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In recent years, there has been an increasing research focus on the luminol-H 2 O electrochemiluminescence (ECL) system due to its ability to address the instability and toxicity of H 2 O 2 , which are common issues associated with the conventional luminol-H 2 O 2 ECL system. To enhance the ECL efficiency of the luminol-H 2 O system, researchers have developed electrocatalytic materials with exceptional oxygen evolution reaction (OER) properties to facilitate water electrolysis into O 2 to produce reactive oxygen species (ROS) and act as co-reactant promoters. However, most of these materials are characterized by their nanoscale or microscale dimensions, resulting in relatively large sizes and low specific surface areas, which hinder the application of the luminol-H 2 O system. To address this challenge, nickel molybdate sub-1 nm nanowires (NiMoO 4 S1 NWs) with a large specific surface area is synthesized that can offer many active sites to enhance the performance of the OER to boost the ECL of luminol. This study demonstrates that the large amount of ROS generated by the OER of NiMoO 4 S1 NWs play a crucial role in enhancing the ECL intensity of luminol. Finally, a NiMoO 4 S1 NWs-based ECL biosensor for the highly sensitive detection of the nucleocapsid proteins of SARS-CoV-2 is successfully constructed., (© 2024 Wiley‐VCH GmbH.)

The entorhinal cortex (EC) is a critical brain area for memory formation, while also the region exhibiting the earliest histological and functional alterations in Alzheimer's disease (AD). The EC thus has been long hypothesized as one of the originating brain areas of AD pathophysiology, although circuit mechanisms causing its selective vulnerability remain poorly understood. We found that dopamine neurons projecting their axons to the lateral EC (LEC), critical for memory formation in healthy brains, become dysfunctional and cause memory impairments in early AD brains. In amyloid precursor protein knock-in mice with associative memory impairment, LEC dopamine activity and associative memory encoding of LEC layer 2/3 neurons were disrupted in parallel from the early pathological stage. Optogenetic reactivation of LEC dopamine fibers, as well as L- DOPA treatment, rescued associative learning behavior. These results suggest that dysfunction of LEC-projecting dopamine neurons underlies memory impairment in AD from early stages, pointing to a need for clinical investigation of LEC dopamine in AD patients.

Objective: To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma. Methods: The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model. Results: Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR =8.50,95% CI : 1.679-8.328, P =0.001), serum albumin ( HR =3.59,95% CI : 1.017-6.551, P =0.048), and with or without chemotherapy ( HR =0.31, 95% CI : 0.246-1.061, P =0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions: Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Background: Pituitary stalk interruption syndrome (PSIS) is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes. It is characterized by a deficiency in anterior pituitary hormones, such as growth hormone, gonadotropins, and thyroid hormones. Due to the syndrome's rarity and nonspecific manifestations, there is a lack of standardized treatment strategies. Consequently, early diagnosis through imaging and on-time intervention are crucial for improving patients' outcomes., Case Summary: A 30-year-old man presented with absent secondary sexual characteristics and azoospermia. Laboratory evaluation revealed a deficiency in gonadotropins, while thyroid function was mostly within normal ranges. Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis, hypoplasia of the anterior pituitary, and ectopic posterior pituitary, leading to the diagnosis of PSIS. Initially, the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics. Pulsatile gonadotropin-releasing hormone therapy was then administered, resulting in the detection of sperm in the semen analysis within 3 mo. After 6 mo, routine semen tests showed normal semen quality. The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination, which was unsuccessful. They also attempted in vitro fertilization, but unfortunately, the woman experienced a miscarriage 10 wk after the embryo transfer., Conclusion: Early detection, accurate diagnosis, and timely treatment are crucial in improving the quality of life and fertility of PSIS patients., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30 + TLPD). Methods: Eight cases of pmCD30 + TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results: There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed "kidney-shaped", "embryonic" and "horseshoe-shaped" cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia. Conclusions: pmCD30 + TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30 + TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.

Objective: To investigate the clinicopathological and genetic features of confined placental mosaicism (CPM) and its effect on fetal intrauterine growth. Methods: Fourteen CPM cases of Haidian Maternal and Children Health Hospital were collected from May 2018 to March 2022. Clinicopathological examination on placental specimens and molecular genetic analysis were performed. Results: The age of the parturient women ranged from 27 to 34 years, with an average age of (30.0±3.54) years. The gestational weeks ranged from 35 +1 to 41 +2 weeks. There were 4 premature births and 10 term births, among which 6 were female and 8 were male fetuses. Nine cases (9/14) had adverse pregnancy outcomes, including 7 cases of fetal growth restriction. The weight of CPM placenta decreased, with 6 cases below the 10th percentile of weight standards and 5 cases between the 10th and 25th percentile. All 14 CPM placental specimens showed morphological changes of perfusion dysfunction to varying degrees, with mainly placental-maternal vascular malperfusion followed by placental-fetal vascular malperfusion. The mosaic chromosomes in different CPM cases varied, with 16-trisomy/monosomy mosaicism being the most common followed by 7-trisomy and 21-trisomy/monosomy mosaicism. The mosaic proportion was unequal in different parts of the same CPM placenta, with the mosaic proportion of umbilical cord, fetal membranes, fetal surface, maternal surface, and edge ranging from 1% to 70%. Conclusions: The mosaic chromosomes in different CPM cases vary, and the mosaic proportion is unequal in different parts of the same CPM placenta. The pathological morphology is mainly manifested as perfusion dysfunction, which can lead to adverse pregnancy outcomes such as fetal growth restriction and preterm birth.

