Evaluation of two laboratory model methods for diarrheal irritable bowel syndrome.

BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. METHODS: The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. RESULTS: Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1ß, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. CONCLUSION: In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling.

Individual Identification in Facial Appearance Biometrics Based on Macroscopical Comparison.

Individual identification is one of the research hotspots in the practice of forensic science, and the judgment is usually built on the comparison of the unique biological characteristics of the individual, such as fingerprints, iris and DNA. With the dramatic increase in the number of cases related to video image investigations, there is an increasing need for the technology to identify individuals based on the macroscopic comparison of facial appearance biometrics. At present, with the introduction of computer three-dimensional (3D) modeling and 3D superimposition comparison technology, considerable progress has been made in individual identification methods based on macroscopic comparison of facial appearance biometrics. This paper reviews individual facial appearance biometric methods based on macroscopical comparison, comprehensively analyzes the advantages and limitations of different methods, and puts forward recommendations and prospects for subsequent research.

pH-sensitive carbon nanotubes graft polymethylacrylic acid self-assembly nanoplatforms for cellular drug release.

pH-Sensitive carbon nanotubes graft polymethylacrylic acid hybrids (CNTs-g-PMAA) were prepared through a three-step process, and self-assembled into core-shell micelle nanoparticles. The chemical structure of the hybrids were characterized by FTIR, 1H NMR and TGA. The critical micelle concentration (CMC) was measured by surface tension, and the value hinged on the Mn values or chain lengths of PMAA segments. The UV-vis transmittance, dynamical light scattering (DLS), and zeta potential measurements indicated that the hybrid self-assembly exhibited pH-sensentive responsiveness. The self-assembly was used to load an anticancer drug, paclitaxel (PTX), with an encapsulation efficiency of 77%. The PTX-loaded hybrid drug preparations were applied for cancer-cellular drug release, finding that the release rate was dependent on pH environments, and faster in acidic media of pH < 6.8 than in pH 7.4. MTT and hemolysis assays manifested that the blank hybrid drug carriers were nontoxic and safe, whereas the PTX-loaded drug preparations possessed comparable and even higher anticancer activity in comparison with free PTX. Consequently, the developed hybrid drug nanocarriers can be used for cancer therapy as a promising candidate.

Preliminary establishment of a spinal stability scoring system for multiple myeloma.

BACKGROUND: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, and the Spinal Instability Neoplastic Score scoring system may not be fully applicable to multiple myeloma (MM) patients. AIM: To evaluate the spinal stability of patients with MM spinal involvement to guide their clinical treatment. METHODS: By using the Delphi method, we collected and extracted information through a series of questionnaires and improved it via feedback. We also preliminarily established a spinal stability scoring system for multiple myeloma. RESULTS: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The MM spinal stability scoring system was created by calculating the scores of the six separate components: location, pain, number of segments, physiological curvature, comorbidities, and neurological function. The minimum value was "0", and the maximum value was "24". A score of "0-10" indicated "spine stability", a score of "11-17" indicated "potential instability", and a score of "18-24" indicated "spine instability". Patients with a score of "11-24" need an intervention such as surgery. CONCLUSION: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM.

Temperature and Photo Dual-Stimuli Responsive Block Copolymer Self-Assembly Micelles for Cellular Controlled Drug Release.

To well adapt to the complicated physiological environments, it is necessary to engineer dual- and/or multi-stimuli responsive drug carriers for more effective drug release. For this, a novel temperature responsive lateral chain photosensitive block copolymer, poly[(N-isopropylacrylamide-co-N,N-dimethylacrylamide) -block-propyleneacylalkyl-4-azobenzoate] (P(NIPAM-co-DMAA)-b-PAzoHPA), is synthesized by atom transfer radical polymerization. The structure is characterized by 1 H nuclear magnetic resonance spectrometry and laser light scattering gel chromatography system. The self-assembly behavior, morphology, and sizes of micelles are investigated by fluorescence spectroscopy, transmission electron microscope, and laser particle analyzer. Dual responsiveness to light and temperature is explored by ultraviolet-visible absorption spectroscopy. The results show that the copolymer micelles take on apparent light and temperature dual responsiveness, and its lower critical solution temperature (LCST) is above 37 °C, and changes with the trans-/cis- isomerization of azobenzene structure under UV irradiation. The blank copolymers are nontoxic, whereas the paclitaxel (PTX)-loaded counterparts possessed comparable anticancer activities to free PTX, with entrapment efficiency of 83.7%. The PTX release from the PTX-loaded micelles can be mediated by changing temperature and/or light stimuli. The developed block copolymers can potentially be used for cancer therapy as drug controlled release carriers.

Multiple-bar Nuss operation: an individualized treatment scheme for patients with significantly asymmetric pectus excavatum.

