.

Increased PPARD Expression May Play a Protective Role in Human Lung Adenocarcinoma and Squamous Cell Carcinoma.

Peroxisome proliferator-activated receptor-δ, encoded by gene PPARD, is overexpressed in a majority of human lung cancer subtypes, but its role in the tumor progression remains poorly understood. We have analyzed the expression of PPARD in lung adenocarcinoma (LA) and squamous cell carcinoma (LSCC) datasets. The potential roles of PPARD in the pathological development of LA and LSCC were explored through literature-based pathway analysis and pathway enrichment analysis. In all LA datasets (N = 11) and in seven out of nine LSCC studies, the levels of PPARD were increased as compared to control tissues (log-fold changes were 0.37 ± 0.20 and 0.10 ± 0.37 for LA and LSCC, respectively). On average, the expression levels of PPARD in LA were higher than those in LSCC (p = 0.036). Pathway analysis showed that the overexpression of PPARD might play both positive and negative roles in the development of both LA and LSCC. Specifically, PPARD inhibits seven LSCC promoters and seven LA promoters and activates one LSCC inhibitor and another LA inhibitor. However, PPARD also activates six and one promoters of LA and LSCC, respectively, which would facilitate the development of LA/LSCC. Our results suggested a mixed role of PPARD in LA/LSCC, which may add new insights into the understanding of the PPARD-lung cancer relationship.

Krüppel-like factor 9 upregulates E-cadherin transcription and represses breast cancer invasion and metastasis.

Aberrant expression of Krüppel-like factor 9 (KLF9) is frequently found in some types of cancer and is implicated in cancer initiation and progression. However, the effects of KLF9 on cancer metastases and the underlying mechanisms still need to be understood. Here, we found that KLF9 evidently inhibited the capabilities of migration and invasion of breast cancer cells. The expression of KLF9 was markedly decreased in breast cancer patients compared with benign tumors, and was positively correlated with the expression of E-cadherin in the tissues of breast cancer patients. Mechanistically, chromatin immunoprecipitation combined with site-directed mutagenesis-luciferase assay revealed that KLF9 activated the E-cadherin promoter by binding to GT-box elements located +84 bp and -143 bp from the TSS in the E-cadherin promoter, leading to elevated expression of E-cadherin mRNA and protein. In vivo experiments confirmed that KLF9 strongly inhibited the lung metastasis of breast cancer and increased mouse E-cadherin expression in 4T1 mouse breast cancer cells. Taken together, our findings demonstrated that KLF9 could suppress breast cancer invasion and metastasis by upregulating E-cadherin, which provided new insight into aggressive treatment of breast cancer by targeting the KLF9/E-cadherin axis.

Investigations into the role of non-bond interaction on gelation mechanism of silk fibroin hydrogel.

Silk fibroin hydrogel not only has biocompatibility, but also has environmental response ability. It plays an important role in the development of material. The gelation mechanism of silk fibroin hydrogel is very important to textile and medicine fields. The molecular dynamics simulation was used to discuss the structure and non-bond interaction of silk fibroin hydrogel. The results show that the non-bond interactions between silk fibroin molecules and water molecules have certain influence on the formation of silk fibroin hydrogel. According to the hydrogen bond analysis, the hydrogen bonds are mainly formed between random coil peptide fragments at the two ends of silk fibroin molecules and residues 252-254 are the key residues. The electrostatic and polar solvation interactions between silk fibroin molecules plays a major role in cross-linking of the coil segments of two silk fibroin molecules.

Effect of aroma-producing yeasts in high-salt liquid-state fermentation soy sauce and the biosynthesis pathways of the dominant esters.

