Unenhanced CT-based predictive model to identify small bowel necrosis in patients with mechanical small bowel obstruction.

OBJECTIVES: To investigate the diagnostic value of unenhanced CT in mechanical small bowel obstruction (SBO) with small bowel necrosis, and to establish a predictive model. METHODS: From May 2017 to December 2021, the patients with mechanical SBO admitted to our hospital were retrospectively collected. Taking pathology-confirmed small bowel necrosis as the gold standard, the experimental group was composed of patients with small bowel necrosis confirmed by pathology, and the control group was composed of patients with no intestinal necrosis confirmed by surgery or successful conservative treatment with no recurrence of intestinal obstruction during 1-month followed-up. RESULTS: A total of 182 patients were enrolled in this study, 157 patients underwent surgery, of which 35 patients were accompanied with small bowel necrosis and 122 patients were not (33 patients with ischemic findings at surgery without necrosis). Finally, there were 35 patients in the experimental group and 147 patients in the control group. Multivariable logistic regression showed that increased attenuation of small bowel wall (P = 0.002), diffuse mesenteric haziness (P = 0.010), difference of CT value between mesenteric vessel and aorta (P = 0.025) and U-/C-shaped small bowel loop (P = 0.010) were independent risk factors for the diagnosis of mechanical SBO with small bowel necrosis. Through internal verification, the area under curve (AUC) of the predictive model reached 0.886 (95%CI: 0.824-0.947), and the calibration result was moderate. CONCLUSION: Multiple features (increased attenuation of small bowel wall; difference of CT values between mesenteric vessel and aorta; diffuse mesenteric haziness; and U-/C-shaped small bowel loop) of unenhanced CT have clinical value in the diagnosis of mechanical SBO with small bowel necrosis. The predictive model based on these four features could achieve satisfactory efficiency.

Comparison of survival outcomes between laparoscopic and open colectomy for transverse colon cancer: a systematic review and meta-analysis.

PURPOSE: This study aimed to compare laparoscopic with open resection for transverse colon cancer (TCC) regarding long-term survival outcomes. METHODS: Systematic literature search was performed on PubMed, Ovid, and Cochrane Library for studies comparing laparoscopic with open resection for TCC. The last search was performed on October 7, 2022. Oncological and survival outcomes were collected and analyzed. This meta-analysis was performed using Review Manager Software (v 5.3). RESULTS: This study included fifteen studies published between 2014 and 2022 with 2556 patients in total. When compared with the laparoscopic group, the open group had significantly more tumors locating on middle transverse colon (P = 0.006, OR = 0.67, 95%CI [0.50, 0.89], I2 = 12%) and more patients received transverse colectomy (P = 0.03, OR = 0.66, 95%CI [0.46, 0.96], I2 = 53%) as results. Comparable tumor stage (P = 0.13, OR = 0.81, 95%CI [0.62, 1.06], I2 = 55%) and number of lymph node harvested (P = 0.22, WMD = -0.81, 95%CI [-2.09, 0.47], I2 = 73%) were observed between the two groups. As for survival outcomes, no significant difference was observed between the two groups for 5-year disease-free survival (DFS; P = 0.61, OR = 0.93, 95%CI [0.72, 1.21], I2 = 0%), 5-year overall survival (OS; P = 0.83, OR = 0.97, 95%CI [0.71, 1.32], I2 = 0%), 3-year DFS (P = 0.97, OR = 0.96, 95%CI [0.69, 1.32], I2 = 0%), and 3-year OS (P = 0.67, OR = 0.92, 95%CI [0.63, 1.35], I2 = 0%). In the subgroup analysis according to tumor stage, the results did not change. CONCLUSION: Current evidence based on studies demonstrated that laparoscopic procedure could be safely performed for TCC, and it would not affect the long-term survival. Randomized clinical trials with a larger sample size are warranted in the future for further investigation.

Chondroitin sulfate and L-Cysteine conjugate modified cationic nanostructured lipid carriers: Pre-corneal retention, permeability, and related studies for dry eye treatment.

