Machine Learning-Based Integrated Multiomics Characterization of Colorectal Cancer Reveals Distinctive Metabolic Signatures.

The metabolic signature identification of colorectal cancer is critical for its early diagnosis and therapeutic approaches that will significantly block cancer progression and improve patient survival. Here, we combined an untargeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry and the machine learning approach to analyze metabolites in 173 pairs of cancer samples and matched normal tissue samples to build robust metabolic signature models for diagnostic purposes. Screening and independent validation of metabolic signatures from colorectal cancers via machine learning methods (Logistic Regression_L1 for feature selection and eXtreme Gradient Boosting for classification) was performed to generate a panel of seven signatures with good diagnostic performance (the accuracy of 87.74%, sensitivity of 85.82%, and specificity of 89.66%). Moreover, seven signatures were evaluated according to their ability to distinguish between cancer and normal tissues, with the metabolic molecule PC (30:0) showing good diagnostic performance. In addition, genes associated with PC (30:0) were identified by multiomics analysis (combining metabolic data with transcriptomic data analysis) and our results showed that PC (30:0) could promote the proliferation of colorectal cancer cell SW480, revealing the correlation between genetic changes and metabolic dysregulation in cancer. Overall, our results reveal potential determinants affecting metabolite dysregulation, paving the way for a mechanistic understanding of altered tissue metabolites in colorectal cancer and design interventions for manipulating the levels of circulating metabolites.

Quantifying carboxymethyl lysine and carboxyethyl lysine in human plasma: clinical insights into aging research using liquid chromatography-tandem mass spectrometry.

OBJECTIVE: The objective of this study was to establish a methodology for determining carboxymethyl lysine (CML) and carboxyethyl lysine (CEL) concentrations in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test results were also used for clinical aging research. METHODS: Human plasma samples were incubated with aqueous perfluorovaleric acid (NFPA), succeeded by precipitation utilizing trichloroacetic acid, hydrolysis facilitated by hydrochloric acid, nitrogen drying, and ultimate re-dissolution utilizing NFPA, followed by filtration. Cotinine-D3 was added as an internal standard. The separation was performed on an Agela Venusil ASB C18 column (50 mm × 4.6 mm, 5 µm) with a 5 mmol/L NFPA and acetonitrile/water of 60:40 (v/v) containing 0.15% formic acid. The multiple reaction monitoring mode was used for detecting CML, CEL, and cotinine-D3, with ion pairs m/z 205.2 > 84.1 (for quantitative) and m/z 205.2 > m/z 130.0 for CML, m/z 219.1 > 84.1 (for quantitative) and m/z 219.1 > m/z 130.1 for CEL, and m/z 180.1 > 80.1 for cotinine-D3, respectively. RESULTS: The separation of CML and CEL was accomplished within a total analysis time of 6 minutes. The retention times of CML, CEL, and cotinine-D3 were 3.43 minutes, 3.46 minutes, and 4.50 minutes, respectively. The assay exhibited linearity in the concentration range of 0.025-1.500 µmol/L, with a lower limit of quantification of 0.025 µmol/L for both compounds. The relative standard deviations of intra-day and inter-day were both below 9%, and the relative errors were both within the range of ±4%. The average recoveries were 94.24% for CML and 97.89% for CEL. CONCLUSION: The results indicate that the developed methodology is fast, highly sensitive, highly specific, reproducible, and suitable for the rapid detection of CML and CEL in clinical human plasma samples. The outcomes of the clinical research project on aging underscored the important indicative significance of these two indicators for research on human aging.

Utilizing serum metabolomics for assessing postoperative efficacy and monitoring recurrence in gastric cancer patients.

