Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of structurally related cytokines and is known to induce proliferation, migration, differentiation, apoptotic cell death, inflammation, and angiogenesis. These physiological processes are induced by the binding of TWEAK to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell-surface receptor that is linked to several intracellular signaling pathways, including the nuclear factor-κB (NF-κB) pathway. This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway.
Arthritis, Rheumatoid ; etiology ; Cytokine TWEAK ; Humans ; Lupus Erythematosus, Systemic ; etiology ; Receptors, Tumor Necrosis Factor ; physiology ; Rheumatic Diseases ; etiology ; Scleroderma, Systemic ; etiology ; TWEAK Receptor ; Tumor Necrosis Factors ; physiology

Child ; Family ; Humans ; Necrosis ; Skin Diseases ; Stevens-Johnson Syndrome/etiology*

Chronic necrotizing pulmonary aspergillosis (CNPA) is an unusual form of pulmonary aspergillosis arising in the setting of mildly immune compromised state or altered local defense system. CNPA rarely shows histological findings mimicking bronchocentric granulomatosis (BCG), which is characterized by peribronchiolar granulomatous destruction. We describe a case representing CNPA with elements of BCG. A-64 year-old woman was admitted because of atypical pneumonia with multi-focal variable sized consolidations and cavitary lesions on high-resolution computed tomography (HRCT). The open lung biopsy specimen showed large areas of necrotizing pneumonia with some scattered aspergillus hyphae within the lung parenchyma. Some terminal bronchioles were found to be destroyed and were replaced by peribronchiolar granulomatous inflammation. There was no evidence of angioinvasion by aspergillus or aspergillous emboli. Despite vigorous antifungal agent and steroid treatment, she died of acute airway obstruction by bronchial casts on the thirty-fourth hospital day.
Aspergillosis/etiology/*pathology ; Case Report ; Chronic Disease ; Female ; Granuloma/etiology/pathology ; Human ; Lung Diseases, Fungal/etiology/*pathology ; Middle Age ; Necrosis

Animals ; Endotoxemia ; complications ; Fatty Liver ; etiology ; Hepatitis ; etiology ; Male ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism

Thirty-six cases of necrotizing lymphadenitis--including 33 cases of unknown etiology, 1 typhoid lymphadenopathy, and 2 cases of suspicious lupus lymphadenopathy--were clinico-pathologically reviewed and analyzed with immunostaining for s-100 and lysozyme. All cases histologically showed architectural effacement by paracortical lesions composed of nuclear karyorrhexis and mononuclear cell proliferation. Immunohistochemical study revealed proliferation of lysozyme-positive macrophages in the necrotizing areas and an increase in the number of s-100-positive cells in the uninvolved paracortical areas. This observation suggests that necrotizing lymphadenitis may be a common morphologic expression of a T cell-mediated hyperimmune condition induced by diverse etiologies.
Adolescent ; Adult ; Female ; Humans ; Immunohistochemistry ; Lymphadenitis/etiology/metabolism/*pathology ; Male ; Muramidase/metabolism ; Necrosis ; S100 Proteins/metabolism

Gastrointestinal Hemorrhage ; etiology ; Humans ; Infant, Newborn ; Intestines ; abnormalities ; pathology ; Male ; Necrosis

OBJECTIVETo establish a new animal model of osteonecrosis of the femoral head(ONFH) with improved consistency and incidence of femoral head collapse for studies on the mechanism of osteonecrosis. and on the assessment of treatment effectiveness.

METHODSTwenty adult male emus were used. Guide instrumentation was constructed to position the customized probe just articularly and at the proximal part of the femoral head. An alternating focal liquid nitrogen freezing and radiofrequency heating was applied. At 2, 4, 8, 12 and 16 weeks after surgery, hip magnetic resonance imaging (MRI) was performed. Before the emus were sacrificed, barium sulfate was infused to lower extremities for microangiography. The femoral samples were scanned by micro-computed tomography (Micro-CT) and evaluated histologically.

RESULTSNo bird demonstrated signs of infection or died unexpectedly. Hip MRI showed changes massive edema at the 4th week, increasingly localized abnormal signals at the 8th'" week, and femoral head collapse at the 12'h week. Micro-CT scans and histological images at the 16th week showed human-like osteonecrotic changes with impaired local blood supply. Bone mineral density of the collapsed head was (380. 31 + 28. 12) mg/cm3 and trabecular spaces were (0. 86 ±0.32) mm; both were significantly lower than those in the control side, which were (415.75 41.28) mg/cm3 and (1. 17 ± 0. 17) mm, respectively (P < 0. 05). Bone volume fraction of the collapsed head was(47.28 ± 17. 14)% and trabecular thickness was (506. 17 ± 220. 58) p.m; both were significantly higher than those at control side, which were (30. 92 ± 4. 01)% and (325. 50 ±44. 53) pm, respectively (P <0. 05). The microangiography at the 16th week showed that vessel volume fraction was (0. 315 ± 0. 055)% , which was significantly higher than the collapsed side [ (0. 142 ± 0. 059)% ] (P <0. 05).

CONCLUSIONSThe emu model of fem-oral head osteonecrosis was successfully established using focal alternating cooling and heating insults. The models, with improved consistency and incidence of femoral head collapse, can be used in studies on the mechanism of osteonecrosis and on the assessment of treatment effectiveness.

Animals ; Disease Models, Animal ; Dromaiidae ; Femur Head Necrosis ; etiology ; Freezing ; adverse effects ; Heating ; adverse effects ; Male

Adult ; Bone Marrow Diseases ; complications ; Humans ; Leukemia, Monocytic, Acute ; etiology ; Male ; Necrosis

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ²=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ²=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.
Humans ; Neoadjuvant Therapy/methods* ; Abscess ; Retrospective Studies ; Intestinal Obstruction/etiology* ; Stents ; Colorectal Neoplasms/therapy* ; Necrosis

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain behavior, synovial inflammatory response and demyelination of saphenous nerve in the rats modeled with knee osteoarthritis (KOA) and explore the effect mechanism of EA for reliving allodynia. METHODS: Eighty-four male SD rats were randomly divided into a control group, a model group and an EA group, 28 rats in each one. Intra-articular injection of sodium monoiodoacetate (MIA) was administered in right knee joint of each rat in the model group and the EA group to establish the KOA model. In the EA group, separately, on day 5, 7 and 9 after modeling, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave (2 Hz/15 Hz), 1 mA in current intensity, for 30 min in one intervention, once a day, and 3 interventions were required. On the 9th day after modeling, the weight-bearing rate was calculated for the affected limbs of the rats in each group, the synovial morphological changes were observed using HE and Masson staining, flow cytometry was adopted to detect the synovial immunocyte counts, and MSD multi-spot assay was used to detected the synovial inflammatory cytokine content. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was observed in each group and the ultrastructure of the saphenous nerve was observed under transmission electron microscopy. RESULTS: On the 9th day after modeling, compared with the control group, the weight-bearing rate of the affected limb was reduced (P<0.01), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis occurred in the affected limb; the counts of synovial CD11b⁺ cells and M1 macrophages (CD11b⁺CD86⁺) were increased (P<0.01), the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-10 and IL-13 in the synovial tissue were elevated (P<0.01, P<0.05) for the rats of the model group. Compared with the model group, the weight-bearing rate of the affected limb was increased (P<0.05), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis were mitigated, the counts of CD11b⁺ cells and M1 macrophages (CD11b⁺CD86⁺) in the synovial tissue, and the contents of TNF-α and IL-6 were reduced (P<0.01, P<0.05) in the EA group. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was reduced in the model group when compared with the control group (P<0.01), and it was increased in the EA group when compared with the model group (P<0.05). Besides, in the model group, obviously, the myelin sheath structure was destroyed, the myelin layer was disintegrated and loosened, the axon was extruded or the layer thicken and cracked. Compared with the model group, the injury of saphenous nerve was alleviated remarkably in the EA group. CONCLUSION The intervention with EA may attenuate the synovial inflammatory response and the injury of saphenous nerve in the affected limb of the rat with KOA, so that the spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage are relieved.
Male ; Rats ; Animals ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; Hyperplasia ; Cytokines ; Pain/etiology*