BACKGROUND: Research into multiple-bar Nuss operations for the treatment of wide-range or significantly asymmetric pectus excavatum is rarely reported. This paper aims to explore the curative effects of multiple-bar Nuss operations on wide-range or significantly asymmetric pectus excavatum. METHODS: We reviewed the clinical data of 153 patients with pectus excavatum who were treated in our hospital from September 2006 to August 2014. All the patients had wide-range or significantly asymmetric pectus excavatum and underwent multiple-bar Nuss operations performed by the author. RESULTS: All 153 patients agreed to undergo the operation. The median age was 17 y (10.2-41 y). The median Haller index was 3.98 (3.2-25). One hundred and fifty-one patients accepted treatment with two bars, and 2 cases accepted treatment with three bars. The median operation time was 123 min (65-500 min), the median blood loss was 20 mL (2-200 mL), and the median postoperative hospital stay was 6 days (3-33 days). The incidence rates of pleural effusion, pneumothorax and hydropneumothorax that required drainage treatment were 0.7% (1/153), 1.3% (2/153) and 3.3% (5/153), respectively. Displacement of a bar occurred in one case, and bar exposure occurred in 7 cases. Therefore, 2 cases had the bars removed early, within 2 years postoperation. One patient with severe depression (Haller index: 8.8) had an unhealed auxiliary incision of the xiphoid process, and although the incision was cured after the early removal of the inferior bar, the deformity recurred. There were no cases of death. Currently, 51.6% (79/153) of the cases have had the bars removed. The most recent follow-up revealed that patients' median satisfaction score for the surgical correction effect was 9 points (10 points indicated full satisfaction). CONCLUSIONS: For patients with significantly asymmetric and severely deformed pectus excavatum, the multiple-bar Nuss operation not only is safe and effective but can also achieve a better cosmetic appearance. However, we should continue to explore technical improvements.

Dual Stimuli-Responsive Supramolecular Self-Assemblies Based on the Host-Guest Interaction between ß-Cyclodextrin and Azobenzene for Cellular Drug Release.

Health has always been a hot topic of concern, whereas cancer is one of the largest security risks to human health. Although the existing drug delivery systems (DDSs) have been extensively reported and commercially applied, there are still some issues that have yet to be well-resolved, including the toxicity, side-effects, and targeted therapy efficiency of drugs. Consequently, it is still necessary to develop a novel, highly efficient, controlled and targeted DDS for cancer therapy. For this, a supramolecular polymer, ß-CD-g-PDMAEMA@Azo-PCL, was designed and developed through the host-guest inclusion complexation interactions between a host polymer, ß-cyclodextrin-graft-poly(2-(dimethylamino)ethyl methacrylate) (ß-CD-g-PDMAEMA), and a guest polymer, azobenzene modified poly(ε-caprolactone) (Azo-PCL), and was characterized by various analysis techniques. The supramolecular assembly was examined in various pH environments and/or under UV-vis irradiation, showing the formation of supramolecular assemblies from regular spherical shapes to irregular aggregates with various hydrodynamic diameters. The 2D NOESY NMR studies showed the formation of inclusion complexation between Azo-PCL and ß-CD-g-PDMAEMA and between ß-CD and the side groups of PDMAEMA. The supramolecular assemblies could encapsulate doxorubicin to form spherical core-shell drug-carrying micelles with an entrapment efficiency of 66.1%. The effects of external environment stimuli on the in vitro drug release were investigated, showing light- and pH-modulated drug release properties. The cytotoxicity assessment indicated that the blank supramolecular micelles were nontoxic, whereas the drug-loaded micelles exhibited comparable or even superior anticancer activity to the anticancer activity of free DOX and inhibition of cancer cell proliferation. Therefore, the developed supramolecular assemblies can potentially be used as drug-controlled release carriers.

TCF19 contributes to cell proliferation of non-small cell lung cancer by inhibiting FOXO1.

Transcription factor 19 (TCF19) harbors a forkhead association (FHA) domain, a proline-rich region, a PHD or RING finger region, suggesting that TCF19 possesses a powerful function. However, its expression and function remains unknown in non-small-cell lung cancer (NSCLC). The function cluster analysis was carried out using Metascape website. 3-(4,5-Dimethyl-2-thiazolyl)2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation, and anchorage-independent growth ability assay were carried out to detect the effect of TCF19 on cell proliferation. Bromodeoxyuridine (Brdu) labeling and flow cytometry assay were used to evaluate the effect of TCF19 on cell-cycle progression. Quantitative polymerase chain reaction and chromatin immunoprecipitation assay were performed to investigate the mechanism by which TCF19 is involved in cell-cycle transition. By analyzing the publicly available dataset, The Cancer Genome Atlas (TCGA), we found that TCF19 is significantly increased in the lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC), two primary histological subtype of NSCLC. Besides, further function cluster analysis exhibited that TCF19 may mainly participate in cell cycle. MTT, colony formation, and anchorage-independent growth ability assay confirmed that overexpression of TCF19 enhances the proliferation of both LAC and SCC cells. Besides, further experiments revealed that TCF19 contributes to cell cycle G1/S transition. Not only that, upregulation of TCF19 can inhibit the expression of p21, p27, and p57, while promote the expression of cyclin D1 by inhibiting FOXO1. Our research offers important evidence that TCF19 can promote cell-cycle progression of NSCLC cells, and TCF19 may served as novel therapeutic targets.