Background: Due to mechanical imbalance in the spine, elderly scoliosis patients tend to develop vertebral fracture nonunion, i.e. , Kümmell disease, when osteoporotic vertebral compression fractures occur. However, accompanying vertebral rotational deformities make surgical procedures challenging risky. Such patients are usually compelled to undergo conservative treatment and there are very few reports on minimally invasive surgeries for them. We first-time report a patient with Kümmell disease and lumbar scoliosis treated with percutaneous kyphoplasty (PKP) under O-arm guidance., Case Summary: An 89-year-old female was admitted to the hospital due to delayed low back pain after a fall. She was diagnosed with Kümmell disease based on physical and radiologic examinations. The patient experienced severe scoliosis and subsequently underwent O-arm-guided kyphoplasty, resulting in a significant alleviation of low back pain., Conclusion: PKP has good efficacy in treating Kümmell disease. However, surgical risks are elevated in scoliosis patients with Kümmell disease due to the abnormal anatomical structure of the spine. O-arm assisted operations play a crucial role in decreasing surgical risks., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The application of adipose-derived stem cells (ADSCs) in treating hard-to-heal wounds has been widely accepted, while the short-term survival rate remains an obstacle in stem cell therapy. The aim of this study is to investigate the effect of preconditioning ADSCs with α-ketoglutarate (α-KG) on the healing of acid burn wounds and cell survival within wounds. Preconditioning of ADSCs was performed by treating cells at passage 3 with 3.5 mM DM-αKG for 24 h. Proliferation and migration of ADSCs was examined. An acid burn wound was created on the dorsal skin of mice. Cell suspension of ADSCs (2 × 10 6  cells/ml), either pre-treated with α-KG or not, was injected subcutaneously around the margin of wound. At 1,4,7,10,14 days after injection, the percentage of wound closure was evaluated. Expression of pro-angiogenic factors, matrix molecules and HIF1-α in pretreated ADSCs or in wounds was evaluated by qRT-PCR and immunohistochemistry staining, respectively. The survival rate of DiO-labelled ADSCs was determined with the in vivo bioluminescent imaging system. Treating with α-KG induced an enhancement in migration of ADSCs, while their proliferation was not affected. Expression of Vegf and Fgf-2 was significantly increased. With injection of pretreated ADSCs, healing of wounds was remarkably accelerated, along with increased ECM deposition and microvessel density. Moreover, pretreatment with α-KG resulted a prolonged survival of engrafted ADSCs was observed. Expression of HIF-1α was significantly increased in ADSCs treated with α-KG and in wounds injected with preconditioned ADSCs. Our results revealed that healing of acid burn wound was accelerated with administration of ADSCs pretreated with α-KG, which induced elevated expression of HIF-1α and prolonged survival of engrafted stem cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear., Results: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis., Conclusion: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD., (© 2024. The Author(s).)

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Objective: Both sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes., Methods: Totally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes., Results: GQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267-5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482-6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218-13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT., Conclusion: SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients., (© 2024. Huazhong University of Science and Technology.)

Objective: To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion. Methods: Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University ( n =5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital ( n =3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results: There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases. Conclusions: DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.

Candida albicans, an opportunistic human pathogen, poses a significant threat to human health and is associated with significant socio-economic burden. Current antifungal treatments fail, at least in part, because C. albicans can initiate a strong drug tolerance response that allows some cells to grow at drug concentrations above their minimal inhibitory concentration. To better characterize this cytoprotective tolerance program at the molecular single-cell level, we used a nanoliter droplet-based transcriptomics platform to profile thousands of individual fungal cells and establish their subpopulation characteristics in the absence and presence of antifungal drugs. Profiles of untreated cells exhibit heterogeneous expression that correlates with cell cycle stage with distinct metabolic and stress responses. At 2 days post-fluconazole exposure (a time when tolerance is measurable), surviving cells bifurcate into two major subpopulations: one characterized by the upregulation of genes encoding ribosomal proteins, rRNA processing machinery, and mitochondrial cellular respiration capacity, termed the Ribo-dominant ( Rd ) state; and the other enriched for genes encoding stress responses and related processes, termed the Stress-dominant ( Sd ) state. This bifurcation persists at 3 and 6 days post-treatment. We provide evidence that the ribosome assembly stress response (RASTR) is activated in these subpopulations and may facilitate cell survival., Competing Interests: VD, SM, VB, AM, AD, SK, AC, RO, SS, JX, MW, JB, MH No competing interests declared, (© 2023, Dumeaux et al.)

