A winged relative of ice-crawlers in amber bridges the cryptic extant Xenonomia and a rich fossil record.

Until the advent of phylogenomics, the atypical morphology of extant representatives of the insect orders Grylloblattodea (ice-crawlers) and Mantophasmatodea (gladiators) had confounding effects on efforts to resolve their placement within Polyneoptera. This recent research has unequivocally shown that these species-poor groups are closely related and form the clade Xenonomia. Nonetheless, divergence dates of these groups remain poorly constrained, and their evolutionary history debated, as the few well-identified fossils, characterized by a suite of morphological features similar to that of extant forms, are comparatively young. Notably, the extant forms of both groups are wingless, whereas most of the pre-Cretaceous insect fossil record is composed of winged insects, which represents a major shortcoming of the taxonomy. Here, we present new specimens embedded in mid-Cretaceous amber from Myanmar and belonging to the recently described species Aristovia daniili. The abundant material and pristine preservation allowed a detailed documentation of the morphology of the species, including critical head features. Combined with a morphological data set encompassing all Polyneoptera, these new data unequivocally demonstrate that A. daniili is a winged stem Grylloblattodea. This discovery demonstrates that winglessness was acquired independently in Grylloblattodea and Mantophasmatodea. Concurrently, wing apomorphic traits shared by the new fossil and earlier fossils demonstrate that a large subset of the former "Protorthoptera" assemblage, representing a third of all known insect species in some Permian localities, are genuine representatives of Xenonomia. Data from the fossil record depict a distinctive evolutionary trajectory, with the group being both highly diverse and abundant during the Permian but experiencing a severe decline from the Triassic onwards.

RNA N6-methyladenosine demethylase FTO targets MOXD1 promoting the malignant phenotype of gastric cancer.

BACKGROUND: The m6A modified demethylase FTO affects the progression of gastric cancer (GC), and the role mechanism of FTO in GC is still unclear. We, here, explored the role of FTO and unrevealed the mechanisms of its function in GC. METHODS: The expression and clinical prognosis of FTO in GC were examined via UALCAN and GEPIA online databases. Effect of FTO shRNA on GC cellular malignant phenotype were proved by CCK-8, Transwell, Wound healing assay and Flow cytometric assay. RNA-sequencing data of FTO depleted AGS cells were downloaded to analyze differentially expressed genes of FTO downstream. The GO and KEGG pathway enrichment were performed for the DEGs by DAVID. RT-qPCR and RIP-qPCR assay were applied to verify the MOXD1 mRNA and methylated mRNA in FTO shRNA group. The expression and clinical prognosis of MOXD1 in GC were explored via UALCAN, GEPIA and Kaplan-Meier plotter. The role and mechanism and of MOXD1 in GC cell lines were detected and analyzed. RESULTS: The expression of FTO was found to be elevated in GC tissues compared with normal tissues, and worse survival were strongly related to high expression of FTO in GC. FTO silencing suppressed the proliferation, migration and promoted apoptosis of GC cells. A total of 5856 DEGs were obtained in between NC and FTO depleted AGS cell groups, and involved in the cancer related pathways. Here, FTO targets MOXD1 mRNA and promotes its expression via m6A methylation. MOXD1 upregulation was associated to poor prognosis of GC. MOXD1 silencing suppressed the malignant phenotype of GC cells. MOXD1 activated cancer -related signaling pathway (MAPK, TGF-ß, NOTCH and JAK/STAT). CONCLUSIONS: Our study demonstrated that FTO silencing decreased MOXD1 expression to inhibit the progression of GC via m6A methylation modification. FTO/MOXD1 may be potential targets for the treatment and prognosis of GC.

Cystic encapsulated papillary carcinoma with ductal carcinoma in situ in the male breast: a clinicopathologic feature with a diagnostic challenge: A case report and review of literature.

RATIONALE: Encapsulated papillary carcinoma (EPC) is a rare subset of breast carcinoma accounting for 0.5% to 2.0% of all patients with breast cancer and occuring mostly in postmenopausal women. It is even rarer in male breast cancer, and male EPC has only been reported in few cases. EPC has a distinctive histological pattern and a better prognosis compared with other types of breast carcinoma. Compared to the previously reported EPC cases, the lesion was unusually cystic made the diagnosis challenging. Accordingly, herein, we describe a rare case of EPC was unusually cystic in an elder male breast, associated with ductal carcinoma in situ (DCIS), along with an indepth literature discussion, and then to improve our understanding more about this uncommon tumor and further to provide more experience to treat this disease. PATIENT CONCERNS: A 73-year-old man noticed a slowly enlarging mass in the right breast 1 year ago and sought medical attention. The patient presented with a right breast mass of 1-year duration and bloody nipple discharge in the first couple of days. The medical history was unremarkable. DIAGNOSES: Physical examination, an elastic hard, smooth and movable 4-cm lesion was palpated below the right papilla. On the sonography, a well-defined predominantly cystic-solid tumor of 3.6 × 2.3 cm was confirmed. Postoperative pathological and immunohistochemical examinations of the surgical specimens revealed a final diagnosis of breast EPC with DCIS. INTERVENTIONS: The patient underwent surgery. A diagnosis of "a little papillary neoplasm of the breast with epithelial atypia and hypertrophy in the fibrous cystic wall" was made by the frozen section. Further, total mastectomy was performed. OUTCOMES: The operation was successful. Then the male patient recovered completely, did not require any additional treatment and continued to do well on postsurgical mammary surgical clinic visits. The patient had been followed-up regularly for 2 years after surgery; he did not experience any complications and remained disease-free.