OBJECTIVE: (1) This study aims to identify distinct serum metabolites in gastric cancer patients compared to healthy individuals, providing valuable insights into postoperative efficacy evaluation and monitoring of gastric cancer recurrence; (2) Methods: Serum samples were collected from 15 healthy individuals, 16 gastric cancer patients before surgery, 3 months after surgery, 6 months after surgery, and 15 gastric cancer recurrence patients. T-test and analysis of variance (ANOVA) were performed to screen 489 differential metabolites between the preoperative group and the healthy control group. Based on the level of the above metabolites in the recurrence, preoperative, three-month postoperative, and six-month postoperative groups, we further selected 18 significant differential metabolites by ANOVA and partial least squares discriminant analysis (PLS-DA). The result of hierarchical clustering analysis about the above metabolites showed that the samples were regrouped into the tumor-bearing group (comprising the original recurrence and preoperative groups) and the tumor-free group (comprising the original three-month postoperative and six-month postoperative groups). Based on the results of PLS-DA, 7 differential metabolites (VIP > 1.0) were further selected to distinguish the tumor-bearing group and the tumor-free group. Finally, the results of hierarchical clustering analysis showed that these 7 metabolites could well identify gastric cancer recurrence; (3) Results: Lysophosphatidic acids, triglycerides, lysine, and sphingosine-1-phosphate were significantly elevated in the three-month postoperative, six-month postoperative, and healthy control groups, compared to the preoperative and recurrence groups. Conversely, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol were significantly reduced in the three-month postoperative, six-month postoperative, and healthy control groups compared to the preoperative and recurrence groups. However, these substances did not show significant differences between the preoperative and recurrence groups, nor between the three-month postoperative, six-month postoperative, and healthy control groups; (4) Conclusions: Our findings demonstrate the presence of distinct metabolites in the serum of gastric cancer patients compared to healthy individuals. Lysophosphatidic acid, triglycerides, lysine, sphingosine-1-phosphate, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol hold potential as biomarkers for evaluating postoperative efficacy and monitoring recurrence in gastric cancer patients. These metabolites exhibit varying concentrations across different sample categories.

Targeted metabolomic profiles of serum amino acids are independently correlated with malnutrition in older adults.

BACKGROUND: Malnutrition is a common geriatric syndrome that is closely associated with adverse clinical outcomes and poses significant harm to older adults. Early assessment of nutritional status plays a crucial role in preventing and intervening in cases of malnutrition. However, there is currently a lack of measurable methods and biomarkers to evaluate malnutrition in older adults accurately. The aim of this study is to investigate the independent correlation between serum levels of amino acids and malnutrition in older adults, and to identify effective metabolomics biomarkers that can aid in the early detection of geriatric malnutrition. METHODS: A total of 254 geriatric medical examination participants from Beijing Hospital were included in the study, consisting of 182 individuals with normal nutritional status (Normal group) and 72 patients at risk of malnutrition or already malnourished (MN group). Malnutrition was assessed using the Mini-Nutritional Assessment Short-Form (MNA-SF). Demographic data were collected, and muscle-related and lipid indexes were determined. Serum amino acid concentrations were measured using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation between serum amino acid levels and malnutrition was analyzed using non-parametric tests, partial correlation analysis, linear regression, and logistic regression. RESULTS: The geriatric MN group exhibited significantly lower serum aromatic amino acid levels (P < 0.05) compared to the normal group. A positive correlation was observed between serum aromatic amino acid levels and the MNA-SF score (P = 0.002), as well as with known biomarkers of malnutrition such as body mass index (BMI) (P < 0.001) and hemoglobin (HGB) (P = 0.005). Multivariable logistic or linear regression analyses showed that aromatic amino acid levels were negatively correlated with MN and positively correlated with the MNA-SF score, after adjusting for some confounding factors, such as age, gender, BMI, smoking status, history of dyslipidemia, diabetes mellitus and frailty. Stratified analyses revealed that these trends were more pronounced in individuals without a history of frailty compared to those with a history of frailty, and there was an interaction between aromatic amino acid levels and frailty history (P = 0.004). CONCLUSION: Our study suggests that serum aromatic amino acids are independently associated with malnutrition in older adults. These results have important implications for identifying potential biomarkers to predict geriatric malnutrition or monitor its progression and severity, as malnutrition can result in poor clinical outcomes.