Recently, the contribution of inorganic salts (nitrates in particular) to the mass concentration of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM 2.5 ) has been increasing across China. However, it is urgent to understand how the increased inorganic salts affect the crucial properties of PM 2.5 . Here, we conducted continuous field observations at Zhenjiang Ecology and Environment Protection Bureau from January 1 to December 31, 2021. The mass concentrations of ammonium sulfate[(NH 4 ) 2 SO 4 ] and ammonium nitrate (NH 4 NO 3 ) were calculated using different methods. The contributions of (NH 4 ) 2 SO 4 and NH 4 NO 3 to the extinction coefficient, hygroscopic growth, and acidity of PM 2.5 were discussed in detail. Our results demonstrated that the mean mass concentrations of (NH 4 ) 2 SO 4 and NH 4 NO 3 during the study period were (6.5±4.5) and (15.0±13.3) μg·m -3 , which contributed (20.5±18.2)% and (34.5±18.4)% to the mass concentration of PM 2.5 , respectively. The total extinction coefficient of PM 2.5 was (224.5±194.2) Mm -1 , in which NH 4 NO 3 was the largest contributor[(40.1±20.9)%] followed by (NH 4 ) 2 SO 4 [(19.1±10.8)%]. (NH 4 ) 2 SO 4 and NH 4 NO 3 were also the dominant contributors to the hygroscopic growth of PM 2.5 . In particular, NH 4 NO 3 contributed from (53.8±13.4)% to (61.6±14.6)% to the aerosol water content of PM 2.5 under pollution conditions. Thus, NH 4 NO 3 was a key air pollutant to be targeted for further improving the visibility and air quality in Zhenjiang in the future. However, the reduction in the precursors of NH 4 NO 3 would lead to an increase in aerosol acidity, particularly in the spring and winter seasons. Our results help us understand the evolution of air quality and the related impacts and also provide important information on air quality improvement in Zhenjiang in the future.

Purpose: To evaluate the accuracy of recording maxillomandibular position relationship with the mandibular kinesiography by surface electromyography analysis of the masticatory muscles and MRI of temporomandibular joint (TMJ)., Methods: Eight edentulous patients were selected randomly, and the maxillomandibular position relationship was determined by mandibular kinesiography and traditional method respectively. Then the corresponding bite plates were made to wear. Surface electromyography test of left and right anterior temporal and masseter muscle and magnetic resonance scan of the temporomandibular joint were performed on closed mouth position to record peak potentials, calculate asymmetric indexes, analyze the position relationship between the joint disc and the condyle, measure TMJ joint space. SPSS 18.0 software package was used for data analysis., Results: There was no significant difference in the amplitude of the anterior temporal or masseter muscle, the asymmetry index of total, asymmetry index of masseter, asymmetry index of temporalis, the anterior, upper and posterior spaces of TMJ between the mandibular kinesiography group and the traditional group (P＞0.05). The temporomandibular articular disc process relationship of the two groups were conformed to the normal physiological position relationship., Conclusions: Mandibular kinesiography could accurately record the maxillomandibular position relationship in patients with edentulous jaws.

Ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HRMS) was employed to systematically analyze the chemical constituents in Lysionoti Herba, and high perfor-mance liquid chromatography-ultraviolet(HPLC-UV) to determine the content of main compounds. A Synergi~(TM) Hydro-RP 100 Å colu-mn(2 mm×100 mm, 2.5 μm) was used for gradient elution with acetonitrile-0.1% aqueous formic acid as the mobile phase at a flow rate of 0.2 mL·min~(-1) and a column temperature of 40 ℃. MS and MS/MS were conducted with electrospray ionization(ESI) in both positive and negative modes. The chemical components in Lysionoti Herba were identified by comparison with the retention time and mass spectra of reference compounds and the relevant mass spectral data reported in MS databases and relevant literature. Furthermore, the content of five constituents(neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin) in different Lysiono-ti Herba samples was simultaneously determined by HPLC-UV at the wavelength of 330 nm. A total of 84 compounds were identified in Lysionoti Herba, including 27 flavonoids, 20 phenylethanoid glycosides, 5 amino acids, 18 organic acids, 1 alkaloid, 6 nucleosides, and 7 others. The content of neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin showed good linear relationship(r>0.999) with the peak area within certain concentration ranges, which were 3.22-102.90, 12.84-410.82, 31.63-1 012.01, 25.00-800.11, and 4.08-130.51 μg·mL~(-1), respectively. The instrument precision, method repeatability, and solution stability all met requirement, and the average recovery rate was 97.31%-100.2%, with RSD ranging from 0.95% to 2.4%. The content of the five components varied among different Lysionoti Herba samples collected from different regions of Guizhou, and the average content of forsythoside B was the highest. The established qualitative method can rapidly and efficiently identify the chemical components of Lysionoti Herba, and the developed HPLC-UV method can simultaneously determine the content of five components in a simple, ra-pid, and accurate manner, providing a scientific basis for the quality evaluation of Lysionoti Herba.

Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.

Eicosapentaenoic acid (EPA) has been reported to play an anti-inflammatory and antioxidative stress role in a series of human diseases, including major depressive disorder. However, its exact mechanism is still largely unknown. Mouse BV-2 cells were treated with lipopolysaccharide (LPS) to induce an in vitro inflammatory cell model of depression. Cytotoxic effects were assessed with MTT and lactate dehydrigebase release assays. Cytokine mediators were elevated by western blot and enzyme-linked immunosorbent assays. Autophagy-relators were determined by immunofluorescence and western blot analyses. Interaction relationships among molecules were evaluated utilizing chromatin immunoprecipitation and dual luciferase assays. Methylated miR-29a-3p was detected via methylation-specific polymerase chain reaction. EPA treatment at 60 μM had no cytotoxic effects on BV2 cells and significantly inhibited the LPS-induced inflammatory response and NLRP3 inflammasome but activated autophagy, while all these effects were reversed by the autophagy inhibitor 3-MA. Importantly, miR-29a-3p exhibited a role similar to that of EPA in LPS-treated BV2 cells. Mechanistically, EPA treatment elevated miR-29a-3p by repressing its promoter methylation. MAPK8 was a direct target of miR-29a-3p. Inhibition of miR-29a-3p greatly diminished the regulatory roles mediated by EPA in LPS-treated BV2 cells, while these roles were further impeded after MAPK8 silencing. To conclude, our data demonstrated that EPA treatment alleviated LPS-induced NLRP3 inflammasomes by activating autophagy via regulation of miR-29a-3p/MAPK8 signaling, which further elucidates the potential antidepressant mechanism of EPA., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

DNA nanosheets (DNSs) have been utilized effectively as a fluorescence anisotropy (FA) amplifier for biosensing. But, their sensitivity needs to be further improved. Herein, CRISPR-Cas12a with strong trans -cleavage activity was utilized to enhance the FA amplification ability of DNSs for the sensitive detection of miRNA-155 (miR-155) as a proof-of-principle target. In this method, the hybrid of the recognition probe of miR-155 (T1) and a blocker sequence (T2) was immobilized on the surface of magnetic beads (MBs). In the presence of miR-155, T2 was released by a strand displacement reaction, which activated the trans -cleavage activity of CRISPR-Cas12a. The single-stranded DNA (ssDNA) probe modified with a carboxytetramethylrhodamine (TAMRA) fluorophore was cleaved in large quantities and could not bind to the handle chain on DNSs, inducing a low FA value. In contrast, in the absence of miR-155, T2 could not be released and the trans -cleavage activity of CRISPR-Cas12a could not be activated. The TAMRA-modified ssDNA probe remained intact and was complementary to the handle chain on the DNSs, and a high FA value was obtained. Thus, miR-155 was detected through the obviously decreased FA value with a low limit of detection (LOD) of 40 pM. Impressively, the sensitivity of this method was greatly improved about 322 times by CRISPR-Cas12a, confirming the amazing signal amplification ability of CRISPR-Cas12a. At the same time, the SARS-CoV-2 nucleocapsid protein was detected by the strategy successfully, indicating that this method was general. Moreover, this method has been applied in the analysis of miR-155 in human serum and the lysates of cells, which provides a new avenue for the sensitive determination of biomarkers in biochemical research and disease diagnosis.