Fermentation with excellent aroma-producing yeasts can enhance the flavour of soy sauce. In this work, Millerozyma farinosa CS2.23, Zygosaccharomyces rouxii CS2.42, and Candida parapsilosis CS2.53 were added to the high-salt liquid-state moromi to promote soy sauce fermentation. All three yeasts improved the TE of soy sauce, the highest of which reached 1.03 g/L with added CS2.42. Other quality indexes of soy sauce, including RS, TA, and AN, were not greatly affected. The volatile esters of soy sauce added to the three yeasts increased by 108.85%, 166.71%, and 113.61% compared with the control through GC-MS analysis. Obviously, CS2.42 had an excellent ability to produce esters. Studying the biosynthesis pathway of esters, CS2.42 has the best esterification ability, while CS2.53 has the advantage of alcoholysis ability. The exploration of the biosynthetic pathway of acetate and ethyl esters has laid a foundation for regulating esters in soy sauce fermentation.

Safety analysis of application of mediastinal CO2 aeration in mediastinal esophagectomy.

BACKGROUND: In recent years, minimally invasive esophagectomy (MIE) has been used gradually in esophageal surgery. The application of CO2 aeration in minimally invasive surgeries, especially in laparoscopic surgery, has been very mature. However, the application of CO2 aeration in mediastinal esophagectomy is still in the exploration stage. This study was designed to investigate the safety of mediastinal CO2 aeration in the mediastinal esophagectomy. METHODS: A total of 15 pigs were used to construct an experimental animal model of mediastinal CO2 aeration. The effects of different inflation pressures on the circulatory respiratory function of pigs were studied by detecting the relevant physiological parameters. Heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were monitored before ventilating CO2 (T0), and also monitored at 30 (T1), 60 (T2), 90 (T3) min after inflation and 30 min after deflation (T4). Arterial blood was collected for PaCO2, blood lactate concentration (cLac), PaO2/FiO2, SaO2, pH value, and cardiac output (CO) was measured by esophageal ultrasound. RESULTS: The results of animal experiments showed that under 5-10 mmHg CO2 inflation pressure, circulation function indicators (CVP, MAP, HR, CO) and respiratory function indicators (PaCO2, cLac, PaO2/FiO2, SaO2, pH value) in pigs had no significant difference compared with the indicators before inflation; and under 15 mmHg CO2 inflation pressure, CVP, HR, PaCO2 and blood cLac increased, while MAP, CO, PaO2, SaO2 and pH values decreased. The visual field using mediastinoscopy under 15 and 10 mmHg CO2 inflation pressure was better than that under 5 mmHg CO2 inflation pressure. CONCLUSIONS: Mediastinal esophagectomy with 5-10 mmHg CO2 inflation pressure has no significant effect on the circulation and respiratory function of the body. Compared with the conventional non-inflated transseptal esophageal cancer (EC) surgery, it can provide a better surgical vision and reduce the difficulty of the surgery.

Isolation, identification and application on soy sauce fermentation flavor bacteria of CS1.03.

Bacillus is a common bacterial genus in Chinese traditional sun-brewed moromi. Some Bacillus species can metabolize sauce flavour and aroma substances. To address the insufficiency of flavour microbes in soy sauce fermentation, we used 16S rDNA sequence analysis to identify the CS1.03 strain, which was isolated from moromi produced through the traditional and natural sun brewing methods. A Box-Behnken design was used to optimize the addition technology of CS1.03, and ammoniacal nitrogen content and sensory evaluation were adopted as determination indices. GC-MS analysis was also performed to analyse the flavour components. Results identified CS1.03 as Bacillus subtilis. The optimal conditions yielded 10.7 g/L ammoniacal nitrogen in fermented soy sauce with rich aroma and flavour, and a sensory evaluation score of 90.5. GC-MS analysis revealed that the contents of phenol, aldehyde and ketone are all increased. These results demonstrated that CS1.03 could improve the flavour of soy sauce and shows good potential for application in soy sauce fermentation.

Clinical and prognostic features of spinal meningioma: a thorough analysis from a single neurosurgical center.