Comparative efficacy of different reconstruction methods after wide local excision of the nail unit: A retrospective study.

BACKGROUND: Wide local excision (WLE) of the nail unit is widely used in treating in situ and minimally invasive malignant subungual tumours. After WLE, diverse reconstruction methods have been reported. However, the best repair method has yet to be determined. OBJECTIVE: To compare the repair effects and postoperative morbidity of secondary intention healing (SIH), artificial dermis grafting combined with secondary intention healing (ADGSIH) and full-thickness skin grafting (FSG) after WLE of the nail unit. METHODS: We retrospectively reviewed 21 patients who underwent WLE of the nail unit. The re-epithelializing time, functional and cosmetic outcomes, postoperative complications and patients' satisfaction were assessed from the follow-up records. RESULTS: The FSG group showed more rapid healing and better functional and cosmetic outcomes than the SIH and ADGSIH groups. The ADGSIH and FSG groups showed significant pain relief compared to the SIH group. No serious early and late postoperative complications were reported. The median follow-up period was 26 months, and no recurrence was observed. All patients were satisfied with the treatment. CONCLUSIONS: FSG after the WLE of the nail unit is a therapeutic option with convenient application, significant pain relief, rapid recovery and satisfying functional and cosmetic outcomes.

Metabolic-Dysregulation-Based iEESI-MS Reveals Potential Biomarkers Associated with Early-Stage and Progressive Colorectal Cancer.

The application of rapid and accurate diagnostic methods can improve colorectal cancer (CRC) survival rates dramatically. Here, we used a non-targeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry (iEESI-MS) to detect metabolite ions associated with the progression of CRC from 172 tissues (45 stage I/II CRC, 41 stage III/IV CRC, and 86 well-matched normal tissues). A support vector machine (SVM) model based on 10 differential metabolite ions for differentiating early-stage CRC from normal tissues was built with a good prediction accuracy of 92.6%. The biomarker panel consisting of lysophosphatidylcholine (LPC) (18:0) has good diagnostic potential in differentiating early-stage CRC from advanced-stage CRC. We showed that the down-regulation of LPC (18:0) in tumor tissues is associated with CRC progression and related to the regulation of the epidermal growth factor receptor. Pathway analysis showed that metabolic pathways in CRC are related to glycerophospholipid metabolism and purine metabolism. In conclusion, we built an SVM model with good performance to distinguish between early-stage CRC and normal groups based on iEESI-MS and found that LPC (18:0) is associated with the progression of CRC.

Association of levels of metabolites with the safe margin of rectal cancer surgery: a metabolomics study.

BACKGROUND: Rectal cancer is one of the most lethal of gastrointestinal malignancies. Metabonomics has gradually developed as a convenient, inexpensive and non-destructive technique for the study of cancers. METHODS: A total of 150 tissue samples from 25 rectal cancer patients were analyzed by liquid chromatography-mass spectrometry (LC-MS), and 6 tissue samples were collected from each patient (group 1: tumor; group 2: 0.5 cm from tumor; group 3:1 cm from tumor; group 4:2 cm from tumor; group 5:3 cm from tumor and group 6:5 cm from tumor). The differential metabolites of tumor tissues and 5 cm from the tumor (normal tissues) were first selected. The differential metabolites between tumor tissues and normal tissues were regrouped by hierarchical clustering analysis, and further selected by discriminant analysis according to the regrouping of clustering results. The potential safe margin of clinical T(cT)1,cT2 stage rectal cancer and cT3,cT4 stage rectal cancer at the metabolomic level was further identified by observing the changes in the level of differential metabolites within the samples from group 1 to group 6. RESULTS: We found 22 specific metabolites to distinguish tumor tissue and normal tissue. The most significant changes in metabolite levels were observed at 0.5 cm (cT1, cT2) and 2.0 cm (cT3, cT4) from the tumor, while the changes in the tissues afterwards showed a stable trend. CONCLUSIONS: There are differential metabolites between tumor tissues and normal tissues in rectal cancer. Based on our limited sample size, the safe distal incision margin for rectal cancer surgery in metabolites may be 0.5 cm in patients with cT1 and cT2 stage rectal cancer and 2.0 cm in patients with cT3 and cT4 stage rectal cancer.