Gastric ectopic pancreas combined with synchronous multiple early gastric cancer: A rare case report.

BACKGROUND: A large percentage of patients with ectopic pancreas are asymptomatic. When present, the symptoms are typically non-specific. These lesions are predominantly located in the stomach and benign in nature. Synchronous multiple early gastric cancer (SMEGC) (two or more simultaneous malignant lesions with early gastric cancer) is relatively rare and particularly easy to overlook during endoscopic examination. The prognosis of SMEGC is generally poor. We report a rare case of ectopic pancreas with concomitant SMEGC. CASE SUMMARY: A 74-year-old woman presented with paroxysmal upper abdominal pain. On initial investigations, she tested positive for Helicobacter pylori (H. pylori). She underwent esophagogastroduodenoscopy which revealed a 1.5 cm × 2 cm major lesion at the greater curvature and a 1 cm minor lesion at the lesser curvature of the stomach. On endoscopic ultrasound, the major lesion showed hypoechoic changes, uneven internal echoes and unclear boundaries between some areas and the muscularis propria. Endoscopic submucosal dissection was performed to excise the minor lesion. A laparoscopic resection was chosen for the major lesion. On histopathological examination, the major lesion contained high grade intraepithelial neoplasia with a small focus of cancer. A separate underlying ectopic pancreas was found under this lesion. The minor lesion contained high grade intraepithelial neoplasia. In this case, the patient was diagnosed with SMEGC with concomitant ectopic pancreas in the stomach. CONCLUSION: Patients with atrophy, H. pylori, and other risk factors should be carefully investigated to avoid missing other lesions including SMEGC and ectopic pancreas.

Clear cell "sugar" tumor of the lung: Diagnostic characteristics of a rare pulmonary tumor: A case report and review of literature.

INTRODUCTION: Clear cell tumors of the lung (CCTLs), also known as "sugar tumors" for an abundant cellular glycogen concentration, are an extremely rare type pulmonary neoplasm. Often, they are incidentally found on chest roentgenogram or computed tomography scan during routine examination. CCTLs usually present with nonspecific symptoms that pose a diagnostic challenge to clinicians. Accordingly, histopathology remains the gold standard for diagnosing. Moreover, some of them can present with either appearances or histopathological features similar to other pulmonary neoplasms under the light microscope, including pulmonary malignancy, thereby causing misdiagnosis prior to or after surgery. Accordingly, herein, we describe a rare case of CCTL, review the literature has been published, and then discuss the benign versus malignant nature of this rare tumor. PATIENT CONCERNS: A 59-year-old man presented due to a high-density chest nodule in the left diaphragm. The patient's medical history was unremarkable and he also denied smoking in the past. DIAGNOSIS: Physical examination, there were no noted signs. A new chest contrast-enhanced computed tomography revealed a 3.2 × 2.5 cm, solitary, circular nodule with a smooth edge located in the beside of the left thoracic aorta. Postoperative pathological and immunohistochemical examinations of the surgical specimens revealed a final diagnosis of CCTLs. INTERVENTIONS: The patient underwent video-assisted thoracoscopic surgery. A wedge resection of left lower lung lobe was carried out and the tumor node was successfully removed alongside normal surrounding parenchyma. OUTCOMES: The operation was successful. Then the patient recovered completely and continued to do well on postsurgical thoracic surgical clinic visits. The tumor was a benign tumor, and the patient did not require any additional treatment. The patient had been followed-up regularly for 4 years after surgery; she did not experience any complications and remained disease-free. CONCLUSION: CCTLs should be considered in the differential diagnosis if a patient shows a solitary, circular chest nodule with a smooth edge. They are extremely rare lung tumors that must be differentiated from other lung tumors, especially the malignant tumors. Although pathological and immunohistochemical findings are important for making the diagnosis, the varying histopathological features on microscope make diagnosis difficult. The current case highlights the importance of physicians being aware of and suspecting CCTLs in similar cases, along with knowing the characteristics of CCTLs for the diagnosis and differential diagnosis.