PURPOSE: The aim of this study was to thoroughly analyze the clinical characteristics of a large cohort of spinal meningioma (SM) from a single neurological center and identify risk factors associated with worse progression free survival and neurological function outcome. METHODS: Clinical information was retrieved from 483 SM and 9806 cranial meningioma cases who were operated in our center between 2003 and 2013. 194 SM patients who were followed at the main branch were used for prognostic analyses that included both recurrence free survival and neurological functions based on Modified McCormick scale (MMS). RESULTS: Females were predominant (P < 0.001). High grade tumors were not common (WHO grade II, 2.9%; grade III, 1.7%), while the clear cell subtype was frequent within grade II SMs (6/14, 42.9%). Macroscopic total resection was achieved in all SMs (Simpson grade I, 30.9%; grade II, 65.5%; grade III, 3.6%) with a low complications rate (4.6%) and provided neurological improvement in 80 patients (41.2%). Recurrence was seen in 9 cases (4.6%) and associated with high WHO grade, male, prior recurrence, and Simpson grade III. High WHO grade and high Ki-67 index were identified to be independent factors predictive of both neurological function deterioration and impaired post-operative neurological status. CONCLUSIONS: Our analysis of the largest SM cohort in scale from a single institution offers a comprehensive view of the clinical characteristics of surgically treated SM, revealing the distinct biology of SM in comparison to its cranial counterparts, and providing guidance to improve surgical management of SM.

The Effects of Two Different Multivitamins on Aging Mice.

Investigating anti-aging factors that is more effective than antioxidants has important theoretical significance and application value. In search for nutritional ingredients that are more effective in anti-aging, two different multivitamins (multivitamin-1 at a dose of 2.5 mg/kg body weight [BW]/day; multivitamin-2 at a dose of 5.4 mg/kg BW/day) were administered to aging mice (N = 40) induced by D-galactose. The content or activity of the biochemical components associated with aging and anti-aging in the brain and the liver of the experimental mice was then determined for analysis of statistically significant difference among the groups. Results showed the mice in the aging model group exhibited obvious senility symptoms. However, the mice in the multivitamin-1 and multivitamin-2 groups were essentially similar to those of the control group, but were obviously better than the mice in the aging model group. Multivitamin-1 and multivitamin-2 decreased significantly the malondialdehyde (MDA) content and monoamine oxidase (MAO) activity (P < 0.01), and increased significantly the activity of glutathione peroxidase (GSH-Px), copper/zinc-superoxide dismutase (Cu/Zn-SOD) and manganese-superoxide dismutase (Mn-SOD) (P < 0.01) in the brain and the liver of the aging mice. There was no significant difference (P > 0.05) between the effects of the two multivitamins on the components associated with aging and anti-aging. In conclusions, this work showed that vitamins B1, B2, B6 and PP (Nicotinic acid or vitamin B3) play key roles in the anti-aging process of multivitamin-2. Vitamins B1, B2, B6, and PP are more effective nutrients in anti-aging in mice.

MiR-31 is involved in the high glucose-suppressed osteogenic differentiation of human periodontal ligament stem cells by targeting Satb2.

Diabetes mellitus (DM) is a chronic metabolic disease that gives rise to impaired bone remodeling. Increasing evidences have shown that miRNAs are associated with osteogenic differentiation of stem cells. However, the underlying mechanism that links DM-induced HG conditions and impaired osteogenic differentiation capacity of periodontal ligament stem cells (PDLSCs) still remains unclear. In this study, we found that diabetic mice with increased miR-31 level in periodontal ligaments exhibited greater bone loss. In vitro, the high expression of miR-31 is associated with the impaired osteogenic differentiation ability of PDLSCs in high glucose environment. Furthermore, miR-31 inhibitors increased mineralized bone matrix formation and raised Runx2, Osx and OCN expression at both mRNA and protein levels. However, PDLSCs pretreated with miR-31 mimics decreased bone matrix formation and reduced Runx2, Osx and OCN expression level in high glucose microenvironment. Moreover, Satb2 was identified as a target of miR-31 which directly binds to its 3'-untranslated region. To further elucidate the effect of Satb2 in miR-31-mediated osteogenic differentiation, PDLSCs were transfected with Satb2 siRNA and miR-31 inhibitors. The results showed that Satb2 siRNA inhibited osteogenic differentiation of PDLSCs in HG, whereas miR-31 inhibitors reversed the repression of osteogenic differentiation in Satb2 siRNA transfected PDLSCs. Taken together, these results demonstrate that miR-31 is involved in the high glucose-suppressed osteogenic differentiation of PDLSCs by targeting Satb2.

