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Objective: To investigate the role of NOD-like receptor protein 3 (NLRP3) inflammatory vesicle activation in the progression of endometriosis (EMT) to endometriosis-associated ovarian cancer (EAOC) and the mechanism. Methods: EOAC tissues (n=15), EMT tissues (n=15), and normal endometrium tissues (CON, n=15) resected from patients during April 2018 and June 2019, as well as the clinical data of patients, were collected from the Shanghai Changning Maternity and Infant Health Hospital. Expression of NLRP3, BRCA1/BRCA2 containing complex subunit 3 (BRCC3), caspase-1 and IL-1β in the tissues of each group was detected by immunohistochemistry and WB methods. BRCC3 overexpression plasmids and si-BRCC3 plasmids were constructed and transfected into EMT CRL-7566 cells. The expression level of BRCC3 protein in the transfected cells was detected by WB method. The changes in cell proliferation, apoptosis, migration and invasion of transfected cells were detected by MTT method, flow cytometry and Transwell test, respectively. The BRCC3-overexpressing cells were further interfered with NLRP3. The expression levels of BRCC3 and NLRP3 proteins after the interference were detected by WB method, and the changes in cell proliferation, apoptosis, migration and invasion after interference were also detected. Results: The expression levels of NLRP3, caspase-1, IL-1 p and BRCC3 in EAOC and EMT tissues were higher than those in CON group (all P<0.01), and there was a positive correlation between the expression of NLRP3 and BRCC3 in EAOC tissues (r=0.65, P<0.01). Overexpression of BRCC3 significantly promoted cell proliferation, migration and invasion and inhibited cell apoptosis in CRL-7566 cells (all P<0.01); While knockdown of BRCC3 had the opposite effects (all P<0.01). Over-expression of BRCC3 increased the expression level of NLRP3 (P<0.01), while interference with BRCC3 inhibited the expression of NLRP3 (P<0.01). Interference with NLRP3 partially attenuated the inhibition on cell apoptosis (P<0.01) and promotion on cell migration (P<0.05) and invasion (P<0.01) brought by BRCC3 overexpression. Conclusion: Both NLRP3 and BRCC3 are highly expressed in EAOC and EMT tissues. Over-expression of BRCC3 can promote the proliferation, migration and invasion but inhibit apoptosis of CRL-7566 cells. BRCC3/NLRP3 is a potential predictive marker and treatment target for the transformation of EMT to EAOC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) occurring in children and adolescence is extremely rare and till present there is a lack of understanding on their clinicopathological and prognostic features of this rare entity. For our study, data of 196 cases children and adolescents with NPC from the past 18 years at a high‐volume cancer center from South China were retrospectively analyzed. Half of the evaluated NPC patients (83/166, 50.0%) were staged as Stage IVa disease, whereas 1.2% (2/166), 27.7% (46/166), 16.9% (28/166) and 4.2% (7/166) had Stage II, III, IVb and IVc disease, respectively. Serum EBV EA‐IgA ≥1:10 and VCA‐IgA ≥1:40 were found in 67.7% (113/167) and 76.6% (128/167) of the evaluated patients, respectively, whereas 56.8% (84/148) of the patients had plasma EBV DNA ≥1000 copies/mL. Histologically, all tumors were classified as nonkeratinizing squamous cell carcinoma (NK‐SCC). Immunohistochemistrically, the expression of CK (AE1/AE3), P63, CK5/6 and P40 were observed in 100% (88/88), 93.2% (68/73), 84.1% (58/69) and 63.2% (12/19) of the detected cases, respectively. All cases show similar immunophenotype compared to that occurring in adult patients. All evaluated cases (71/71 100%) harbored EBER. Patients with plasma EBV DNA ≥1000 copies/mL and positive serum EBV antibodies had significantly inferior 3‐year OS (88% vs 100%, P =.007) compared to other corresponding groups. The combination of EBV serology and plasma EBV DNA are useful to predict the outcome of patients with NPC in children and adolescents. What's new Nasopharyngeal carcinoma (NPC) is extremely rare in children and adolescents, and the clinicopathological characteristics and prognostic features of pediatric NPC remain largely unknown. In this retrospective study, the authors describe the largest series of NPC in children and adolescents in southern China, the most endemic area of NPC, and reveal that all cases histologically belonged to nonkeratinizing squamous cell carcinoma. Moreover, they provide evidence that the combination of Epstein‐Barr virus (EBV) serology and plasma EBV DNA is useful for predicting patient outcome, with potential clinical applications for risk group stratification and prognostic prediction for pediatric NPC patients. [ABSTRACT FROM AUTHOR]

