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Backgroundβ-thalassemia (β-TH) is a hereditary hemolytic anemia that results in deficient hemoglobin (Hb) synthesis. It is characterized by ineffective erythropoiesis, anemia, splenomegaly, and systemic iron overload. Exploration new potential biomarkers and drug candidates is important to facilitate the prevention and treatment of β-TH.MethodsWe applied quasi-targeted metabolomics between wild type (Wt) and heterozygous β-TH mice (Th3/+), a model of non-transfusion-dependent β-TH intermedia, in plasma and peripheral blood (PB) cells. Futher data was deeply mined by Kyoto Encyclopedia of Genomes (KEGG) and machine algorithms methods.ResultsUsing KEGG enrichment analysis, we found that taurine and hypotaurine metabolism disorders in plasma and alanine, aspartate and glutamate metabolism disorders in PB cells. After systematically anatomize the metabolites by machine algorithms, we confirmed that alpha-muricholic acidUP and N-acetyl-DL-phenylalanineUP in plasma and Dl-3-hydroxynorvalineUP, O-acetyl-L-serineUP, H-abu-OHUP, S-(Methyl) glutathioneUP, sepiapterinDOWN, and imidazoleacetic acidDOWN in PB cells play key roles in predicting the occurrence of β-TH. Furthermore, Sepiapterin, Imidazoleacetic acid, Methyl alpha-D-glucopyranoside and alpha-ketoglutaric acid have a good binding capacity to hemoglobin E through molecular docking and are considered to be potential drug candidates for β-TH.ConclusionThose results may help in identify useful molecular targets in the diagnosis and treatment of β-TH and lays a strong foundation for further research.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Objective Isolated intra‐articular anterior cruciate ligament (ACL) reconstruction is not capable of restoring instability in many cases leading some to recommend concomitant anterolateral ligament (ALL) reconstruction. The satisfactory fixation site and graft length change are crucial in ligament reconstruction to restore the ALL function and avoid some unwanted graft behavior. The purpose of this investigation is to determine the optimal isometric region on the anterolateral aspect of the knee for ALL reconstruction using a three‐dimensional optical instrument and a suture similar to an intraoperative isometric test. Methods Six freshly frozen cadaveric human knees were used in this study. Data regarding the anterolateral surface were obtained using an optical measurement system to create a three‐dimensional model. Nine points were selected on the femur (F1‐F9) and tibia (Ta‐Ti) respectively. The three‐dimensional length change between each pair of tibial and femoral points was measured during passive knee flexion from 0° to 90° in 15° increments. Subsequently, five femoral points (A–E) were selected from the lateral femur, located in different areas relative to the lateral femoral epicondyle, and three tibial reference points (T1‐T3) were selected in the isometric test. The changes in the length between each pair of reference points were measured using sutures. The 95% confidence interval for the rate of length change was estimated using the mean and standard deviation of the maximum rate of length change at different flexion angles, and the data were expressed as the mean (95% confidence interval) and compared with the maximum acceptable rate of change (10%). Results The maximum acceptable change rate for ligament reconstruction is 10%, and the mean maximum rates and the 95% confidence interval (CI) of length change for the point combinations were calculated. Among all the combined points measured using the optical measurement system and the suture, the qualified point combination for reconstruction was F3 (8mm posterior and 8mm proximal to the lateral femoral epicondyle)‐Tb (8mm proximal to the midpoint between the center of Gerdy's tubercle and the fibula head), A (posterior and proximal to the lateral femoral epicondyle)‐T2 (10mm below the joint line)and A‐T3 (15 mm below the joint line). The position of F3‐Tb and A‐T2 are close to each other. Conclusion The most isometric area of the femur for ALL reconstruction was posterior and proximal to the lateral femoral epicondyle. We recommend that the initial location of the femoral point be set at 8 mm posterior and 8 mm proximal to the lateral femoral epicondyle and the tibial point at approximately 10 mm below the joint line, midway between Gerdy's tubercle and fibular head, and subsequently adjusted to the most satisfactory position according to the isometric test.