In this study, a novel bioadhesive material, a conjugate of chondroitin sulfate and L-cysteine (CS-Cys), was synthesized and modified on the surface of the cationic nanostructured lipid carriers loaded dexamethasone to prepare a novel nano-lipid ocular delivery system (Dex-CS-Cys-cNLC). Through the permeation and retention studies of isolated cornea, it was demonstrated that Dex-CS-Cys-cNLC has better corneal permeation and retention ability and can better overcome the barrier effect of the ocular surface. In addition, the fluorescent probe (RhB) was used to replace the drug, and fluorescence imaging was used to investigate the ocular surface retention ability of the formulation, and the results showed that CS-Cys-cNLC has stronger retention ability and can effectively prolong the time of drug action in the ocular surface. Dex-CS-Cys-cNLC was not irritating to rabbit eye tissues and was a safe delivery system. The results of rabbit dry eye pharmacodynamic experiments also showed that Dex-CS-Cys-cNLC could effectively alleviate dry eye symptoms in rabbits, effectively repair corneal damage, and improve the stability of tear film. All these experimental results suggest that Dex-CS-Cys-cNLC is a promising drug delivery carrier for the treatment of anterior segment of the eye disease.

T1 rectal mucinous adenocarcinoma with bilateral enlarged lateral lymph nodes and unilateral metastasis: A case report.

BACKGROUND: There are a few cases of lateral lymph node (LLN) metastasis (LLNM) of T1 rectal cancer. Moreover, LLNM is easily missed, especially in patients with early-stage rectal cancer. To our knowledge, the possibility of bilateral LLNM before surgery has not been reported in previous studies. CASE SUMMARY: A 36-year-old woman underwent endoscopic submucosal dissection at a local hospital owing to a clinical diagnosis of a rectal polyp. The pathology report showed a diagnosis of T1 rectal mucinous adenocarcinoma. She was considered to have bilateral LLNM after the examination at our hospital. Laparoscopic total mesorectal excision plus bilateral LLN dissection was performed and the pathological outcomes indicated unilateral LLNM. The patient received long-course adjuvant chemoradiotherapy with no recurrence or metastasis observed during the 1-year follow-up period. CONCLUSION: T1 rectal cancer could lead to LLNM and possibly, bilateral LLNM. Therefore, adequate clinical evaluation is essential for these patients.

Construction and Evaluation of Hyaluronic Acid-Coated Flurbiprofen-Layered Double Hydroxide Ocular Drug Delivery System.