The effect of dermoscopy in assisting on defining surgical margins of basal cell carcinoma.

To investigate the diagnostic value of dermoscopy in defining the tumor margin of basal cell carcinoma (BCC) for the appropriate surgical margin. A total of 107 BCC patients were enrolled for this study. The tumor boundaries were observed by naked eye and dermoscope respectively, and 5 mm outward was used as surgical margin according to the dermoscopy-defined margin. Pathological examinations were performed at 2 mm intervals in the direction previously marked and the effect was assessed accordingly. There were still 16.8% of patients whose visual margin was insufficient to the dermoscopy-detected margin. With 2 mm excision margin from the dermoscopy-guided tumor margin, excision range in 12 patients (11.2%) proved to be inadequate, but only 18 surgical margins (4.2%) in the whole 428 excision margin specimens proved to be tumor-positive. While with 4 mm margin, residual lesion was observed in 2 (0.5%) of 107 BCC patients, and positive margin was found in 2 (0.3%) of 428 margin specimen. There has been no recurrence in our study so far. Dermoscopy is superior to visual inspection for defining BCC tumor margin. Under preoperative dermoscopy detection, a 4 mm excision margin of BCC can achieve a radical resection rate of 98.1%, and 92.3% for a 2 mm excision margin of pigmented BCC.

Specific lysophosphatidylcholine and acylcarnitine related to sarcopenia and its components in older men.

BACKGROUND: Metabolic profiling may provide insights into the pathogenesis and identification of sarcopenia; however, data on the metabolic basis of sarcopenia and muscle-related parameters among older adults remain incompletely understood. This study aimed to identify the associations of metabolites with sarcopenia and its components, and to explore metabolic perturbations in older men, who have a higher prevalence of sarcopenia than women. METHODS: We simultaneously measured the concentrations of amino acids, carnitine, acylcarnitines, and lysophosphatidylcholines (LPCs) in serum samples from a cross-sectional study of 246 Chinese older men, using targeted metabolomics. Sarcopenia and its components, including skeletal muscle index (SMI), 6-m gait speed, and handgrip strength were assessed according to the algorithm of the Asian Working Group for Sarcopenia criteria. Associations were determined by univariate and multivariate analyses. RESULTS: Sixty-five (26.4%) older men with sarcopenia and 181 (73.6%) without sarcopenia were included in the study. The level of isovalerylcarnitine (C5) was associated with the presence of sarcopenia and SMI. Regarding the overlapped metabolites for muscle parameters, among ten metabolites associated with muscle mass, six metabolites including leucine, octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14), and LPC18:2 were associated with handgrip strength, and three of which (C12, C14, and LPC18:2) were also associated with gait speed. Specifically, tryptophan was positively associated and glycine was negatively associated with handgrip strength, while glutamate was positively correlated with gait speed. Isoleucine, branched chain amino acids, and LPC16:0 were positively associated with SMI. Moreover, the levels of LPC 16:0,18:2 and 18:0 contributed significantly to the model discriminating between older men with and without sarcopenia, whereas there were no significant associations for other amino acids, acylcarnitines, and LPC lipids. CONCLUSIONS: These results showed that specific and overlapped metabolites are associated with sarcopenic parameters in older men. This study highlights the potential roles of acylcarnitines and LPCs in sarcopenia and its components, which may provide valuable information regarding the pathogenesis and management of sarcopenia.

Does Social Support Moderate Wound Pain and Health-Related Quality of Life in Patients With Chronic Wounds? A Multicenter Descriptive Cross-sectional Study.

