Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.

Clinical efficacy of combined goserelin and anastrozole in neoadjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer.

OBJECTIVE: The objective of this study is to assess the efficacy and safety of combining goserelin with anastrozole in neoadjuvant endocrine therapy (NET) for patients diagnosed with premenopausal breast cancer. METHODS: A retrospective analysis was conducted on the clinicopathological data of 34 patients diagnosed with premenopausal breast cancer who underwent NET in the Department of Breast Surgery at Baotou Cancer Hospital between March 2016 and December 2019. Additionally, the feasibility of using goserelin combined with anastrozole for premenopausal endocrine therapy was assessed. RESULTS: The duration of NET ranged from 6 to 72 months, with a mean of 22.5 months and a median of 18 months. In patients with progressive disease, endocrine therapy was assessed over a period of 6 to 18 months, with a mean of 13.1 months and a median of 13 months. Among the 28 patients assessed, 12 (42.86%) were found to have stable disease, subsequently receiving chemotherapy. Of these, seven patients demonstrated good compliance, and 5 achieved a pathological complete response. Including the 2 patients who responded favorably to NET alone, a total of 7 patients attained a pathological complete response. Additionally, 16 patients achieved complete cell cycle arrest following treatment. A significant correlation was observed between the clinical efficacy assessment and the pathological assessment of NET (P < 0.05). CONCLUSION: Although NET was safe for patients diagnosed with premenopausal breast cancer, it should not be considered in isolation from chemotherapy. Transitioning to chemotherapy in a timely manner can significantly enhance treatment outcomes. The duration of NET should be guided by clinical assessment rather than being constrained by a predetermined time frame.

Cepharanthine sensitizes gastric cancer cells to chemotherapy by targeting TRIB3-FOXO3-FOXM1 axis to inhibit autophagy.

BACKGROUND: Gastric cancer is among the common solid tumors. Chemotherapy resistance is the most common issue in gastric cancer treatment. Inhibiting intracellular autophagy may be a feasible method for overcoming chemotherapy resistance. Cepharanthine (CEP), a natural small molecule extracted from the stephania cephalantha Hayata plant, has been demonstrated to significantly inhibit cancer growth and can regulate autophagy. Although CEP can significantly inhibit cancer growth, it remains unclear whether CEP can regulate autophagy in gastric cancer. This study aimed to investigate whether CEP can enhance the sensitivity of gastric cancer to chemotherapy and elucidate its molecular mechanism. METHODS: Three gastric cancer cell lines (AGS, SGC7901, and MFC) and one normal gastric mucosal epithelial cell line (GES-1) were used for in vitro experiments. The characterization of autophagy in gastric cancer cells included the detection of autophagy markers and autophagy flux through immunofluorescence staining and Western blotting, as well as the assessment of lysosomal function using fluorescence staining (LysoTracker Red DND-99, Acridine Orange staining) and Western blotting. The cytotoxicity of CEP, autophagy inhibitors (chloroquine [CQ] and 3-methyladenine [3MA]), and chemotherapy drugs (doxorubicin [DOX] and cisplatin [CIS]) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell colony formation, and fluorescence staining techniques (H2DCFDA, Dihydroethidium, and JC-1 staining). The interaction between CEP and autophagy inhibitors was tested in a 615 mice model, and changes in the gut microbiota were determined through accurate 16S absolute quantification sequencing. The signaling pathway and autophagy regulatory target TRIB3-FOXO3-FOXM1 were confirmed through molecular docking, RNA sequencing, bioinformatic analysis, transfection techniques, and Western blotting. RESULTS: CEP blocked autophagic flux in gastric cancer cells without affecting lysosomal function. As a novel autophagy inhibitor, CEP could combine with conventional autophagy inhibitors (CQ and 3MA) to block intracellular autophagy, thereby inhibiting gastric cancer growth. During this process, changes in the gut microbiota were observed, including low-level changes in Odoribacterium, Erysipelatoclostridium, and ParaPrevotella and high-level changes in Ileibacterium, Enterorhabdus, and Bifidobacterium. Additionally, CEP synergistically inhibited the growth of gastric cancer when combined with chemotherapy drugs. Mechanistically, the TRIB3-FOXO3-FOXM1 signaling axis was found to be involved in the inhibition of gastric cancer by CEP combined with autophagy inhibitors and chemotherapy drugs, thereby mediating cell apoptosis. CONCLUSION: This study links the TRIB3-FOXO3-FOXM1 axis with chemotherapy efficacy. Our findings demonstrated that CEP inhibits autophagy by modulating the FOXO3-FOXM1 axis. When combined with chemotherapy drugs (DOX and CIS), CEP, as an autophagy inhibitor, can limit TRIB3 protein expression, thereby regulating the FOXO3-FOXM1 axis and enhancing its ability to prevent gastric cancer growth. These findings may contribute to improving the prognosis of patients with gastric cancer. Furthermore, these results enrich the fundamental understanding of how autophagy inhibition can enhance clinical cancer treatment efficacy and provide insights into the potential mechanisms by which CEP functions as an anti-tumor drug, thereby exploring its value for clinical application.