A Practical Predictive Model Based on Ultrasound Imaging and Clinical Indices for Estimation of Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer.

PURPOSE: Clinical responses of neoadjuvant chemotherapy (NACT) are associated with prognosis in patients with breast cancer. The selection of suitable variables for the prediction of clinical responses remains controversial. Herein, we developed a predictive model based on ultrasound imaging and clinical indices to identify patients most likely to benefit from NACT. PATIENTS AND METHODS: We recruited a total of 225 consecutive patients who underwent NACT followed by surgery and axillary lymph node dissection at the Sixth Hospital of Ning Bo City of Zhe Jiang Province between January 1, 2018, and March 31, 2021. All patients had been diagnosed with breast cancer following the clinical examination. First, we created a training cohort of patients who underwent NACT+surgery (N=180) to develop a nomogram. We then validated the performance of the nomogram in a validation cohort of patients who underwent NACT+ surgery (N=45). Multivariate logistic regression was then used to identify independent risk factors that were associated with the response to NACT; these were then incorporated into the nomogram. RESULTS: Multivariate logistic regression analysis identified several significant differences as to clinical responses of NACT, including neutrophil-lymphocyte ratio (NLR), body mass index (BMI), pulsatility index (PI), resistance index (RI), blood flow, Ki67, histological type, molecular subtyping, and tumor size. The performance of the nomogram score exhibited a robust C-index of 0.89 (95% confidence interval [CI]: 0.83 to 0.95) in the training cohort and a high C-index of 0.87 (95% CI: 0.81 to 0.93) in the validation cohort. Clinical impact curves showed that the nomogram had a good predictive ability. CONCLUSION: We successfully established an accurate and optimized nomogram incorporated ultrasound imaging and clinical indices that could be used preoperatively to predict clinical responses of NACT. This model can be used to evaluate the risk of clinical responses to NACT and therefore facilitate the choice of personalized therapy.

Modified Predictive Model and Nomogram by Incorporating Prebiopsy Biparametric Magnetic Resonance Imaging With Clinical Indicators for Prostate Biopsy Decision Making.

PURPOSE: The purpose of this study is to explore the value of combining bpMRI and clinical indicators in the diagnosis of clinically significant prostate cancer (csPCa), and developing a prediction model and Nomogram to guide clinical decision-making. METHODS: We retrospectively analyzed 530 patients who underwent prostate biopsy due to elevated serum prostate specific antigen (PSA) levels and/or suspicious digital rectal examination (DRE). Enrolled patients were randomly assigned to the training group (n = 371, 70%) and validation group (n = 159, 30%). All patients underwent prostate bpMRI examination, and T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences were collected before biopsy and were scored, which were respectively named T2WI score and DWI score according to Prostate Imaging Reporting and Data System version 2 (PI-RADS v.2) scoring protocol, and then PI-RADS scoring was performed. We defined a new bpMRI-based parameter named Total score (Total score = T2WI score + DWI score). PI-RADS score and Total score were separately included in the multivariate analysis of the training group to determine independent predictors for csPCa and establish prediction models. Then, prediction models and clinical indicators were compared by analyzing the area under the curve (AUC) and decision curves. A Nomogram for predicting csPCa was established using data from the training group. RESULTS: In the training group, 160 (43.1%) patients had prostate cancer (PCa), including 128 (34.5%) with csPCa. Multivariate regression analysis showed that the PI-RADS score, Total score, f/tPSA, and PSA density (PSAD) were independent predictors of csPCa. The prediction model that was defined by Total score, f/tPSA, and PSAD had the highest discriminatory power of csPCa (AUC = 0.931), and the diagnostic sensitivity and specificity were 85.1% and 87.5%, respectively. Decision curve analysis (DCA) showed that the prediction model achieved an optimal overall net benefit in both the training group and the validation group. In addition, the Nomogram predicted csPCa revealed good estimation when compared with clinical indicators. CONCLUSION: The prediction model and Nomogram based on bpMRI and clinical indicators exhibit a satisfactory predictive value and improved risk stratification for csPCa, which could be used for clinical biopsy decision-making.

Adult granulosa cell tumors of bilateral ovaries with pure cystic presentation: A case report and review of literature.

