Comparing upfront surgery with neoadjuvant treatments in patients with resectable, borderline resectable or locally advanced pancreatic cancer: a systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use. PATIENTS AND METHODS: The authors reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, The Cochrane Library, Web of Science from 2009 to 2023 to estimate relative odds ratios for resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials. RESULTS: A total of nine studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer (RPC) patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline RPC. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer. CONCLUSIONS: The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline RPC. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.

Impact of PD-L1 Gene Polymorphisms and Interactions with Cooking with Solid Fuel Exposure on Tuberculosis.

INTRODUCTION: Given that PD-L1 is a crucial immune checkpoint in regulating T-cell responses, the aim of this study was to explore the impact of PD-L1 gene polymorphisms and the interaction with cooking with solid fuel on susceptibility to tuberculosis (TB) in Chinese Han populations. METHODS: A total of 503 TB patients and 494 healthy controls were enrolled in this case-control study. Mass spectrometry technology was applied to genotype rs2297136 and rs4143815 of PD-L1 genes. The associations between single nucleotide polymorphism (SNPs) and TB were assessed using unconditional logistic regression analysis. Marginal structural linear odds models were used to estimate the gene-environment interactions. RESULTS: Compared with genotype CC, genotypes GG and CG+GG at rs4143815 locus were significantly associated with susceptibility to TB (OR: 3.074 and 1.506, respectively, p < 0.05). However, no statistical association was found between rs2297136 SNP and TB risk. Moreover, the relative excess risk of interaction between rs4143815 of the PD-L1 gene and cooking with solid fuel was 2.365 (95% CI: 1.922-2.809), suggesting positive interactions with TB susceptibility. CONCLUSION: The rs4143815 polymorphism of the PD-L1 gene was associated with susceptibility to TB in Chinese Han populations. There were significantly positive interactions between rs4143815 and cooking with solid fuel.

Study on the Nanoaggregate Formation Mechanism and Antipyretic Effect of Maxing Shigan Decoction.

Traditional Chinese medicine (TCM) formula decoctions easily form nanoaggregates due to self-assembly during the decoction process. However, research on nanoaggregates in TCM is still in its infancy with limited systematic studies. Maxing Shigan Decoction (MXSGT), a TCM formula, has been commonly used for the treatment of fever for thousands of years in China. This study used MXSGT as an example to investigate the antipyretic effects of MXSGT nanoaggregates (MXSGT-NAs) in its decoction, shedding light on the compatibility mechanisms of Chinese medicine. MXSGT-NAs were isolated by using high-speed centrifugation and dialysis techniques. The morphology, particle size distribution, and electrical potential of MXSGT-NAs were characterized. High-performance liquid chromatography (HPLC) was used to detect ephedrine and pseudoephedrine in MXSGT-NAs. The self-assembly mechanism of MXSGT-NAs was investigated by deconstructing the prescription. In pharmacodynamic experiments, a rat fever model was established through the subcutaneous injection of dry yeast to investigate the antipyretic effects of MXSGT-NAs. The results showed the presence of regularly shaped spherical nanoaggregates in MXSGT. It contains carbon, oxygen (O), sulfur (S), sodium, aluminum (Al), calcium (Ca), iron, magnesium, bismuth (Bi), etc. MXSGT-NAs exerted substantial antipyretic effects on febrile rats. Furthermore, we found micrometer-sized particles composed of Ca, O, S, potassium, and Bi in Shi gao decoctions. This study is the first to provide evidence for the self-assembling property of Shi gao, elucidate the scientific connotation of dispensing Shi gao in MXSGT, and provide a novel perspective for the study of TCM decoctions.

Comparative efficacy of different repetitive transcranial magnetic stimulation protocols for lower extremity motor function in stroke patients: a network meta-analysis.