In this study, flurbiprofen (FB) was selected as the model drug, and hyaluronic acid-coated flurbiprofen-layered double hydroxide ophthalmic drug delivery system (HA-FB-LDH) was designed and prepared. In this system, the model drug flurbiprofen was intercalated in layered double hydroxide and coated with hyaluronic acid (HA), so as to prolong the corneal residence time and increase the corneal permeability of the drug. Layered double hydroxide (LDH) was prepared by alcohol-water coprecipitation method. Through single factor investigation, the optimum preparation conditions were obtained as follows: The Mg/Al ratio was 2:1, the reaction pH was 11.0, the hydrothermal reaction time was 24 h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8 nm, the potential was 42.2 ± 1.2 mV, and a relatively regular crystal structure could be had. Then FB was intercalated into the LDH layer to prepare flurbiprofen-layered double hydroxide (FB-LDH). In the end, HA-FB-LDH was prepared by the stirring-ultrasonic method, in which through prescription screening, the molecular weight of HA was 200-400 kDa and the concentration of HA solution was 1.25 mg·mL -1, the final particle size of HA-FB-LDH was 185.8 ± 3.3 nm, and potential of - 31.4 ± 0.7 mV. The successful loading of FB and the coating of HA were verified by XRD, FTIR, TGA, TEM, and other characterization methods. The results of in vitro stability experiment indicated that the coating of HA could significantly enhance the stability of LDH in the presence of electrolytes. The in vitro release results suggested that the cumulative release amounts of FB-LDH and HA-FB-LDH within 12 h were 92.99 ± 0.37% and 74.82 ± 0.29% respectively, showing a certain sustained release effect. At the same time, the release mechanism of FB-LDH was preliminarily explored by in vitro release experiment, which proved that the release mechanism of FB-LDH was mainly ion exchange. The results of in vivo ocular irritation experiments demonstrated that the ophthalmic preparation studied in this paper was safe and non-irritating. The results of tear pharmacokinetics in rabbits showed that the area under the curve(AUC), the average residence time (MRT), and the highest concentration (Cmax) in tears in the HA-FB-LDH group were 4.43, 4.48, and 2.27 times higher than those in eye drops group separately. Furthermore, the AUC of the HA-FB-LDH group was 1.48 times higher than that of the FB-LDH group. The above results suggested that HA-FB-LDH could improve the precorneal residence time. The results of aqueous humor pharmacokinetics in rabbits indicated that the AUC, MRT, and maximum concentration (Cmax) in aqueous humor in the HA-FB-LDH group were 6.88, 2.15, and 4.08 times of those in the eye drop group respectively. Additionally, the AUC and MRT of the HA-FB-LDH group were 1.55 and 1.63 times those of the FB-LDH group separately. These mentioned findings verified that HA-FB-LDH could enhance the corneal permeability of the drug. The fluorescent substance-fluoresce isothiocyanate (FITC) was substituted for FB intercalation in LDH for in vitro tissue imaging study of rabbits, whose results stated clearly that FITC-LDH and HA-FITC-LDH could both prolong the precorneal residence time of drugs, and HA-FITC-LDH could increase the corneal permeability of the drug to a certain extent. To sum up, HA-FB-LDH, which can overcome the shortcomings of low bioavailability of traditional eye drops to a certain degree, is a safe and effective ophthalmic drug delivery system.

Design of ROS-Responsive Hyaluronic Acid-Methotrexate Conjugates for Synergistic Chemo-Photothermal Therapy for Cancer.

Combining chemotherapy with photothermal therapy (PTT) for cancer treatment could overcome the inherent limitations of both single-modality chemotherapy and PTT. However, the obstacle of accurate drug delivery to tumor sites based on chemo-photothermal remains challenging. This article describes development of a reactive oxygen species (ROS)-responsive hyaluronic acid-based nanoparticle to overcome these drawbacks. Herein, HA-TK-MTX (HTM) was synthesized by a ROS-responsive cleaved thioketal moiety linker (TK) of methotrexate (MTX) and hyaluronic acid (HA). Through hydrophobic interaction and π-π stacking interaction, a photothermal agent IR780 was integrated into the HTM, and the IR780/HTM nanoparticles (IHTM NPs) were obtained. The IHTM NPs show high photostability, excellent photothermal performance, remarkable tumor-targeting ability, and ROS sensibility. Due to the accurate drug delivery ability and superior chemo-photothermal treatment effect of IHTM NPs, the tumor inhibition rate reached 70.95% for 4T1 tumor-bearing mice. This work serves as a precedent for the chemo-photothermal therapy of cancer by rationally designing ROS-responsive nanoparticles.

A core-shell nanoplatform as a nonviral vector for targeted delivery of genes to the retina.

