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The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).

The region coverage control problem of multiple stratospheric airships system is firstly addressed in this paper. Towards it, we propose a two-layer control framework with the artificial potential field (APF)-based region coverage control law and the adaptive tracking control law. The APF-based region coverage control law ensures the coverage task is achieved until every single stratospheric airship ends up performing station keeping where near the respective global minimum point, in which an innovative solution to the local minimum problem is put forward. The adaptive tracking control law is designed to realize motion control using tracking the desired velocity and angular velocity given by coverage control law, with the consideration of several practical control problems as unknown individual differences and external disturbances. To save resources, the combined self-/event-triggered mechanism designed therein significantly reduces the times of state information transmission and control law calculation. The effectiveness of the proposed control framework is verified through simulations.

IntroductionUbiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA).MethodsTo identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development.ResultsThrough univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down.ConclusionsTo summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.

High myopia is a state of refractive error with myopia over -6.00D. High myopia is typically accompanied by multiple fundus lesions, thus making patients with high myopia suffer from varying degrees of impairment in visual function. As an emerging auxiliary way in ophthalmology, optical coherence tomography angiography(OCTA)can efficiently and non-invasively obtain microvascular stratified images of the retina and choroid and quantitatively analyze blood flow signals. Since the advent of OCTA, there have been numerous studies observing fundus changes in those with high myopia through OCTA. In this paper, some studies in which OCTA is applied to obtain retinal and choroidal thickness from patients with high myopia are reviewed, with a view to revealing the correlation between high myopia and the parameters such as retinal thickness, choroidal thickness, vessel density and the area of the foveal avascular zone and providing novel ideas to deeply investigate the mechanism of high myopia and delay the occurrence and development of high myopia.

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans.

Abstract Background and aims The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single‐cell level is rare due to the need for fresh and high‐quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. Methods Five paired samples of intramucosal ESCC, para‐ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA‐seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. Results A total of 164 715 cells were profiled. Epithelial cells exhibited high intra‐tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEXs, Tregs and PD1+CD4+T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand–receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK–NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. Conclusion This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

BackgroundTo determine the reproducibility of measuring the gross total volume (GTV) of primary rectal tumor with manual and semi-automatic delineation on the diffusion-weighted image (DWI), examine the consistency of using the same delineation method on DWI images with different high b-values, and find the optimal delineation method to measure the GTV of rectal cancer.Methods41 patients who completed rectal MR examinations in our hospital from January 2020 to June 2020 were prospectively enrolled in this study. The post-operative pathology confirmed the lesions were rectal adenocarcinoma. The patients included 28 males and 13 females, with an average age of (63.3 ± 10.6) years old. Two radiologists used LIFEx software to manually delineate the lesion layer by layer on the DWI images (b=1000 s/mm2 and 1500 s/mm2) and used 10% to 90% of the highest signal intensity as thresholds to semi-automatically delineate the lesion and measure the GTV. After one month, Radiologist 1 performed the same delineation work again to obtain the corresponding GTV.ResultsThe inter- and intra-observer interclass correlation coefficients (ICC) of measuring GTV using semi-automatic delineation with 30% to 90% as thresholds were all >0.900. There was a positive correlation between manual delineation and semi-automatic delineation with 10% to 50% thresholds (P < 0.05). However, the manual delineation was not correlated with the semi-automatic delineation with 60%, 70%, 80%, and 90% thresholds. On the DWI images with b=1000 s/mm2 and 1500 s/mm2, the 95% limit of agreement (LOA%) of measuring GTV using semi-automatic delineation with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% thresholds were -41.2~67.4, -17.8~51.5, -16.1~49.3, -26.2~50.1, -42.3~57.6, -57.1~65.4, -67.3~66.5, -101.6~91.1, -129.4~136.0, and -15.3~33.0, respectively. The time required for GTV measurement by semi-automatic delineation was significantly shorter than that of manual delineation (12.9 ± 3.6s vs 40.2 ± 13.1s).ConclusionsThe semi-automatic delineation of rectal cancer GTV with 30% threshold had high repeatability and consistency, and it was positively correlated with the GTV measured by manual delineation. Therefore, the semi-automatic delineation with 30% threshold could be a simple and feasible method for measuring rectal cancer GTV.

Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic stress may be mediated by hydrogen peroxide (H2O2). The effects of the ROS scavenger N,N′-dimethylthiourea (DMTU) on maize seed germination through endogenous H2O2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H2O2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H2O2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes (ZmAPX2 and ZmCAT2) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm−3 DMTU). We suggest the use of 200 mmol·dm−3 DMTU as an H2O2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.

Abstract Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-β was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-β was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship.

In this study, Qin et al. present a murine-adapted SARS-CoV-2 strain, MASCp36, as a model for studying the pathogenicity, evolution and adaptation of the virus to human and animal hosts.

ARCoV is a candidate mRNA vaccine encoding receptor-binding domain of SARS-CoV-2. Its safety, tolerability, and immunogenicity profile have been confirmed in the phase 1 clinical trial in China. A multi-regional phase 3 clinical trial is currently underway to test the efficacy of ARCoV (NCT04847102). Here, we tested the cross-neutralization against SARS-CoV-2 variants of concern (VOCs) of a panel of serum samples from participants in the phase 1 clinical trial of ARCoV by pesudo- and authentic SARS-CoV-2. Our data suggest the immunity induced by the ARCoV vaccine reduced but still has significant neutralization against the Alpha and Delta variants. Moreover, ARCoV maintained activity against the Beta variant, despite of its obvious reduction in neutralizing titers. Our findings further support the solid protective neutralization activity against VOCs induced by ARCoV vaccine.

Abstract Background Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts. Methods The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured. Results The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown. Conclusion Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract Graphic abstract

Abstract Background To establish and validate a high-resolution magnetic resonance imaging (HRMRI)-based radiomic nomogram for prediction of preoperative perineural invasion (PNI) of rectal cancer (RC). Methods Our retrospective study included 140 subjects with RC (99 in the training cohort and 41 in the validation cohort) who underwent a preoperative HRMRI scan between December 2016 and December 2019. All subjects underwent radical surgery, and then PNI status was evaluated by a qualified pathologist. A total of 396 radiomic features were extracted from oblique axial T2 weighted images, and optimal features were selected to construct a radiomic signature. A combined nomogram was established by incorporating the radiomic signature, HRMRI findings, and clinical risk factors selected by using multivariable logistic regression. Results The predictive nomogram of PNI included a radiomic signature, and MRI-reported tumor stage (mT-stage). Clinical risk factors failed to increase the predictive value. Favorable discrimination was achieved between PNI-positive and PNI-negative groups using the radiomic nomogram. The area under the curve (AUC) was 0.81 (95% confidence interval [CI], 0.71–0.91) in the training cohort and 0.75 (95% CI, 0.58–0.92) in the validation cohort. Moreover, our result highlighted that the radiomic nomogram was clinically beneficial, as evidenced by a decision curve analysis. Conclusions HRMRI-based radiomic nomogram could be helpful in the prediction of preoperative PNI in RC patients.

Summary: Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p

The design simulation and fabrication results of a bandpass filter based on micro-electro-mechanical system (MEMS) switches are presented in this paper. The MEMS filter element consists of a MEMS capacitance switch and two resonant rings that are fixed onto coplanar waveguide lines through anchor points. The micromachine characteristics of the filter could be optimized to change the center frequency from 8.5 to 12 GHz by improving the geometrical parameters; other electrical parameters of the filter, such as stopband rejection, insertion loss, and return loss at each center frequency, were simulated and calculated. In order to evaluate the MEMS filter design methodology, a filter working at 10.5 GHz fabricated with an aluminum top electrode was used, and it displayed a low insertion loss of 1.12 dB and a high stopband rejection of 28.3 dB. Compared with the simulation results, these proposed filter showed better electrical performance. Our results demonstrated that the filter with the integrated RF MEMS switch not only provides the benefit of reduced size compared with a traditional filter, but also improves stopband rejection, insertion loss, and return loss.

Ovarian cancer (OC) is one of the deadliest gynecological malignancies worldwide and has a high mortality rate. Its dismal prognosis is closely related to late diagnosis and drug resistance. Exosomes are a novel means of intercellular communication that are involved in the genesis and development of tumors by delivering a variety of biologically active molecules, including proteins, lipids, and nucleic acids. As an important component, noncoding RNAs (ncRNAs) are selectively enriched in exosomes and participate in the regulation of specific aspects of OC development, such as proliferation, invasion, metastasis, angiogenesis, immune escape, and treatment resistance. Therefore, strategies that specifically target exosomal ncRNAs may be attractive therapeutic options. Exosomes are readily available in almost all types of human biological fluids and are biocompatible, making them promising biomarkers of OC as well as targets for therapeutic applications. In this review, we briefly summarize the biology of exosomes, the function of exosomal ncRNAs in OC development, and their potential clinical applications as biomarkers and therapeutic tools. Ideally, exosomal ncRNAs will become increasingly valuable in the diagnosis and treatment of OC in the near future.

Objective: Graphene oxide (GO) has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to investigate the effects of cell penetrating peptide (CPP) modified and polyethylene-glycol- (PEG-) grafted GO (pGO) loaded with photosensitive agent 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH) and Epirubicin (EPI) (HPPH/EPI/CPP-pGO) on tumor growth in osteosarcoma.Methods: The HPPH/EPI/CPP-pGO were prepared, and then in vitro drug release assay was conducted. The detection of singlet oxygen (1O2) and cellular uptake of HPPH was performed as well. Next, the effects of control (saline solution), CPP-pGO, EPI, HPPH, HPPH/CPP-pGO, EPI/CPP-pGO, HPPH/EPI/pGO, and HPPH/EPI/CPP-pGO were evaluated by MTT assay, colony-forming assay, and cell apoptosis assay in MG-63 cells. Furthermore, the antitumor effects of HPPH/EPI/CPP-pGO on osteosarcoma xenograft mice were unraveled.Results: The 1O2 generation and cellular uptake of HPPH were significantly increased after CPP and pGO modification compared with free HPPH. In addition, compared with control cells, CPP-pGO treatment had low cytotoxicity in MG-63 cells. Compared with free HPPH or EPI, HPPH/CPP-pGO or EPI/CPP-pGO treatment significantly inhibited cell viability and colony forming number, as well as inducing cell apoptosis. HPPH/EPI-pGO treatment showed stronger inhibition effects on MG-63 cells than HPPH/CPP-pGO or EPI/CPP-pGO, and HPPH/EPI/CPP-pGO was the most effective one. Similarly, in vivo experiments revealed that, compared with control group, the tumor size and weight of osteosarcoma xenograft mice were obviously decreased after free HPPH or EPI treatment, which were further reduced in other groups, especially in HPPH/EPI/CPP-pGO group.Conclusion: HPPH/EPI/CPP-pGO had superior tumor-inhibiting effects in vitro and in vivo on osteosarcoma.

Objective To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations. Methods Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔC SG,max ) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested. Results Using the direct comparison method, the geometric mean ratios of C SG,max , AUEC (0-2h) , and AUEC (0-4h) were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for C SG,max , AUEC (0-2h), and AUEC (0-4h) all fell between 80% and 125%. Conversely, ΔC SG,max and ΔAUEC (0-4h) were less reliable measures of acarbose bioequivalence. Conclusions Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.

We present a study of charm and beauty isolation based on a data-driven method with recent measurements on heavy flavor hadrons and their decay electrons in Au+Au collisions at sNN = 200 GeV at RHIC. The individual electron pT spectra, RAA and v2 distributions from charmed and beauty hadron decays are obtained. We find that the electron RAA from beauty hadron decays (RAAb→e) is suppressed in minimum bias Au+Au collisions but less suppressed compared with that from charmed hadron decays at pT > 3.5 GeV/c, which indicates that beauty quark interacts with the hot-dense medium with depositing its energy and is consistent with the mass-dependent energy loss scenario. For the first time, the non-zero electron v2 from beauty hadron decays (v2b→e) at pT > 3.0 GeV/c is observed and shows smaller elliptic flow compared with that from charmed hadron decays at pT < 4.0 GeV/c. At 2.5 GeV/c < pT < 4.5 GeV/c, v2b→e is smaller than a number-of-constituent-quark (NCQ) scaling hypothesis. This suggests that beauty quark is unlikely thermalized and too heavy to be moved in a partonic collectivity in heavy-ion collisions at the RHIC energy.

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca2+]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca2+]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

Objective: To investigate the clinical efficacy of roxithromycin combined with azithromycin sequential therapy in the treatment of mycoplasma pneumoniae pneumonia in children. Methods: A retrospective study was conducted on 100 patients with mycoplasma pneumoniae pneumonia admitted to The First Affiliated Hospital of Yangtze University from January 2020 to December 2022. All patients were divided into the observation group (roxithromycin combined with azithromycin sequential therapy) and the control group (azithromycin sequential therapy), with 50 cases in each group. The clinical efficacy, improvement time of clinical symptoms/signs, inflammation indexes, oxidative stress indexes and immune function levels of the two groups were compared. Moreover, the improvement of lung function indexes and the adverse reactions were observed. Results: The overall response rate of the observation group was 96.00%, which was higher than the control group (84.00%) (p<0.05). The time of clinical symptoms/signs in the observation group were significantly lower than those in the control group(p<0.05). After treatment, significant improvements were seen in the levels of CRP, TNF-α, IL-6, GSH-Px, SOD, MDA, CD3+, CD4+, CD4+/CD8+, IgM, IgG, IgA, FEV1, FEV1%, FVC and FEV1/FVC of the two groups compared with those before treatment (p<0.05), and the improvement in the observation group was more obvious than that in the control group (p<0.05). The overall incidence of adverse reactions in the observation group was 6.00%, which was slightly lower than that in the control group (8.00%) (c²=0.154, P=0.695). Conclusion: Roxithromycin combined with azithromycin sequential therapy is a safe regimen for the treatment of mycoplasma pneumoniae pneumonia in children. [ABSTRACT FROM AUTHOR]

Objective: To analyze the factors affecting the long-term clinical efficacy and quality of life in the treatment of pediatric acute lymphoblastic leukemia (ALL). Methods: This is a retrospective study. One hundred children with ALL were collected before June, 2018 at The First Affiliated Hospital of Yangtze University and followed up for five years. Not only were their five-years survival rates analyzed, but univariate and multivariate analyses were also performed for factors that might affect their five-year survival rates. The MOS 36-Item Short Form of Health Survey (SF-36) was utilized to investigate the surviving children after five years in order to analyze the factors that may affect the quality of life of the children. Results: The five-years survival rate of one hundred children with ALL after treatment was 91.00% (91/100). Univariate and multivariate Logistic regression analyses were performed on the factors that may affect the long-term efficacy of pediatric ALL. The results showed that white blood cell count at first diagnosis, prednisone response test, treatment compliance and recurrence were independent risk factors for the long-term efficacy of pediatric ALL(p<0.05). The SF-36 survey of 91 surviving children after five years showed that prednisone response test and treatment compliance were independent risk factors affecting the quality of life of pediatric ALL (p<0.05). Conclusion: In the initial diagnosis of pediatric ALL, sufficient attention and control should be given to the factors that may affect the long-term clinical efficacy and quality of life, and appropriate treatment plans should be adopted. Meanwhile, the treatment compliance of children should be improved during treatment to improve the survival rate and quality of life of pediatric ALL. [ABSTRACT FROM AUTHOR]