[Effect of resveratrol on expression of TLR4 and inflammatory factors in gingival epithelial cells under high glucose environment].

PURPOSE: Through a study of the molecular mechanism of the effect of resveratrol(RSV) on expression of TLR4 and inflammatory factors in gingival epithelial cells under high glucose environment, the therapeutic effect and molecular mechanism of resveratrol on periodontitis in patients with diabetes mellitus was investigated. METHODS: Gingival epithelial cells were cultured in vitro; according to the way of action, the cultured cells were divided into control group, high glucose group(HG) and HG+RSV group. The mRNA expression of TLR4 was detected by PCR; The third generation of gingival epithelial cells were pre-treated with or without RSV for 24 h under high glucose conditions, and subsequently treated with LPS at 100 ng/mL for 2 h. ELISA was used to detect the secretion of IL-1 beta, IL-6, IL-8 and TNF- alpha; the activation of TLR4 downstream signaling molecules NF-κB p65, p38 MAPK, and STAT3 was determined by Western blot. SPSS17.0 software package was used for statistical analysis. RESULTS: RSV could reverse the increase of TLR4 level in gingival epithelial cells in high glucose medium.LPS markedly increased the expression and secretion of IL-1ß, IL-6, IL-8, and TNF-α in GECs cultured in high glucose medium, which was partly blocked in the presence of RSV. Furthermore, Western blot results showed that RSV significantly suppressed the phosphorylation of TLR4 downstream factors NF-κB p65, p38MAPK, and STAT3. CONCLUSIONS: RSV reduces inflammatory cytokine secretion in gingival epithelial cells, through negative regulation of TLR4 signaling pathway.

Enhanced gap junctional channel activity between vascular smooth muscle cells in cerebral artery of spontaneously hypertensive rats.

The aim of the present study is to investigate the effects of hypertension on the gap junctions between vascular smooth muscle cells (VSMCs) in the cerebral arteries (CAs) of spontaneously hypertensive rats (SHRs). The functions of gap junctions in the CAs of VSMCs in SHRs and control normotensive Wistar-Kyoto (WKY) rats were studied using whole-cell patch clamp recordings and pressure myography, and the expression levels of connexins were analyzed using reverse transcription-quantitative polymerase chain reaction and Western blot analyses. Whole-cell patch clamp measurements revealed that the membrane capacitance and conductance of in situ VSMCs in the CAs were significantly greater in SHRs than in WKY rats, suggesting that gap junction coupling is enhanced between VSMCs in the CAs of SHRs. Application of the endothelium-independent vasoconstrictors KCl or phenylephrine (PE) stimulated a greater vasoconstriction in the CAs of SHRs than in those of WKY rats. The EC50 value of KCl was 24.9 mM (n = 14) and 36.9 mM (n=12) for SHRs and WKY rats, respectively. The EC50 value of PE was 0.9 µM (n = 7) and 2.2 µM (n = 7) for SHRs and WKY rats, respectively. Gap junction inhibitors 18ß-glycyrrhetinic acid (18ß-GA), niflumic acid (NFA), and 2-aminoethoxydiphenyl borate (2-APB) attenuated KCl-induced vasoconstriction in SHRs and WKY rats. The mRNA and protein expression levels of the gap junction protein connexin 45 (Cx45) were significantly higher in the CAs of SHRs than in those of WKY rats. Phosphorylated Cx43 protein expression was significantly higher in the CAs of SHRs than in those of WKY rats, despite the total Cx43 mRNA and protein expression levels in the cerebral artery (CA) exhibiting no significant difference between SHRs and WKY rats. Increases in the expression of Cx45 and phosphorylation of Cx43 may promote gap junction communication among VSMCs in the CAs of SHRs, which may enhance the contractile response of the CA to vasoconstrictors.

Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24), a novel tubulin inhibitor, causes G2/M arrest and cell apoptosis by disrupting tubulin polymerization in human cervical and breast cancer cells.

Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24) is a newly synthesized analogue of nocodazole by our group and has been found to be active for some cancer cells. However, its sensitivity to different cell lines and the underlying anticancer mechanism are still unclear. In this study, we proved that M-24 had strong time- and dose-dependent anti-proliferative effects on human cervical cancer HeLa cells and human breast carcinoma MCF-7 cells. We demonstrated that the growth inhibitory effects of M-24 in both cell lines were associated with microtubule depolymerization. Furthermore, M-24 treatment resulted in cell cycle arrest at the G2/M phase in a dose-dependent manner with subsequent apoptosis induction. Western blotting analysis revealed that up-regulation of cyclin B1 and cdc2 was related with G2/M arrest in both cell lines. In addition, M-24-induced HeLa cell apoptosis was mainly associated with mitochondria-dependent intrinsic pathway. However, M-24-induced MCF-7 cell apoptosis was associated with both mitochondrial and death receptor pathway. In conclusion, M-24 caused apoptosis through disrupting microtubule assembly and inducing cell cycle arrest in HeLa and MCF-7 cells. Therefore, the novel compound M-24 is a promising microtubule-destabilizing agent that has great potential for the therapy of various malignancies especially human cervical and breast cancers.

EFFECTS AND MECHANISMS OF A NEW MULTIVITAMIN ON CHRONIC METABOLIC SYNDROMES AND AGING.

BACKGROUND: Increased occurrence of chronic syndromes has prompted researchers to investigate and develop drugs and methods for controlling chronic syndromes with a view to improve human health and reduce early aging. MATERIAL AND METHODS: Human trials: After the allotted multivitamin pills or placebo pills had been taken for a stipulated period of about 2 months, the volunteers filled out feedback forms on curative effects of the pills in line with the health examination reports. The effects of the multivitamin on various symptoms or diseases and dysfunctions of the chronic metabolic syndromes were noted and evaluated based on the information provided in forms. Animal experiments: Mouse aging model induced by D-galactose were administered the multivitamin by oral gavage every morning. At the end of the sixth week, activity or content of the components associated with ageing and anti-aging in the brain and liver of the aging mice were determined to investigate the mechanisms of the new multivitamin on chronic metabolic syndromes and aging. RESULTS: We found that multivitamin can eliminate or attenuate 38 types of symptoms or dysfunctions of the investigated metabolic syndromes; and that it has both preventive and curative/adjunctive therapeutic effects on the metabolic syndromes. The effects of this multivitamin on components associated with aging and anti-aging were significantly decreased - malondialdehyde content and monoamine oxidase activity but significantly increased activity of superoxide dismutase and glutathione peroxidase. This multivitamin has significant anti-aging effects. CONCLUSION: Supplementing with this multivitamin can prevent and provide treatment/adjunctive therapy for these chronic metabolic syndromes and delay the aging process. List of AbbreviationsBWbody weight; Cu/Zn-SOD, cuprum/zinc-superoxide dismutaseMAOmonoamine oxidaseMDAmalondialdehyde; Mn-SOD, manganese-superoxide dismutase; T-SOD, total superoxide dismutase; TP, total protein.

Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy.

Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.