Age-dependent decrease of circulating T follicular helper cells correlates with disease severity in elderly patients with COVID-19.

Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4+ T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.

Penehyclidine hydrochloride improves cognitive function of rats with brain injury via CAMP/CREB signaling pathway.

This study explored the impact of penehyclidine hydrochloride on cognitive function in rats with brain injury. Sprague-Dawley rats (n=36) were randomly assigned to sham-operation, model, and penehyclidine hydrochloride groups. Rats in the sham-operation group underwent craniotomy, while the model and penehyclidine hydrochloride groups received brain injury models and interventions with normal saline and penehyclidine hydrochloride, respectively. Specimens were obtained two weeks post-intervention. Neurological deficits were evaluated using Zea-Longa scores, and memory was assessed with the Morris water maze test. ELISA determined brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) content. mRNA expressions of BDNF and NGF were assessed via qPCR, and phosphorylated CREB (p-CREB) protein expression was measured by Western blotting. Compared to the sham-operation group, both model and penehyclidine hydrochloride groups showed increased Zea-Longa scores. Escape latencies were longer and platform crossings were fewer in model and penehyclidine hydrochloride groups compared to the sham-operation group, but penehyclidine hydrochloride demonstrated a shorter latency and more platform crossings than the model group. BDNF and NGF content decreased in model and penehyclidine hydrochloride groups compared to the sham-operation group, with an increase in the penehyclidine hydrochloride group compared to the model group. mRNA expression levels declined in model and penehyclidine hydrochloride groups but were higher in the latter. p-CREB protein expression was lower in model and penehyclidine hydrochloride groups compared to the sham-operation group but higher in the penehyclidine hydrochloride group than the model group. Penehyclidine hydrochloride exhibited neuroprotective effects by upregulating the cAMP/CREB signaling pathway, improving cognitive function in rats with brain injury.

Incidences of aortic and mitral valve strands in patients with migraine with aura.

OBJECTIVE: To analyze the potential association between valvular strands and migraine with aura. METHODS: During a 1-year period,transesophageal echocardiography was performed in 51 consecutive patients with migraine with aura and 75 control subjects who underwent transesophageal echocardiography for other purposes and had no history of migraine. The presence of aortic and mitral valve strands was evaluated. RESULTS: The incidence of valvular strands was 21.5% (11/51) in migraine patients and 28.0% (21/75) in control subjects (Χ²=0.663, P=0.416). The incidence of patent foramen ovale was significantly higher in patients with migraine with aura than in control subjects (50.9% vs.29.3%) (Χ²=6.302, P=0.012). The incidence of aortic valve strands was significantly higher than that of mitral valve strands in migraine patients (Χ²=4.320,P=0.038). CONCLUSION: Valvular strands are not associated with migraine with aura and show little clinical significance.

Varying correlation between 18F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI in carotid atherosclerosis: implications for plaque inflammation.

BACKGROUND AND PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI have been proposed to quantitatively assess plaque inflammation by probing macrophages and neovessels, respectively. We examined their correlation to study the in vivo relationship between macrophage and neovessel activities in atherogenesis. METHODS: Forty-one patients (34 men; aged 65±12 years) with a total of 68 carotid plaques (thickness ≥2 mm on ultrasound; 20 symptomatic) were assessed by both (18)F-fluorodeoxyglucose positron emission tomography/computed tomography and dynamic contrast-enhanced MRI within 2 weeks, measured as target-to-background ratio and transfer constant (K(trans)), respectively. RESULTS: Overall, the correlation between target-to-background ratio and K(trans) was weak and marginal (r=0.22; P=0.068). They were correlated in the symptomatic plaques (r=0.59; P=0.006) but not in the asymptomatic plaques (r=0.07; P=0.625; P=0.033 for difference in r). Neither target-to-background ratio nor K(trans) was significantly higher in the symptomatic plaques, but both showed an inverse relationship with time since last neurological event (r=-0.94 and -0.69 for target-to-background ratio and K(trans), respectively). CONCLUSIONS: The correlation between (18)F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI measurements varied with clinical conditions, pointing to a complex interplay between macrophages and neovessels under different pathophysiological conditions. The moderate correlation shown only in symptomatic plaques indicates the presence of acute plaque inflammation with increased metabolic activity and cytokine production by inflammatory cells.

Which technique is better for detection of right-to-left shunt in patients with patent foramen ovale: comparing contrast transthoracic echocardiography with contrast transesophageal echocardiography.

BACKGROUND: At present there is no consensus on which technique is more suitable for the detection of right-to-left shunt (RLS) in patients with patent foramen ovale (PFO). The aim of study was to compare the efficacy of contrast transthoracic echocardiography (cTTE) and contrast transesophageal echocardiography (cTEE) in the detection of RLS. METHODS: A prospective study was undertaken in 29 patients with PFO. Both cTTE with harmonic imaging modality and cTEE with fundamental imaging modality were performed for all the patients. The severity of RLS were semiquantitatively assessed with a four-level grade system by scaling the numbers of microbubbles (MBs) in the left atrium after complete opacification of the right atrium within the first 3 cardiac cycles. Level 1 represents no MBs, indicating no RLS. Level 2, ≤10 MBs, indicating mild RLS. Level 3, 11-30 MBs, indicating moderate RLS and Level 4, >30 MBs, indicating severe RLS. RESULTS: Contrast TTE demonstrated significantly higher sensitivity for detection of RLS than cTEE (86% vs. 56%, P < 0.05). For cTTE, there were 4, 1, 5, and 19 cases determined at levels 1, 2, 3, and 4, respectively, whereas for the same group of patients 13, 2, 6, and 7 cases were identified by cTEE at levels 1, 2, 3, and 4, respectively. The severity of RLS detected by cTTE was significantly greater than that by cTEE (P < 0.01). CONCLUSIONS: Contrast TTE is more efficacious in the detection of RLS than cTEE. The former can be used as an alternative to the latter in clinical practice.

Prognostic analysis of stage IIIC1p cervical cancer patients.

Background: Stage IIIC1p cervical cancer is characterized by marked heterogeneity and considerable variability in the postoperative prognosis. This study aimed to identify the clinical and pathological characteristics affecting the survival of patients diagnosed with stage IIIC1p cervical cancer. Methods: We retrospectively analyzed patients diagnosed with stage IIIC1p cervical cancer who underwent radical hysterectomy and lymph node dissection between March 2012 and March 2022. Overall survival (OS) was estimated using Kaplan-Meier survival curves. Univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors for OS and forest plots were used to visualize these findings. Nomogram charts were created to forecast survival rates at 3 and 5 years, and the accuracy of predictions was evaluated using Harrell's concordance index (C-index) and calibration curves. Results: The study cohort comprised 186 women diagnosed with stage IIIC1p cervical cancer. The median follow-up duration was 51.1 months (range, 30-91 months), and the estimated 5-year OS rate was 71.5%. Multivariate analysis revealed that concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT + AC), monocyte-lymphocyte ratio (MLR), ratio of lymph node metastasis (LNM), and squamous cell carcinoma antigen (SCCA) levels independently predicted OS. Conclusions: Significant prognostic disparities exist among patients diagnosed with stage IIIC1p cervical cancer. MLR, ratio of LNM, and SCCA were associated with poor OS. In contrast, the CCRT + AC treatment regimen appeared to confer a survival advantage.

Dose-Volume Parameters of Spared Magnetic Resonance Imaging-Defined Active Bone Marrow Predict Hematologic Toxicity in Pelvic Malignancies Patients Undergoing Radiotherapy: A Cohort Study.

Background: The objective of this investigation is to evaluate the superiority of dose-volume parameters relying on magnetic resonance imaging (MRI)-defined active bone marrow (ABM) over those based on total bone marrow (TBM) contoured via CT in the prediction of hematologic toxicity (HT) occurrence among patients with pelvic malignancies undergoing radiotherapy. Methods: The clinical data of 116 patients with pelvic malignancies treated with pelvic radiotherapy were analyzed retrospectively. The ABM areas on T1-weighted MRI were contoured. The statistical significance between TBM and ABM dose-volume measures was assessed through the utilization of either Student's t-test or Wilcoxon signed rank test. Logistic and linear regression models were employed to analyze the correlation between dose-volume parameters (V5-V50) and HT occurrence in pelvic ABM and TBM. Receiver operating characteristic (ROC) curves were used to compare predictors of HT2+. Results: There were significant differences in dosimetric parameters between ABM and TBM. Logistic regression analysis showed that ABM V5, ABM V10, ABM V15, ABM V20, and TBM V5 were significantly associated with the occurrence of HT2+ in pelvic malignancies. Linear regression analysis showed that ABM V5, ABM V10, and ABM V15 were significantly associated with white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), and lymphocyte (Lym) nadir. ABM V5, ABM V10, ABM V15, and ABM V30 were predictive of HT2+. Conclusions: More accurate prediction of HT in patients receiving pelvic radiotherapy may be achieved by relying on dose-volume parameters of MRI-based ABM. Further prospective studies are needed to confirm this.

Hierarchical Multiple Precursors Induced Heterogeneous Structures in Super Austenitic Stainless Steels by Cryogenic Rolling and Annealing.

Multiple deformed substructures including dislocation cells, nanotwins (NTs) and martensite were introduced in super austenitic stainless steels (SASSs) by cryogenic rolling (Cryo-R, 77 K/22.1 mJ·m-2). With the reduction increasing, a low stacking fault energy (SFE) and increased flow stress led to the activation of secondary slip and the occurrence of NTs and martensite nano-laths, while only dislocation tangles were observed under a heavy reduction by cold-rolling (Cold-R, 293 K/49.2 mJ·m-2). The multiple precursors not only possess variable deformation stored energy, but also experience competition between recrystallization and reverse transformation during subsequent annealing, thus contributing to the formation of a heterogeneous structure (HS). The HS, which consists of bimodal-grained austenite and retained martensite simultaneously, showed a higher yield strength (~1032 MPa) and a larger tensile elongation (~9.1%) than the annealed coarse-grained Cold-R sample. The superior strength-ductility and strain hardening originate from the synergistic effects of grain refinement, dislocation and hetero-deformation-induced hardening.

Prognostic Factors of Gliosarcoma in the Real World: A Retrospective Cohort Study.

Purpose: Gliosarcoma is a histopathological variant of glioblastoma, which is characterized by a biphasic growth pattern consisting of glial and sarcoma components. Owing to its scarcity, data regarding the impact of available treatments on the clinical outcomes of gliosarcoma are inadequate. The purpose of this retrospective cohort study was to analyze the prognostic factors of gliosarcoma. Methods: By screening the clinical database of neurosurgical cases at a single center, patients with gliosarcoma diagnosed histologically from 2013 to 2021 were identified. Clinical, pathological, and molecular data were gathered founded on medical records and follow-up interviews. Prognostic factors were derived using the Cox proportional hazards model with backward stepwise regression analysis. Results: Forty-five GSM patients were included. Median overall survival was 25.6 months (95% CI 8.0-43.1), and median relapse-free survival was 15.2 months (95% CI 9.7-20.8). In multivariable analysis, total resection (p = 0.023, HR = 0.192, 95% CI 0.046-0.797) indicated an improved prognosis. And low expression of Ki-67 (p = 0.059, HR = 2.803, 95% CI 0.963-8.162) would be likely to show statistical significance. However, there might be no statistically significant survival benefit from radiotherapy with concurrent temozolomide (n = 33, 73.3%, log-rank p = 0.99) or adjuvant temozolomide (n = 32, 71.1%, log-rank p = 0.74). Conclusion: This single-center retrospective study with a limited cohort size has demonstrated the treatment of gross total resection and low expression of Ki-67 which are beneficial for patients with GSM, while radiotherapy or temozolomide is not.

Simultaneous Improvement of Strength and Ductility of Dual-Phase Steel Processed by Multi-Step Cyclic Rolling and Intercritical Annealing.

In the present study, a multi-step (MS) cyclic rolling and intercritcal annealing process was proposed and applied for dual-phase (DP) steel. The MS process performed three times with 27% deformations and intercritical annealing, while the single-step (SS) process performed an 81% rolling, along with intercritical annealing. A microstructure with an average grain size of 3 µm and a martensite content of ~40% was obtained after MS treatment, which is similar to results obtained from the SS treatment. However, the distribution exhibits significant differences between the two different routes. A more homogenous distribution of ferrite-martensite was achieved after the multi-step compared with the single-step treatment. The yield strength of MS is slightly smaller than that of SS, while the ultimate tensile strength is better, which results in a decrease in yield ratio. Furthermore, the ductility was greatly improved after MS, which is mainly attributed to the uniform chain-like distribution of martensite.

