Chemoradiotherapy combined with immunotherapy in stage III non-small cell lung cancer: a systematic review and meta-analysis of efficacy and safety outcomes.

Background Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods We searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results Chemoradiotherapy combined with immunotherapy can improve PFS (HR: 0.60, 95%CI :0.55-0.60) and OS (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%). Conclusions Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Retracted: Inhibition of Proliferation of SGC7901 and BGC823 Human Gastric Cancer Cells by Ursolic Acid Occurs Through a Caspase-Dependent Apoptotic Pathway.

This publication has been retracted by the Editor due to concerns regarding the originality of the figure images. Reference: Jing Zhang, Fengjun Liu, Xin Zhang. Inhibition of Proliferation of SGC7901 and BGC823 Human Gastric Cancer Cells by Ursolic Acid Occurs Through a Caspase-Dependent Apoptotic Pathway. Med Sci Monit, 2019; 25: 6846-6854. DOI: 10.12659/MSM.916740.

Mitochondrial small heat shock protein mediates seed germination via thermal sensing.

Seed germination is an energy demanding process that requires functional mitochondria upon imbibition. However, how mitochondria fine tune seed germination, especially in response to the dynamics of environmental temperature, remains largely unknown at the molecular level. Here, we report a mitochondrial matrix-localized heat shock protein GhHSP24.7, that regulates seed germination in a temperature-dependent manner. Suppression of GhHSP24.7 renders the seed insensitive to temperature changes and delays germination. We show that GhHSP24.7 competes with GhCCMH to bind to the maturation subunit protein GhCcmFc to form cytochrome C/C1 (CytC/C1) in the mitochondrial electron transport chain. GhHSP24.7 modulates CytC/C1 production to induce reactive oxygen species (ROS) generation, which consequently accelerates endosperm rupture and promotes seed germination. Overexpression of GhHSP24.7's homologous genes can accelerate seed germination in Arabidopsis and tomato, indicating its conserved function across plant species. Therefore, HSP24.7 is a critical factor that positively controls seed germination via temperature-dependent ROS generation.

Longitudinal trajectories of pneumonia lesions and lymphocyte counts associated with disease severity among convalescent COVID-19 patients: a group-based multi-trajectory analysis.

BACKGROUND: To explore the long-term trajectories considering pneumonia volumes and lymphocyte counts with individual data in COVID-19. METHODS: A cohort of 257 convalescent COVID-19 patients (131 male and 126 females) were included. Group-based multi-trajectory modelling was applied to identify different trajectories in terms of pneumonia lesion percentage and lymphocyte counts covering the time from onset to post-discharge follow-ups. We studied the basic characteristics and disease severity associated with the trajectories. RESULTS: We characterised four distinct trajectory subgroups. (1) Group 1 (13.9%), pneumonia increased until a peak lesion percentage of 1.9% (IQR 0.7-4.4) before absorption. The slightly decreased lymphocyte rapidly recovered to the top half of the normal range. (2) Group 2 (44.7%), the peak lesion percentage was 7.2% (IQR 3.2-12.7). The abnormal lymphocyte count restored to normal soon. (3) Group 3 (26.0%), the peak lesion percentage reached 14.2% (IQR 8.5-19.8). The lymphocytes continuously dropped to 0.75 × 109/L after one day post-onset before slowly recovering. (4) Group 4 (15.4%), the peak lesion percentage reached 41.4% (IQR 34.8-47.9), much higher than other groups. Lymphopenia was aggravated until the lymphocytes declined to 0.80 × 109/L on the fourth day and slowly recovered later. Patients in the higher order groups were older and more likely to have hypertension and diabetes (all P values < 0.05), and have more severe disease. CONCLUSIONS: Our findings provide new insights to understand the heterogeneous natural courses of COVID-19 patients and the associations of distinct trajectories with disease severity, which is essential to improve the early risk assessment, patient monitoring, and follow-up schedule.

Ultrasonic liver steatosis quantification by a learning-based acoustic model from a novel shear wave sequence.

BACKGROUND: An efficient and accurate approach to quantify the steatosis extent of liver is important for clinical practice. For the purpose, we propose a specific designed ultrasound shear wave sequence to estimate ultrasonic and shear wave physical parameters. The utilization of the estimated quantitative parameters is then studied. RESULTS: Shear wave attenuation, shear wave absorption, elasticity, dispersion slope and echo attenuation were simultaneously estimated and quantified from the proposed novel shear wave sequence. Then, a regression tree model was utilized to learn the connection between the space represented by all the physical parameters and the liver fat proportion. MR mDIXON quantification was used as the ground truth for liver fat quantification. Our study included a total of 60 patients. Correlation coefficient (CC) with the ground truth were applied to mainly evaluate different methods for which the corresponding values were - 0.25, - 0.26, 0.028, 0.045, 0.46 and 0.83 for shear wave attenuation, shear wave absorption, elasticity, dispersion slope, echo attenuation and the learning-based model, respectively. The original parameters were extremely outperformed by the learning-based model for which the root mean square error for liver steatosis quantification is only 4.5% that is also state-of-the-art for ultrasound application in the related field. CONCLUSIONS: Although individual ultrasonic and shear wave parameters were not perfectly adequate for liver steatosis quantification, a promising result can be achieved by the proposed learning-based acoustic model based on them.

Inhibition of Proliferation of SGC7901 and BGC823 Human Gastric Cancer Cells by Ursolic Acid Occurs Through a Caspase-Dependent Apoptotic Pathway.

BACKGROUND Worldwide, gastric cancer is one of the most common malignant tumors. Ursolic acid is a plant metabolite and pentacyclic triterpenoid used in traditional Chinese medicine. This study aimed to investigate the effects of ursolic acid the growth and apoptosis of SGC7901 and BGC823 human gastric cancer cells in vitro. MATERIAL AND METHODS SGC7901 and BGC823 human gastric cancer cells and normal GES-1 gastric epithelial cells were cultured with increasing doses of ursolic acid at 50, 60, and 100 µM. Cell viability and proliferation were assessed using an MTT assay. Flow cytometry was used to assess cell apoptosis. Western blot was used to measure procaspase-8, procaspase-9, procaspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) expression. The expression of receptor interaction protein 3 (RIP3) was examined by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Morphological changes in the gastric cancer cells were determined using Hoechst 33342 staining following ursolic acid treatment. RESULTS Ursolic acid inhibited the viability of SGC7901 and BGC823 cells but not GES-1 cells. Ursolic acid treatment significantly induced apoptosis in SGC7901 and BGC823 cells when compared with GES-1 cells (P<0.05), and significantly increased the activation of caspase-3, caspase-8, caspase-9, poly ADPribose polymerase (PARP), and the production of reactive oxygen species (ROS). Treatment of SGC7901 and BGC823 cells with ursolic acid for 72 h did not induce necroptosis. CONCLUSIONS Ursolic acid inhibited the proliferation of SGC7901 and BGC823 human gastric cancer cells in vitro through a caspase-dependent apoptotic pathway.

MiR-411 suppressed vein wall fibrosis by downregulating MMP-2 via targeting HIF-1α.

This study was aim to investigate the specific mechanisms of miR-411 in vein wall fibrosis remodeling. Vein wall fibrosis injury-induced deep venous thrombosis (DVT) rat model was well established. The expression of miR-411 at mRNA levels and Collagen I, hypoxia-inducible factor (HIF)-1α together with matrix metalloproteinase (MMP)-2 at protein levels in vein wall tissues and vascular smooth muscle cells (VSMCs) following transfection were determined using quantitative real-time PCR (qRT-PCR) and western blotting, respectively. Luciferase reporter assay was used to confirm the potential target of miR-411. MiR-411 mimic injected into rat model of DVT was to verify the role of miR-411 in vein wall fibrosis in vivo. MiR-411 was downregulated while Collagen I, HIF-1α and MMP-2 was upregulated in vein wall tissues and VSMCs obtained from rat model of DVT. MiR-411 overexpression in VSMCs separated from rats of vascular remodeling group (VR-VSMCs) upregulated miR-411, HIF-1α and inhibited cell proliferation and Collagen I expression, while miR-411 knockdown in VSMCs isolated from healthy rats (Control-VSMCs) reversed the effects. Furthermore, luciferase reporter assay demonstrated that HIF-1α was a target of miR-411. In addition, overexpression of miR-411 and HIF-1α in VR-VSMCs promoted HIF-1α, Collagen I expression and cell proliferation, however, tissue inhibitor of metalloproteinase (TIMP)-2 treatment led to adverse trends. MiR-411 mimic injected into rat model of DVT could suppress vein wall fibrosis in vivo. MiR-411 inhibited vein wall fibrosis by downregulating MMP-2 mediated by HIF-1α.

TUSC3: a novel tumour suppressor gene and its functional implications.

The tumour suppressor candidate 3 (TUSC3) gene is located on chromosome region 8p22 and encodes the 34 kD TUSC3 protein, which is a subunit of the oligosaccharyl transferase responsible for the N-glycosylation of nascent proteins. Known to be related to autosomal recessive mental retardation for several years, TUSC3 has only recently been identified as a potential tumour suppressor gene. Based on the structure and function of TUSC3, specific mechanisms in various diseases have been investigated. Several studies have demonstrated that TUSC3 is an Mg2+ -transporter involved in magnesium transport and homeostasis, which is important for learning and memory, embryonic development and testis maturation. Moreover, dysfunction or deletion of TUSC3 exerts its oncological effects as a modulator by inhibiting glycosylation efficiency and consequently inducing endoplasmic reticulum stress and malignant cell transformation. In this study, we summarize the advances in the studies of TUSC3 and comment on the potential roles of TUSC3 in diagnosis and treatment of TUSC3-related diseases, especially cancer.

microRNA-335 inhibits colorectal cancer HCT116 cells growth and epithelial-mesenchymal transition (EMT) process by targeting Twist1.

Colorectal cancer is one of the most commonly diagnosed cancers. Recently, several microRNAs (miRNAs) have been characterized as oncogenes or tumor suppressors in colorectal cancer. This study was aimed to explore the tumor suppressive effects and its underling mechanism of miR-335 on colorectal cancer cells. Human colorectal cancer HCT116 cells were employed and the expression of miR-335 in cells was altered by transfection with miR-335 mimic and miR-335 inhibitor. Thereafter, CCK-8 assay, flow cytometry, Transwell assay and Western blotting were used to detect cell viability, apoptosis, migration, invasion, and the expression of epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase activity assay was performed to test whether Twist1 was a direct target of miR-335. Moreover, cells were co-transfected with miR-335 inhibitor and Twist1 siRNA, and then cell growth and metastasis were re-evaluated. miR-335 overexpression inhibited cell viability, migration and invasion, and promoted apoptotic cells rate. miR-335 overexpression up-regulated E-Cadherin, while down-regulated N-Cadherin, Vimentin and Snail. Twist1 was a direct target of miR-335, and Twist1 silence promoted apoptosis, and abolished miR-335 suppression induced increases in cell viability, migration, invasion, and abnormal expressions of EMT-related proteins. Besides, Twist1 silence abolished miR-335 suppression induced activations of p65 and IκBα, and miR-335 suppression induced up-regulations of Wnt3a, Wnt5a and ß-Catenin. miR-335 inhibited HCT116 cells growth, migration, invasion, and ETM process. miR-335 exhibited tumor suppressive effects possibly by inhibition of Twsit1 and thus inactivating NF-κB and Wnt/ß-catenin pathways.

NTRK2 is an oncogene and associated with microRNA-22 regulation in human gastric cancer cell lines.

In this study, we examined the roles of neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene in regulating in vitro proliferation and invasion in human gastric cancer. Gene expression of NTRK2 was compared between non-carcinoma gastric epithelial cells and gastric cancer (GC) cells by quantitative RT-PCR (qRT-PCR). NTRK2 was either downregulated or upregulated in MKN-28 and SNU-719 cells. The effect of NTRK2 downregulation or upregulation on GC in vitro development was analyzed by qRT-PCR, western blot, proliferation assay, and invasion assay, respectively. The upstream regulator of NTRK2, microRNA-22 (miR-22), was evaluated by dual-luciferase assay. MiR-22 was then upregulated in MKN-28 and SNU-719 cells to examine its regulation on NTRK2 and its encoded protein, tyrosine kinase receptor B (TrkB). In miR-22-upregulated MKN-28 and SNU-719 cells, NTRK2 was further overexpressed to evaluate functional interaction between miR-22 and NTRK2 in GC. NTRK2 was aberrantly upregulated in GC cell lines than in normal gastric cells. In MKN-28 and SNU-719 cells, NTRK2 downregulation inhibited whereas NTRK2 upregulation promoted GC proliferation and invasion in vitro. MiR-22 was verified to be an inverse upstream regulator of NTRK2. In miR-22-upregulated MKN-28 and SNU-719 cells, NTRK2 overexpression partially reversed the miR-22-induced inhibition on cancer proliferation and invasion. NTRK2 is an oncogene and reversely associated with miR-22 in regulating in vitro cancer development in GC.

Decreased Tumor Suppressor Candidate 3 Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma.

TUSC3 was recently identified as a potential tumor suppressor gene in a variety of human malignancies. However, no data are currently available regarding the expressions of TUSC3 in esophageal cancer (ESCC).The purposes of this study was to investigated the expressions of TUSC3 in ESCC tissues and assess the relationship between TUSC3 levels and clinico-pathological characteristics of ESCC patients. TUSC3 protein expressions were evaluated by immunohistochemistry (IHC) on tissue microarray slides in esophageal cancer, which included 95 esophageal squamous carcinoma specimens (ESCC), and 75 normal esophageal mucosa (NEM). We found that TUSC3 in ESCC was significant lower than that in NEM (P=0.000). According to multi-clinical classifications, TUSC3 level varied significantly with TNM stage, T stage, and N stage (p<0.001, p=0.0368, p<0.0001, respectively). Univariate analysis showed that gender, TNM stage, T stage, N stage, TUSC3 expression were prognostic factors for survival. Multivariate analysis showed that in our study, only TUSC3 expression was independent prognostic factors for ESCC. Our results indicated for the first time, a combined analysis of TUSC3 expressions as well as the clinical variables will help predict the prognosis of ESCC patients. Further large-sample validation and functional analysis should be performed to evaluate its potential prognostic and therapeutic values for ESCC patients.

Evaluation of Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Primary Craniopharyngioma by Fourier-Domain Optical Coherence Tomography.

BACKGROUND The aim of this study was to compare the differences in macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) in child and adult patients with primary craniopharyngioma by Fourier-domain optical coherence tomography (FD-OCT) and to evaluate their significance in the diagnosis of primary craniopharyngioma. MATERIAL AND METHODS Ninety-six participants were divided into 3 groups: 32 in the child craniopharyngioma group (CCG) and 32 in the adult craniopharyngioma group (ACG) who were treated in Beijing Tiantan Hospital between November 2013 and October 2014, and 32 in the normal group (NG). All subjects were scanned by FD-OCT to map GCC and pRNFL thicknesses. Spearman correlation coefficient was used to assess the correlation between GCC and pRNFL thickness, and pRNFL thickness and optic nerve head (ONH) parameters, including horizontal cup-disc ratio (HCDR), vertical cup-disc ratio (VCDR), optic disc area (ODA), and cup area (CA), respectively. RESULTS The correlation between GCC and pRNFL thickness in the CCG was slightly stronger compared with the ACG. A significant difference in GCC thickness was observed among the CCG, ACG, and NG. Although the pRNFL thickness in both the CCG and ACG was significantly higher than that in NG, no significant difference in pRNFL thickness was detected between the 2 craniopharyngioma groups. The average, superior, and inferior pRNFL thicknesses were negatively correlated with VCDR in the CCG (in double eyes) and ACG (only in left eyes). CONCLUSIONS GCC was more sensitive than pRNFL in detecting optic nerve damage in the eyes of craniopharyngioma patients. A thinner pRNFL was especially correlated with VCDR in child craniopharyngioma patients.

The management of patients with esophageal cancer and coronary artery stenosis undergoing radiotherapy or concurrent chemoradiotherapy: a single-center experience.

PURPOSE: The incidence of esophageal cancer (EC) patients with coronary artery stenosis presents particular challenges. The aim of this retrospective study was to evaluate the efficiency of management on patients with both diseases treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: Fifty-three patients with both EC and coronary artery stenosis from June 2009 to August 2012 were retrospectively analyzed. The patients received RT or CCRT with coronary artery stenosis management. Cardiac treatments often prescribed included aspirin, ß-blockers, statins etc. The adverse effects, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Most of the patients were 40-70 years old. There were 25 patients in the CCRT group and 28 patients in the RT group. The complete response (CR) rate was higher in the patients in the CCRT group than in those in the RT group (48.0 vs 21.4%; p=0.041). The median PFS was 15.9 months in the CCRT group and 11.6 months in the RT group (p=0.025). OS was 22.4 months in the CCRT group and 15.8 months in the RT group (p=0.013). Though adverse effects were less in the RT group, no significance differences in grade 3-4 toxicity were observed. CONCLUSION: With the appropriate of coronary artery stenosis management, RT and CCRT were both tolerable and effective in EC patients with coronary artery stenosis.

Advanced research on vasculogenic mimicry in cancer.

Vasculogenic mimicry (VM) is a brand-new tumour vascular paradigm independent of angiogenesis that describes the specific capacity of aggressive cancer cells to form vessel-like networks that provide adequate blood supply for tumour growth. A variety of molecule mechanisms and signal pathways participate in VM induction. Additionally, cancer stem cell and epithelial-mesenchymal transitions are also shown to be implicated in VM formation. As a unique perfusion way, VM is associated with tumour invasion, metastasis and poor cancer patient prognosis. Due to VM's important effects on tumour progression, more VM-related strategies are being utilized for anticancer treatment. Here, with regard to the above aspects, we make a review of advanced research on VM in cancer.

Long non-coding RNA HOTAIR promotes HLA-G expression via inhibiting miR-152 in gastric cancer cells.

Recent studies have shown that the long non-coding RNA HOTAIR plays critical roles in tumor biology, including cancer progression and metastasis. However, the potential biological role HOTAIR in tumor escape remains undefined. Here, HOTAIR expression was measured in sixty paired gastric cancer (GC) tissue samples by real-time PCR, and then subjected to correlation analysis with human leukocyte antigen (HLA)-G levels which show close links with tumor escape mechanisms. Significant HOTAIR overexpression was observed in GC tissues, as well as strong positive correlations with HLA-G levels in both tissue and peripheral blood samples, detected by real-time PCR and ELISA assays respectively. Further gain- and loss-of-function studies indicated that HLA-G could be upregulated HOTAIR at both mRNA and secretion levels in vitro. On the other hand, bioinformatics analysis indicated the interaction between HOTAIR and miR-152, which shows potential regulation on HLA-G. And, altered miR-152 expression in GC tissues was also identified, and showed negative correlation with HOTAIR expression. Moreover, the negative regulation of miR-152 on HLA-G was verified in GC cells, while miR-152 induced decrease of HLA-G 3'UTR activity could be attenuated by HOTAIR co-overexpression with the assistant of mutation studies. Therefore, it was concluded that HOTAIR overexpression might also get involved in tumor escape mechanisms, involving HLA-G upregulation via inhibiting miR-152. Furthermore, this study recommended the potential application of HOTAIR in GC immunotherapy for better prognosis and improved survival.

TGF-ß induces HLA-G expression through inhibiting miR-152 in gastric cancer cells.

BACKGROUND: Mounting evidences have showed the important role of transforming growth factor-ß (TGF-ß) in immunological surveillance of tumors. Some studies have also indicated human leukocyte antigen (HLA)-G-associated immune escape involving TGF-ß management in gastric cancer (GC). However, the mechanism underlying it is unclear. This study aims to verify the correlations between HLA-G and TGF-ß, involving the potential targeting of miR-152 on HLA-G. RESULTS: TGF-ß and HLA-G levels were analyzed in blood samples from twenty GC patients with ELISA assays, while TGF-ß showed directly proportional to HLA-G levels in GC patients, and TGF-ß induced HLA-G up-regulation was also confirmed in GC cell lines. Furthermore, miR-152 expression could be inhibited by TGF-ß, and the negative post-transcriptionally regulation of miR-152 on HLA-G was also demonstrated through gain- and loss-of-function studies. Besides, miR-152 overexpression repressed HLA-G up-regulation induced by TGF-ß. And, miR-152 expression levels showed inversely proportional to both HLA-G and also TGF-ß levels in GC patients. CONCLUSION: TGF-ß could induce HLA-G expression in GC by inhibiting miR-152, involving its negative regulation on HLA-G. Since TGF-ß induced HLA-G up-regulation plays important role in immune escape, a potential application of miR-152 was suggested in GC treatment, or miR-152 might be one potential biomarker for GC.

[Analysis of ocular changes in children craniopharyngioma].

OBJECTIVE: To analyze the characteristics of ocular changes in children craniopharyngioma. METHODS: Retrospective case series study. The clinical data of 34 eyes from 17 patients with children craniopharyngioma treated at the affiliated Beijing Tiantan Hospital, Capital Medical University from September 2011 to May 2012 were collected. Records of preoperative clinical examinations including best corrected visual acuity (BCVA), visual field test, optic disc findings, size and location of the tumor were analyzed. RESULTS: The age of the patients was from 5 to 14 years old [mean (10.29 ± 3.22) years] with the male/female ratio of 1.83: 1. The most affected age group was 8 to 12 years old. Deficits in BCVA occurred in 79.41% (27/34). Abnormal optic disc findings occurred in 44.12% which included optic disk edema 5.9% (2/34), atrophic changes of the optic nerve 32.35% (11/34) and pale optic disc 5.9% (2/34). Various visual field defects were 76.47% (26/34). CONCLUSION: Declines of visual acuities and defects of visual fields were more severe than optic disc damages in children patients with craniopharyngioma.

[Effects of amantadine and biphenyl dimethyl dicarboxylate on hepatitis B virus in hepatitis B virus replication mice].

This study sought to investigate the in vivo antiviral effect of amantadine (AM) and biphenyl dimethyl dicarboxylate (DDB) on hepatitis B virus (HBV) in HBV replication mice. HBV replication-competent plasmid was transferred into male BALB/c mice by using hydrodynamics-based in vivo transfection procedure to develop HBV replication mouse model. The model mice were matched by body weigh, age and serum levels of hepatitis B e antigen (HBeAg) and were divided into four groups: AM group, DDB group, AM+DDB group and NS group, with the last one as control, and the mice of each group were administered corresponding agent orally twice a day, in a medication course lasting 3 d. On the third day, the mice were sacrificed 4-6 h after the last oral intake. HBV DNA replication intermediates in liver were analyzed by Southern blot hybridization. The serum hepatitis B surface antigen (HBsAg) and HBeAg were detected by enzyme linked immunosorbent assay (ELISA). Compared to the animals in the control group, HBV DNA replication intermediates in liver and HBsAg and HBeAg in serum from the AM and AM plus DDB group of mice decreased, and there was no difference between these two groups of mice. The levels of HBV DNA intermediate from liver and the serum HBsAg and HBeAg between the control and DDB group, however, were not obviously different. In conclusion, the inhibition effect of AM on HBV was detected, but treatment with DDB for 3 days did not influence the viral replication and expression of HBV in the HBV replication mice.

Diagnostic value of tuberculosis-specific antigens ESAT-6 and CFP10 in lymph node tuberculosis.

Objective: To assess the diagnostic value of immunohistochemical (IHC) staining for detecting the tuberculosis-secreted antigens ESAT-6 and CFP10 in lymph node tuberculosis. Methods: Archived, paraffin-embedded lymph node specimens from 72 patients diagnosed with lymph node tuberculosis and 68 patients with lymphoma were retrospectively collected from the Department of Pathology at the Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China between January 2016 and March 2023. These specimens were subjected to acid-fast and immunohistochemical staining to compare the effectiveness of these methods, with their sensitivity and specificity evaluated against a comprehensive reference standard. Results: Acid-fast staining demonstrated a sensitivity of 12.3% and a specificity of 100%. IHC staining for ESAT-6 showed a sensitivity of 87.5% and a specificity of 85.3%, whereas IHC staining for CFP10 exhibited a sensitivity of 75.0% and a specificity of 89.7%. Conclusion: The study indicates that IHC detection of ESAT-6 and CFP10 in paraffin-embedded lymph node tuberculosis tissues has a markedly higher sensitivity compared to acid-fast staining. Thus, IHC staining may serve as a supplementary diagnostic tool for the pathological evaluation of lymph node tuberculosis.

HCMV IE1/IE1mut Therapeutic Vaccine Induces Tumor Regression via Intratumoral Tertiary Lymphoid Structure Formation and Peripheral Immunity Activation in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM.