Application of fibrin glue with bandage contact lens in pterygium surgery

AIM: To explore the efficacy of fibrin glue with bandage contact lens for pain relief after pterygium surgery performed with limbal autograft transplantation.<p>METHODS: A prospective clinical trial was carried out in 52 patients(72 eyes)operated for primary nasal pterygium. All patients were randomly divided into the fibrin glue with bandage contact lens group(experimental group, 28 cases, 38 eyes)and suture group(control group, 24 cases, 34 eyes). Autologous limbal graft taken from the superotemporal limbus was used to cover the sclera after pterygium excision under local anesthesia with 20g/L lidocaine. In experimental group, the transplant was attached to the sclera with fibrin tissue adhesive and in control group with 10-0 Virgin silk sutures. Experimental group weared bandage contact lens after surgery while the control group did not. The degree of pain after surgery was evaluated at 1, 2, 3, 5 and 7d after surgery. Follow-up was 6mo, matching degree of graft and complication such as infection, relapse, implant healing badness and subconjunctival cyst were mainly observed and recorded.<p>RESULTS: The pain index scores of the experimental group were significantly less than those of control group(all <i>P</i>=0.000). In observation period, all conjunctival autografts in both groups were successfully attached and were intact without falling off, dissolution or recurrence and there were no complications such as infection, relapse, implant healing badness and subconjunctival cyst.<p>CONCLUSION: Fibrin glue with bandage contact lens could significantly release pain response afterpterygium excision surgery

Preliminary study based on methylation and transcriptome gene sequencing of lncRNAs and immune infiltration in hypopharyngeal carcinoma

BackgroundHypopharyngeal squamous cell cancer (HSCC) is one of the most malignant tumors of the head and neck. It is not easy to detect in the early stage due to its hidden location; thus, lymph node metastasis is highly likely at diagnosis, leading to a poor prognosis. It is believed that epigenetic modification is related to cancer invasion and metastasis. However, the role of m6A-related lncRNA in the tumor microenvironment (TME) of HSCC remains unclear.MethodsThe whole transcriptome and methylation sequencing of 5 pairs of HSCC tissues and adjacent tissues were performed to identify the methylation and transcriptome profiles of lncRNAs. The biological significance of lncRNAs differentially expressing the m6A peak was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. By constructing an m6A lncRNA-microRNA network, the mechanism of m6A lncRNAs in HSCC was analyzed. The relative expression levels of selected lncRNAs were examined by quantitative polymerase chain reaction. The CIBERSORT algorithm was used to evaluate the relative proportion of immune cell infiltration in HSCC and paracancerous tissues.ResultsBased on an in-depth analysis of the sequencing results, 14413 differentially expressed lncRNAs were revealed, including 7329 up-regulated and 7084 down-regulated lncRNAs. Additionally, 4542 up-methylated and 2253 down-methylated lncRNAs were detected. We demonstrated methylation patterns and gene expression profiles of lncRNAs of HSCC transcriptome. In the intersection analysis of lncRNAs and methylated lncRNAs, 51 lncRNAs with up-regulated transcriptome and methylation and 40 lncRNAs with down-regulated transcriptome and methylation were screened, and significantly differentiated lncRNAs were further studied. In the immune cell infiltration analysis, B cell memory was significantly elevated in cancer tissue, while γδT cell amount was significantly decreased.Conclusionm6A modification of lncRNAs might be involved in HSCC pathogenesis. Infiltration of immune cells in HSCC might provide a new direction for its treatment. This study provides new insights for exploring the possible HSCC pathogenesis and searching for new potential therapeutic targets

In vitro models for the study of liver biology and diseases - advances and limitations.

In vitro models of liver (patho)physiology, new technologies and experimental approaches are progressing rapidly. Based on cell lines, induced pluripotent stem cells (iPSCs) or primary cells derived from mouse or human liver as well as whole tissue (slices), such in vitro single- and multi-cellular models, including complex microfluidic organ-on-a-chip systems, provide tools to functionally understand mechanisms of liver health and disease. The International Society of Hepatic Sinusoidal Research (ISHSR) commissioned this working group to review the currently available in vitro liver models and describe the advantages and disadvantages of each in the context of evaluating their use for the study of liver functionality, disease modelling, therapeutic discovery and clinical applicability

Nrf2, a Potential Therapeutic Target against Oxidative Stress in Corneal Diseases

Corneal diseases are one of the major causes of blindness worldwide. Conservative medical agents, which may prevent sight-threatening corneal disease progression, are urgently desired. Numerous evidences have revealed the involvement of oxidative stress in various corneal diseases, such as corneal wound healing and Fuchs endothelial corneal dystrophy (FECD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology- (ECH-) associated protein 1 (Keap1)/antioxidant response element (ARE) signaling is well known as one of the main antioxidative defense systems. To the best of our knowledge, this is the first review to elucidate the different expression profiles of Nrf2 signaling as well as the underlying mechanisms in corneal diseases, implicating that Nrf2 may serve as a potentially promising therapeutic target for corneal diseases

A cross-sectional study of appropriateness evaluation of anticoagulation therapy for inpatients with nonvalvular atrial fibrillation

Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF.Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the “no-use of OACs” using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire.Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as “underdosing-use of OACs,” 134 (25%) who needed anticoagulation therapy were “no-use of OACs” and eight (1.5%) were “over-use of OACs.” The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57–13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11–3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67–17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44–7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11–2.35) were associated with “no-use of OACs” in patients with NVAF who had indications for anticoagulation therapy.Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient’s needs

PROKINETIC AND LAXATIVE EFFECTS OF XIAO'ER QIXINGCHA, A HOUSEHOLD PEDIATRIC HERBAL FORMULA

Background: Xiao'er Qixingcha, a household Chinese Medicinal formula, has been extensively applied in pediatric clinic for dyspepsia and constipation for hundreds of years. The present study firstly inspected whether the extract of Xiao'er Qixingcha (EXQ) has in vivo and in vitro prokinetic and laxative effects, and evaluated its acute toxicity. Materials and methods: In the in vivo study, small intestinal transit rates and fecal output characters (number and fecal weight) were measured on normal and two models of constipated mice (induced by diphenoxylate and by water-fasting respectively). In the in vivo study, the contraction rates of ileum smooth muscle were examined with EXQ treatment. Moreover, in acute toxicity study, EXQ was administered orally for 14 days to juvenile SD rats, and clinical signs, viscera lesion and body weight were monitored daily. Results: EXQ at all doses significantly increased the small intestinal transit rates, and ameliorated the fecal output characters of normal mice. In diphenoxylate-induced constipated mice, EXQ dose-dependently improved the small intestinal transit rates and fecal output. In water-fasting-induced constipated mice, EXQ dose-dependently improved the small intestinal transit rates, and significantly ameliorated the fecal output characters at 2.92 and 6.75 g/kg. Furthermore, in the in vitro study, EXQ dose-dependently raised the contraction rates of the isolated rabbit ileum smooth muscle. Finally, the acute toxicity study indicated that no toxicological effect was observed in terms of clinical signs, viscera lesion or change of body weight. Conclusions: Taken together, EXQ exhibited prominent prokinetic and laxative activities, promising it as a safe and effective alternative pharmaceutical therapy for constipation

Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study)

BackgroundThe efficacy of current adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. ctDNA could serve as a potential marker to identify patients who are at higher risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly improve clinical outcome, albeit such evidence is rare in GA/GEJA. Here, we intend to explore the clinical benefit of the reinforcement of adjuvant immunotherapy and antiangiogenics alongside with chemotherapy in patients who are deemed in high risk of recurrence by ctDNA analysis, which might shed light on further improvements in adjuvant therapy for GA/GEJA.Methods/DesignThis study is designed as a prospective, multicenter, randomized, controlled phase II study in patients histologically or cytologically diagnosed with GA/GEJA who underwent D2 gastrectomy and achieved R0 or R1 resection. From February 2022, a total of 300 stage III patients will be enrolled and subjected according to ctDNA sequencing results, and those with positive results will subsequently be randomized 1:1 to arm A or B. Patients in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while patients in arm B will receive XELOX alone for 6-8 cycles. ctDNA-negative patients will be assigned to arm C, and patients who are ctDNA positive but failed in randomization will be assigned to arm D. Patients in arms C and D will receive the investigator’s choice of therapy. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the DFS of ctDNA positive patients versus ctDNA negative patients, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules on the treatment response, adverse events (AEs), and the impact of nutrition status or exercise on recurrence.DiscussionWe expect that ctDNA would be a strong prognostic factor and ctDNA-positive patients are at higher risk of relapse than ctDNA-negative patients. The addition of anlotinib and penpulimab to XELOX, may contribute to delaying relapse in ctDNA-positive patients.Trial registrationhttps://www.clinicaltrials.gov, identifier NCT05494060

Cytokine-induced killer cells efficiently kill stem-like cancer cells of nasopharyngeal carcinoma via the NKG2D-ligands recognition

Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment failure. Thus, there remains an urgent need for more potent and safer therapies against CSCs for curing cancer. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma (NPC) was fully evaluated in vitro and in vivo. To visualize putative CSCs in vitro by fluorescence imaging, and image and quantify putative CSCs in tumor xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were engineered with CSC detector vector encoding GFP and luciferase (Luc) under control of Nanog promoter. Our study reported in vitro intense tumor-killing activity of CIK cells against putative CSCs of NPC, as revealed by percentage analysis of side population cells, tumorsphere formation assay and Nanog-promoter-GFP-Luc reporter gene strategy plus time-lapse recording. Additionally, time-lapse imaging firstly illustrated that GFP-labeled or PKH26-labeled putative CSCs or tumorspheres were usually attacked simultaneously by many CIK cells and finally killed by CIK cells, suggesting the necessity of achieving sufficient effector-to-target ratios. We firstly confirmed that NKG2D blockade by anti-NKG2D antibody significantly but partially abrogated CIK cell-mediated cytolysis against putative CSCs. More importantly, intravenous infusion of CIK cells significantly delayed tumor growth in NOD/SCID mice, accompanied by a remarkable reduction in putative CSC number monitored by whole-body bioluminescence imaging. Taken together, our findings suggest that CIK cells demonstrate the intense tumor-killing activity against putative CSCs of NPC, at least in part, by NKG2D-ligands recognition. These results indicate that CIK cell-based therapeutic strategy against CSCs presents a promising and safe approach for cancer treatment