The Activation of PKM2 Induces Pyroptosis in Hippocampal Neurons via the NLRP3/Caspase-1/GSDMD Pathway in Neonatal Rats With Hypoxic-Ischemic Brain Injury.

INTRODUCTION: The presence of hypoxic-ischemic brain damage (HIBD) in neonates triggers a strong neuroinflammatory reaction. Pyroptosis, a programmed cell death mechanism associated with inflammation, plays a crucial role in HIBD. Pyruvate kinase M2 (PKM2) plays a significant role in connecting metabolic processes and inflammatory responses, but whether it affects hippocampus pyroptosis in HIBD is unclear. The aim of this study is to elucidate the role of PKM2 in HIBD and to propose a novel therapeutic approach for neonatal ischemic-hypoxic encephalopathy. METHODS: In this study, we employed neonatal 7-day-old Sprague Dawley rats to establish a model of HIBD using the Rice-Vannucci surgical technique and a hypoxia device. To inhibit the elevation of PKM2, we utilized the PKM2 inhibitor shikonin. The rats were categorized into four groups: Sham, Shikonin, HIBD, and Shikonin + HIBD. Behavioral tests, hematoxylin eosin staining, immunofluorescence staining, ELISA (IL-1ß, IL-18), and LDH were conducted in each group to evaluate neurological function, hippocampal damage, the occurrence of neuronal pyroptosis, and the neuroinflammation. Western blot was used to assess the expression levels of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN, and IL-1ß. RESULTS: The expression of PKM2 elevated in hippocampal tissues of the HIBD model and the localization of PKM2 in the hippocampus was activated in neurons instead of microglia during the HIBD. Meanwhile, the inhibition of PKM2 improved the behavioral test scores and the body weight of rats, the neuronal damage in the CA1 region of hippocampal tissue was also attenuated. In addition, inhibiting PKM2 alleviated neuronal pyroptosis by decreasing the expression of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN. Furthermore, serum levels of LDH and inflammatory factors IL-1ß and IL-18 decrease with PKM2 inhibition. CONCLUSIONS: Based on these findings, we can conclude that PKM2 plays a crucial role in regulating hippocampal neuronal pyroptosis of HIBD rats via NLRP3/Caspase-1/GSDMD pathway. Therefore, inhibiting PKM2 could be a promising therapeutic strategy for the treatment of neonatal ischemic-hypoxic encephalopathy.

Research Progress of Drugs in Prevention and Treatment of Nephrolithiasis.

With the improvement of people's living standards,the incidence of nephrolithiasis is increasing year by year.Nephrolithiasis poses a serious threat to the patients due to the unclear etiology,complicated composition of stones,and high recurrence rate after surgery.As the research on the pathogenesis and pathophysiology of nephrolithiasis keeps deepening in recent years,researchers have made achievements in the drug treatment,which has become a hot topic for urologists.This paper reviews the advances in the research on the possible formation mechanism and drug-induced litholysis and prevention for nephrolithiasis,aiming to provide theoretical references for subsequent clinical research.

Cardiac tumour necrosis factor receptor-associated factor 7 mediates the ubiquitination of apoptosis signal-regulating kinase 1 and aggravates cardiac hypertrophy.

