Search

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.

Abstract Background Understanding the molecular mechanism of early lymph node metastasis among lung adenocarcinoma (LUAD) is essential for developing novel therapeutic agents. Proteomic studies helped generate molecular landscape for LUAD. However, the molecular basis of early lymph node metastases remains unknown in patients with LUAD. Methods Surgically resected LUAD tissues and paired normal tissues were selected from 25 patients with stage pT1bN2M0 (group of metastases [GM]) and 27 patients with stage T2b‐3N0M0 (group of large primary focus, GL) who had not undergone any anti‐tumor treatment. 4D‐Label‐free proteomics sequencing was performed among these tissues. The clinicopathological information was retrieved from the electronic medical record system in Guangdong Provincial People's Hospital. Results Compared with GL tumor tissue, 89 upregulated and 155 downregulated proteins were identified in GM tumor tissue. Upregulated proteins of GM were enriched in the ECM‐receptor interaction and PI3K‐AKT pathway under Kyoto Encyclopedia of Genes and Genomes enrichment analysis. And then, the median disease‐free survival (DFS) of GM phenotype patients was used as the cut‐off value, and GM was divided into two groups with significantly different survival outcomes (DFS good vs. DFS Poor: DFS: p

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Background This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies. Methods Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR). Results In pretreatment tumors, the percentages of infiltrating CD8+, PD1+, PD1+CD8+, and the ratio of PD1+CD8+/CD8+ cells, were higher in pCR than non‐pCR patients in either the stromal or intratumoral area, but PD1+CD4+, TIM3+CD4+, TIM3+CD8+ cells and CD4+/CD8+ ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8+ cells (OR, 1.712; 95% CI: 1.052–2.786; P = 0.030) and stromal PD1+CD8+/CD8+ ratio (OR, 1.109; 95% CI: 1.009–1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1+, CD8+ and PD1+CD8+ cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1+CD8+ cells, rather than TIM3+CD8+, were shown in tumors from non‐pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR. Conclusions PD1+CD8+ rather than TIM3+CD8+ cells are main predictive components within tumor‐infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1+CD8+ cells occurred in non‐pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients. Key points Significant findings of the study PD1+CD8+, rather than TIM3+CD8+, T cells are the main component to predict the response of neoadjuvant therapies in breast cancer. What this study adds Incremental levels of PD1+CD8+ T cells in non‐pCR post‐NAT tumors suggest PD1 inhibition might benefit in the neoadjuvant setting.

A 53‐year‐old man diagnosed with disease stage IIIB pulmonary adenocarcinoma underwent chemotherapy and radiotherapy in the first‐line setting. After disease progression, he received targeted therapy because of subsequent detection of EGFR exon 19 del mutation. Following an increase in his adrenal metastases, a combination of immunotherapy and antiangiogenic therapy (sintilimab plus bevacizumab) was commenced. After one month, imaging showed that the adrenal metastases had shrunk and a progression‐free survival (PFS) of 6.0 months was achieved. In this case, we showed that the PD1 inhibitor sintilimab plus bevacizumab was effective in a refactory advanced EGFR‐mutant NSCLC with positive PD‐L1 expression. Key points Our case report provides clinical evidence of the durable response of a patient with advanced EGFR‐mutant lung adenocarcinoma to a combination of immunotherapy and anti‐angiogenic agent, sintilimab and bevacizumab, as subsequent‐line therapy. Sintilimab and bevacizumab combination therapy was well‐tolerated and effective, resulting in dramatic tumor reduction and improvement in clinical symptoms.