Rationale: Heterotopic pregnancy (HP) is defined as the simultaneous presence of intrauterine pregnancy and ectopic pregnancy (EP). HP after bilateral salpingectomy is extremely rare and may lead to serious complications if it is misdiagnosed and untreated timely. Here, we presented the first reported case of uterine serosal HP in a woman after assisted reproductive technology with bilateral salpingectomy because of bilateral tubal ectopic pregnancy., Patient Concerns: A 27-years-old pregnant woman after in vitro fertilization with bilateral salpingectomy complained of a sudden onset of unprovoked abdominal pain, which was persistent and dull. She denied vaginal bleeding., Diagnoses: Serum beta-human chorionic gonadotropin levels are difficult to predict HP. Transvaginal ultrasonography demonstrated 1 gestational sac in the uterine cavity and 1 thick-walled cystic mass over the upper of the uterus, with a large amount of fluid in the Pouch of Douglas. Emergency laparotomy revealed a uterine serosal pregnancy combined with intrauterine pregnancy., Interventions: This patient was successfully managed via emergency laparotomy to remove residual tissue and repair the rupture of the uterine serosal pregnancy., Outcomes: At postoperative 4 days, repeat transvaginal ultrosonography presented 1 intrauterine gestational sac with a visible fetal bud and cardiac tube pulsation. Now the patient recover well and is in an ongoing pregnancy., Lessons: It is noteworthy that HP/ectopic pregnancy is still not prevented after bilateral salpingectomy. In cases of multiple embryo transfer, even if intrauterine pregnancy has been established, it is important to rule out HP/ectopic pregnancy in time. Early diagnosis and early management can significantly improve clinical outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The role of inflammation in the formation of idiopathic pulmonary fibrosis (IPF) has gained a lot of attention recently. However, the involvement of genes related to inflammation and immune exchange environment status in the prognosis of IPF remains to be further clarified. The objective of this research is to establish a new model for the prediction of the overall survival (OS) rate of inflammation-related IPF., Methods: Gene Expression Omnibus (GEO) was employed to obtain the three expression microarrays of IPF, including two from alveolar lavage fluid cells and one from peripheral blood mononuclear cells. To construct the risk assessment model of inflammation-linked genes, least absolute shrinkage and selection operator (lasso), univariate cox and multivariate stepwise regression, and random forest method were used. The proportion of immune cell infiltration was evaluated by single sample Gene Set Enrichment Analysis (ssGSEA) algorithm., Results: The value of genes linked with inflammation in the prognosis of IPF was analyzed, and a four-genes risk model was constructed, including tpbg, Myc, ffar2, and CCL2. It was highlighted by Kaplan Meier (K-M) survival analysis that patients with high-risk scores had worse overall survival time in all training and validation sets, and univariate and multivariate analysis highlighted that it has the potential to act as an independent risk indicator for poor prognosis. ROC analysis showed that the prediction efficiency of 1-, 3-, and 5-year OS time in the training set reached 0.784, 0.835, and 0.921, respectively. Immune infiltration analysis showed that Myeloid-Derived Suppressor Cells (MDSC), macrophages, regulatory T cells, cd4+ t cells, neutrophils, and dendritic cells were more infiltrated in the high-risk group than in the low-risk group., Conclusion: Inflammation-related genes can be well used to evaluate the IPF prognosis and impart a new idea for the treatment and follow-up management of IPF patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Peng, Situ, Xie, Tan, Wei, Jiang, Zhang and Liu.)

Objective: To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma pattern Ⅰ (AITL Pattern Ⅰ). Methods: The clinicopathological data of 11 AITL Pattern Ⅰ cases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University (10 cases) and Beijing Lu Daopei Hospital (1 cases) from January 2019 to October 2021 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of the tumor cells were tested, and clinicopathological features of cases were analyzed. Results: Among the 11 AITL Pattern Ⅰ cases, the male to female ratio was 1.2∶1.0. The median age was 59 years (range 47-78 years). Seven cases had B symptoms, while eleven cases presented with systemic lymphadenopathy. According to Ann Arbor system staging, two cases were classified as stage Ⅰ-Ⅱ, and 9 cases as stage Ⅲ-Ⅳ. Hepatosplenomegaly was present in two cases (2/11), three cases (3/11) had skin rash and pruritus, and two cases (2/11) had pleural effusion. Previously, 6 cases (6/11) were diagnosed as reactive hyperplasia, 1 case (1/11) as EBV-associated lymphoproliferative disorder, and 4 cases (4/11) as hyperplasia of lymphoid tissue, which was unable to exclude lymphoma. Histologically, all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers. The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases. Mantle zones completely disappeared in 4 cases. The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm. In 2 cases, the clear cells were located between the germinal centers and the thin residual mantle cell layers, showing a circular growth pattern. The cells were medium in size, with irregular karyotype, coarse chromatin and indistinct nucleoli. Immunohistochemically, CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles. There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders. The atypical cells surrounding the follicles expressed CD3 (11/11), CD4 (11/11), PD-1 (11/11), CXCL13 (6/11), ICOS (10/11) and CD10 (7/11). PD-1 staining showed a strong perifollicular pattern, and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region. CXCL13, ICOS and CD10 showed similar distribution patterns. EBV-encoded small RNA probe (EBER) in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region (5-20/HPF) in all cases. T cell receptor gene rearrangement was monoclonal in all cases. Conclusions: Diagnosing AITL Pattern Ⅰ may be challenging and requires comprehensive analysis of clinical manifestations, histological morphology, immunophenotype and gene rearrangement results.

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Wang, Li, Tao, Teng and Saijilafu.)