AIMS: Cardiac remodelling is a common pathophysiological process in the development of various cardiovascular diseases, but there is still a lack of effective interventions. Tumour necrosis receptor-associated factor 7 (TRAF7) belongs to the tumour necrosis factor receptor-associated factor family and plays an important role in biological processes. Previous studies have shown that TRAF7 mutations lead to congenital defects and malformations of the heart. However, the molecular mechanisms of TRAF7 in the underlying pathogenesis of pathological cardiac hypertrophy remain unknown. We aim to study the molecular mechanisms and effects of TRAF7 in cardiac remodelling and whether it has the potential to become a therapeutic target for cardiac remodelling. METHODS AND RESULTS: The pressure overload-induced cardiac hypertrophy model in mice was established via transverse aortic constriction (TAC) surgery, and cardiomyocytes were treated with phenylephrine (PE) to induce hypertrophic phenotype. Levels of cardiac dysfunction and remodelling were measured with echocardiography and tissue or cell staining. RNA sequencing, western blot, qRT-PCR, co-immunoprecipitation, and in vivo ubiquitination assays were used to explore the molecular mechanisms. The results showed that the expression of TRAF7 increased gradually during the development of hypertrophy. Accordingly, TRAF7 significantly exacerbated the PE-induced enlargement of primary neonatal Sprague-Dawley rat cardiomyocytes, whereas TRAF7 knockdown alleviated the hypertrophic phenotype in primary cardiomyocytes. Cardiac-specific overexpression of TRAF7 accelerated hypertrophic phenotype in mice and cardiac-specific Traf7 conditional knockout mice improved hypertrophic phenotype induced by TAC. Mechanistically, TRAF7 directly interacted with apoptosis signal-regulating kinase-1 (ASK1) and promoted ASK1 phosphorylation by mediating the K63-linked ubiquitination of ASK1 in response to PE stimulation, which then promoted ASK1 activation and downstream signalling during cardiac hypertrophy. Notably, the pro-hypertrophic effect of TRAF7 was largely blocked by GS4997 in vitro and cardiac-specific Ask1 conditional knockout in vivo. CONCLUSION: In summary, we identified TRAF7 as an essential regulator during cardiac hypertrophy, and modulation of the regulatory axis between TRAF7 and ASK1 could be a novel therapeutic strategy to prevent this pathological process.

Modulating the cavity micro-environments of Fe-MOFs for high-performance gas chromatographic separations.

Precise modulation of cavity micro-environment in metal-organic frameworks (MOFs) is important for achieving significant separation performance. Herein, the Fe-MOF (MIL-142-BTB-BDC) with different tridentate and bidentate ligands to form cavities, was chosen as the platform to precisely modulate the cavity micro-environment and investigate the influence of cavity windows and cavity walls on gas chromatographic separations. Changing tridentate ligands on the cavity walls led to MIL-142-TATB-BDC while changing bidentate ligands on the cavity windows produced MIL-142-BTB-BDC-NH2. Mechanism investigation revealed that for MIL-142-BTB-BDC and MIL-142-TATB-BDC, altering the ligands of cavity walls had little influence on the thermodynamic interactions between MOFs and analytes while slightly reducing the kinetic diffusion rate of analytes. On the contrary, introducing amino groups on cavity windows in MIL-142-BTB-BDC-NH2 not only increased the thermodynamic interactions with analytes but also slowed down the kinetic diffusion of analytes, which resulted in poor separation performance of the MIL-142-BTB-BDC-NH2 coated column. This work provides a guide to precisely modulating the cavity micro-environment and analyzing the relationship between the cavity micro-environment and application properties of MOFs.

Acute lymphoblastic leukemia with pneumatosis cystoides intestinalis after hematopoietic stem cell transplantation: a case report.

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by air accumulation within the subserosa or submucosa of the gastrointestinal wall. We herein report a case involving a woman in her early 30s who developed PCI after undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. The patient had a history of multiple COVID-19 infections. Imaging revealed extensive pneumoperitoneum and mesenteric emphysema; nevertheless, the patient remained clinically stable with a benign abdominal examination. She eventually recovered after 1 month of conservative treatment. We believe the PCI in this case had a multifactorial etiology, potentially involving both HSCT and COVID-19. Raising awareness of PCI may help avoid unnecessary surgical interventions and associated morbidity.

Revealing the Corrosion Resistance Mechanism of Plain Carbon Steel Micro-Alloyed by La in Simulated Industrial Atmosphere.

Plain carbon steel is the most widely applied steel in current engineering construction. With the increased application property needs, the service life of plain carbon steel has been severely tested. As one of the most destructive failure modes, corrosion resistance of carbon steel has attracted wide attention. Rare earth La, as the microalloying element, was employed in plain carbon steel, Q355, to improve its corrosion resistance. As the content of La increased, the microstructure was refined. The fraction of pearlite decreased, while the content of acicular increased. Within the La addition of 230 ppm, the tensile strength and impact energy were jointly improved. Furthermore, the microalloying element of La modified the inclusion types and refined the inclusion size. The modified microstructure and inclusions by La co-improved the corrosion resistance. The formula of effective La content was proposed to estimate the effect of La on corrosion. As the effective content of La increased, the relative corrosion rate decreased. La3+ promoted the protective rust layer to increase corrosion resistance.

TRPV4 Blockage Inhibits the Neurogenesis in the Adult Hippocampal Dentate Gyrus Following Pilocarpine­Induced Status Epilepticus.

Aberrant neurogenesis in the adult hippocampal dentate gyrus (DG) contributes to synapse remodeling during temporal lobe epilepsy (TLE). Transient receptor potential vanilloid 4 (TRPV4) is involved in the pathogenesis of TLE. Activation of TRPV4 can modulate neurogenesis in the adult hippocampal DG. The present study examined whether TRPV4 is responsible for the aberrant neurogenesis in the adult hippocampal DG during TLE. Herein, administration of a TRPV4-specific antagonist, HC-067047, attenuated the enhanced neural stem cell proliferation in the adult hippocampal DG in mice following pilocarpine­induced status epilepticus (PISE). HC-067047 reduced the heightened hippocampal protein levels of cyclin-dependent kinase (CDK) 2, CDK6, cyclin E1, cyclin A2, and phosphorylated retinoblastoma (p-Rb) observed following PISE. Meanwhile, HC-067047 inhibited the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) pathways that were enhanced and responsible for the increased proliferation of stem cells and higher levels of CDKs, cyclins, and p-Rb protein. HC-067047 reduced the 28-day-old BrdU+ cells but increased the ratio of 28-day-old BrdU+ cells to 1-day-old BrdU+ cells, indicating that TRPV4 blockage reduced the number but increased the survival rate of newborn cells following PISE. Finally, HC-067047 increased the Akt signaling that was inhibited and responsible for the decreased survival rate of newborn cells following PISE. It is concluded that TRPV4 blockage inhibits stem cell proliferation in the hippocampal DG following PISE, likely through inhibiting ERK1/2 and p38 MAPK signaling to decrease cell cycle-related protein expression, and increases newborn cell survival rate likely through increasing phosphoinositide 3 kinase-Akt signaling.

[Risk factors for postoperative mortality within 1 year in more than 90-year-old super advanced age patients with hip fractures].

OBJECTIVE: To investigate the 1 year mortality after hip fractures in super advanced age patients and summarize the death associated risk factors in order to provide basis for targeted intervention countermeasures. METHODS: The clinical data of 332 super advanced age patients with femoral neck or intertrochanteric fractures treated by hip replacement or intramedullary femoral nail fixation from January 2015 to January 2023 were retrospectively analyzed. There were 128 males and 204 females with the mean age of (92.2±2.5) years ranging from 90 to 103 years old. Among them, 92 cases died within 1 year after surgery. Correlation with the occurrence of death on age, gender, body mass index, fracture type, treatment method, timing of operation, preoperative hemoglobin and serum albumin level, operation time, combined medical diseases, pre-injury mobilityand American Society of Anesthesiology(ASA) classification were analyzed. The risk factors of death within 1 year after operation were screened by univariate analysis. The results were entered into the multivariate Logistic regression analysis, screening the high risk factors for 1 year mortality after hip fractures. RESULTS: The mortality of super advanced age patients with hip fracture within 1 year after surgery accounted for 27.7%(92/332). Univariate analysis showed high body mass index, long interval from injury to surgery, low preoperative serum albumin levels, inability to walk independently before injury, accompanied by heart failure, pulmonary infection, obstructive pulmonary disease, stroke, and a higher proportion of ASA grades Ⅲ-Ⅳ. Multivariate Logistic regression analysis showed preoperative serum albumin below 30g g·L-1[OR=2.973, 95%CI(2.461, 5.344), P=0.039], inability to walk independently before injury [OR=3.519, 95%CI(2.224, 5.413), P=0.018], heart function grade C-D[OR=4.213, 95%CI(2.952, 6.99), P=0.021], pulmonary infection[OR=3.927, 95%CI(2.187, 7.731), P=0.016] and ASA Ⅲ-Ⅳ[OR=5.124, 95%CI(3.092, 8.235), P=0.032] were the independent risk factors for death within 1 year in super advanced age patients with hip fractures. CONCLUSION: Preoperative serum albumin below 30g.L-1, poor preinjury activity, heart function grade C-D, pulmonary infection, and ASA grade Ⅲ-Ⅳ are independent risk factors for postoperative mortality in super advanced age patients with hip fractures.

Multidose transient transfection of human embryonic kidney 293 cells modulates recombinant adeno-associated virus2/5 Rep protein expression and influences the enrichment fraction of filled capsids.

Recombinant adeno-associated virus (rAAV) is a commonly used in vivo gene therapy vector because of its nonpathogenicity, long-term transgene expression, broad tropism, and ability to transduce both dividing and nondividing cells. However, rAAV vector production via transient transfection of mammalian cells typically yields a low fraction of filled-to-total capsids (~1%-30% of total capsids produced). Analysis of our previously developed mechanistic model for rAAV2/5 production attributed these low fill fractions to a poorly coordinated timeline between capsid synthesis and viral DNA replication and the repression of later phase capsid formation by Rep proteins. Here, we extend the model by quantifying the expression dynamics of total Rep proteins and their influence on the key steps of rAAV2/5 production using a multiple dosing transfection of human embryonic kidney 293 (HEK293) cells. We report that the availability of preformed empty capsids and viral DNA copies per cell are not limiting to the capsid-filling reaction. However, optimal expression of Rep proteins (<240 ± 13 ag per cell) enables enrichment of the filled capsid population (>12% of total capsids/cell) upstream. Our analysis suggests increased enrichment of filled capsids via regulating the expression of Rep proteins is possible but at the expense of per cell capsid titer in a triple plasmid transfection. Our study reveals an intrinsic limitation of scaling rAAV2/5 vector genome (vg) production and underscores the need for approaches that allow for regulating the expression of Rep proteins to maximize vg titer per cell upstream.

The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia.

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

Adeno-associated virus perfusion enhanced expression: A commercially scalable, high titer, high quality producer cell line process.

With safety and efficacy demonstrated over hundreds of clinical trials in the last 30 years, along with at least six recent global marketing authorizations achieved since 2017, recombinant adeno-associated viruses (rAAVs) have been established as the leading therapeutic gene transfer vector for rare, monogenic diseases. Significant advances in manufacturing technology have been made in the last few decades to address challenges with GMP production of rAAV products, although yield, cost, scalability, and quality remain a challenge. With transient transfection processes established as a manufacturing platform for multiple commercial AAV products, there remains significant yield, cost, robustness, and scalability constraints that need to be resolved to enable a reliable supply of rAAV products for global patient access. The development of stable producer cell lines for rAAV products has enabled scalability and, in some cases, improvements in productivity. Herein we describe a novel AAV perfusion-enhanced expression (APEX) process, resulting in higher maximum cell densities in the production bioreactor with a 3- to 6-fold increase in volumetric productivity. This process has been successfully demonstrated across multiple serotypes in large scale cell culture with titers approaching 1 × 1012 GC/mL. The APEX production platform marks a significant leap forward in the efficient and effective manufacturing of rAAV vector products.

Ethyl pyruvate alleviates NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis in neonatal rats with hypoxic-ischemic brain damage.

Pyroptosis is an inflammation-associated programmed cell death, and neuroinflammation is strongly associated with severe neurological deficits in neonatal hypoxic-ischemic encephalopathy (HIE). Ethyl pyruvate (EP), a known anti-inflammatory agent, has shown promise in the treatment of hypoxic-ischemic brain damage (HIBD) rats; nevertheless, the therapeutic mechanism of EP and its capacity to suppress neuronal pyroptosis in HIBD rats remain unclear. In both the neonatal Rice-Vannucci rat model and the OGD/R model, this study examined alterations in the NLRP3/Caspase-1/GSDMD classical pyroptosis pathway in hippocampal neurons during HIE and the potential inhibitory impact of ethyl pyruvate on this pathway. We used HE staining, immunofluorescence double staining, transmission electron microscopy, and western blot to demonstrate that EP effectively inhibited hippocampal neuronal pyroptosis and attenuated the activation of the NLRP3/Caspase-1/GSDMD signaling pathway in HIBD rats, which resulted in a reduction of neuroinflammation and facilitated neural recovery. The results suggest that EP may be a promising neuroprotective agent for treating HIE.

[Research progress in preparations of Panax ginseng].

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.

Observation on the Curative Effect of Different Anti-infective Treatment Regimens for Children with Acute Appendicitis.

Objective: To observe the efficacy of different anti-infective treatment regimens on acute appendicitis in children, a retrospective study was conducted by collecting previous cases. Methods: Ninety children with acute appendicitis who received laparoscopic appendectomy from May 2020 to September 2022 were included in this retrospective study. According to the different anti-infective treatment regimens, they were divided into Piperacillin-Tazobactam group, Piperacillin-Tazobactam+Metronidazole group, and Cefminox+Metronidazole group (n=30). Three groups of children received medication treatment before surgery. The postoperative recovery, treatment effect, bacterial clearance, complication rate, pharmacoeconomic evaluation, and adverse reactions were compared. Results: The effective rates in the three groups were 83.33%, 90.00%, and 90.00%, respectively (P > .05). There were no differences in the bacterial clearance, complication incidence, and incidence of pharmaceutical side effects among the three groups (P > .05). The total hospitalization cost, total drug cost, and antimicrobial drug cost in Cefminox + Metronidazole group were lower than those in Piperacillin-Tazobactam group and Piperacillin-Tazobactam + Metronidazole group, respectively (P < .05). The intensity of antibacterial drug use in Piperacillin-Tazobactam group was the lowest, followed by Piperacillin-Tazobactam + Metronidazole group and Cefminox + Metronidazole group (P < .05). Conclusion: The three anti-infective regimens have the same therapeutic effect on acute appendicitis in children. However, the regimen of Cefminox + Metronidazole is the most economical option and can be used as the preferred treatment for acute appendicitis in children. As the preferred treatment for acute appendicitis in children. The Piperacillin-Tazobactam group has the lowest intensity of antibiotic use and can reduce bacterial resistance.

Promoting psychological support services for parents of children with sarcoma through health-social partnership: A quality improvement project.

PURPOSE: A significant portion of parents of children diagnosed with sarcoma experience excessive stress and anxiety disorder. This quality improvement project aimed to implement a psychological support service program tailored for parents of children with sarcoma and evaluate its effects. DESIGN AND METHODS: An interprofessional team was formed through a health-social partnership to deliver comprehensive psychological support service program involving multiple cognitive-behavioral components to parents of children with sarcoma. Parents who were identified as having excessive stress and/or anxiety disorder and voluntarily agreed to participate were enrolled. Pre- and post-intervention assessments were conducted, and previously recorded data from parents of children hospitalized in the year prior to this quality improvement project were included as historical controls. RESULTS: A total of 48 parents, including 35 mothers and 13 fathers, participated in the quality improvement project. Results showed that participants achieved greater reduction in emotional, somatic, and behavioral stress when compared with historical controls (all p < .001). Significantly lower prevalence of moderate to severe anxiety disorder was also found (4.2% vs. 85.4%, p < .001). CONCLUSIONS: The implementation of a psychological support service program, informed by cognitive-behavioral theory and delivered through a health-social partnership, effectively alleviated multiple facets of stress and anxiety disorder in parents of children newly diagnosed with sarcoma. PRACTICE IMPLICATIONS: Nurses can facilitate and coordinate the collaboration among interprofessional team to deliver specialized psychological support services and ensure that parents of children with sarcoma have access to these services, ultimately enhancing their psychological well-being.

Radiating blood flow signal: A new ultrasound feature of thyroid carcinoma.

OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.