Background: Lower extremity motor dysfunction is one of the most severe consequences after stroke, restricting functional mobility and impairing daily activities. Growing evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can improve stroke patients' lower extremity motor function. However, there is still controversy about the optimal rTMS protocol. Therefore, we compared and analyzed the effects of different rTMS protocols on lower extremity motor function in stroke patients using network meta-analysis (NMA). Methods: We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases (from origin to 31 December 2023). Randomized controlled trials (RCTs) or crossover RCTs on rTMS improving lower extremity motor function in stroke patients were included. Two authors independently completed article screening, data extraction, and quality assessment. RevMan (version 5.4) and Stata (version 17.0) were used to analyze the data. Results: A total of 38 studies with 2,022 patients were eligible for the NMA. The interventions included HFrTMS-M1, LFrTMS-M1, iTBS-Cerebellum, iTBS-M1, dTMS-M1, and Placebo. The results of NMA showed that LFrTMS-M1 ranked first in FMA-LE and speed, and HFrTMS-M1 ranked first in BBS, TUGT, and MEP amplitude. The subgroup analysis of FMA-LE showed that HFrTMS-M1 was the best stimulation protocol for post-stroke time > 1 month, and LFrTMS-M1 was the best stimulation protocol for post-stroke time ≤ 1 month. Conclusion: Considering the impact of the stroke phase on the lower extremity motor function, the current research evidence shows that HFrTMS-M1 may be the preferred stimulation protocol to improve the lower extremity motor function of patients for post-stroke time > 1 month, and LFrTMS-M1 for post-stroke time ≤ 1 month. However, the above conclusion needs further analysis and validation by more high-quality RCTs.Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier (CRD42023474215).

Integrated transcriptomic and CGAs analysis revealed IbGLK1 is a key transcription factor for chlorogenic acid accumulation in sweetpotato (Ipomoea batatas [L.] Lam.) blades.

Sweetpotato blades are rich in the functional secondary metabolite chlorogenic acid (CGA), which deepen potential for effective utilization of the blade in industry. In this study, we evaluated the type and content of CGA in the blades of 16 sweetpotato genotypes and analyzed the correlation between CGA content and antioxidant capacity. Then we isolated and characterized IbGLK1, a GARP-type transcription factor, by comparative transcriptome analysis. A subcellular localization assay indicated that IbGLK1 is located in the nucleus. Overexpression and silencing of IbGLK1 in sweetpotato blade resulted in a 0.90-fold increase and 1.84-fold decrease, respectively, in CGA content compared to the control. Yeast one-hybrid and dual-luciferase assays showed that IbGLK1 binds and activates the promoters of IbHCT, IbHQT, IbC4H, and IbUGCT, resulting in the promotion of CGA biosynthesis. In conclusion, our study provides insights into a high-quality gene for the regulation of CGA metabolism and germplasm resources for breeding sweetpotato.

A phase I study of docetaxel plus synthetic lycopene in metastatic prostate cancer patients.

PURPOSE: Our preclinical studies showed that lycopene enhanced the anti-prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer. METHODS: Subjects were treated with 21-day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel and multiple correlative studies were carried out. RESULTS: Twenty-four participants were enrolled, 18 in a dose escalation cohort to define the maximum tolerated dose (MTD), and six in a pharmacokinetic cohort. Docetaxel/ADT plus 150 mg/day synthetic lycopene resulted in dose-limiting toxicity (pulmonary embolus) in one out of 12 participants with an estimated probability of .106 and thus was chosen as the MTD. Lycopene increased the AUCinf and Cmax of plasma docetaxel by 9.5% and 15.1%, respectively. Correlative studies showed dose-related changes in circulating endothelial cells and vascular endothelial growth factor A, and reduction in insulin-like growth factor 1R phosphorylation, associated with lycopene therapy. CONCLUSIONS: The combination of docetaxel/ADT and synthetic lycopene has low toxicity and favourable pharmacokinetics. The effects of lycopene on biomarkers provide additional support for the toxicity-dependent MTD definition. HIGHLIGHTS: The maximum tolerated dose was identified as 150 mg/day of lycopene in combination with docetaxel/ADT for the treatment of metastatic prostate cancer patients. Small increases in plasma exposure to docetaxel were observed with lycopene co-administration. Mechanistically significant effects were seen on angiogenesis and insulin-like growth factor 1 signalling by lycopene co-administration with docetaxel/ADT.

The relationship between dietary phosphorus and peripheral neuropathy in the general population of the United States: A preliminary research.