Adipose tissue transplantation ameliorates lipodystrophy-associated metabolic disorders in seipin-deficient mice.

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue and can lead to hepatic steatosis, insulin resistance (IR), and dyslipidemia in humans. Adipose tissue secretes many adipokines that are central to the regulation of metabolism. In this study, we investigated whether transplantation of normal adipose tissue could ameliorate severe hepatic steatosis, IR, and dyslipidemia in lipoatrophic seipin knockout (SKO) mice. Normal adipose tissue from wild-type mice was transplanted into 6-wk-old SKO mice. At 4 mo after adipose tissue transplantation (AT), the transplanted fat survived with detectable blood vessels, and the reduced levels of plasma leptin, a major adipokine, were dramatically increased. Severe hepatic steatosis, IR, and dyslipidemia in SKO mice were ameliorated after AT. In addition, abnormal hepatic lipogenesis and ß-oxidation gene expression in SKO mice were improved after AT. Our results suggest that AT may be an effective treatment to improve lipodystrophy-associated metabolic disorders.

[Predictive value of c-met for long-term mortality in patients with esophageal squamous cell carcinoma].

OBJECTIVE: To explore the correlation of c-met protein with the clinical staging and cell differentiation of esophageal squamous cell carcinoma (ESCC). METHODS: A total of 100 patients with ESCC were enrolled were examined for expression of c-met protein using immunohistochemistry, and the patients in negative and positive c-met expression groups were compared for clinicopathological characteristics and overall survival. RESULTS: s The 100 ESCC patients included 67 male and 33 female patients with a median age of 59 years; 49 of the patients were negative and 51 were positive for c-met expression. Positive c-met expression was significantly correlated with advanced TMN stages and lower tumor differentiation. Kaplan-Meier survival curve showed that the median survival time of c-met-positive patients was significantly reduced compared with that of c-met-negative patients (30.9 vs 48.2 months, P<0.05). COX regression analysis showed that c-met was a independent risk factor for the overall survival of the patients (HR: 2.34, 95% CI: 1.63-4.54, P<0.05). CONCLUSION: A positive expression of c-met protein is significantly correlated with an advanced TMN stage, lower tumor differentiation and a poor prognosis, and may serve as a indicator for predicting the prognosis of ESCC.

Surgical correction of 639 pectus excavatum cases via the Nuss procedure.

BACKGROUND: To review the clinical experience and short- to middle-term effects of the Nuss procedure for correction of pectus excavatum (PE). METHODS: From September 2006 to August 2014, 639 patients with PE were treated using the Nuss procedure. Of these, 546 were male and 93 were female. The mean age was 15.3±5.8 years (2.5-49 years). Preoperative chest CT scans Haller index (HI) was 4.3±1.7 (2.9-17.4), with 75 cases of mild PE (HI <3.2), 114 cases of moderate PE (HI 3.2-3.5), 393 cases of severe PE (HI 3.6-6.0), and 57 cases of extremely severe PE (HI >6.0). RESULTS: A total of 638 patients successfully completed the surgery, an 11-year-old male patient who died after the surgery had undergone ventricular septal defect closure surgery through a sternal incision 7 years ago. The mean operative time was 64.3±41.7 min (40-310 min). Excluding the patient who died, the average blood loss was 24.5±17.8 mL (10-160 mL). The average length of postoperative hospital stay was 5.2±2.9 days (4-36 days). A total of 484 cases (75.7%) required 1 steel bar insertion, 153 cases (24.0%) required 2 steel bars, and 2 cases (0.3%) required 3 bars. Postoperative evaluation of the surgery outcomes revealed the following: excellent in 504 cases, good in 105, fair in 28 and poor in 2, good quality rate was 95.3%. CONCLUSIONS: Correction of PE via the Nuss procedure is minimally invasive and simple to perform with good short and mid-term effects, while long-term efficacy remains to be determined.

Quantitative study of cellular heterogeneity in doxorubicin uptake and its pharmacological effect on cancer cells.

Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF-7 cells with different schedules of DOX with or without surface P-glycoprotein (P-gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single-cell analysis using capillary electrophoresis coupled with laser-induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium and flow cytometry assays. The expression of cellular membrane surface P-gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single-high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P-gp expression, with r = -0.7680 to ~ -0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P-gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation.