Analysis of Cytological Misdiagnosis and Oversight of Adenoid Cystic Carcinoma of Salivary Gland.

OBJECTIVE: In this article on adenoid cystic carcinoma (ACC) of salivary gland, we intend to summarize the causes of misdiagnosis and oversight of ACC hoping to improve cytological diagnostic accuracy, clinical management and patient treatment. METHODS: The study retrospectively reviewed 32 patients with ACC of salivary gland, registered at the Affiliated Hospital of Southwest Medical University from July 2014 to June 2021. These cases were diagnosed by FNA and surgical excision biopsy. All cytopathological results were retrospectively categorized according to Milan system for reporting salivary gland cytopathology (MSRSGC). The accuracy of FNA was verified by surgical excision biopsy. RESULTS: Of these 32 patients, 16 (50.0%) cases were male, and 16 (50.0%) were female. Their age ranged from 21 to 79 years, with an average age of 50.32 years. The highest incidence (15/32, 46.9%) of ACC was observed in patients between 41 and 50 years of age. 10 cases (31.3%) occurred in the parotid gland, 9 cases (28.1%) in the submandibular gland, 9 cases (28.1%) in the sublingual gland, 3 cases (9.4%) in the palate, and 1 case (3.1%) in the lip. Among the 32 cases of ACC, 23 cases (71.9%) were classified to VI, 4 cases (12.5%) to IVa, and 5 cases (15.6%) to II by MSRSGC. A comparison of the FNA results with biopsy showed that the accuracy of FNA in ACC of salivary gland is 71.9%. Being able to identify the cytomorphological features is the key factor for accurate diagnosis of ACC of the salivary gland. CONCLUSION: Our results confirm that FNA is an important initial screening in the diagnosis of ACC of salivary gland. Increased study of the cytomorphology of ACC is beneficial for more accurate diagnosis of ACC, to reduce misdiagnosis and oversight.

Giant cell tumor of tendon sheath: A report of 216 cases.

BACKGROUND: In this article on giant cell tumor of tendon sheath (GCTTS), we intend to summarize and analyze the clinical and pathological features of GCTTS hoping to improve clinical management and patient treatment. METHODS: The study retrospectively reviewed 216 patients of GCTTS, registered at the Affiliated Hospital of Southwest Medical University from January 2010 to December 2020. These cases were diagnosed by surgical excision. The clinicopathological features and the prognosis were reviewed in the light of the current literature. RESULTS: Of these 216 GCTTS patients, 72 were males (33.3%) and 144 females (66.7%), with a ratio male-to-female of 1:2. The patients' age ranged from 5 to 82, the average being 41.5 years at diagnosis. A total of 96 cases (44.4%) occurred in the hand region, followed by 35 cases (16.2%) in the knee, 32 cases (14.8%) in the foot, 25 cases (11.6%) in the ankle, 12 cases (5.6%) in the wrist, 12 cases (5.6%) in the leg, 2 cases (0.9%) in the head, 1 case (0.5%) in the forearm, and 1 case (0.5%) inside and outside the spinal channel. Histopathology mainly revealed large synovial-like monocytes, small monocytes, and osteoclast-like giant cells. CONCLUSION: Our results confirm that GCTTS predominantly occurs in the hands of young women. Complete surgical resection with long-term follow-up is the preferred management.