PURPOSE: We sought to explore the relationships among social support, health-related quality of life (HRQOL), and wound pain, and to examine whether social support would moderate the relationship between wound pain and HRQOL. DESIGN: A multicenter descriptive cross-sectional study. SUBJECTS AND SETTINGS: Individuals with chronic wounds attending wound clinics affiliated with 3 public hospitals in Beijing, China. METHODS: Sociodemographic and wound characteristics of 162 participants were retrieved from medical records. Participants completed questionnaires for wound-related pain intensity (Numerical Rating Scale), social support (Social Support Rating Scale), and HRQOL (Medical Outcome Study Short Form-36). The moderating effect analysis was examined using the PROCESS analytic tool developed by Hayes, based on the bias-corrected bootstrapping method. RESULTS: Results revealed that higher pain intensity was significantly related to lower HRQOL (P < .01), and higher social support was associated with better HRQOL (P < .01). However, there was no significant correlation between social support and wound pain (P = .55). Importantly, the moderating effect of social support on the relationship between wound pain and HRQOL was statistically significant (P = .008). CONCLUSIONS: We found that social support moderated the impact of wound pain on HRQOL in patients with chronic wounds. This finding suggests that support obtained from social networks may be a beneficial intervention to improve the HRQOL of patients with chronic wounds, especially those suffering from high-intensity wound pain.

Robust Biological Fibers Based on Widely Available Proteins: Facile Fabrication and Suturing Application.

Lightweight and mechanically strong protein fibers are promising for many technical applications. Despite the widespread investigation of biological fibers based on spider silk and silkworm proteins, it remains a challenge to develop low-cost proteins and convenient spinning technology for the fabrication of robust biological fibers. Since there are plenty of widely available proteins in nature, it is meaningful to investigate the preparation of fibers by the proteins and explore their biomedical applications. Here, a facile microfluidic strategy is developed for the scalable construction of biological fibers via a series of easily accessible spherical and linear proteins including chicken egg, quail egg, goose egg, bovine serum albumin, milk, and collagen. It is found that the crosslinking effect in microfluidic chips and double-drawn treatment after spinning are crucial for the formation of fibers. Thus, high tensile strength and toughness are realized in the fibers, which are comparable or even higher than that of many recombinant spider silks or regenerated silkworm fibers. Moreover, the suturing applications in rat and minipig models are realized by employing the mechanically strong fibers. Therefore, this work opens a new direction for the production of biological fibers from natural sources.

Clinicopathological Analysis of Acquired Melanocytic Nevi and a Preliminary Study on the Possible Origin of Nevus Cells.

BACKGROUND: The pathogenesis of acquired melanocytic nevi (AMN) is still unclear, and the origin of nevus cells has not been clarified. OBJECTIVE: To analyze the clinical features and pathological types of AMN and identify the possible origin of nevus cells. METHODS: A retrospective study of 2929 cases of AMN was conducted, and 96 specimens of intradermal and junctional nevi were selected. Immunohistochemical assays were performed to detect the expression of basement membrane component receptor DDR-1 and the molecular markers on epidermal melanocytes, dermal stem cells (DSCs), and hair follicle stem cells. RESULTS: Junctional nevi and compound nevi were prone to occur on glabrous skin, such as the palms, soles, and vulva, and on the extremities in children, whereas intradermal nevi tended to develop on the trunk, head, and face of adults. The immunohistochemical data revealed that both junctional nevi and intradermal nevi expressed the epidermal melanocyte surface markers E-cadherin, DDR-1, and integrin α6 and the DSC molecular markers NGFRp-75 and nestin. CD34 was expressed only in junctional nevi, whereas K19 was not expressed in any type of melanocytic nevi. There was no significant difference in molecular expression at different sites or in different ages of onset. Nestin expression was markedly stronger in the intradermal nevi than in the junctional nevi, but there was no difference between the superficial and deep nevus cell nests of intradermal nevi. CONCLUSION: AMN may have a multicellular origin that commonly follows the mode of Abtropfung. Furthermore, DSCs may partly or independently participate in the formation of nevus cells.

Serious postoperative complications induced by medical glue: three case reports.

