Pan-cancer analysis of the tumorigenic role of Fanconi anemia complementation group D2 (FANCD2) in human tumors.

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.

Molecular Mechanism of Vitamin D Receptor Modulating Wnt/ß-catenin Signaling Pathway in Gastric Cancer.

Background: Gastric cancer is the most common gastrointestinal cancer worldwide. The latest data showed that it was the fourth leading cause of cancer-related death. The unobvious symptom and the difficulties lying in the early diagnosis largely affect the effect of the treatment. Therefore, it becomes particularly important to investigate the related genes and signal transduction pathways in gastric cancer. Our previous study found that the vitamin D receptor (VDR) gene FokI polymorphism may be associated with susceptibility to gastric cancer in the Chinese Han population. However, the mechanism of VDR affecting gastric cancer is unknown. In this study, we explored the molecular mechanism and the possible signaling pathway of VDR modulating carcinogenesis and progression of gastric cancer. Methods: The expression of VDR in gastric cancer cell lines was interfered by plasmid transfection and RNA interference technology. And then we analyzed the cell viability and invasive ability by MTT assay, colony formation assay, and transwell migration assay, and detected the expression of VDR and several signaling proteins in gastric cancer cells by SDS-PAGE and Western blotting. Results: The overexpression of VDR can significantly inhibit the viability and invasive ability of gastric cancer cells; on the contrary, when VDR siRNA inhibits the expression of VDR, the viability and invasive ability of gastric cancer cells enhanced. VDR expression levels in gastric cancer cells treated with 1,25 (OH) 2D3 showed a time-dependent increased expression; and with the increase of the VDR expression, the expression of ß-catenin decreased gradually, but the expression of E-cadherin showed a time-dependent increase (P < 0.05). Compared with the mutant-type VDR gene(ff) cells, the degree of ß-catenin decline was significantly enhanced after transfected with homozygous wild-type VDR gene (FF) plasmids (p<0.05). Conclusions: The results of this study indicate that VDR FokI polymorphism plays an important role in the malignant phenotype of gastric cancer cells, such as proliferation, invasion, and clone formation. When the VDR is activated by its ligand, it can prevent the nuclear import of ß-catenin, affect the E-cadherin level, inhibit the proliferation of gastric cancer cells, which suggested that VDR FokI gene may play a role of cancer suppressor via Wnt/ß-catenin signaling pathway.

The Application of Biometric Approaches in Agri-Food Marketing: A Systematic Literature Review.

A challenge in social marketing studies is the cognitive biases in consumers' conscious and self-reported responses. To help address this concern, biometric techniques have been developed to obtain data from consumers' implicit and non-verbal responses. A systematic literature review was conducted to explore biometric applications' role in agri-food marketing to provide an integrated overview of this topic. A total of 55 original research articles and four review articles were identified, classified, and reviewed. It was found that there is a steady growth in the number of studies applying biometric approaches, with eye-tracking being the dominant method used to investigate consumers' perceptions in the last decade. Most of the studies reviewed were conducted in Europe or the USA. Other biometric techniques used included facial expressions, heart rate, body temperature, and skin conductance. A wide range of scenarios concerning consumers' purchase and consumption behaviour for agri-food products have been investigated using biometric-based techniques, indicating their broad applicability. Our findings suggest that biometric techniques are expanding for researchers in agri-food marketing, benefiting both academia and industry.

Food Technology Neophobia Scales in cross-national context: Consumers' acceptance of food technologies between Chinese and New Zealand.

An increasing number of novel food technologies have been developed to meet consumers' growing desire for safe and high-quality foods. However, consumers can be cautious of novel food technologies, and their acceptance cannot be guaranteed. Food Technology Neophobia Scales (FTNS) have been proven to be an effective tool to predict consumers' behavior toward novel food technologies in a range of individual countries, but not for cross-national contexts. To fill the gap, this study designed a survey involving 604 Chinese and 614 New Zealand respondents, investigating the influence of consumers' food technology neophobia (FTN) on their acceptance of food technologies. Chinese respondents' FTNS score (50.62) was lower than that of New Zealand respondents (55.02), which was in line with the finding that Chinese respondents' acceptance of all tested food technologies was higher than New Zealand respondents (0.34-0.86 in a Likert-7 scale). Chinese respondents' acceptance was determined by their perception of benefits, whereas New Zealand respondents were influenced by their perception of both benefits and risks. The findings conclude that FTNS is a valid tool to reflect consumers' acceptance of novel food technologies in cross-national contexts, although the influence of FTN varies among consumers from different countries. PRACTICAL APPLICATION: China has the largest food market, and New Zealand is a leading food exporter. Understanding their consumers' acceptance of and attitudes toward food technologies will help food companies implement appropriate strategies in developing and using novel technologies. Because FTNS first was constructed in 2008, it has been applied in Australia, Italy, Canada, Finland, Korea, China, Chile, Brazil, and Uganda; the findings of this study will allow these individual studies on FTNS to better connect, help food companies predict consumer acceptance of food technologies in the global market, and help them identify early adopters of novel food technologies in new food markets.