Physcion-8-O-ß-d-glucoside interferes with the nuclear factor-κB pathway and downregulates P-glycoprotein expression to reduce paclitaxel resistance in ovarian cancer cells.

OBJECTIVE: This study assessed whether physcion-8-O-beta-D-monoglucoside (PG) sensitises paclitaxel (PTX)-resistant ovarian cancer cells and explored the underlying mechanism. METHODS: Ovarian cancer SK-OV-3 cells were used to establish PTX-resistant SK-OV-3 (SK-OV-3/PTX) cells. The Cell Counting Kit-8 assay and crystal violet staining were used to determine cell viability. P-glycoprotein (P-gp) and nuclear factor (NF)-κB expression and cell distributions were detected using immunofluorescence. Cell apoptosis and protein expression changes were detected using flow cytometry and western blotting, respectively. Effect of PG in vivo was evaluated using a xenograft tumour model. P-gp expression in tumour tissues was detected using immunohistochemical staining. KEY FINDINGS: PG (1-10 µm) did not significantly affect SK-OV-3/PTX cell proliferation but significantly downregulated P-gp expression. PG pretreatment (1-10 µm) enhanced PTX cytotoxicity. PG treatment decreased the quantity of phosphorylated-NF-κB p65 in SK-OV-3/PTX cell total proteins and upregulated IKBα expression. Simultaneously, it decreased NF-κB p65 levels in nuclear proteins. PG (1-10 µm) inhibited NF-κB p65 entry into the nucleus. PTX plus PG significantly inhibited SK-OV-3/PTX xenograft tumour growth. PG (1-10 µm) reduced P-gp expression in transplanted tumour tissue. CONCLUSIONS: PG can enhance the sensitivity of PTX-resistant ovarian cancer cells SK-OV-3/PTX to PTX, and this effect is related to inhibiting NF-κB from entering the nucleus and down-regulating the expression of P-gp protein.

miRNA­199b­3p suppresses growth and progression of ovarian cancer via the CHK1/E­cadherin/EMT signaling pathway by targeting ZEB1.

Ovarian cancer is one of the most common gynecological malignancies and its pathogenesis and progression are regulated by multiple genes. MicroRNAs (miRNAs) are endogenous non­coding RNAs that regulate body function by altering post­transcriptional gene expression. Previous studies have suggested that miRNAs are closely associated with the pathogenesis and progression of several malignancies, including breast cancer, hepatocellular carcinoma and glioma, among others. Therefore, miRNAs are promising novel targets for the diagnosis, treatment and determination of prognostic factors in patients with ovarian cancer. In the present study, the role of miRNA­133b­3p in ovarian cancer progression and its possible mechanism of action were investigated. The results demonstrated that the expression of miRNA­199b­3p and zinc finger E­box binding homeobox (ZEB)1 were increased in patients with ovarian cancer. The overall survival (OS) and disease­free survival (DFS) of patients with ovarian cancer and high miRNA­199b­3p expression were prolonged compared with those of patients with low miRNA­199b­3p expression. Additionally, the OS and DFS of patients with ovarian cancer and low ZEB1 expression were longer compared with those of patients with high ZEB1 expression. Furthermore, miRNA­199b­3p overexpression reduced cell proliferation and promoted apoptosis in an in vitro model of ovarian cancer. miRNA­199b­3p overexpression also suppressed ZEB1 and checkpoint kinase 1 expression and induced E­cadherin expression and epithelial­to­mesenchymal transition in this model. Furthermore, the effects of miRNA­199b­3p­mediated apoptosis and migration were attenuated by ZEB1 and E­cadherin, respectively. The results of the present study indicated that miRNA­199b­3p suppressed ovarian cancer progression by targeting ZEB1, which may represent a promising therapeutic target for ovarian cancer.

LncRNA PLAC2 Positively Regulates CDK2 to Promote Ovarian Carcinoma Cell Proliferation.

BACKGROUND: PLAC2 has been reported to participate in glioma, but its role in ovarian carcinoma (OC) is unclear. This study investigated the role of lncRNA PLAC2 in OC. METHODS: A 5-year follow-up study of 64 patients was carried out in Weihai Municipal Hospital after the admission of patients. A total of 64 OC patients were selected from 178 OC patients admitted in the aforementioned hospital from August 2011 to January 2014. Cell transfections, cell cycle analysis, cell proliferation assay and Western blot were carried out during the research. RESULTS: The expression levels of PLAC2 and CDK2 were both upregulated in OC and they were positively correlated. During the 5-year follow-up, patients with high levels of PLAC2 and CDK2 showed significantly lower overall survival rate. In OC cells, overexpression of PLAC2 resulted in upregulated, while silencing of PLAC2 resulted in downregulated expression of CDK2. Cell proliferation assay showed that overexpression of PLAC2 resulted in increased, while silencing of PLAC2 resulted in decreased proliferation rate of OC cells. In addition, overexpression of CDK2 attenuated the effects of silencing of PLAC2. CONCLUSION: PLAC2 positively regulates CDK2 to promote OC cell proliferation.

Effect of Shear Bands Induced by Asymmetric Rolling on Microstructure and Texture Evolution of Non-Oriented 3.3% Si Steel.

In the present work, the microstructure and texture of non-oriented 3.3% Si steel processed by asymmetric rolling (ASR) and subsequent annealing at different temperatures were compared with those obtained when using traditional symmetric rolling (SR). This work aims to reveal the effect of shear bands introduced by the ASR on the microstructure and texture evolution. The ASR sample reaches a recrystallization fraction of 62% at an annealing temperature of 650 °C, which is 32% higher than that of the SR sample annealed at the same temperature. This can be attributed to the abundant shear bands introduced by the ASR, which serve as the heterogeneous nucleation sites for the recrystallized grains. When increasing the annealing temperature to 750 °C, complete recrystallization could be observed in both asymmetric- and symmetric-rolled samples. When using an annealing temperature of 650 °C, the γ-oriented grains were dominant in the surface layer, while strong Goss-oriented grains could be observed in the center in the ASR sample. This is due to the fragmented small subgrains with different orientations in the surface layer inhibiting the nucleation of Goss- and cube-oriented grains during the annealing. In contrast, numerous Goss- and cube-oriented grains were formed in the surface layer after complete recrystallization when the ASR sample was annealed at a temperature of 750 °C. This may be related to the higher thermal energy, which benefits the nucleation of the Goss- and cube-oriented grains. In addition, ASR significantly increased the strength of η-fiber after complete recrystallization when compared with SR. This work might be helpful to design the rolling and the subsequent annealing processes.

Rosmarinic Acid Analogue-11 Induces Apoptosis of Human Gastric Cancer SGC-7901 Cells via the Epidermal Growth Factor Receptor (EGFR)/Akt/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND According to the latest statistics from the American Cancer Society, there will be 1.73 million cancer cases and more than 600 000 cancer deaths in the United States in 2018, among which there will be 26 240 new cases of gastric cancer and around 10 800 deaths arising from gastric cancer. The objective of this study was to use RAA-11 to intervene in SGC-7901 cells to understand its effects on cell proliferation and apoptosis, and to explore the apoptosis mechanism. MATERIAL AND METHODS MTT assay was used to detect the survival of human gastric mucosal epithelial GES-1 cells and human gastric cancer SGC-7901 cells. Colony formation assay was used to observe the colony forming ability in SGC-7901 cells. The apoptotic rate of SGC-7901 cells was evaluated by Hoechst33258 staining and flow cytometry. qRT-PCR was used to analyze the epidermal growth factor receptor (EGFR) mRNA expression level in SGC-7901 cells. Western blot was used to examine the expression levels of caspase-3, Bcl-2, BAX, EGFR, Akt, p-Akt, and NF-κB in SGC-7901 cells. RESULTS RAA-11 is capable of inhibiting the proliferation and inducing the apoptosis of SGC-7901 cells in a time- and dose-dependent manner. Western blot showed that the expression levels of caspase-3 and BAX were upregulated, while the expression levels of Bcl-2, EGFR, Akt, p-Akt, and NF-κB in the SGC-7901 cells were downregulated. CONCLUSIONS Apoptosis can be induced in SGC-7901 cells by RAA-11, potentially via the EGFR/Akt/NF-κB pathway, indicating that RAA-11 might be a potent agent for cancer treatment.