Background: The clinicopathological features and Epstein-Barr virus (EBV) infection status of lymphoma in children and adolescents in South China is under-researched. South China is a well-known high-incidence area of EBV-associated nasopharyngeal carcinoma. Methods: A cohort of 662 consecutive children and adolescents’ lymphomas was retrospectively analyzed and Epstein-Barr virus encoded RNAs (EBERs) in situ hybridization was performed to detect the EBV infection. Results: The majority (501/662, 75.7%) of lymphomas in children and adolescents was Non-Hodgkin lymphoma (NHL). One hundred sixty one cases (24.3%) were Hodgkin lymphoma (HL). Of the NHL, precursor cell lymphoma, mature B-cell lymphoma and peripheral T/NK-cell lymphoma accounted for 32.0%, 41.1% and 26.9% respectively. The five common subtypes were lymphoblastic lymphoma (32.0%), Burkitt lymphoma (BL) (21.0%), anaplastic large-cell lymphoma (ALCL) (14.2%), diffuse large B-cell lymphoma (DLBCL) (13.8%) and extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (6.2%). EBV infection was detected in 58.9% classical Hodgkin lymphomas (CHLs), 21.4% mature B-cell lymphomas and 52.4% peripheral T/NK-cell lymphomas. Moreover, EBV was associated with high grade NHL including ENKTCL (100.0%), BL (30.5%) and DLBCL (17.6%). Conclusion: The high proportion of peripheral T/NK-cell lymphomas in children and adolescents in South China are presented in this study and compared to western countries due to the high percentage of ENKTCL. ENKTCL is firmly associated with EBV infection, while more than half of HL, a portion of BL and DLBCL are related to EBV infection. This study conclusively demonstrates that EBV infection is more prevalent in children and adolescents with lymphomas in South China compared to western countries. [ABSTRACT FROM AUTHOR]

Phyllanthus reticulatus (Euphorbiaceae) is a medicinal plant that has been used in Zhuang medicine since ancient times. Traditionally, it has the effect of removing toxins and detumescence and can be used to treat hepatitis in China and India. Our previous studies have proved that the ethyl acetate extract of its leaves (PRPE) has an anti-hepatoma effect. To predict targets of an ethyl acetate extract of Phyllanthus reticulatus leaves (PRPE) in hepatoma treatment via network pharmacology and verify the predictions in a mouse model of liver cancer. Chemical constituents and therapeutic targets of P. reticulatus (PRP) were searched and predicted via public databases. A protein-protein interaction network comprising common targets was constructed, and the key gene targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for biological function and pathway enrichment analyses. The effects of PRP on BEL-7404 and HepG 2 cells were determined by MTT assay, apoptosis was measured by flow cytometry and hoechst44432/PI. And a nude mouse xenograft model was established to verify the anti-tumour effect in vivo. The histopathology of tumours was observed by staining with haematoxylin and eosin (H&E). Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine the gene and protein expression levels of phosphoinositide 3-kinase (PI3K), Akt1, p53, caspase-3, Bcl-2 and Bax, respectively. Twenty-seven chemical components and 567 potential therapeutic targets of PRP were identified. GO analysis indicated that these targets are mainly associated with peptidyl-tyrosine phosphorylation and steroid metabolic process. KEGG analysis showed that the targets are mainly located in the PI3K/Akt, apoptosis, mitogen-activated protein kinase (MAPK), Ras and vascular endothelial growth factor (VEGF) signalling pathways. According to the p -adjust value, the PI3K/Akt pathway is the core pathway. In vitro, PRPE could inhibit proliferation and induce apoptosis in hepatoma cells. IC 50 values of PRPE were 2.48 and 6.34 mg/mL for BEL-7404 and hepG 2 cells, respectively. PRPE significantly reduced tumour volume and weight. H&E results showed that PRPE repaired necrotic areas in hepatoma cells. PRPE reduced the protein expression of PI3K, Akt1 and Bcl-2 and increased the protein expression of p53 and Bax. Meanwhile, PRPE reduced the mRNA expression of PI3K, AKT1 and BCL 2 and increased the mRNA expression of TP53, CASP3 and BAX. The targets of PRPE are the PI3K/Akt, apoptosis, MAPK, Ras and VEGF signalling pathways. Passing through the PI3K/Akt pathway to induce apoptosis is the main mechanism of PRPE. [Display omitted] • The targets of PRP are mainly located in the PI3K/Akt and apoptosis signalling pathways. • PRPE could induce apoptosis in hepatoma cells. • PRPE reduced the protein expression of PI3K, Akt1 and Bcl-2 and increased the protein expression of p53 and Bax. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-positive plasma cell neoplasms (PCNs) in immunocompetent patients are a rare entity, the clinicopathological and prognostic features of which have not been well characterized. Fifteen cases of EBV-positive PCN arising in immunocompetent patients from south China were retrospectively analyzed, and an additional 44 cases from the literature were reviewed. The overall EBV-positive rate defined by EBV-encoded small RNAs (EBERs) in-situ hybridization of PCNs was 12.3% (15/122), and it was significantly higher in plasmacytoma (17.1%, 13/76) than in plasma cell myeloma/multiple myeloma (4.3%, 2/46; P=0.031). The age of the patients ranged from 17 to 79 years, with a median age of 56 years. There was a large preponderance of men, with a male-to-female ratio of 4:1. Solitary plasmacytoma of bone (23.8%, 5/21) had comparable EBV-encoded small RNAs-positive rates with extramedullary plasmacytoma arising in the upper respiratory tract (19.5%, 8/41; P=0.949). Anaplastic and classic cytologic appearance was observed in 61.5% (8/13) and 38.5% (5/13) of EBV-positive plasmacytomas, respectively. Cases with an anaplastic cytologic appearance had a significantly higher Ki-67 proliferation index than those with a classic cytologic appearance (median: 55% vs. 10%, P=0.001). In the combined cohorts, anaplastic/plasmablastic cytologic appearance was significantly more common in extramedullary plasmacytoma arising in the upper respiratory tract (72.0%, 18/25) than outside the upper respiratory tract (11.1%, 1/9; P=0.006). Among the 59 cases of EBV-positive PCN, survival data of 34 cases were available for analysis, including 30 cases of plasmacytoma and 4 cases of plasma cell myeloma/multiple myeloma. There was no statistically significant difference in overall survival between patients with EBV-positive plasmacytomas in the combined cohorts and EBV-negative plasmacytomas in the present cohort. The prevalence of EBV in PCN in immunocompetent patients varies according to histologic subtype and tumor location. Compared with EBV-negative cases, EBV-positive plasmacytomas tend to have an anaplastic/plasmablastic cytologic appearance. No significant impact of EBV infection on clinical outcomes is observed in the limited number of reported cases., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Non-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive., Methods: Four Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA., Results: We identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM&#95;002440.4: c.805&#95;812del: p.V269Qfs*15) and one patient with NOA (P21504) in another Chinese family (NM&#95;002440.4: c.2220&#95;2223del:p.K741Rfs*2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM&#95;002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs*11), and the patient with NOA (P9540) (NM&#95;002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs*3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers., Conclusions: We identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA., (© 2022. The Author(s).)

Inhibin βA (INHBA) serves a prognostic and tumor‑promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non‑small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor‑promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. In vivo loss‑ and gain‑of‑function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes‑associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription‑quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non‑cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5‑year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion in vitro . In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.

This study aimed to evaluate the efficacy and safety of vasal vessel-sparing modified single-armed 2-suture longitudinal intussusception vasoepididymostomy (SA-LIVE) to epididymal obstructive azoospermia patients. Forty consecutive epididymal obstructive azoospermia cases, who underwent microsurgical vasoepididymostomy in Shanghai General Hospital from January 2019 to October 2019, were included in this study. Twenty cases underwent SA-LIVE (group A), and 20 cases underwent vasal vessel-sparing SA-LIVE (group B). Until March 2021, the mean follow-up period was 16.9 ± 4.1 (12-23) months. The overall patency rate was 82.5%, and 80% and 85% for group A and group B respectively. The mean time to achieve patency was 4.11 ± 2.74 months. The overall natural pregnancy rate was 51.5%(17/33) at the mean follow-up of 16.9 months. The natural pregnancy rate was 50.0% for group A and 52.9% for group B (p > .05). At the time of 6 months post-operation, the patency rate was 70% for group A and 80% for group B (p = .465); the natural pregnancy rate was 0% for group A and 31.3% for group B (p = .022). Vasal vessel-sparing SA-LIVE is safe and effective to achieve favourable patency and pregnancy rates. Preserving vasal vessel would improve natural pregnancy rate at a very early stage., (© 2021 Wiley-VCH GmbH.)