Real-World Efficacy and Safety of Thoracic Radiotherapy after First-Line Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.

(1) Background: At present, the efficacy and safety of thoracic radiotherapy (TRT) after chemo-immunotherapy (CT-IT) in patients with extensive-stage small-cell lung cancer (ES-SCLC) still remain unclear. The purpose of this study was to evaluate the role of TRT after CT-IT in patients with ES-SCLC. (2) Methods: From January 2020 to October 2021, patients with ES-SCLC treated with first-line anti-PD-L1 antibody plus platinum-etoposide chemotherapy were enrolled retrospectively. The survival data and adverse events data of patients treated with or without TRT after CT-IT were collected for analysis. (3) Results: A total of 118 patients with ES-SCLC treated with first-line CT-IT were retrospectively enrolled, with 45 patients with TRT and 73 patients without TRT after CT-IT. The median PFS and OS in the CT-IT + TRT group and CT-IT only group were 8.0 months versus 5.9 months (HR = 0.64, p = 0.025) and 22.7 months versus 14.7 months (HR = 0.52, p = 0.015), respectively. The median PFS and OS in all 118 patients treated with first-line CT-IT were 7.2 and 19.8 months with an ORR of 72.0%. In multivariate analyses, liver metastasis and response to CT-IT were shown to be independent prognostic factors of PFS (p < 0.05), while liver metastasis and bone metastasis were independent predictive factors of OS (p < 0.05). Although TRT was significantly associated with better PFS and OS in univariate analysis, the association of TRT and OS failed to reach statistical significance (HR = 0.564, p = 0.052) in multivariate analysis. There was no significant difference in adverse events (AEs) between two treatment groups (p = 0.58). (4) Conclusions: ES-SCLC patients treated with TRT after first-line CT-IT had prolonged PFS and OS with an acceptable safety profile. Further prospective randomized studies are necessary to explore the efficacy and safety of this treatment modality for ES-SCLC in future.

Immune Checkpoint Inhibitor-Induced Primary Hyperparathyroidism in a Small-Cell Lung Cancer Patient: A Case Report.

Immunotherapy is increasingly being used in the treatment of tumors. Adverse effects, however, are not uncommon, with the most common immune-related adverse events (IrAEs) including rash, fatigue, anemia, diarrhea, constipation, and elevated transaminase, among others. Rare IrAEs, which may include thrombocytopenia, hypoparathyroidism, pancreatitis glomerulonephritis, Guillain-Barré syndrome, and celiac disease, may also present. Immune checkpoint inhibitor (ICI)-induced primary hyperparathyroidism (PHPT) has not yet been reported on, and no research currently exists regarding its pathogenesis. We describe how a 50-year-old man diagnosed with advanced small-cell lung cancer (SCLC) developed severe PHPT after receiving the programmed cell death (PD)-1 inhibitor camrelizumab. The patient eventually died of respiratory failure and a progressive malignancy. We speculate that the hypercalcemia and hypophosphatemia observed in this case were secondary to ICI-induced PHPT. Although fatal PHPT is rare, early intervention may reduce the risk of future complications. Therefore, further exploration of the underlying mechanisms is needed to guide solutions.

Multifaceted roles of aerobic glycolysis and oxidative phosphorylation in hepatocellular carcinoma.

