BACKGROUND: Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-a-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord. METHODS: α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints. RESULTS: Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group. CONCLUSIONS Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.GRAPHICAL ABSTRACT Putative mechanism of therapeutic action by α-gal nanoparticles. A. Nanoparticles injected into the injured cord bind to anti-Gal antibodies leaked from ruptured capillaries. The binding of anti-Gal to α-gal epitopes on the α-gal nanoparticles activates the complement system to release complement cleavage chemotactic peptides such as C5a, C3a that recruit macrophages and microglia. These recruited cells bind to the anti-Gal coated α-gal nanoparticles and are further polarized into the M2 state. B. Recruited M2 macrophages and microglia secrete neuroprotective and prohealing factors to promote tissue repair, neovascularization and axonal regeneration (C.).

Methods: Among the patients who underwent TSA, 119 shoulders were retrospectively analyzed. Preoperative and postoperative clinical outcome data were collected. Linear regression analysis (univariate and multivariate) was conducted to evaluate the associations of clinical outcomes with age. Kaplan-Meier curves and Cox regression analyses were performed to evaluate implant survival. Results: At final follow-up, patients of all ages undergoing aTSA experienced significant and sustained improvements in all primary outcome measures compared with preoperative values. Based on multivariate analysis, age at the time of surgery was a significant predictor of postoperative outcomes. Excellent implant survival was observed over the course of this study, and Cox regression survival analysis indicated age and sex to not be associated with an increased risk of implant failure. Conclusions When controlling for sex and follow-up duration, older age was associated with significantly better patient-reported outcome measures. Despite this difference, we noted no significant effects on range of motion or implant survival.Level of evidence: IV.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.
Female ; Humans ; Anastrozole ; Aromatase Inhibitors/therapeutic use* ; Bilirubin ; Breast Neoplasms/drug therapy* ; Letrozole ; Liver ; Retrospective Studies ; Toremifene ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.
Humans ; Stomach Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Prospective Studies ; Retrospective Studies ; Lymph Nodes/pathology* ; Lymph Node Excision ; Gastrectomy ; Multicenter Studies as Topic

Objective: To clarify the values of autotaxin (ATX) in patients with primary biliary cholangitis (PBC) and PBC-related hepatocellular carcinoma (HCC). Methods: 179 patients with PBC were selected from prospective cohorts of autoimmune liver diseases at the time of first diagnosis of PBC in Department of Hepatology, the Fifth Medical Center of PLA General Hospital, from January 2016 to January 2018, all patients with PBC received UDCA therapy, primary endpoint was event of HCC, the follow-up period was censored at the date of HCC. The relationship between level of ATX and clinical features in patients with PBC and its potential value in predicting disease progression and PBC-related HCC were analyzed. Results: The ATX level in the peripheral blood of patients with PBC was significantly higher than that of alcoholic liver cirrhosis(ALC) (t = 3.278, P = 0.001) and healthy controls(HC) (t = 6.594, P < 0.001), however, when comparing PBC to non-PBC related HCC, no significant difference was found between the groups(t=-0.240, P = 0.811). Consistent with peripheral blood levels, histochemical staining indicated that ATX in the liver of patients with PBC was significantly higher than that of HC (Z=-3.633, P < 0.001) and ALC (Z=-3.283, P < 0.001), and the expression of ATX in PBC with advanced histological stage was significantly higher than PBC with early stage (Z=-2.018, P = 0.034). The baseline ATX level in PBC patients without developing to HCC during follow-up had significant difference to patients with developing to HCC (228.451 ± 124.093 ng/ml vs 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). The result in multivariate logistic regression analysis showed that ATX were independent predictors of PBC related HCC(OR 1.245, 95%CI 1.097-1.413). The optimal critical value of peripheral blood ATX level at baseline for predicting HCC was 235.254 ng/ml, with the cut-off value of 0.714 in AUC of the ROC (95% CI was 0.597~ 0.857), sensitivity and specificity were 84.6% and 59.0%, respectively. Conclusion: ATX level was significantly higher in PBC patients over controls, and it's concentration was correlated with UDCA efficacy and fibrosis stage. ATX has potential values in predicting disease progression and PBC-related HCC.

Objective: To investigate the clinicopathological features, immunophenotype and prognosis of nuclear protein in testis (NUT) midline carcinoma. Methods: Twenty-four resection cases of NUT midline carcinoma diagnosed at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China from January 2018 to September 2022, were collected, and retrospectively analyzed for their clinicopathological characteristics. Relevant literature was reviewed. Results: All 24 cases of NUT midline carcinoma occurred in the chest or head and neck, including 14 men and 10 women, with a median age of 40 years. Histological examination showed that the tumors were poorly differentiated, with solid nested or sheet-like arrangement, small to medium-sized cells, sparse cytoplasm and coarse granular chromatin, including 5 cases with abrupt squamous epithelial differentiation. Immunohistochemistry showed that all 24 cases were positive for NUT protein, while 16 cases were p63 positive, 19 cases were p40 positive, 15 out of 18 cases were CK5/6 positive. Follow-up data were obtained for 21 patients (follow-up time range, 1-21 months), of which 11 survived, 10 died, and 3 were lost to follow-up. Conclusions: NUT midline carcinoma is a rare and highly aggressive malignancy with unique histological, immunophenotypic and molecular features. It has a poor prognosis.
Male ; Humans ; Female ; Adult ; Neoplasm Proteins/genetics* ; Nuclear Proteins/genetics* ; Retrospective Studies ; Carcinoma/surgery* ; Testicular Neoplasms

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Desmin/analysis* ; China ; Lipoma/pathology* ; Fibroblasts/pathology* ; S100 Proteins/analysis* ; Diagnosis, Differential ; Fibrocartilage/pathology* ; Biomarkers, Tumor/analysis*

Humans ; Thyroid Cancer, Papillary ; Neck/pathology* ; Lymph Nodes/pathology* ; Thyroid Neoplasms/pathology* ; Lymphoma, T-Cell/pathology*