RATIONALE: Granulosa cell tumors (GCTs) are rare, hormonally active sex cord-stromal tumors that generally present as solid unilateral ovarian lesions. It's quite uncommon that they present as pure bilateral ovarian cysts. Histopathology remains the gold standard for making a diagnosis of GCTs. However, as the differential diagnosis is difficult, cystic GCTs are frequently misdiagnosed as benign or other cystic tumors either prior to surgery or during pathologic diagnosis. Accordingly, herein, we describe a fairly rare case of bilateral ovarian cystic GCTs, along with a review of the related literature. PATIENT CONCERNS: A 43-year-old woman presented with abdominal distension and chronic pain since 1 day. The patient had a history of dysmenorrhea. DIAGNOSES: Physical examination revealed palpable bilateral adnexal tumors; ultrasonography revealed cystic and septate masses with a maximum diameter of 7.8 and 10.7 cm, respectively, in the bilateral ovaries. Hormonal analysis revealed that the blood estradiol levels were elevated. Postoperative pathological and immunohistochemical examinations of the surgical specimens revealed a final diagnosis of cystic adult GCTs of the ovaries. INTERVENTIONS: The patient first underwent laparoscopic bilateral ovarian cystectomy. On the basis of the final pathological diagnosis report, abdominal total hysterectomy, bilateral oophoro-salpingectomy, and partial omentectomy were then performed. Microscopic examination revealed that there were no residual CGT cells. The patient's federation international of gynecology and obstetrics (FIGO) Stage was IB period. OUTCOMES: The surgeries were successful. The tumor was a FIGO Stage IB tumor, and the patient did not require any additional treatment. The patient had been followed-up regularly for 2 years after surgery; she did not experience any complications and remained disease-free. LESSONS SUBSECTIONS: Cystic GCTs should be considered in the differential diagnosis if a female patient shows bilateral ovarian cysts. They are extremely rare ovarian malignant tumors that must be differentiated from other ovarian tumors, especially purely cystic tumors and benign cysts. Although pathological and immunohistochemical findings are important for making the diagnosis, the varying histopathological features on microscope make diagnosis difficult, including tumor cells with luteinization or free cell clusters. The current case highlights the importance of physicians being aware of and suspecting cystic CGTs in similar cases, along with knowing the characteristics of GCTs for the diagnosis and differential diagnosis.

A rare coexistence of parathyroid adenoma and medullary and papillary thyroid carcinoma.

The combination of parathyroid adenoma, medullary thyroid carcinoma (MTC), and papillary thyroid carcinoma (PTC) has been reported occasionally, but it has now been recognized more often through effective evaluations. However, the etiology and risk factors remain unclear, so we discuss them in this article. Here, we report the case of a 64-year-old woman with parathyroid adenoma, MTC, and PTC diagnosed incidentally. This woman was admitted to the Xingtai People's Hospital affiliated to Hebei Medical University for an apparently aggravating symptom of hypodynamia. Her past medical history included diabetes and a left nephrolith. Upon admission, her bloodwork showed hypercalcemia, hypophosphatemia, and elevated serum parathyroid hormone. Subsequently, the sonographic findings revealed dominant nodules in both the right and left lobes with a left inferior suspected parathyroid adenoma. The patient underwent fine needle aspiration (FNA) of the bilateral thyroid lobes, the results of which were both thyroid carcinoma. Therefore, a thyroidectomy, a neck dissection, and the excision of a suspected parathyroid adenoma were performed. A histological examination revealed a combination of parathyroid adenoma, MTC, and PTC. Her serum calcium and parathyroid hormone levels returned to the normal range after the surgery. Our case highlighted the fact that even though the concurrent existence of parathyroid adenoma, MTC, and PTC is rare, the diagnosis of this coexistence should be considered in primary hyperparathyroidism (PHPT). To avoid repeat surgeries, patients with coexisting diseases should be screened cautiously. Therefore, we recommend a preoperative check of the calcium levels in patients with thyroid cancer and a preoperative thyroid check in all patients with PHPT.

Expression of Rab5a correlates with tumor progression in pancreatic carcinoma.

Rab family protein Rab5a has been implicated in cancer progression. To date, its expression pattern in human pancreatic cancer has not been investigated. This study aims to examine clinical significance, biological role, and potential mechanism of action of mRab5a in human pancreatic cancer. We analyzed Rab5a protein in cancer tissue of 111 cases of pancreatic cancer using immunohistochemistry. The results show that Rab5a overexpression correlates with high T stage, positive nodal status, and advanced TNM stage. We performed knockdown of Rab5a through transfection of Rab5a-specific siRNA in the Capan-2 cell line, which shows high endogenous expression, and of Rab5a plasmid in the CFPAC-1 cell line, which shows low endogenous expression. Rab5a knockdown inhibited cell proliferation and invasion while its overexpression promoted cell proliferation and invasion. In addition, overexpression of Rab5a induced resistance to 5-FU and gemcitabine while its knockdown reduced resistance to 5-FU and gemcitabine. Furthermore, our results show that Rab5a overexpression upregulates Wnt signaling and expression of Wnt target genes including c-myc and MMP7. Blocking Wnt signaling abolished the effects of Rab5a on Wnt targets and on cancer cell proliferation. In summary, our results show that Rab5a is overexpressed in pancreatic cancer and promotes aggressive biological behavior through regulation of the Wnt/ß-catenin signaling pathway.