Liver cancer is a common malignancy with high morbidity and mortality rates. Changes in liver metabolism are key factors in the development of primary hepatic carcinoma, and mitochondrial dysfunction is closely related to the occurrence and development of tumours. Accordingly, the study of the metabolic mechanism of mitochondria in primary hepatic carcinomas has gained increasing attention. A growing body of research suggests that defects in mitochondrial respiration are not generally responsible for aerobic glycolysis, nor are they typically selected during tumour evolution. Conversely, the dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) may promote the proliferation, metastasis, and invasion of primary hepatic carcinoma. This review presents the current paradigm of the roles of aerobic glycolysis and OXPHOS in the occurrence and development of hepatocellular carcinoma (HCC). Mitochondrial OXPHOS and cytoplasmic glycolysis cooperate to maintain the energy balance in HCC cells. Our study provides evidence for the targeting of mitochondrial metabolism as a potential therapy for HCC.

Wool keratin as a novel alternative protein: A comprehensive review of extraction, purification, nutrition, safety, and food applications.

The growing global population and lifestyle changes have increased the demand for specialized diets that require protein and other essential nutrients for humans. Recent technological advances have enabled the use of food bioresources treated as waste as additional sources of alternative proteins. Sheep wool is an inexpensive and readily available bioresource containing 95%-98% protein, making it an outstanding potential source of protein for food and biotechnological applications. The strong structure of wool and its indigestibility are the main hurdles to achieving its potential as an edible protein. Although various methods have been investigated for the hydrolysis of wool into keratin, only a few of these, such as sulfitolysis, oxidation, and enzymatic processes, have the potential to generate edible keratin. In vitro and in vivo cytotoxicity studies reported no cytotoxicity effects of extracted keratin, suggesting its potential for use as a high-value protein ingredient that supports normal body functions. Keratin has a high cysteine content that can support healthy epithelia, glutathione synthesis, antioxidant functions, and skeletal muscle functions. With the recent spike in new keratin extraction methods, extensive long-term investigations that examine prolonged exposure of keratin generated from these techniques in animal and human subjects are required to ascertain its safety. Food applications of wool could improve the ecological footprint of sheep farming and unlock the potential of a sustainable protein source that meets demands for ethical production of animal protein.

High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary diseases with acute-moderate hypercapnic respiratory failure: a randomized controlled trial of non-inferiority / 中华急诊医学杂志

Objective:To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with moderate typeⅡ respiratory failure, to clarify the feasibility of HFNC in the treatment of AECOPD, and to explore the influencing factors of HFNC failure.Methods:This study was a randomized controlled trial of non-inferiority. Patients with AECOPD with moderate type Ⅱ respiratory failure [arterial blood gas pH 7.25-7.35, partial pressure of arterial blood carbon dioxide (PaCO 2)> 50 mmHg] admitted to the Intensive Care Unit (ICU) from January 2018 to December 2021 were randomly assigned to the HFNC group and NIV group to receive respiratory support. The primary endpoint was the treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 h, 12 h, and 48 h, total duration of respiratory support, 28-day mortality, comfort score, ICU length of stay, and total length of stay. Multivariate logistic regression analysis was used to evaluate the failure factors of HFNC treatment. Results:Totally 228 patients were randomly divided into two groups, 108 patients in the HFNC group and 110 patients in the NIV group. The treatment failure rate was 29.6% in the HFNC group and 25.5% in the NIV group. The risk difference of failure rate between the two groups was 4.18% (95% CI: -8.27%~16.48%, P=0.490), which was lower than the non-inferiority value of 9%. The most common causes of failure in the HFNC group were carbon dioxide retention and aggravation of respiratory distress, and the most common causes of failure in the NIV group were treatment intolerance and aggravation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (-29.02%, 95% CI -49.52%~-7.49%; P=0.004). After 1 h of treatment, the pH in both groups increased significantly, PaCO 2 decreased significantly and the oxygenation index increased significantly compared with baseline (all P < 0.05). PaCO 2 in both groups decreased gradually at 1 h, 12 h and 48 h after treatment, and the pH gradually increased. The average number of daily airway care interventions and the incidence of nasal and facial lesions in the HFNC group were significantly lower than those in the NIV group ( P < 0.05), while the comfort score in the HFNC group was significantly higher than that in the NIV group ( P=0.021). There was no significant difference between the two groups in the total duration of respiratory support, dyspnea score, ICU length of stay, total length of stay and 28-day mortality (all P > 0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health evaluation Ⅱ score (≥15), family NIV, history of cerebrovascular accident, PaCO 2 (≥60 mmHg) and respiratory rate (≥32 times/min) at 1 h were independent predictors of HFNC failure. Conclusions:HFNC is not inferior to NIV in the treatment of AECOPD complicated with moderate type Ⅱ respiratory failure. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

Changes in Patellar Morphology Following Soft Tissue Surgical Correction of Recurrent Patellar Dislocation in Children with Low-Grade Trochlear Dysplasia.