Comparison of MRI and CT-Based Radiomics and Their Combination for Early Identification of Pathological Response to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: Current radiomics for treatment response assessment in gastric cancer (GC) have focused solely on Computed tomography (CT). The importance of multi-parametric magnetic resonance imaging (mp-MRI) radiomics in GC is less clear. PURPOSE: To compare and combine CT and mp-MRI radiomics for pretreatment identification of pathological response to neoadjuvant chemotherapy in GC. STUDY TYPE: Retrospective. POPULATION: Two hundred twenty-five GC patients were recruited and split into training (157) and validation dataset (68) in the ratio of 7:3 randomly. FIELD/SEQUENCE: T2-weighted fast spin echo (fat suppressed T2-weighted imaging [fs-T2WI]), diffusion weighted echo planar imaging (DWI), and fast gradient echo (dynamic contrast enhanced [DCE]) sequences at 3.0T. ASSESSMENT: Apparent diffusion coefficient (ADC) maps were generated from DWI. CT, fs-T2WI, ADC, DCE, and mp-MRI Radiomics score (Radscores) were compared between responders and non-responders. A multimodal nomogram combining CT and mp-MRI Radscores was developed. Patients were followed up for 3-65 months (median 19) after surgery, the overall survival (OS) and progression free survival (PFS) were calculated. STATISTICAL TESTS: A logistic regression classifier was applied to construct the five models. Each model's performance was evaluated using a receiver operating characteristic curve. The association of the nomogram with OS/PFS was evaluated by Kaplan-Meier survival analysis and C-index. A P value <0.05 was considered statistically significant. RESULTS: CT Radscore, mp-MRI Radscore and nomogram were significantly associated with tumor regression grading. The nomogram achieved the highest area under the curves (AUCs) of 0.893 (0.834-0.937) and 0.871 (0.767-0.940) in training and validation datasets, respectively. The C-index was 0.589 for OS and 0.601 for PFS. The AUCs of the mp-MRI model were not significantly different to that of the CT model in training (0.831 vs. 0.770, P = 0.267) and validation dataset (0.797 vs. 0.746, P = 0.137). DATA CONCLUSIONS: mp-MRI radiomics provides similar results to CT radiomics for early identification of pathologic response to neoadjuvant chemotherapy. The multimodal radiomics nomogram further improved the capability. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: 2.

Inhibition of GSK3ß and RIP1K Attenuates Glial Scar Formation Induced by Ischemic Stroke via Reduction of Inflammatory Cytokine Production.

In the chronic phase following ischemic stroke, glial scars can prevent axonal regeneration and the intensification of inflammation. The protective effect of inhibition of glycogen synthase kinase-3ß (GSK3ß) or receptor-interacting protein 1 kinase (RIP1K) on ischemic stroke has been previously reported. The current study examined the effects of RIP1K and GSK3ß on ischemic stroke-induced glial scar formation. To investigate this, we used an in vivo model of ischemic stroke based on middle cerebral artery occlusion for 90 min followed by reperfusion for 7 d, and an in vitro model in primary cultured astrocytes involving oxygen and glucose deprivation for 6 h followed by reoxygenation for 24 h. Both in vivo and in vitro, we found that SB216763, a GSK3ß inhibitor, and necrostatin-1 (Nec-1), a RIP1K inhibitor, decreased levels of glial scar markers, including glial fibrillary acidic protein (GFAP), neurocan, and phosphacan. SB216763 and Nec-1 also decreased levels of inflammatory related cytokines, including interleukin-6 (IL-6), interleukin-1 ß (IL-1ß), and tumor necrosis factor-α (TNF-α). However, only Nec-1 increased the level of interleukin-1 receptor antagonist. Concurrent neutralization of TNF-α, IL-1ß, and IL-6 with their antibodies provided better reduction in oxygen and glucose deprivation-induced increases in scar markers than obtained with separate use of each antibody. Further investigations showed that SB216763 reduced the levels of necroptosis-related proteins, including RIP1K, p-RIP1K, RIP3K, p-RIP3K, mixed lineage kinase domain-like protein (MLKL), and p-MLKL, while Nec-1 decreased the expression of p-GSK3ß. Compared with Nec-1 (10 µM) and SB216763 (1 µM) alone, Nec-1 and SB216763 in combination reduced levels of GFAP, neurocan, and inflammatory-related cytokines. In conclusion, inhibition of GSK3ß or RIP1K reduced glial scar formation induced by ischemic stroke. The underlying mechanisms might be at least, partially related to reducing levels of inflammatory-related cytokines and to blocking an interaction between GSK3ß- and RIP1K-mediated pathways.