BACKGROUND: Various types of medical glues/adhesives/topical coagulants' (referred to as MG hereinafter) have widespread application as surgical adhesives, and have been shown to be safe and effective for a broad range of usage, such as in hemostasis, reinforcement of intestinal anastomoses or sites of potential fluid leakage, adhesion of two surfaces, wound closure, and vascular embolization. However, inappropriate application of MG may sometimes lead to serious complications. Herein, we describe three cases of serious postoperative complications induced by a possible inappropriate use of N-butyl-2-cyanoacrylate MG (NBCA MG). CASE PRESENTATION: Three patients presented with abdominal pain (chronic pain in cases 1 and 2, and acute pain in Case 3), hematochezia (Case 2), and intestinal obstruction (Case 3). All patients had a history of abdominal surgery and intraoperative use of NBCA MG. Abdominal computed tomography and gastroenterological endoscopy revealed foreign bodies (solidified MG in cases 1 and 2) and intestinal obstruction related to a mass of residual non-absorbed MG causing an internal hernia from a dense adhesion (Case 3). All patients underwent exploratory laparotomy, which revealed duodenal perforation, colonic erosion, and an internal hernia, all of which was related to MG use. We undertook removal of the foreign bodies (cases 1 and 2), surgical closure of the site of duodenal erosion (Case 1), partial colectomy (Case 2), and partial enterectomy (Case 3). CONCLUSION: Inappropriate application of MG may induce serious complications. We emphasize the importance of careful evaluation of the indications, dosage, and spraying thickness of MG in clinical practice. Serious complications caused by inappropriate application of MG should be reported to raise awareness in the surgical fraternity.

Modified shave surgery combined with nail window technique for the treatment of longitudinal melanonychia: Evaluation of the method on a series of 67 cases.

BACKGROUND: Nail matrix histopathologic examination is still the criterion standard to diagnose longitudinal melanonychia (LM). OBJECTIVE: To introduce modified shave surgery combined with the nail window technique for managing LM and evaluate the postoperative outcome of the procedure. METHODS: We retrospectively reviewed the medical records of 67 patients with LM who underwent shave surgery combined with the longitudinal-strip nail window technique at our institution from March 2015 to June 2018. RESULTS: Pathologic diagnosis was accessible in all cases, and 60 cases were assessable for the postoperative outcomes. A total of 45 cases (75.0%) had no postoperative nail dystrophy, and recurrence of nail pigmentation was found in only 8 cases (13.3%). LIMITATIONS: This was a retrospective study. CONCLUSION: Modified shave surgery combined with the nail window technique is the preferable management for LM cases, with limited postoperative nail dystrophy and recurrence of pigmentation.

Protein expression profiles and clinicopathologic characteristics associate with gastric cancer survival.

BACKGROUND: Prognosis remains one of most crucial determinants of gastric cancer (GC) treatment, but current methods do not predict prognosis accurately. Identification of additional biomarkers is urgently required to identify patients at risk of poor prognoses. METHODS: Tissue microarrays were used to measure expression of nine GC-associated proteins in GC tissue and normal gastric tissue samples. Hierarchical cluster analysis of microarray data and feature selection for factors associated with survival were performed. Based on these data, prognostic scoring models were established to predict clinical outcomes. Finally, ingenuity pathway analysis (IPA) was used to identify a biological GC network. RESULTS: Eight proteins were upregulated in GC tissues versus normal gastric tissues. Hierarchical cluster analysis and feature selection showed that overall survival was worse in cyclin dependent kinase (CDK)2, Akt1, X-linked inhibitor of apoptosis protein (XIAP), Notch4, and phosphorylated (p)-protein kinase C (PKC) α/ß2 immunopositive patients than in patients that were immunonegative for these proteins. Risk score models based on these five proteins and clinicopathological characteristics were established to determine prognoses of GC patients. These proteins were found to be involved in cancer related-signaling pathways and upstream regulators were identified. CONCLUSION: This study identified proteins that can be used as clinical biomarkers and established a risk score model based on these proteins and clinicopathological characteristics to assess GC prognosis.