OBJECTIVE: To investigate the changes in patellar morphology following soft tissue surgical correction of recurrent patellar dislocation in children with low-grade trochlear dysplasia. METHODS: The prospective cohort study was performed between November 2007 and December 2012. Finally, 25 cases, with the mean age of 8.4 years (range from 7 to 10 years), were admitted to the study. All patients were diagnosed as bilateral recurrent patellar dislocation associated with femoral trochlear dysplasia. The knee that suffered injury or was dislocated was treated with medial patellar retinacular plasty (surgery group). The contralateral knee, which served as a control, was treated conservatively (conservative group). Axial CT scans were undertaken in all patients to assess the patellar morphological characteristics. RESULTS: The mean follow-up time was 60.8 months (range 48 to 75 months). Preoperatively, there were no statistically significant differences between the patellar morphology in the two groups (P > 0.05). Many radiological parameters of patellar morphology were significantly different between the two groups at the final follow-up, including well-known parameters, such as the mean patellar width (surgery group, 40.58 mm [SD 1.26]; conservative group, 36.41 mm [SD 1.17]; P < 0.05), the mean patellar thickness (surgery group, 11.59 mm [SD 0.74]; conservative group, 9.38 mm [SD 0.56]; P < 0.05) and the mean Wiberg index (surgery group, 0.54 [SD 0.06]; conservative group, 0.72 [SD 0.08]; P < 0.05). There are also little-known parameters, such as the ratio of length of lateral patella to medial patella (surgery group, 1.26 [SD 0.17]; conservative group, 1.69 [SD 0.21]; P < 0.05), which was a measurement of facet asymmetry. However, the Wiberg angle was not significantly different between the two groups (surgery group, 128.63° [SD 9.05]; conservative group, 125.47° [SD 13.96°]; P > 0.05) at the final follow-up. No complications were found. CONCLUSIONS: The patellar morphology can be significantly improved by early soft tissue surgical correction in children with patellar instability associated with low-grade femoral trochlear dysplasia.

[Clinical effect of cortical incision with rapid maxillary expansion to assist orthodontic-orthognathic treatment of skeletal Class â ¢ malocclusion].

PURPOSE: To investigate the clinical effect of rapid maxillary expansion with cortical osteotomy combined with orthodontic- orthognathic treatment for skeletal Class Ⅲ malocclusion. METHODS: A total of 84 patients with skeletal Class Ⅲ malocclusion admitted to Jining Dental Hospital from March 2018 to May 2020 were randomly divided into experimental group and control group, with 42 cases in each group. The control group was treated with orthodontic-orthognathic treatment, while the experimental group was treated with orthodontic-orthognathic treatment with rapid maxillary arch expansion by cortical incision. The time of closing gap, alignment time, maxillary first molar and maxillary central incisor tooth movement distance in the sagittal direction were compared between the two groups. Before treatment and 4 weeks after treatment, the vertical distance from the end of the upper central incisor edge to the horizontal plane(U1I-HP), the distance from the apex of the upper central incisor to the coronal plane(U1I-CP), the vertical distance from the edge of the upper pressure groove to the coronal plane(Sd-CP), the vertical distance from the upper alveolar seat point to the horizontal plane(A-HP), the vertical distance from the point of the upper lip to the coronal plane(Ls-CP), and the vertical distance from the inferior point of nose to coronal plane(Sn-CP) were measured, and the relevant changes were calculated. During the treatment period, the complications of the two groups were compared. SPSS 20.0 software package was used for statistical analysis of the data. RESULTS: There was no significant difference in alignment time, A-HP change, Sn-CP change, maxillary first molar movement distance and maxillary central incisor movement distance between the two groups (P＞0.05). The closing interval in the experimental group was significantly shorter than that of the control group (P＜0.05). The changes of U1I-HP, U1I-CP, Sd-CP, and Ls-CP in the experimental group were significantly higher than those in the control group (P＜0.05). There was no significant difference in the incidence of complications between the two groups during treatment (P＞0.05). CONCLUSIONS: Rapid maxillary expansion of cortical incision assisted orthodontic-orthognathic treatment of skeletal Class Ⅲ malocclusion patients can shorten the closing gap time and improve the treatment effect, which has no obvious influence on the sagittal direction of the teeth.