BACKGROUND: Dietary phosphorus intake may serve as a potential predictor for peripheral neuropathy (PN). While past research has predominantly focused on the relationship between dietary phosphorus and bone health, relatively little is known about its role in the nervous system, particularly its association with PN. METHODS: A cross-sectional study was conducted using data from NHANES 1999-2004. Participants were categorized into different dietary phosphorus intake groups, and the relationship between dietary phosphorus and PN was explored using multifactorial logistic regression, restricted cubic splines (RCS) analysis, and threshold effect analysis based on dietary intake. RESULTS: The final study included 7726 participants, with 1378 diagnosed with PN and 6348 without. The study revealed a U-shaped non-linear relationship between dietary calcium and magnesium intake levels and PN, indicating that both excessive and insufficient dietary phosphorus intake may increase the risk of PN. Specifically, the incidence rates in the first quintile (1.433, 95% CI: 1.080-1.901), the fourth quintile (1.284, 95% CI: 1.000-1.648), and the fifth quintile (1.533, 95% CI: 1.155-2.035) significantly higher than the second quintile, with an overall trend showing a decrease followed by an increase in incidence rates. The results of RCS and threshold effect analysis indicate that when dietary phosphorus intake is below 939.44mg, the risk of PN decreases with increasing dietary phosphorus intake. On the contrary, when dietary phosphorus intake exceeds 939.44mg, the risk of PN increases with increasing dietary phosphorus intake. CONCLUSION: This study reveals a U-shaped correlation between dietary phosphorus intake and PN. Future research should further elucidate the molecular mechanisms underlying this association, providing guidance for more scientifically informed dietary adjustments to prevent the occurrence of PN.

Total laparoscopic partial hepatectomy versus open partial hepatectomy for primary left-sided hepatolithiasis: study protocol for a randomized controlled trial.

BACKGROUND: The advantages of laparoscopic left-sided hepatectomy (LLH) for treating hepatolithiasis in terms of the time to postoperative length of hospital stay (LOS), morbidity, long-term abdominal wall hernias, hospital costs, residual stone rate, and recurrence of calculus have not been confirmed by a randomized controlled trial. The aim of this trial is to compare the safety and effectiveness of LLH with open left-sided hepatectomy (OLH) for the treatment of hepatolithiasis. METHODS: Patients with hepatolithiasis eligible for left-sided hepatectomy will be recruited. The experimental design will produce two randomized arms (laparoscopic and open hepatectomy) at a 1:1 ratio and a prospective registry. All patients will undergo surgery in the setting of an enhanced recovery after surgery (ERAS) programme. The prospective registry will be based on patients who cannot be randomized because of the explicit treatment preference of the patient or surgeon or because of ineligibility (not meeting the inclusion and exclusion criteria) for randomization in this trial. The primary outcome is the LOS. The secondary outcomes are percentage readmission, morbidity, mortality, hospital costs, long-term incidence of incisional hernias, residual stone rate, and recurrence of calculus. It will be assumed that, in patients undergoing LLH, the length of hospital stay will be reduced by 1 day. A sample size of 86 patients in each randomization arm has been calculated as sufficient to detect a 1-day reduction in LOS [90% power and α = 0.05 (two-tailed)]. The trial is a randomized controlled trial that will provide evidence for the merits of laparoscopic surgery in patients undergoing liver resection within an ERAS programme. CONCLUSIONS: Although the outcomes of LLH have been proven to be comparable to those of OLH in retrospective studies, the use of LLH remains restricted, partly due to the lack of short- and long-term informative RCTs pertaining to patients with hepatolithiasis in ERAS programmes. To evaluate the surgical and long-term outcomes of LLH, we will perform a prospective RCT to compare LLH with OLH for hepatolithiasis within an ERAS programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT03958825. Registered on 21 May 2019.

New pyrrolidine-carboxamide derivatives as dual antiproliferative EGFR/CDK2 inhibitors.

Cancer is one of the leading causes of mortality worldwide, making it a public health concern. A novel series of pyrrolidine-carboxamide derivatives 7a-q were developed and examined in a cell viability assay utilizing a human mammary gland epithelial cell line (MCF-10A), where all the compounds exhibited no cytotoxic effects and more than 85% cell viability at a concentration of 50 µM. Antiproliferative activity was evaluated in vitro against four panels of cancer cell lines A-549, MCF-7, Panc-1, and HT-29. Compounds 7e, 7g, 7k, 7n, and 7o were the most active as antiproliferative agents capable of triggering apoptosis. Compound 7g was the most potent of all the derivatives, with a mean IC50 of 0.90 µM compared to IC50 of 1.10 µM for doxorubicin. Compound 7g inhibited A-549 (epithelial cancer cell line), MCF-7 (breast cancer cell line), and HT-29 (colon cancer cell line) more efficiently than doxorubicin. EGFR inhibitory assay results of 7e, 7g, 7k, 7n, and 7o demonstrated that the tested compounds inhibited EGFR with IC50 values ranging from 87 to 107 nM in comparison with the reference drug erlotinib (IC50 = 80 nM). 7e, 7g, 7k, 7n, and 7o inhibited CDK2 efficiently in comparison to the reference dinaciclib (IC50 = 20 nM), with IC50 values ranging from 15 to 31 nM. The results of inhibitory activity assay against different CDK isoforms revealed that the tested compounds had preferential inhibitory activity against the CDK2 isoform.

Targeting the SPHK1/S1P/S1PR2 axis ameliorates GH-secreted pituitary adenoma progression.

BACKGROUND: Growth hormone-secreted pituitary adenoma (GHPA) is a prominent subtype of pituitary adenoma (PA) associated with progressive somatic disfigurement, various complications, and elevated mortality rates. Existing treatment options have limited efficacy, highlighting the urgent need for novel pharmacological interventions. Previous studies have revealed that sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptors (S1PRs) signalling have critical roles in the tumour microenvironment, but their role in GHPA remains unclear. METHODS: We performed integrative analyses including bioinformatics analyses, functional studies, and clinical validation to investigate the pathological roles of SPHK1/S1P and evaluated the effectiveness of the S1P receptor 2 (S1PR2) inhibitor JTE-013 in GHPA treatment. RESULTS: SPHK1/S1P signalling is abnormally expressed in patients with GHPA. Knockdown of SPHK1 suppresses S1P-mediated cell proliferation in GH3 Cells. Mechanistically, S1P inhibits apoptosis and autophagy while promoting the secretion of Growth Hormone (GH) by binding to the S1P receptor subtype 2 (S1PR2) in GH3 cells. Moreover, the function of S1PR2 in GH3 cells is mediated by the downstream Akt-Creb pathway. We then identify the S1PR2 as a novel target for therapeutic intervention in GHPA. Systemic administration of the potent and selective S1PR2 antagonist, JTE-013, significantly reduces both tumour size and GH secretion. Importantly, we identify preoperative serum S1P levels as a biomarker predicting poor prognosis in GHPA patients at follow-up. CONCLUSION: Our study shows that blocking SPHK1/S1P/S1PR2 axis can ameliorate the progression of GHPA, providing evidence of a promising therapeutic target for GHPA.

Lysine demethylase 5B (KDM5B): A key regulator of cancer drug resistance.

Chemoresistance, a roadblock in the chemotherapy process, has been impeding its effective treatment. KDM5B, a member of the histone demethylase family, has been crucial in the emergence and growth of malignancies. More significantly, KDM5B has recently been linked closely to cancer's resistance to chemotherapy. In this review, we explain the biological properties of KDM5B, its function in the emergence and evolution of cancer treatment resistance, and our hopes for future drug resistance-busting combinations involving KDM5B and related targets or medications.

Relationship between serum endothelin-1 and in-stent restenosis following vertebral artery stenting.

The study objective was to investigate the relations between serum endothelin-1 and in-stent restenosis in vertebral artery stenting. Sixty-eight patients undergoing re-examination of vertebral artery stenting in the Department of Cerebrovascular Disease, Hangzhou Third People's Hospital, between April 2019 and October 2022, were invited to participate. According to the presence of vertebral artery stenting, patients were divided into the restenosis (n = 19) or non-restenosis (n = 49) groups. General clinical data and endothelin-1 levels were compared between the groups. Logistic regression analysis was used to explore the relations between endothelin-1 level and risk for in-stent restenosis. Receiver operating characteristic curves were drawn to test the diagnostic value of serum endothelin-1 level for in-stent restenosis. Compared with the non-restenosis group, restenosis group levels of low-density lipoprotein, triglycerides, and endothelin-1 were significantly higher (p < 0.05) Multivariate logistic regression analysis showed that endothelin-1, stent length, and low-density lipoprotein were independently associated with in-stent restenosis (odds ratio = 1.502, 95% confidence interval: 0.042 ~ 0.212, p = 0.000; odds ratio = 1.899, 95% confidence interval: 1.116 ~ 2.237, p = 0.000; odds ratio = 1.899, 95% confidence interval: 1.228 ~ 3.337, p = 0.001, respectively). Area under the curve for serum endothelin-1 in the diagnosis of vertebral artery in-stent restenosis was 0.938. The best diagnostic cut-off value was 11.94 ng/L. Sensitivity was 89.5%. Specificity was 85.7%. These cumulative data indicate that endothelin-1 level is independently associated with in-stent restenosis.

Polymorphisms in PI3K/AKT genes and gene­smoking interaction are associated with susceptibility to tuberculosis.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages. AIM: This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB. METHODS: This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction. RESULTS: Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction. CONCLUSION: We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB.

[Neurovascular coupling responses and cognitive function: The impact of aging and the interventional effect of exercise].

Aging is a natural process accompanied with a progressive deterioration of cognitive functions. With an aging population, more and more elderly people are suffering from cognitive impairment. Previous studies have paid more attention to the impact of inflammation and oxidative stress on cognitive function during aging. Recently, it has been discovered that neurovascular coupling (NVC), a mechanism regulating cerebral blood flow, may play a significant role in aging-related cognitive impairment. NVC responses regulate the supply of energy substances and oxygen during brain activity, which in turn enhances cognitive function. However, as people grow older, NVC responses gradually weaken, which may be one of the mechanisms underlying aging-induced cognitive impairment. Given the important role of NVC responses in the brain, it is necessary to search for intervention methods that can improve NVC responses and promote cognitive function. Exercise is an effective means to delay aging and improve cognitive function. It also has a certain promoting effect on NVC responses. This article reviews the regulatory mechanisms of NVC responses, the relationship between NVC responses and cognitive function, and explores the effects of aging and exercise intervention on NVC responses, hoping to provide new research ideas for exercise intervention to improve NVC responses and promote cognitive function in the elderly.

Interpetrosal sphingosine-1-phosphate ratio predicting Cushing's disease tumor laterality and remission after surgery.

Background: Cushing's disease (CD) poses significant challenges in its treatment due to the lack of reliable biomarkers for predicting tumor localization or postoperative clinical outcomes. Sphingosine-1-phosphate (S1P) has been shown to increase cortisol biosynthesis and is regulated by adrenocorticotropic hormone (ACTH). Methods: We employed bilateral inferior petrosal sinus sampling (BIPSS), which is considered the gold standard for diagnosing pituitary sources of CD, to obtain blood samples and explore the clinical predictive value of the S1P concentration ratio in determining tumor laterality and postoperative remission. We evaluated 50 samples from 25 patients who underwent BIPSS to measure S1P levels in the inferior petrosal sinuses bilaterally. Results: Serum S1P levels in patients with CD were significantly higher on the adenoma side of the inferior petrosal sinus than on the nonadenoma side (397.7 ± 15.4 vs. 261.9 ± 14.88; P < 0.05). The accuracy of diagnosing tumor laterality with the interpetrosal S1P and ACTH ratios and the combination of the two was 64%, 56% and 73%, respectively. The receiver operating characteristic curve analysis revealed that the combination of interpetrosal S1P and ACTH ratios, as a predictor of tumor laterality, exhibited a sensitivity of 81.82% and a specificity of 75%, with an area under the curve value of 84.09%. Moreover, we observed that a high interpetrosal S1P ratio was associated with nonremission after surgery. Correlation analyses demonstrated that the interpetrosal S1P ratio was associated with preoperative follicle-stimulating hormone (FSH), luteinizing hormone (LH), and postoperative ACTH 8 am levels (P < 0.05). Conclusion: Our study demonstrated a significant association between the interpetrosal S1P ratio and tumor laterality, as well as postoperative remission in CD, suggesting that the interpetrosal S1P ratio could serve as a valuable biomarker in clinical practice.

High prevalence of vertebral fractures associated with preoperative cortisol levels in patients with recent diagnosis of Cushing disease.

BACKGROUND/OBJECTIVE: Morphometric vertebral fractures (VFs) and osteopathy are prevalent and clinically significant complications of Cushing disease (CD). However whether they represent an early occurrence in the natural progression of the disease is an ongoing debate. This study aimed to assess the prevalence and determinants of VFs in patients newly diagnosed with CD. PATIENTS AND METHODS: This cross-sectional case-control study recruited 75 newly diagnosed CD patients and compared them with a control group of individuals without pituitary disorders or secondary forms of osteoporosis. Demographic, clinical and biochemical data were collected. The VFs were assessed using preoperative lateral chest radiography. RESULTS: We found a significantly higher prevalence of VFs in the CD group than in the control group (58.7% vs. 14.5%; P < 0.001). Among the CD patients with VFs, 27 (61.4%) showed moderate/severe VFs. The CD patients with VFs had significantly higher preoperative 8 am serum cortisol (8ASC) levels than those without VFs (P < 0.001). The preoperative 4 pm adrenocorticotropic hormone (ACTH) levels (P = 0.031), preoperative 0 am ACTH levels (P = 0.021) and systolic blood pressure were slightly higher in CD patients with VFs than in those without VFs (P = 0.028). A binary multiple logistic analysis showed that 8ASC was an independent predictor of VF risk (P = 0.003). The optimal cut-off value of the preoperative serum 8ASC level for predicting VFs was 22.18 ng/mL. CONCLUSIONS: This is the first study reporting a high prevalence of radiologic VFs in recently diagnosed CD patients. VFs may represent an early manifestation of CD and may be related to cortisol levels. Therefore, VF assessment should be included in the workup during CD diagnosis.

Sensitivity and Reliability Analysis of Ultrasonic Pulse Parameters in Evaluating the Laboratory Properties of Asphalt Mixtures.

The ultrasonic test is a promising non-destructive testing technique for evaluating the properties of asphalt mixtures. To investigate the applicability and reliability of ultrasonic testing technology (UTT) in evaluating the performance of asphalt mixtures, ultrasonic tests, indirect tensile tests, compression tests, and dynamic modulus tests were carried out at various temperatures. Subsequently, the distribution characteristics of ultrasonic traveling parameters for asphalt mixtures were analyzed. The variation of ultrasonic pulse velocity and amplitude in dry and wet states with temperature was studied. Then, the correlation between the ultrasonic parameters and both the volume parameters and the mechanical performance parameters of asphalt mixtures was revealed, and the functional relationship between ultrasonic pulse velocity and compressive strength was established. Finally, the reliability of predicting high-frequency dynamic modulus by ultrasonic velocity was verified. The laboratory tests and analysis results indicate that both ultrasonic pulse velocity and amplitude in dry and wet conditions show a decreasing trend with an increase in temperature. Ultrasonic parameters are greatly influenced by asphalt content and mineral aggregate content of 9.5~13.2 mm and 13.2~16 mm. The dynamic modulus at a high-frequency load can be predicted by using ultrasonic velocity, and predicting the results for OGFC and SMA mixtures deduced by using the UPV at a high-frequency load have higher reliability.

Silencing MFHAS1 Induces Pyroptosis via the JNK-activated NF-κB/Caspase1/ GSDMD Signal Axis in Breast Cancer.

INTRODUCTION: Breast cancer has emerged as the most widespread cancer globally surpassing lung cancer, and has become a primary cause of mortality among women. While MFHAS1 has been implicated in the pathophysiology of various diseases, its precise involvement in breast cancer remains unclear. METHODS: This study endeavors to elucidate the regulatory function of MFHAS1 in breast cancer cell pyroptosis and the associated molecular mechanisms. Our findings indicate that the inhibition of MFHAS1 can impede the proliferation and invasion of breast cancer cells, while also inducing cell pyroptosis via caspase1-dependent activation of GSDMD. RESULTS: This process results in the cleavage of cell membranes, leading to the release of inflammatory factors and LDH. Subsequent investigations revealed that the silencing of MFHAS1 can promote JNK phosphorylation, thereby activating the JNK signaling cascade. Notably, this effect can be counteracted by the JNK-specific inhibitor sp600125. Ultimately, our investigation substantiated the identical function of MFHAS1 in breast cancer tissue derived from animal models. CONCLUSION: To summarize, our findings demonstrate that the inhibition of MFHAS1 elicits pyroptosis in human breast cancer cells through the facilitation of JNK phosphorylation and the activation of the downstream NF-κB/caspase-1/GSDMD signaling cascade, thereby proposing the prospect of MFHAS1 as a viable therapeutic target for breast cancer.

Classification of five SARS-CoV-2 serotypes based on RBD antigenicities.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a significant number of variants, particularly with the emergence of Omicron with many sub-variants. These variants have exhibited increased immune escape, leading to reduced efficacy of existing vaccines and therapeutic antibodies. Given the diminished cross-neutralization observed among these variants, it is plausible that SARS-CoV-2 has developed multiple serotypes. As the major antigenic site, the receptor-binding domain (RBD) of viral spike (S) protein was chosen for serotyping. We selected 23 representative variants, including pre-Omicron variants and Omicron sub-variants, and classified them into five serotypes based on systematic evaluation of the antigenicities of their RBDs. Each serotype includes several genetically distinct variants. Serotype-I encompasses all pre-Omicron variants (with two subtypes), while the remaining four serotypes are all comprised of Omicron sub-variants at different stages of evolution. We propose that these serotypes can serve as a foundation for rapid classification of newly emerging SARS-CoV-2 variants, and guide the development of future broad-spectrum vaccines and neutralizing antibodies against the coronavirus disease 2019 (COVID-19).