Background: Preeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated., Methods: Preeclampsia patients ( n = 110) and healthy age- and gravidity-matched pregnant women ( n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis ( n = 10/group) or laboratory validation ( n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12-14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia., Results: We observed that preeclampsia patients exhibited significantly elevated plasma TC ( P = 0.037) and TG ( P < 0.001) levels and increased body mass index ( P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A , APOBEC3A&#95;B , BTNL3 , and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC ( P < 0.001) and LDL ( P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight., Conclusion: Our findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Guo, Wang, Ma, He, Zhang, He, Xie, Zhuang, Liu, Sun, Chen, Lin, Gong and Wang.)

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40 +6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

Objective: To investigate the clinicopathological features and prognosis of cytotoxic T-cell lymphoma (CTL). Methods: The clinicopathological data of 134 CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University, the 989 Hospital of PLA Joint Logistics Support force (formerly the 152 Hospital) and the Fourth Hospital of Hebei Medical University from 2008 to 2020 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of tumor cells were assessed, and clinicopathological features and prognosis of patients were analyzed. Results: Among the 134 CTL patients, the male to female ratio was 1.7∶1.0, the median age was 49.5 years (range 3-83 years), and 100 cases (74.6%) were under 60 years old. Forty-six point nine percent of the patients (53/113) had B symptoms. Most of the patients presented with systemic superficial lymphadenopathy. According to the Ann Arbor staging system, 36.8% (39/106) of the patients were in stage Ⅰ-Ⅱ, and 63.2% (67/106) in stage Ⅲ-Ⅳ. The rate of extranodal involvement was 51.6% (66/128). Spleen was involved in 24.2% (31/128) of the cases. Morphology showed diffuse growth of abnormal lymphocytes, infiltrating and destroying normal tissue structure. Immunohistochemical staining showed that tumor cells expressed T cell antigens (CD2, CD3, CD5, and CD7), and 72.0% (77/107) of them had decreased or lost expression of one or more antigens. According to the numbers of CD4 and CD8 expression in tumor cells, 70 cases (52.2%) were grouped into CD8 + >CD4 + group. The expression rates of TIA-1 and granzyme B were 99.2% (119/120) and 79.8% (95/119), respectively. CD20 abnormal expression rate was 27.6% (37/134) and CD56 was negative in all cases. The median Ki-67 proliferative index was 45.0% (range 5%-80%). In situ hybridization of small RNA encoded by Epstein-Barr virus was negative. Clonal TCR gene rearrangement analysis was performed on 49 cases and was positive in all cases. Ninety-one patients were followed up for a median of 36 months (range, 1 to 240 months), and 40 of the 91 patients (44.0%) died. The twenty-three patients were in complete remission (including 13 cases with localized single extranodal mass). The 3-year and 5-year overall survival rates were 53.5% and 49.4%, respectively. Univariate analysis showed that B symptom, spleen involvement, extranodal involvement, clinical stage, CD8 + >CD4 + phenotype, abnormal expression of CD20 and Ki-67 proliferation index (>60%) were associated with overall survival ( P <0.05). The multivariate Cox regression analyses showed that spleen involvement and CD8 + >CD4 + phenotype were independent prognostic factors for overall survival in CTL patients. Conclusions: CTL are more commonly found in adult males under 60 years old, often accompanied by B symptom, with a high proportion of extranodal involvement and more CD8 positive phenotypes. Spleen involvement and CD8 + >CD4 + phenotype are independent predictors of CTL overall survival. Some patients with localized extranodal CTL may have a good prognosis.

Gelsolin (GSN) is a calcium-regulated actin-binding protein that can sever actin filaments. Notably, actin dynamics affect the structure and function of epithelial barriers. The present study investigated the role of GSN in the barrier function of pancreatic ductal epithelial cells (PDECs) in hypertriglyceridemia-induced pancreatitis (HTGP). The human PDEC cell line HPDE6-C7 underwent GSN knockdown and was treated with caerulein (CAE) + triglycerides (TG). Intracellular calcium levels and the actin filament network were analyzed under a fluorescence microscope. The expression levels of GSN, E-cadherin, nectin-2, ZO-1 and occludin were evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. Ultrastructural changes in tight junctions were observed by transmission electron microscopy. Furthermore, the permeability of PDECs was analyzed by fluorescein isothiocyanate-dextran fluorescence. The results revealed that CAE + TG increased intracellular calcium levels, actin filament depolymerization and GSN expression, and increased PDEC permeability by decreasing the expression levels of E-cadherin, nectin-2, ZO-1 and occludin compared with the control. Moreover, changes in these markers, with the exception of intracellular calcium levels, were reversed by silencing GSN. In conclusion, GSN may disrupt barrier function in PDECs by causing actin filament depolymerization in HTGP in vitro ., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yang et al.)

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements ( P <0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement ( P <0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements ( P >0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29 +5 to 40 +4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

Objective: To investigate the clinicopathological features and prognosis of skeletal-muscle cytotoxic T-cell lymphoma (CTL). Methods: The clinical data of 14 cases of skeletal muscle CTL and 47 cases of non-skeletal muscle extranodal CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University and the 989 Hospital of the joint logistics support force of the people's Liberation Army (the former 152 hospital) from 2008 to 2019 were collected retrospectively. Immunophenotype, EBV infection status and T-cell receptor (TCR) clonality of tumor cells were evaluated. The clinicopathological features and prognosis of the two groups were compared. Results: Skeletal-muscle CTL accounted for 23.0% (14/61) of extranodal CTL in the same period. The median age of the patients was 42.3 years (range 11-76 years), including six males and eight females. The main clinical manifestations were painless masses. Two patients (2/14) had B symptoms. The tumors occurred in the cheek (7 cases), the tongue (4 cases), the lower lip (3 cases) and the left upper arm (2 cases), and in two cases had two sites. Ten cases were of stage ⅠE and four cases stage ⅡE. Compared with non-skeletal-muscle extranodal CTL, many patients of skeletal-muscle CTL did not have B symptoms, the clinical stage was lower, and the tumor mainly involved the oral cavity (cheek, tongue and lip, P <0.05). Morphologically, the tumor showed diffuse infiltration of heterotypic lymphocytes in skeletal muscle. Immunohistochemistry showed that in 11/14 cases, there were reduced or loss of expression of some the T cell antigens (CD2, CD3, CD5, CD7). TIA-1, Gr B and CD8 (CD8 + >CD4 + ) were expressed in all cases, and CD56 was negative. The median Ki-67 proliferation index was 35.0% (range 5%-60%). EBER in situ hybridization was negative in all cases. The results of TCR clonality analysis showed clonal TCR gene rearrangement were detected in eight cases. The median follow-up time was 40 months (range 10-67 months). Ten patients were tumor free; the 5-year survival rate of skeletal-muscle CTL was 100%. Compared with non-skeletal-muscle extranodal CTL (5-year overall survival rate was 35.9%), the difference was statistically significant (χ²=8.277, P =0.004). Conclusions: Skeletal-muscle CTL mostly occurs in the skeletal muscle of cheek and mouth. Tumor cells show morphologic characteristics of muscle invasion and myositis-like feature. It also shows CD8 + >CD4 + immunophenotype, cytotoxic molecular pattern and is associated with low clinical stage and good prognosis.

Objective: Numerous studies show association of particular matter (PM) in air pollution with cardiovascular dysfunction, and increased morbidity and mortality. The main mechanisms of this adverse effect involve increasing oxidative stress, inflammatory responses, and genotoxicity. Several recent studies investigated the ability of PM2.5 to cause myocardial injury in animal models using various methods, such as intratracheal instillation, intraperitoneal injection or tail vein injection. The purpose of this study is to explore the PM2.5-induced myocardial inflammatory reaction in rats through the new technology of multi-functional aerosol concentration and enrichment system., Materials and Methods: Thirty Wistar rats were divided into two groups, 15 in each group. In the exposure group, PM2.5 multi-functional aerosol concentration and enrichment system was used for PM2.5 online oral and nasal exposure (5 times a week, 4 hours exposure, for the duration of 3 months). Histopathological examination of the left ventricular myocardial tissue of both groups was done using hematoxylin and eosin (H&E) staining. Ultrastructural changes of the heart specimens were assessed using electron microscopy. The levels of CRP and ICAM-1 were detected by immunohistochemistry., Results: Compared with the control group, myocardial tissue of the exposure group exhibited edema, widened myocardial space and infiltration of inflammatory cells. There was nuclear pyknosis, mitochondrial membrane and spinal fusion, rough endoplasmic reticulum expansion, degranulation and cell swelling in the exposed group. The area of CRP positive staining in the exposed group was 3.7-fold higher than that in the control group (p < 0.05), and the ICAM-1 positive staining area of the exposed group was 12-fold higher than that of the control group (p < 0.05)., Conclusions: Prolonged exposure to PM2.5 inhalation promotes significant upregulation of ICAM-1 and CRP expression in myocardial tissues, ultrastructural alterations in myocardial cells, and influx of inflammatory cells.

Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning 1,2 . However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network that is crucial for learning and memory 3-5 . Here, using cell-type-specific electrophysiological recording 6 , we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue-reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue-reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To analyze the medication rules of traditional Chinese medicine (TCM) preventive oral prescriptions for COVID-19., Methods: The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication., Results: The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi -tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional Chinese Medicinal Materials , Traditional Chinese Medicinal Materials for Health Food, and New Resources of Food published by National Health Commission of the People's Republic of China, there are 35 species belonging to the group of edible traditional Chinese medicinal materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional Chinese medicinal materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic TCMs., Conclusion: We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of "Preventive Treatment of Disease" was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special attention should be paid to their safety in clinical application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Objective: "Same treatment for different diseases" is a unique treatment strategy in traditional Chinese medicine. Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease (COPD) and lung cancer. Citrus Grandis Exocarpium (Huajuhong in Chinese, HJH), a famous herbal, is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on "syndrome differentiation and treatment" theory. However, the common mechanism for HJH's treatment of COPD and lung cancer is not clear., Methods: In this study, based on network pharmacology and molecular docking technology, the common mechanism of HJH in the treatment of COPD and lung cancer was studied. The active ingredients and related targets of HJH were integrated from TCMSP, BATMAN-TAM, STP, and Pubchem databases. The standard names of these targets were united by UniProt database. Targets of COPD and lung cancer were enriched through GeneCards, NCBI (Gene), Therapeutic Target Database, and DisGeNET (v7.0) databases. Then the intersection targets of HJH and diseases were obtained. The STRING network and the Cytoscape 3.7.2 were used to construct PPI network, the DAVID database was used to perform GO and KEGG analysis. Then Cytoscape 3.6.1 was used to build "ingredient-target-signal pathway" network. Finally, AutoDock 1.5.6 software was used to perform molecular docking of key proteins and molecules., Results: Eleven active ingredients in HJH were obtained by searching the database, corresponding to 184 HJH-COPD-lung cancer targets intersection. The results of biological network analysis showed that naringenin, the active component in HJH, could mainly act on target proteins such as AKT1, EGFR. Then through positive regulation of vasoconstriction and other biological processes, naringenin could regulate estrogen signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer., Conclusion: Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer. And then, the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described. Furthermore, naringenin was proved to strongly bind with AKT1 and EGFR. It may provide the scientific basis for understanding the "Same treatment for different diseases" strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD, lung cancer and other malignant lung diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Objective: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen., Methods: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed., Results: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05)., Conclusion: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

Objective: To investigate the translocations of MYC, bcl-2 and bcl-6 genes, the Epstein-Barr virus (EBV) status and the clinicopathological features of primary cardiac large B cell lymphoma (LBCL). Methods: Seven cases of primary cardiac LBCL were collected at Beijing Friendship Hospital, Capital Medical University, China from February 2013 to May 2019. The clinical feature, pathological morphology and immunophenotype were analyzed. The detections of EBV and gene rearrangements of MYC, bcl-2 and bcl-6 were conducted. The 2017 WHO classification of tumors of haematopoietic and lymphoid tissues was used to classify the tumors. Results: Four patients with right atrial lesions showed diffuse infiltration of medium size lymphoid cells with small vascular hyperplasia, without evidence of EBV infection. Without detectable gene rearrangements of MYC and bcl-2, 2 of the patients showed bcl-6 gene break-apart. The diagnosis was revised from diffuse LBCL to high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS). There was a case of CD5 + diffuse LBCL involving the right atrium and ventricle and 2 cases of fibrin-associated diffuse LBCL located at left atrium without gene rearrangements of MYC, bcl-2 and bcl-6. However, EBER and EBNA2 were highly expressed in fibrin-associated diffuse LBCL. The patients were followed up for 10-71 months. Four cases of HGBL-NOS and a case of CD5 + diffuse LBCL received R-CHOP with/without autologous stem cell transplantation. All but two patients survived. Two cases of fibrin-associated diffuse LBCL were disease free without adjuvant chemotherapy and radiotherapy. Conclusions: Primary cardiac LBCL is heterogeneous, including at least HGBL-NOS. Primary cardiac HGBL-NOS most frequently occurs in the right atrium. Tumor cells of primary cardiac LBCL have the morphological characteristics similar to Burkitt lymphoma, lacking MYC and bcl-2 gene rearrangements, but usually show bcl-6 gene disruption. Fibrin-associated diffuse LBCL has a good prognosis and postoperative chemotherapy seems unnecessary.

The Faraday-effect based polarimeter and interferometer are developed for non-perturbation magnetic field and density measurements on the Keda Reconnection eXperiment (KRX) device. The magnetic reconnection is externally driven by a pair of parallel current plates. To design this instrument and provide an alternative way to facilitate theory-experiment comparisons via forward modeling of the diagnostics process with full plasma dynamics given by simulation, we develop a synthetic diagnostics based on 2D photonic integrated circuit simulation for magnetic reconnection on the KRX. The view-line geometry is optimized and wavelengths (1 mm) of the polarimeter and interferometer are selected to ensure the sensitivity of measurement on the KRX. We have simulated magnetic reconnection on the x-line (x-z plane) with horizontal viewing and vertical viewing for line of sight measurements. It is found that the current sheet width and indicator of magnetic reconnection can be inferred directly from the dynamics of Faraday rotation even with the line-integrated character of polarimeter-interferometer diagnostics.