Hepatic arterial infusion chemotherapy following simultaneous metallic stent placement and iodine-125 seed strands for advanced cholangiocarcinoma causing malignant obstructive jaundice: a propensity score matching study.

OBJECTIVE: This study aims to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) following the simultaneous placement of self-expandable metallic stent (SEMS) and iodine-125 (125I) seed strands for the management of advanced cholangiocarcinoma (CCA) patients presenting with malignant obstructive jaundice (MOJ). METHODS: Data from 74 patients with MOJ caused by advanced CCA treated with stent placement with 125I seed strands with or without HAIC between November 2015 and October 2020 were analysed retrospectively. Eighteen patients received 5 sessions of HAIC after SEMS placement with 125I seed strands (HAIC group), and 56 patients only underwent SEMS placement with 125I seed strands and served as controls (control group). HAIC consisted of infusions of gemcitabine (600-1000 mg/m2 given over 30 min) followed by oxaliplatin (60-100 mg/m2 given over 2 h), with an interval of 4 weeks. Propensity score matching (PSM) analysis was used to adjust for differences in the baseline characteristics of the groups (including age, total bilirubin, and serum alanine aminotransferase level). Overall survival (OS), stent patency, and adverse events were compared between the two groups. RESULTS: OS and stent patency were significantly better in patients in the HAIC group than in those in the control group (median survival time: before PSM, 362 vs. 185 days, p = 0.005; after PSM, 357 vs. 183 days, p = 0.012; median duration of stent patency: before PSM, 294 vs. 156 days, p = 0.001; after PSM, 287 vs. 183 days, p = 0.039). All adverse reactions were controllable by temporary symptomatic treatment. Serious complications and treatment-related deaths were not observed. CONCLUSION: Our preliminary study showed that HAIC following SEMS placement with 125I seed strands is effective and safe for the management of advanced CCA patients presenting with MOJ and could improve stent patency and patient survival.

Gender specific eRNA TBX5-AS1 as the immunological biomarker for male patients with lung squamous cell carcinoma in pan-cancer screening.

As an innate feature of human beings, gender differences have an influence on various biological phenotypes, yet it does not attract enough attention in genomics studies. The prognosis of multiple carcinomas usually exhibits a favorable ending for female patients, but the neglect of gender differences can cause serious bias in survival analysis. Enhancer RNAs (eRNAs) are mostly downstream of androgens or estrogen. The present study was aimed to screen eRNAs in patients with non-small-cell lung cancer. The findings revealed that eRNA TBX5-AS1 was expressed differently between female and male patients. Meanwhile, its prognostic significance appeared only in male patients with squamous cell carcinoma (SCC) type. The Gene Set Enrichment Analysis proved that the expression level of TBX5-AS1 increased following the activation of the androgen signaling pathway. In pan-cancer analysis, the prognostic prediction based on gender grouping obtained more meaningful results, and the synergy between TBX5-AS1 and its homologous target was more consistent. Furthermore, immunity variations between sexes prompted us to explore the role that TBX5-AS1 played in tumor microenvironment and immunotherapy. The robust evidence proved that male patients with high expression of TBX5-AS1 possessed a malignant immune microenvironment and urgently needed immune checkpoint inhibitor treatment. In conclusion, TBX5-AS1 may be one of the strongest candidates to predict prognosis for male patients with SCC and provide a reference for immunotherapy.

The short-term safety and effectiveness of a new distal perforating stent graft in Type B aortic dissection: a retrospective study.

BACKGROUND: Spinal artery ischemia (SCI) events can result from over coverage of the descending thoracic aorta with a coated stent during Thoracic Endovascular Aortic Repair (TEVAR). The aim of this study was to determine whether a new distal perforating stent could reduce the incidence of spinal cord ischemia while remodeling the true lumen. METHODS: TBAD patients treated with Talos stent in the vascular surgery Department of Yan 'an Hospital affiliated to Kunming Medical University between December 2017 and October 2019 were retrospectively analyzed to investigate the short-term safety and effectiveness of Talos stent. RESULTS: A total of the 20 patients, including 14 males and 6 females, with an average age of 52.65 ± 8.98 years (range 37-68 years), were included in the analysis. Stent-grafts were successfully implanted in all patients under local anesthesia, with a technical success rate of 100%. The average operation time was 50.75 ± 13.01 min. A total of 2 cases (10%) presented chest pain associated with intercostal artery ischemia that was relieved on the 3rd and 5th postoperative day, respectively. Postoperative mean follow-up was 16.15 ± 3.99 months. No paraplegia or other complications occurred. And stenting did not induce new tears. No migration, deformation, or fracture of the stents occurred. There was a significant difference in the remolding of the true lumen preoperatively and at 12 months postoperatively (P < 0.05). CONCLUSIONS: Talos stent has achieved satisfactory clinical treatment results in short term.

Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases.

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder. Most cases are reported as sporadic disorder due to de novo variants, and few with family members involved. Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months. During the course of the disease, there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body. Genetic testing showed that both patients carried heterozygous missense mutations in theATP1A3 gene (OMIM: 614820): c.3025 (exon 22) A>G (p.K1009E) and c.2443 (exon 18) G>A (p.E815K). Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.

Hemocompatible, biocompatible and antifouling Acylated dextran-g-polytetrahydrofuran graft copolymer with silver nanoparticles: Synthesis, characterization and properties.

The novel amphiphilic acylated dextran-g-polytetrahydrofuran (AcyDex-g-PTHF) graft copolymers have been successfully synthesized via combination of living cationic ring-opening polymerization of tetrahydrofuran (THF) to prepare living PTHF chains with different molecular weights (Mn, PTHF) of 800-2800 g/mol with nucleophile substitution to mediate grafting numbers (GN) of 4-25 per 1000 Dex monosaccharide. The microphase separation in the graft copolymer exists for the incompatibility of hard dextran backbone and soft PTHF branches and the confined crystallization of backbone. This copolymer behaves excellent hemocompatibility with red blood cells, good biocompatibility with HeLa cells and strong resistance to bovine serum albumin adsorption. The microspheres (~1 µm) of graft copolymers loaded with drug ibuprofen exhibit pH sensitive controlled drug release behavior. Moreover, the AcyDex-g-PTHF/Ag nanocomposites show good antibacterial property against E. coli and S. aureus. This novel hemocompatible, biocompatible and antifouling AcyDex-g-PTHF graft copolymer will have potential application in biological and medical fields.

Assessment of Patellar Morphology in Trochlear Dysplasia on Computed Tomography Scans.

OBJECTIVE: To evaluate the patellar morphology of trochlear dysplasia and normal knees in different genders and in different severities of trochlear dysplasia on CT scans. METHODS: A total of 75 patients with trochlear dysplasia (110 knees) treated at the Third Hospital of Hebei Medical University from December 2013 to December 2018 were included in an experimental group, and an age-matched and sex-matched cohort of 46 patients with normal trochlear shape (61 knees) were randomly selected into a control group. The experimental group was divided into a female experimental group (Group FE, 47 patients, 72 knees) and a male experimental group (Group ME, 28 patients, 38 knees); the control group was divided into a female control group (Group FC, 31 knees, 24 female patients) and a male control group (Group MC, 30 knees, 22 male patients). Furthermore, according to the severity of trochlear dysplasia, Group FE was divided into a female low-grade dysplasia group (Group FL, 20 knees) and a female high-grade dysplasia group (Group FH, 52 knees); Group ME was divided into a male low-grade dysplasia group (Group ML, 16 knees) and a male high-grade dysplasia group (Group MH, 22 knees). All participants had undergone CT scans in the supine position; the patellar width and thickness, the lateral patellar facet angle, the Wiberg angle, and the Wiberg index were measured and compared. RESULTS: In trochlear dysplasia knees, the mean patellar width and thickness and the lateral patellar facet angle were significantly smaller; the mean Wiberg index was significantly larger than in normal knees, regardless of gender (P < 0.05); and there was no statistically significant difference in the mean Wiberg angle (P > 0.05). In the female groups, the mean patellar width and thickness and the Wiberg angle were significantly smaller; the mean lateral patellar facet angle was significantly larger than those in the male groups (P < 0.05); and there was no significant difference in the mean Wiberg index (P > 0.05). In the low-grade dysplasia group, the mean Wiberg index was smaller than that in the high-grade dysplasia group (P < 0.05), regardless of gender; however, there was no significant difference in the mean patellar width and thickness, the lateral patellar facet angle, and the Wiberg angle in low-grade and high-grade dysplasia (P > 0.05). CONCLUSION: On CT scans, the patella in trochlear dysplasia had a smaller width, a thinner thickness, a lengthened lateral facet, and a more flattened articular facet. In addition, the patellar articular facet was more prominent in female patients. With the severity of trochlear dysplasia increased, the lateral patellar facet became longer. In addition, the abnormal stress distribution on the patella influenced the patellar morphology in trochlear dysaplasia.

Alternating Hemiplegia of Childhood Caused by / 中国医学科学杂志(英文版)

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder. Most cases are reported as sporadic disorder due to

The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study.

BACKGROUND: Microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. However, a recent Japanese trial showed that regorafenib plus nivolumab had encouraging anti-cancer activity in MSS or pMMR mCRCs. MATERIALS AND METHODS: We retrospectively reviewed the efficacy and safety data of combination therapy with regorafenib plus anti-PD-1 antibody in patients with refractory MSS or pMMR mCRC in the medical centers of Shandong Province in China. RESULTS: Twenty-three patients with MSS or pMMR mCRC received regorafenib plus anti-PD-1 antibody. Eighteen (78.3%) patients experienced stable disease as best response, five (21.7%) patients had progressive disease, and no partial response was observed. The disease control rate (DCR) was 78.3% (18/23), and the median progression-free survival (PFS) was 3.1 months (95% CI, 2.32-3.89). Four of five (80.0%) patients with progressive disease had baseline liver metastasis, while nine of 18 (50.0%) patients with stable disease displayed no liver metastasis. One patient receiving radiofrequency ablation treatment for liver and abdominal wall metastases prior to combination treatment experienced a remarkably prolonged PFS of 9.2 months with SD. Neither liver metastasis status nor previous exposure to regorafenib was associated with treatment outcome. Treatment-related grade 3 toxicities were observed in 5/23 (21.7%) patients. CONCLUSION: No objective response was observed with the combination of regorafenib plus anti-PD-1 antibody, suggesting its little clinical activity in unselected Chinese patients with pMMR/MSS mCRC. Meanwhile, it exhibited some potential benefit in this cohort in terms of DCR and PFS. Adverse events were generally tolerable and manageable. Prospective studies with large sample sizes are needed to verify the findings. This combination strategy plus local ablative therapy might be worthy of further exploration.

Endovascular aortic repairs combined with looping-chimney technique for repairing aortic arch lesions and reconstructing left common carotid artery.

BACKGROUND: The aim of this retrospective study was to evaluate the feasibility and efficacy of thoracic endovascular aortic repairs (TEVAR) combined with looping chimney technique (LCT) for repairing aortic arch lesions and reconstructing left common carotid artery. METHODS: Total of 14 patients (mean age 52.86±14.46 years; range, 27-79; 10 men, 4 women) were included in the study from December 2016 to December 2018. Aortic arch pathologies of all patients with insufficient proximal landing zone (PLZ) were repaired by TEVAR under local anesthesia, before TEVAR, the left common carotid artery (LCCA) was protected by the guiding sheath from the retrograde brachial access, after aortic stent graft deployed, chimney graft was implanted to restore LCCA by LCT if necessary. All patients underwent computed tomography angiograph (CTA) 2 weeks, 3 months, 6 months and 1 year after surgery. RESULTS: Pathology results of 14 patients included: type B aortic dissection (n=8), penetrating aortic ulcers (n=1), retrograde type A aortic dissection (n=1), thoracic aortic aneurysm (TAA) (n=2), and thoracic aortic pseudoaneurysm (n=2). In all patients, aortic arch lesions were repaired by TEVAR; while LCCA were successfully reconstructed by the LCT. In one case, the innominate artery (IA) was simultaneously reconstructed through the same percutaneous right brachial artery (RBA) access. Coiling eliminated type Ia endoleak in 3 patients, and type II endoleak vanished by plugging left subclavian artery (LSA) in 2 patients. In four patients, the chimney stent (CG) of LCCA was partially compressed and then another bare stent was implanted to restore patency rate. The mean follow-up duration was 9.77±6.64 months (range, 0-24) and no combinations were observed in 13 patients; except in one patient who died of cerebral hemorrhage due to abnormal coagulation function. CONCLUSIONS: TEVAR combined with LCT has shown to be suitable surgical approach for aortic arch lesions. Either covered intentionally or inadvertently, the LCCA could be safely and effectively reconstructed via percutaneous RBA access. Short-term follow-up demonstrated satisfactory morbidity and mortality in high-risk patients; however, longer follow-up is required to assess the effectiveness and durability of this innovative endovascular procedure.