Identification of a New B-Cell Epitope on the Capsid Protein of Avian Leukosis Virus and Its Application.

Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 106.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that 218IIKYVLDRQK227 was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup's specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV.

Effects of Ward Noise Reduction Administration on Mental Health and Lung Function of Patients with Lung Cancer.

OBJECTIVE: This study aimed to analyze the effects of ward noise reduction administration on the lung function and mental health of patients with lung cancer. METHODS: A total of 195 patients who underwent lung cancer surgery in PLA Northern Theater Command Air Force Hospital from November 2020 to November 2022 were selected to be divided into a control group (routine nursing) and an observation group (routine nursing and ward noise reduction administration) in accordance with the medical record system. The general demographic data, noise level, lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC)), and complications of patients in the two groups were collected. Propensity score matching (PSM) was used to balance the baseline data of the two groups, and t-test and chi-square test were used to analyze the data. RESULTS: After PSM was conducted, 50 patients were enrolled in each group. No statistical difference was found in the baseline data, preadministration noise levels, and FEV1, FVC, FEV1/FVC, state-anxiety inventory (S-AI), and trait anxiety inventory scale (T-AI) scores between the two groups (P > 0.05). After ward noise reduction was administered, the noise level in the observation group was lower than that in the control group (P < 0.05). The FEV1, FVC, and FEV1/FVC scores of the observation group were higher than those of the control group but were not statistically significant (P > 0.05). The S-AI and T-AI scores of the observation group were lower than those of the control group (P < 0.05). No differences were found in the complications between the two groups (P > 0.05). CONCLUSION: Administering ward noise reduction in patients with lung cancer can alleviate their negative emotions, thus worthy of clinical adoption.

Case report: Endoscopic full-thickness resection of gastric metastatic tumor from renal cell carcinoma.

Renal cell carcinoma (RCC) is a common malignant kidney tumor; however, gastric metastasis is rare. We report the case of an 82-year-old male patient who developed gastric metastasis 12 years after an initial diagnosis of RCC. The patient underwent endoscopic full-thickness resection (EFTR), and the gastric metastatic focus was successfully removed. Postoperative pathology and immunohistochemistry showed that the gastric metastasis originated from RCC. Although gastric metastasis of RCC is rare, it should be suspected in patients with a history of RCC or gastrointestinal symptoms. EFTR is associated with reduced trauma and greater retention of gastric tissue and function. It is a more appropriate choice than surgical resection; however, it requires more endoscopists.

Immunological alterations in the endothelial barrier: a new predictive and therapeutic paradigm for sepsis.

INTRODUCTION: Despite the fact incidence and mortality vary widely among regions, sepsis remains a major cause of morbidity and cost worldwide. The importance of the endothelial barrier in sepsis and infectious diseases is increasingly recognized; however, the underlying pathophysiology of the endothelial barrier in sepsis remains poorly understood. AREAS COVERED: Here we review the advances in basic and clinical research for relevant papers in PubMed database. We attempt to provide an updated overview of immunological alterations in endothelial dysfunction, discussing the central role of endothelial barrier involved in sepsis to provide new predictive and therapeutic paradigm for sepsis. EXPERT OPINION: Given its physiological and immunological functions in infectious diseases, the endothelial barrier has been dramatically altered in sepsis, suggesting that endothelial dysfunction may play a critical role in the pathogenesis of sepsis. Although many reliable biomarkers have been investigated to monitor endothelial activation and injury in an attempt to find diagnostic and therapeutic tools, there are no specific therapies to treat sepsis due to its complex pathophysiology. Since sepsis is initiated by both hyperinflammation and immunoparalysis occurring simultaneously, a 'one-treatment-fits-all' strategy for sepsis-induced immune injury and immunoparalysis is bound to fail, and an individualized 'precision medicine' approach is required.

Identification of potential immune-related mechanisms related to the development of multiple myeloma.

BACKGROUND: Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. METHODS: This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. RESULTS: A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG + Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages are enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don't eat me"-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, especially the migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. CONCLUSIONS: Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Molecular findings in patients for whole exome sequencing and mitochondrial genome assessment.