A New Co-P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance Imaging-Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy.

Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)-functionalized Co-P nanocomposites (Co-P@PDA) for magnetic resonance imaging (MRI)-guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm-1 s-1 can enable Co-P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis. Moreover, Co-P@PDA exhibit excellent photothermal performance owing to the strong near-infrared (NIR) absorbance of both Co-P nanocomposite and PDA. Highly effective ablation of tumors is achieved in a murine tumor model because the NIR laser not only induces photothermal effects but also triggers the chemotherapeutic drug on-demand release, which endows the Co-P@PDA with high curative effects but little toxicity and few side effects. These findings demonstrate that Co-P@PDA are promising agents for highly effective and precise antitumor treatment and warrant exploration as novel theranostic nanoagents with good potential for future clinical translation.

Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus.

BACKGROUND: Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. OBJECTIVE: This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO2 ) fractional laser together with tacrolimus. METHODS: Forty-five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. RESULTS: Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. CONCLUSIONS: The treatment of vitiligo by CO2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO2 fractional laser together with tacrolimus. Lasers Surg. Med. 50:829-836, 2018. © 2018 Wiley Periodicals, Inc.

Anatomical variation of infra-pyloric artery origination: A prospective multicenter observational study (IPA-Origin).

OBJECTIVE: Infra-pyloric artery (IPA) is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA. METHODS: We did this prospective, multicenter, open-label, observational study at gastric surgery departments of 34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ2 tests and Fisher's tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov (No. NCT03071237). RESULTS: Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419 (97.7%) patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398 (95.0%) patients, including gastroduodenal artery (GDA) in 154 (36.8%) patients, anterior superior pancreaticoduodenal artery (ASPDA) in 130 (31.0%) patients, and right gastroepiploic artery (RGEA) in 114 (27.2%) patients. Fifteen (3.6%) patients were identified with multiple IPA and 6 (1.4%) patients were identified as IPA absence. The differences in the distribution of surgical approach (P=0.003) and geographic area (P=0.030) were statistically significant. No difference was shown in sex, age, gastrectomy type, tumor location, and clinical T, N and M stage. CONCLUSIONS: Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions. Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.

An extract from pork bones containing osteocalcin improves glucose metabolism in mice by oral administration.

Osteocalcin (OC) is a bone-derived hormone that regulates energy metabolism. OC exists in two forms, carboxylated (GlaOC) and uncaboxylated (GluOC), but only the latter appears to have an endocrine function. In this study, we prepared an extract containing both Gla- and GluOC from boiled pork bone using 0.2 M carbonate buffer at pH 9.5, and tested whether the extract had beneficial effects on improving metabolic parameters in obese mice. The extract equivalent of 1.2 µg of GluOC/mouse was orally administrated to C57BL/6 female mice fed a high-fat, high-sucrose diet. Daily oral administration of the extract for four weeks decreased blood glucose levels and promoted glucose tolerance as well as insulin sensitivity. Our study shows for the first time that boiled pork bones are a source material for osteocalcin in the large-scale production of supplements designed to improve glucose metabolism.

Protein profiling of Helicobacter pylori-associated gastric cancer.

Helicobacter pylori infection is an initiating factor in the development of gastric cancer. Gastric cancer can be divided into two groups on the basis of H. pylori serological status; seropositive H. pylori status predicts favorable prognosis in patients with gastric cancer. By using the protein pathway array, we identified 20 differentially expressed proteins in primary gastric cancer tissues between the H. pylori-seropositive and H. pylori-seronegative groups. Our results indicate that both brassinosteroid insensitive 1-associated kinase 1 and calpastatin are favorable prognostic factors in H. pylori-seropositive gastric cancer patients. In contrast, dachshund homolog 1 is a favorable prognostic factor in H. pylori-seronegative gastric cancer patients. Different signaling pathways were found to be altered between H. pylori-seropositive and H. pylori-seronegative gastric cancer, which may account for the different tumorigenesis and outcomes between these two subsets of patients.