Double-hit/triple-hit lymphomas (DH/THLs) are high-grade B-cell lymphomas with MYC and BCL2 rearrangements and/or BCL6 rearrangements, which have poor outcomes after standard chemoimmunotherapy. This retrospective study analyzed 51 patients (range, 19 to 82 y) diagnosed from 2016 to 2019 and treated for DH/THL (n=34 MYC/BCL6 DHL, n=14 MYC/BCL2 DHL, n=3 THL) at one institution in South China. Extranodal lesions occurred in 32 patients (62.7%), more frequently in MYC/BCL6 DHL (22/34, 64.7%) than in MYC/BCL2 DHL (7/14, 50%). The most common extranodal sites were the stomach (8/32, 25.0%) and intestine (5/32, 15.6%). Most patients (33/45, 73.3%) presented with Ann Arbor stage III/IV. Interestingly, 14.3% (4/28) of MYC/BCL6 DHL tumors showed diffuse, medium-intensity CD30 expression. Epstein-Barr virus-encoded RNA was positive in 3 cases, all MYC/BCL6 DHL. Among 48 patients (94.1%) with follow-up data, 18 (37.5%) died owing to the disease, and the median survival was 5.5 months. Germinal center B cells were observed more frequently in MYC/BCL2 DHL (14/14, 100.0%) than in MYC/BCL6 DHL (15/34, 44.1%; P<0.001). Bone marrow involvement tended to lower overall survival (OS) (P=0.033). No association was observed between stage, B symptoms, lactate dehydrogenase levels, and central nervous system involvement and OS. A total of 25 patients (25/47, 53.2%) with previous hepatitis B virus (HBV) infections had significantly poorer OS (P=0.014). Chronic HBV infection was positively correlated with MYC/BCL6 DHL (r=0.317, P=0.030). Compared with DH/THL in western countries, the disease in South China has distinct characteristics with a higher prevalence of MYC/BCL6 DHL. We speculate that HBV is important in DH/THL tumorigenesis. These findings might provide clues for novel treatment strategies.

Incidental detection of lymphoma in lymph node (LN) dissection for carcinoma is extremely rare. The occurrence and clinicopathological features of this rare condition have not been characterised. The medical records of 11,889 consecutive patients who underwent LN dissection for carcinoma in the abdominopelvic cavity were retrospectively reviewed. Among these patients, 11 had lymphomas detected in LN dissections and 7 had no previous history of lymphoma, representing an incidental detection rate of 0.06% (7/11889). The patients had a median age of 63 years (range, 48-69 years), and the male-to-female ratio was 1:2.5. The sites and histological types of the carcinoma were as follows: adenocarcinoma of the sigmoid colon (2 cases), endometrioid adenocarcinoma of the endometrium (2 cases), squamous carcinoma of the uterine cervix (1 case), adenocarcinoma of the stomach (1 case), and adenocarcinoma of the rectum (1 case). All incidental lymphoma cases (100%, 7/7) were low-grade B cell non-Hodgkin lymphoma (B-NHL), including 5 cases of follicular lymphoma (grades 1-2) and 2 cases of small lymphocytic lymphoma. The median follow-up interval was 39 months (5-65 months). All the patients were alive at the end of the follow-up period. Low-grade B-NHL can be incidentally detected during LN dissection for carcinoma in the abdominopelvic cavity. The subtype of incidental lymphoma is likely related to the epidemiology of lymphoma classes in the corresponding area. We should be aware of simultaneous occurrence of incidental lymphoma during lymphadenectomy for carcinoma.

Aims: Although ultrastructural studies showed that minute pulmonary meningothelial-like nodules (MPMNs) cells closely resembled meningothelial cells, their immunophenotype has not been well characterised, partly due to their rarity., Methods: Somatostatin receptor 2a (SSTR2a) and other markers of meningioma, including epithelial membrane antigen (EMA), progesterone receptor (PR) and S100, were analysed retrospectively in 19 MPMN cases from two institutions in China., Results: The median age of patients with MPMNs was 62.5 years (32-73 years), with a male-to-female ratio of 1:8.5. Most (15/19) patients with MPMNs had coexisting diseases, including adenocarcinomas (12 cases), bronchiectasis (1 case) and tuberculosis (2 cases). Just over half of the cases (10/19) were multifocal lesions (2-5 lesions). An additional 53 cases with 123 lesions from the literature were reviewed with reported immunophenotype information. In total, 162 lesions were included in the analysis. The size of nodules was 1-4 mm. All MPMN lesions (39/39) in the 19 cases showed strong and diffuse cytoplasmic expression of SSTR2a. The expression rate of SSTR2a was higher than that of conventional markers of meningioma, including EMA (86/138), PR (32/68) and S100 (1/125)., Conclusions: Our observations expand the spectrum of recognised SSTR2a-positive lesions and once again demonstrated that MPMNs show immunohistochemical characteristics similar to meningothelial cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)