OBJECTIVE: Whole exome sequencing (WES) is becoming more widely used as a diagnostic tool in the field of medicine. In this article, we reported the diagnostic yield of WES and mitochondrial genome assessment in 2226 consecutive cases in a single clinical laboratory. MATERIALS AND METHODS: We retrospectively analyzed consecutive WES reports from 2226 patients with various genetic disorders. WES-process was focused exclusively on the probands and aimed at a higher diagnostic capacity. We determined the diagnostic rate of WES overall and by phenotypic category, mode of inheritance, mitochondrial genome variant, and copy number variants (CNVs). RESULTS: Among the 2226 patients who had diagnostic WES proband-only, the overall diagnostic yield of WES was 34.59% (770/2226). The highest diagnostic yield was observed in autosomal dominant disorders, at 45.58% (351/770), followed by autosomal recessive at 31.95%(246/770), X-linked disorder at 9.61%(74/770), and mitochondrial diseases at a notably lower 0.65%(5/770). The 12.21% (94/770) diagnoses were based on a total of 94 copy number variants reported from WES data. CNVs in children accounted for 67.02% of the total CNVs. While majority of the molecular diagnoses were related to nuclear genes, the inclusion of mitochondrial genome sequencing in the WES test contributed to five diagnoses. all mitochondrial diseases were identified in adults. CONCLUSIONS: The proband-only WES provided a definitive molecular diagnosis for 34.59% of a large cohort of patients while analysis of WES simultaneously analyzed the SNVs, exons, mitochondrial genome, and CNVs, thereby improving the diagnostic yield significantly compared to the single-detection WES method; and facilitating the identification of novel candidate genes.

Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China.

PURPOSE: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. METHODS: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. RESULTS: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. CONCLUSIONS: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.

[Expert consensus on the prenatal diagnosis and genetic counseling for uniparental disomy-related imprinting disorders].

Uniparental disomy (UPD)-related imprinting disorders are a group of congenital disorders which can lead to severe birth defects. Their molecular etiology is the occurrence of UPD in the genomic imprinting regions, which may cause disturbed expression of parent-of-origin imprinted genes. With the widespread applications of genetic testing techniques, the prenatal diagnosis of UPD-related imprinted diseases has gradually become clinical routines. However, due to the complicated pathogenesis of such disorders, currently there is still a lack of standards and norms for the understanding, diagnosis, management and genetic counseling. By referring to the relevant guidelines and consensus, the latest progress of research, and opinions from experts in the relevant fields, the writing group has formulated a consensus over the prenatal diagnosis and genetic counseling for UPD-related imprinting disorders, with an aim to provide a more accurate and rational evaluation in prenatal clinics.

UKLF/PCBP2 axis governs the colorectal cancer development by transcriptionally activating SLC39A4.

Colorectal cancer (CRC) is one of the most prevalent malignant tumors with limited treatment options. Therefore, there is an urgent need to investigate new therapeutic targets against CRC. Ubiquitous Kruppel-like factor (UKLF) is involved in various cancer processes, but its effect and detailed molecular mechanism in CRC are not yet fully understood. Here, this study aimed to investigate the function and mechanism of UKLF in the development of CRC. The results showed that UKLF was highly expressed in CRC tissues from clinical patients and its high expression was related to poor prognosis. UKLF promoted cell proliferation, migration and invasion, and inhibited cell apoptosis. The promotion effect of UKLF on tumor growth was further confirmed in vivo. As far as the mechanism was concerned, poly (C) binding protein 2 (PCBP2) was verified to bind to the 3'-UTR of UKLF mRNA and enhance its mRNA stability. Moreover, UKLF modulated the expression of solute carrier family 39 member 4 (SLC39A4) at the transcriptional level. Taken together, these findings elucidated the regulatory mechanism of UKLF and uncovered the importance of the PCBP2/UKLF/SLC39A4 pathway. The targeting of UKLF may be a novel direction for molecular-targeted CRC therapy.

Selective eradication of venetoclax-resistant monocytic acute myeloid leukemia with iron oxide nanozymes.

The clinical treatment of human acute myeloid leukemia (AML) is rapidly progressing from chemotherapy to targeted therapies led by the BCL-2 inhibitor venetoclax (VEN). Despite its unprecedented success, VEN still encounters clinical resistance. Thus, uncovering the biological vulnerability of VEN-resistant AML disease and identifying effective therapies to treat them are urgently needed. We have previously demonstrated that iron oxide nanozymes (IONE) are capable of overcoming chemoresistance in AML. The current study reports a new activity of IONE in overcoming VEN resistance. Specifically, we revealed an aberrant redox balance with excessive intracellular reactive oxygen species (ROS) in VEN-resistant monocytic AML. Treatment with IONE potently induced ROS-dependent cell death in monocytic AML in both cell lines and primary AML models. In primary AML with developmental heterogeneity containing primitive and monocytic subpopulations, IONE selectively eradicated the VEN-resistant ROS-high monocytic subpopulation, successfully resolving the challenge of developmental heterogeneity faced by VEN. Overall, our study revealed an aberrant redox balance as a therapeutic target for monocytic AML and identified a candidate IONE that could selectively and potently eradicate VEN-resistant monocytic disease.

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma.

INTRODUCTION: Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. AIM: We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. SUBJECTS AND METHODS: 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. RESULTS: The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P < 0.05). The CD4/CD8 ratio and proportion of monocyte-derived dendritic cells were also higher in the experimental group than in the control group, but the difference was not statistically significant (P ≥ 0.05). Comparisons of 3-year overall survival, local-regional recurrence-free survival, progression-free survival, and distant metastasis-free survival between the two groups showed percentages of 92.9% vs. 78.6%, 92.9% vs. 92.9%, 78.6% vs. 71.4%, and 85.7% vs. 0.78 0.6% respectively, but these differences were not significant (P > 0 0.05 ). CONCLUSION: Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. TRIAL REGISTRATION: NCT02958111, date of registration 04-11-2016.

Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

A Cerebellar Tumor-to-Tumor Metastasis in a Patient With Von Hippel-Lindau Disease.

Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.

Transition metals of Pt and Pd on the surface of topological insulator Bi2Se3.

Transition metal catalysts supported on topological insulators are predicted to show improved catalytic properties due to the presence of topological surface states, which may float up to the catalysts and provide robust electron transfer. However, experimental studies of surface structures and corresponding catalytic properties of transition metal/topological insulator heterostructures have not been demonstrated so far. Here, we report the structures, chemical states, and adsorption behaviors of two conventional transition metal catalysts, Pt and Pd, on the surface of Bi2Se3, a common topological insulator material. We reveal that Pt forms nanoparticles on the Bi2Se3 surface. Moreover, the interaction between Pt and surface Se is observed. Furthermore, thermal dosing of O2 onto the Pt/Bi2Se3 heterostructure leads to no oxygen adsorption. Detailed scanning tunneling microscopy study indicates that Pt transforms into PtSe2 after the thermal process, thus preventing O2 from adsorption. For another transition metal Pd, it exhibits approximate layer-island growth on Bi2Se3, and Pd-Se interaction is also observed. Our work provides significant insights into the behaviors of transition metals on top of a common topological insulator material and will assist in the future design of catalysts built with topological materials.

Assembly and comparative analysis of the complete multichromosomal mitochondrial genome of Cymbidium ensifolium, an orchid of high economic and ornamental value.

BACKGROUND: Orchidaceae is one of the largest groups of angiosperms, and most species have high economic value and scientific research value due to their ornamental and medicinal properties. In China, Chinese Cymbidium is a popular ornamental orchid with high economic value and a long history. However, to date, no detailed information on the mitochondrial genome of any species of Chinese Cymbidium has been published. RESULTS: Here, we present the complete assembly and annotation of the mitochondrial genome of Cymbidium ensifolium (L.) Sw. The mitogenome of C. ensifolium was 560,647 bp in length and consisted of 19 circular subgenomes ranging in size from 21,995 bp to 48,212 bp. The genome encoded 35 protein-coding genes, 36 tRNAs, 3 rRNAs, and 3405 ORFs. Repeat sequence analysis and prediction of RNA editing sites revealed a total of 915 dispersed repeats, 162 simple repeats, 45 tandem repeats, and 530 RNA editing sites. Analysis of codon usage showed a preference for codons ending in A/T. Interorganellar DNA transfer was identified in 13 of the 19 chromosomes, with plastid-derived DNA fragments representing 6.81% of the C. ensifolium mitochondrial genome. The homologous fragments of the mitochondrial genome and nuclear genome were also analysed. Comparative analysis showed that the GC content was conserved, but the size, structure, and gene content of the mitogenomes varied greatly among plants with multichromosomal mitogenome structure. Phylogenetic analysis based on the mitogenomes reflected the evolutionary and taxonomic statuses of C. ensifolium. Interestingly, compared with the mitogenomes of Cymbidium lancifolium Hook. and Cymbidium macrorhizon Lindl., the mitogenome of C. ensifolium lost 8 ribosomal protein-coding genes. CONCLUSION: In this study, we assembled and annotated the mitogenome of C. ensifolium and compared it with the mitogenomes of other Liliidae and plants with multichromosomal mitogenome structures. Our findings enrich the mitochondrial genome database of orchid plants and reveal the rapid structural evolution of Cymbidium mitochondrial genomes, highlighting the potential for mitochondrial genes to help decipher plant evolutionary history.

Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients.

BACKGROUND: Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population. RESULTS: We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants. CONCLUSIONS: Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.

The circadian clock gene, BMAL1, promotes radiosensitization in nasopharyngeal carcinoma by inhibiting the epithelial-to-mesenchymal transition via the TGF-ß1/Smads/Snail1 axis.

Acquired radio-resistance is thought to be one of the main causes of recurrent metastasis after failure of nasopharyngeal carcinoma (NPC) radiotherapy, which may be related to X-ray-induced epithelial-mesenchymal transition (EMT) activation. The circadian clock gene, BMAL1, has been shown to correlate with the sensitivity of NPCs to radiotherapy, but the specific mechanism has not been reported. NPC cells were irradiated by conventional fractionation to generate radiotherapy-resistant cells. NPC cells with BMAL1 gene stabilization/overexpression and interference were obtained by lentiviral transfection. Western blotting, colony formation analysis, cell counting kit-8 assays, wound-healing tests, Transwell assays, flow cytometry, the EDU method, nuclear plasma separation experiments, HE staining, immunohistochemical staining and TUNEL staining were performed to explore the influence and molecular mechanism of the circadian clock gene, BMAL1, on NPC-acquired radio-resistance and EMT through in vitro and in vivo experiments. The results indicated that there was a gradual downregulation of BMAL1 gene protein expression during the routine dose induction of radio-resistance in NPC cells. EMT activation was present in the radiation-resistant cell line 5-8FR, and was accompanied by the significant enhancement of proliferation, migration and invasion. The BMAL1 gene significantly increased the radiosensitivity of the radiation-resistant cell line 5-8FR and reversed the acquired radio-resistance of NPCs, which was accomplished by inhibiting the TGF-ß1/Smads/Snail1 axis-mediated EMT.

A Bacterium-like Particle Vaccine Displaying Envelope Proteins of Canine Distemper Virus Can Induce Immune Responses in Mice and Dogs.

Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies' response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.

Analysis of atypical glandular cells in ThinPrep Pap smear and follow-up histopathology.

Background: Diagnosing atypical glandular cells (AGC) is a significant challenge in cytomorphology. Methods: A retrospective study was undertaken to assess the prevalence of AGC and the subsequent histological outcomes over 5 years at a single institution. Results: A total of 159,649 ThinPrep Pap tests, including 395 cases of AGC, were retrieved, of which 330 AGC cases had follow-up histopathology. Among these 330 cases, 43.9% were classified as AGC not otherwise specified, followed by AGC-endocervical cells at 33.3%. The most frequently observed histological findings at follow-up included CIN1 and benign mucosa with reactive changes, followed by high-grade squamous intraepithelial lesion and cervical squamous cell carcinoma. The overall 5-year insignificant AGC rate was 0.12%, and the overall 5-year significant AGC rate was 0.08%. Notably, 36.7% of AGC cases tested positive for high-risk human papillomavirus. Interestingly, the level of experience did not significantly impact the rates for significant or insignificant AGC diagnosis. However, senior cytopathologists had a higher AGC report rate compared to their junior peers. Conclusion: The AGC diagnostic rate at our institution falls within the range given by the College of American Pathologists. A significant number of cases had follow-up histologic results available, and the overall 5-year insignificant AGC rate was 0.12%.

Long-term survival, toxicities, and the role of chrono-chemotherapy with different infusion rates in locally advanced nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy: a retrospective study with a 5-year follow-up.

Purpose: This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. Results: After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Conclusion: Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.