Inhibition of cysteine cathepsin B and L activation in astrocytes contributes to neuroprotection against cerebral ischemia via blocking the tBid-mitochondrial apoptotic signaling pathway.

The roles of cathepsins in the ischemic astrocytic injury remain unclear. Here, we test the hypothesis that activation of cathepsin B and L contributes to the ischemic astrocyte injury via the tBid-mitochondrial apoptotic signaling pathways. In the rat models of pMCAO, CA-074Me or Clik148, a selective inhibitor of cathepsin B or cathepsin L, reduced the infarct volume, improved the neurological deficits and increased the MAP2 and GFAP levels. In OGD-induced astrocyte injury, CA-074Me or Clik148 decreased the LDH leakage and increased the GFAP levels. In the ischemic cortex or OGD-induced astrocytes injury, Clik148 or CA-074Me reversed pMCAO or OGD-induced increase in active cathepsin L or cathepsin B at 3 h or 6 h, increase in tBid, reduction in mitochondrial cytochrome-c (Cyt-c) and increase in cytoplastic Cyt-c and active caspase-3 at 12-24 h of the late stage of pMCAO or OGD. CA-074Me or Clik148 also reduced cytosolic and mitochondrial tBid, increased mitochondrial Cyt-c and decreased cytoplastic Cyt-c and active caspase-3 at 6 h of the early stage of Bid activation. CA-074Me or Clik148 blocked the pMCAO-induced release of cathepsin B or L from the lysosomes into the cytoplasm and activation of caspase-3 in ischemic astrocytes at 12 h after ischemia. Concurrent inhibition of cathepsin B and cathepsin L provided better protection on the OGD-induced astrocytic apoptosis than obtained with separate use of each inhibitor. These results suggest that inhibition of the cysteine cathepsin B and cathepsin L activation in ischemic astrocytes contributes to neuroprotection via blocking the tBid-mitochondrial apoptotic signaling pathway.

[Effect of UV-B radiation on release of nitrogen and phosphorus from leaf litter in subtropical region in China].

The release of nitrogen and phosphorus from leaf litter of six representative species, Cunninghamia lanceolata, Pinus massoniana, Schima superba, Cinnamanun camphora, Cyclobalanopsis glauca and Castanopsis eyeri, was investigated with litterbag method under ambient and reduced UV-B radiation (22.1% below ambient) treatments in subtropical region. The results showed that, the N dynamics exhibited three patterns: immobilization, mineralization-immobilization and mineralization-immobilization-mineralization. P dynamics also exhibited three different patterns: mineralization, immobilization-mineralization-immobilization and no large change. Compared with ambient treatment, the reduced treatment significantly delayed the N release from C. eyeri and P release from both C. glanca and C. eyeri (P<0.05), but significantly stimulated P release from C. camphora (P<0.05). The initial N contents and C: N ratios can not account for the N dynamics during leaf litter decomposition. The C: P ratios can partly explain the P dynamics during decomposition. The more works need to be done to better understand the role of UV-B radiation in the forest ecosystem in humid subtropical China under global environment change.

[Effects of UV-B radiation on the decomposition of Cunninghamia lanceolata leaf litter].

A litterbag experiment was conducted to study the decomposition of Cunninghamia lanceolata leaf litter under ambient and reduced UV-B radiation (22.1% below ambient). Comparing with ambient treatment, the reduced treatment decreased the decomposition rate of C. lanceolata leaf litter by 69.6% (P<0.001), making the relative contents of nitrogen (N), phosphorus (P), and lignin in the litter increased by 150%, 83.3%, and 13.8%, respectively, and the release of potassium (K) and carbon (C) slowed down. In the process of litter decomposition, photo-degradation of lignin didn't play crucial role. The results suggested that UV-B radiation could accelerate the decomposition rate of C. lanceolata leaf litter, promote the release of N, P, K, and C from it, and increase the nutrients turnover rate in litter layer as well as the carbon flux on the ground, giving potential effects on the function of C. lanceolata forest as a carbon source or sink in humid subtropical China.

Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia.

The present study evaluated autophagy activation in astrocytes and its contribution to astrocyte injury induced by cerebral ischemia and hypoxia. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion (pMCAO) in rats. In vitro hypoxia in cultured primary astrocytes was induced by the oxygen-glucose deprivation (OGD). Alterations of astrocytes were evaluated with astroglia markers glial fibrillary acidic protein (GFAP). The formation of autophagosomes in astrocytes was examined with transmission electron microscopy (TEM). The expression of autophagy-related proteins were examined with immunoblotting. The role of autophagy in OGD or focal cerebral ischemia-induced death of astrocytes was assessed by pharmacological inhibition of autophagy with 3-methyladenine (3-MA) or bafilomycin A(1) (Baf). The results showed that GFAP staining was reduced in the infarct brain areas 3-12 h following pMCAO. Cerebral ischemia or OGD induced activation of autophagy in astrocytes as evidenced by the increased formation of autophagosomes and autolysosomes and monodansylcadaverine (MDC)-labeled vesicles; the increased production of microtubule-associated protein 1 light chain 3 (LC3-II ); the upregulation of Beclin 1, lysosome-associated membrane protein 2 (LAMP2) and lysosomal cathepsin B expression; and the decreased levels of cytoprotective Bcl-2 protein in primary astrocytes. 3-MA inhibited OGD-induced the increase in LC3-II and the decline in Bcl-2. Furthermore, 3-MA and Baf slightly but significantly attenuated OGD-induced death of astrocytes. 3-MA also significantly increased the number of GFAP-positive cells and the protein levels of GFAP in the ischemic cortex core 12 h following pMCAO. These results suggest that ischemia or hypoxia-induced autophagic/lysosomal pathway activation may at least partly contribute to ischemic injury of astrocytes.

p53-mediated neuronal cell death in ischemic brain injury.

p53 is a key modulator of cellular stress responses. It is activated in the ischemic areas of brain, and contributes to neuronal apoptosis. In various stroke models, p53 deficiency or applications of p53 inhibitors can significantly attenuate brain damage. p53-mediated neuronal apoptosis occurs through various molecular mechanisms. The transcriptional pathway is an important mechanism through which p53 induces neuronal apoptosis by up-regulating the expression of its target gene p21(WAF), Peg3/Pw1 or p53-up-regulated modulator of apoptosis (PUMA). In addition, p53 disrupts NF-kappaB binding to p300 and blocks NF-kappaB-mediated survival signaling. On the other hand, the transcription-independent pathway mechanism is also of great importance. In this pathway, p53 is translocated to mitochondrial and mediates the release of cytochrome c. In both pathways, p53 seems to play a key role in post-ischemic brain damage and has become a therapeutic target against stroke pathology.

Protective effect of Ginkgolids (A+B) is associated with inhibition of NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia.

BACKGROUND AND PURPOSE: We have previously reported that Ginkgolids which contain Ginkgolids A and B (Ginkgolids (A+B), GKAB) reduce infarct size in a rat model of focal ischemia. NF-kappaB-inducing kinase (NIK)-IkappaBalpha kinase (IKK) pathway plays an important role in activation of nuclear factor kappaB (NF-kappaB). A previous study demonstrated that Ginkgolid B inhibited lipopolysaccharide (LPS)- and platelet activating factor (PAF)-induced NF-kappaB activation in rat pleural polymorphonuclear granulocytes. However, little is known about the inhibitory mechanisms of Ginkgolids on the activation of NF-kappaB. The present study evaluated the effects of GKAB on NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia. METHODS: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. GKAB was injected intravenously (iv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in IkappaBalpha, phosphorylated NIK (p-NIK) and phosphorylated IKKalpha (p-IKKalpha). Immunohistochemistry was used to confirm the nuclear translocation of NF-kappaB p65. RT-PCR was used to detect induction of NF-kappaB target gene c-Myc mRNA. RESULTS: The results showed a brief increase in p-NIK levels after ischemia. GKAB blocked ischemia-induced increases in p-NIK and p-IKKalpha levels, and reversed the decline in IkappaBalpha levels. Ischemia-induced nuclear translocation of NF-kappaB p65 was attenuated by GKAB(.) GKAB also repressed the ischemia-induced increase in expression of NF-kappaB target gene c-Myc mRNA. CONCLUSIONS: These findings suggest that GKAB-mediated neuroprotective effect against ischemia appears to be associated with blocking NF-kappaB activation by suppressing the NIK-IKK pathway.

Neuroprotective effects of prostaglandin A(1) in rat models of permanent focal cerebral ischemia are associated with nuclear factor-kappaB inhibition and peroxisome proliferator-activated receptor-gamma up-regulation.

We have previously reported that prostaglandin A(1) (PGA(1)) reduces infarct size in rodent models of focal ischemia. This study seeks to elucidate the possible molecular mechanisms underlying PGA(1)'s neuroprotective effects against ischemic injury. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. PGA(1) was injected intracerebroventricularly (icv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in IkappaBalpha, pIKKalpha, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Immunohistochemistry was used to confirm the nuclear translocation of nuclear factor-kappaB (NF-kappaB) p65 and the expression of PPAR-gamma. RT-PCR was used to detect levels of c-Myc mRNA. The contribution of PPAR-gamma to PGA(1)'s neuroprotection was evaluated by pretreatment with the PPAR-gamma irreversible antagonist GW9662. A brief increase in pIKKalpha levels and rapid reduction in IkappaBalpha were observed after ischemia. PGA(1) blocked ischemia-induced increases in pIKKalpha levels and reversed the decline in IkappaBalpha levels. Ischemia-induced nuclear translocation of NF-kappaB p65 was attenuated by PGA(1). PGA(1) also repressed the ischemia-induced increase in expression of NF-kappaB target gene c-Myc mRNA. Immunohistochemistry demonstrated an increase in PPAR-gamma immunoreactivity in the nucleus of striatal cells at 3 hr after pMCAO. Western blot analysis revealed that the expression of PPAR-gamma protein significantly increased at 12 hr and peaked at 24 hr. PGA(1) enhanced the ischemia-triggered induction of PPAR-gamma protein. Pretreatment with the irreversible PPAR-gamma antagonist GW9662 attenuated PGA(1)'s neuroprotection against ischemia. These findings suggest that PGA(1)-mediated neuroprotective effect against ischemia appears to be associated with blocking NF-kappaB activation and likely with up-regulating PPAR-gamma expression.

Opiate and acetylcholine-independent analgesic actions of crotoxin isolated from crotalus durissus terrificus venom.

The venom of Crotalus durissus terrificus is reported to have analgesic activity and the administration of Crotoxin (Cro) to cancer patients is reported to reduce the consumption of analgesics. This study investigated the analgesia induced by Cro and the effects of atropine and naloxone on the antinociceptive activity of Cro in mice and rats. The results showed that Cro at 66.5, 44.3 and 29.5microg/kg (ip) exhibited a dose-dependent analgesic action in mice using the hotplate and acetic acid writhing tests. Cro at 44.3microg/kg (ip) had significant analgesic action in the rat tail-flick test. In the mouse acetic acid-writhing test, intracerebral ventricular administration of Cro 0.3microg/kg produced marked analgesic effects. Microinjection of Cro (0.15microg/kg) into the periaqueductal gray area also elicited a robust analgesic action in rat hotplate test. Atropine at 0.5mg/kg (im) or 10mg/kg (ip) or naloxone at 3mg/kg (ip) failed to block the analgesic effects of Cro. These results suggest that Cro has analgesic effects mediated by an action on the central nervous system. The muscarinic and opioid receptors are not involved in the antinociceptive effects of Cro.