In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Proliferation/drug effects* ; Hep G2 Cells ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Caspase 3/genetics*

Acori Tatarinowii Rhizoma is the dried rhizome of Acorus tatarinowii in the family of Tennantiaceae, which has the efficacy of opening up the orifices and expelling phlegm, awakening the mind and wisdom, and resolving dampness and opening up the stomach. Modern studies have shown that volatile oil is the main active ingredient of Acori Tatarinowii Rhizoma, and α-asarone and β-asarone have been proved to be the active ingredients in the volatile oil of Acori Tatarinowii Rhizoma, with pharmacological effects such as anti-Alzheimer's disease, antiepileptic, anti-Parkinson's disease, antidepressant, anticerebral ischemia/reperfusion injury, anti-thrombosis, lipid-lowering, and antitumor. By summarising and outlining the pharmacological effects of α-asarone and β-asarone and elucidating the possible mechanisms of their pharmacological effects, we can provide theoretical basis for the further research and clinical application of Acori Tatarinowii Rhizoma.
Allylbenzene Derivatives ; Acorus/chemistry* ; Anisoles/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Animals

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To compare the therapeutic efficacy and safety of local anesthesia and spinal anesthesia for the patients with varicocele (VC) who underwent microsurgical varicocelectomy (MV). METHODS: We retrospectively analyzed the data of VC patients who underwent MV treatment at the Andrology Department of the Affiliated Ruikang Hospital of Guangxi University of Chinese Medicine from May 2020 to March 2023. Cases with complete clinical data and follow-up evaluation were selected and divided into a control group (spinal anesthesia) and an observation group (local anesthesia) according to different anesthesia methods. The surgical time (including anesthesia time), visual analogue scale (VAS) score for pain, hospital stay, treatment cost, sperm concentration, forward motile sperm rate, and normal sperm morphology rate after three months of surgery, as well as postoperative complications and recurrence rate were compared between the two groups. RESULTS: A total of 107 eligible cases were included, with 56 cases in the control group and 51 cases in the observation group. There was no significant difference in the VAS score for pain during and after four hours of surgery, as well as postoperative complications, and recurrence rate between the two groups (P> 0.05). There was an significant increase in sperm concentration, forward motile sperm rate, and normal sperm morphology rate in both of two groups after three months of surgery (P<0.05). However, there was no significant difference between the two groups three months after surgery (P>0.05). The surgical time and hospital stay were shorter than those of the control group (P<0.05). And the treatment cost in observation group was lower than that of the control group (P<0.05). CONCLUSION Both local anesthesia and lumbar anesthesia for MV treatment of VC have good efficacy and safety. However, patients treated with MV under local anesthesia for VC have obvious advantages in terms of operation time (including anesthesia time), hospital stay, and treatment cost, which is worthy of clinical promotion and application.
Humans ; Male ; Varicocele/surgery* ; Retrospective Studies ; Microsurgery ; Anesthesia, Spinal ; Adult ; Treatment Outcome ; Anesthesia, Local

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.