HbA1c is an established index of glycaemic control and correlates strongly with risk of chronic diabetic complications. However, the accuracy of HbA1c measurement can be affected by many factors, among which is the presence of haemoglobin (Hb) variants. The aim of the study was to determine the percentage of Hb variant detected during HbA1c monitoring in Hospital Kuala Lumpur. The study also analysed non-reportable HbA1c results in the presence of Hb variants. A cross-sectional study using retrospective data of HbA1c results over fi ve months’ period was analysed on Biorad Variant II Turbo, a high performance liquid chromatography (HPLC) assay. The Hb variants were grouped either as HbS, HbC, others (Hb variant apart from HbS or C), and a combination of HbS or C with Others. A total of 11,904 patients were included. Only 2.3% (273) had Hb variants; HbS trait (10.3%), others (89%), and the combination of HbS trait with others (0.7%). No patient with HbC variant or its combination was found. Only 2.2% of those with Hb variant had non-reportable HbA1c. Although the percentage of Hb variants detected during HbA1c analysis and non-reportable HbA1c results were low, their presence should be noted.

Tendon/ligament injury is one of the most common impairments in sports medicine. The traditional treatments of damaged tissue repair are unsatisfactory, especially for athletes, due to lack of donor and immune rejection. The strategy of tissue engineering may break through these limitations, and bring new hopes to tendon/ligament repair, even regeneration. Silk is a kind of natural biomaterials, which has good biocompatibility, wide range of mechanical properties and tunable physical structures; so it could be applied as tendon/ligament tissue engineering scaffolds. The silk-based scaffold has robust mechanical properties; combined with other biological ingredients, it could increase the surface area, promote more cell adhesion and improve the biocompatibility. The potential clinical application of silk-based scaffold has been confirmed by in vivo studies on tendon/ligament repairing, such as anterior cruciate ligament, medial collateral ligament, achilles tendon and rotator cuff. To develop novel biomechanically stable and host integrated tissue engineered tendon/ligament needs more further micro and macro studies, combined with product development and clinical application, which will give new hope to patients with tendon/ligament injury.
Biocompatible Materials ; Humans ; Ligaments ; growth & development ; Regeneration ; Silk ; chemistry ; Tendons ; growth & development ; Tissue Engineering ; Tissue Scaffolds ; chemistry

[This corrects the article DOI: 10.1016/j.apsb.2022.10.016.].

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10⁺ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10⁺ M2 macrophage production.

Platelet-enriched plasma (PRP) contains high concentration of platelets and abundant growth factors, which is made by centrifuging of blood and separating of blood elements. PRP promotes tendon repair by releasing various cytokines to enhance cell proliferation, tenogenic differentiation, formation and secretion of matrix; meantime, it can reduce pain by inhibiting the expression of pain-associated molecules. A number of clinical studies demonstrated that PRP was effective in treatment of tendinopathy, including patellar tendinopathy, lateral epicondylitis and plantar fasciopathy. However, some studies did not support this conclusion, because of disparity of PRP types, therapeutic courses and injections protocols in clinical application. Based on its safety, PRP can be a choice of treatment for tendinopathy, in case other non-surgical therapies are of no effect.
Blood Platelets ; cytology ; Cytokines ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Platelet-Rich Plasma ; Tendinopathy ; therapy

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. METHODS: Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. RESULTS: A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. CONCLUSIONS This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; Idiopathic Pulmonary Fibrosis/genetics* ; Adenocarcinoma ; Cancer-Associated Fibroblasts ; Prognosis ; Tumor Microenvironment ; Sulfotransferases

Embryonic stem cells have unlimited proliferative capacity, which may provide a source of tendon stem/progenitor cells for tissue engineering. Experts of International Science and Technology Collaborative Program of Ministry of Science and Technology have developed a protocol consensus on differentiation of human embryonic stem cells into the tendon cells. The consensus recommends a protocol of two-step generation of human embryonic stem cells into tendon cells: the human embryonic stem cells are first differentiated into mesenchymal stem cells on different material surfaces; then with the scaffold-free tissue engineering tendon formed by high-density planting, the mesenchymal stem cells are induced into tendon cells under static or dynamic mechanical stimulation in vivo and in vitro. Tissue engineering tendon established in vitro by the protocol can be used as a model in toxicological analysis and safety evaluation of tendon-relevant small molecule compounds, medical materials and drugs.
Cell Differentiation ; Consensus ; Human Embryonic Stem Cells ; cytology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Tendons ; cytology ; Tissue Engineering

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

OBJECTIVETo investigate the prognostic significance of Follicular Lymphoma International Prognostic Index 2 (FLIPI2) in FL patients treated with rituximab maintenance.

METHODSA tatol of 140 newly diagnosed FL patients who received Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy in our department were retrospectively analyzed from December 2002 to December 2014. Among 140 patients with FL 122 patients achieved response, from them 56 patients received R maintenance (RM) every 2 months for median 8 times (RM group) while the rest 66 patients did not receive further anti-lymphoma treatment (non-RM group).

RESULTSThere was no statistical difference in age, sex, pathologic grading, staging, FLIPI or FLIPI2 between RM and non-RM groups. The 2-year progression-free survival (PFS) of RM and non-RM groups were 89.7% and 77.6% (P=0.043) while the 2-year overall survival were 100% and 98.6% (P=0.131). FLIPI2 is a significant prognostic model either in the total cohort, RM or non-RM groups (P<0.001 all). In subgroup analysis, RM was able to decrease disease progression in low and intermediate-risk group of FLIPI2, while the 2-year PFS of RM and non-RM groups in high-risk group were similar (55.6% vs 46.9%)(P=0.920).

CONCLUSIONFLIPI2 presents robust prognostic significance either in RM or OBS patients, the patients in FLIPI2 low and intermediate-risk group may benefite from RM, but the role of RM in high-risk patients should be further to investigate.

OBJECTIVETo investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells.

METHODSParallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation.

RESULTSParallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder.

CONCLUSIONParallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing.

Collagen ; chemistry ; Extracellular Matrix ; physiology ; Freeze Drying ; Freezing ; Humans ; Stem Cells ; cytology ; Tendons ; cytology ; growth & development ; Tissue Engineering ; Tissue Scaffolds ; chemistry