Retinal diseases, including age-related macular degeneration (AMD), are a major cause of blindness. Efficient delivery of therapeutic genes to retinal cells to treat retinal disease is a formidable challenge. In this study, we developed a core-shell nanoplatform composed of a core and two external layers for targeted delivery of the gene to the retina. The inner core was composed of amino acid-functionalized dendrimers and a nuclear localization signal (NLS) for DNA complexation, nuclear transport and efficient transfection. The inner core was coated in a lipid bilayer that comprised pH-sensitive lipids as the inner shell layer. Hyaluronic acid (HA)-1,2-dioleoylphosphatidylethanolamine (DOPE) as the outermost shell layer was used for retinal cell targeting. This core-shell nanoplatform was developed so that the mobility in the vitreous body of these negatively charged carriers would not be affected by their surface charge, allowing diffusion into the retina, uptake into the retinal cells via CD44-mediated internalization, and finally transport into the nucleus by the NLS. The designed nanoparticles showed safety both in vitro and in vivo and inhibited the expression of VEGF under hypoxia-mimicking conditions. In vitro angiogenesis assays exhibited significant inhibitory effects on cell migration and tube formation. The in vivo assays indicated that this nanoplatform could be delivered to the retina. Taken together, this nanoplatform has the potential to transfer gene material into the retina for the treatment of retinal diseases, including AMD. STATEMENT OF SIGNIFICANCE: It remains a challenge to develop an efficient nonviral vector for gene therapy, especially retinal gene therapy. Various barriers exist in gene delivery and the unique ocular environment, making gene delivery to the retina difficult. In this study, we designed a negatively charged core-shell nanoplatform (HD-NPPND) for the targeted delivery of gene to the retina. The developed nanoplatform possessed excellent transfection efficiency and safety both in vitro and in vivo. It efficiently delivered a gene to the retina. The results of this study suggested that this core-shell nanoplatform has the potential to deliver genes to the retina to treat retinal diseases, including age-related macular degeneration (AMD).

Amino acids functionalized dendrimers with nucleus accumulation for efficient gene delivery.

Gene therapy is a promising approach to many diseases, however, the barriers in the gene delivery restrict its application. Therefore, in the present study, an efficient non-viral gene vector (PRHF/N/D) for overcoming the barriers in gene delivery was prepared. The synthesized PRHF integrated the advantages of PAMAM and amino acids, which could improve the cellular uptake, enhance the endosomal escape ability and minimize cytotoxicity. To further enhance nuclear entry of carrier, the nuclear localization signal (NLS) peptide was selected to add in the PRHF/D polyplexes. The PRHF/N/D polyplexes demonstrated good condensation capacity, wonderful pDNA protection and low toxicity. Moreover, the PRHF/N/D polyplexes showed the excellent transfection efficiency than P/D. PRHF/N/D further improve transfection capability than PRHF/D in the presence of NLS. After 4 h of incubation, the mean fluorescence intensity of PRHF/N/D was also higher than the P/D and PRHF/D complexes. We then investigated the intracellular dissociation, the DNA is able to disassemble from PRHF/N/D gene carriers. Taken together, we exhibited that this PRHF/N/D polyplexes has the potential for use in the gene delivery.

Allelic distributions of CYP2D6 gene copy number variation in the Eastern Han Chinese population.

AIM: The human cytochrome P450 2D6 (CYP2D6) gene copy number variation, involving CYP2D6 gene deletion (CYP2D6*5) and duplication or multiduplication (CYP2D6*xN), can result in reduced or increased metabolism of many clinically used drugs. The identification of CYP2D6*5 and CYP2D6*xN and the investigation of their allelic distributions in ethnic populations can be important in determining the right drug and dosage for each patient. METHODS: The CYP2D6*5 and CYP2D6 genes, and CYP2D6 gene duplication were identified by 2 modified long PCR, respectively. To determine duplicated alleles, a novel long PCR was developed to amplify the entire duplicated CYP2D6 gene which was used as template for subsequent PCR amplification. A total of 363 unrelated Eastern Han Chinese individuals were analyzed for CYP2D6 gene copy number variation. RESULTS: The frequency of CYP2D6*5 and CYP2D6*xN were 4.82% (n=35) and 0.69% (n=5) in the Eastern Han Chinese population, respectively. Of the 5 duplicated alleles, 3 were CYP2D6*1xN and 2 were CYP2D6*10xN. One individual was a carrier of both CYP2D6*5 and CYP2D6*1xN. Taken together, the CYP2D6 gene rearrangements were present in 10.74% of subjects. CONCLUSION: Allelic distributions of the CYP2D6 gene copy number variation differ among Chinese from different regions, indicating ethnic variety in Chinese. Long PCR are convenient, cost effective, specific and semiquantitative for the detection of the CYP2D6 gene copy number variation, and amplification of the entire duplicated CYP2D6 gene is necessary for the accurate identification of duplicated alleles.