Research trends and hotspots of circular RNA in cardiovascular disease: A bibliometric analysis.

From a global perspective, cardiovascular diseases (CVDs), the leading factor accounting for population mortality, and circRNAs, RNA molecules with stable closed-loop structures, have been proven to be closely related. The latent clinical value and the potential role of circRNAs in CVDs have been attracting increasing, active research interest, but bibliometric studies in this field are still lacking. Thus, in this study, we conducted a bibliometric analysis by using software such as VOSviewer, CiteSpace, Microsoft Excel, and the R package to determine the current research progress and hotspots and ultimately provide an overview of the development trends and future frontiers in this field. In our study, based on our search strategy, a total of 1206 publications published before July 31, 2023 were accessed from the WOSCC database. According to our findings, there is a notable increasing trend in global publications in the field of circRNA in CVDs. China was found to be the dominant country in terms of publication number, but a lack of high-quality articles was a significant fault. A cluster analysis on the co-cited references indicated that dilated cardiomyopathy, AMI, and cardiac hypertrophy are the greatest objects of concern. In contrast, a keywords analysis indicated that high importance has been ascribed to MI, abdominal aortic aneurysm, cell proliferation, and coronary artery diseases.

Astragaloside IV attenuates sunitinib-associated cardiotoxicity by inhibiting COUP-TFII.

Sunitinib (SU) is widely used to treat solid tumors but it can be cardiotoxic and often leads to drug withdrawn or discontinuation. Astragaloside IV (ASIV) is the essential active component of the Chinese herb Astragalus membranaceus which shows potential cardioprotective effects. Herein, we investigated the effect of ASIV on SU-associated cardiotoxicity and its mechanisms. We showed that ASIV significantly ameliorated SU-induced myocardial injury in mice, as evidenced by an improvement in left ventricular ejection fraction (EF) and a decrease in blood pressure and serum concentration of myocardial injury markers. ASIV attenuated SU-induced myocardial inflammatory infiltration and fibrotic lesions. In addition, ASIV suppressed SU-induced myocardial oxidative stress and apoptosis both in vitro and in vivo. Furthermore, SU increased COUP-TFII expression both in mRNA and protein levels in mice myocardial tissue, primary neonatal rat cardiomyocytes (NRCMs) and H9c2 cell lines, and this effect was rescued by ASIV. Knockdown of COUP-TFII reduced the oxidative stress and apoptosis induced by SU in NRCMs and H9c2 cell lines. However, the overexpression of COUP-TFII blocked the protective effects of ASIV on SU-treated cardiomyocytes. Thus, our results demonstrated that ASIV ameliorated SU-indued cardiotoxicity by inhibiting COUP-TFII, suggesting that ASIV might be a potential therapeutic strategy for the prevention of SU-associated cardiotoxicity.

Primary salivary duct carcinoma of the lung: clinicopathological features, diagnosis and practical challenges.

AIMS: To investigate the clinicopathological features, molecular characteristics and diagnostic criteria of primary salivary duct carcinoma of the lung (LSDC). METHODS: We analysed the clinicopathological and molecular features of five cases of LSDC retrieved from the archives of Shanghai Pulmonary Hospital from 2020 to 2022, and reviewed the relevant literature. RESULTS: All patients were men, with an average age of 66 years (age range: 49-79 years), and all lesions were central masses with a mean maximum diameter of 42.6 mm (range: 16-70 mm). Morphologically, LSDC comprised of intraductal and invasive components. Both the intraductal and invasive components of LSDC can exhibit papillary, micropapillary, cribriform, tubule structures and solid proliferation. The intraductal component can exhibit Roman bridge structures, which were usually accompanied by central comedo-like necrosis. Immunohistochemically, LSDCs consistently expressed cytokeratin (CK)7 (5 of 5) and showed variable positivity of androgen receptor (AR) (5 of 5) focally or diffusely; additionally, the tumour cells expressed human epidermal growth factor receptor 2 (HER2) (3+, n=3; 2+, n=2), GATA-binding protein 3 (3 of 5), and gross cystic disease fluid protein-15 (1 of 5), and all of which were negative for thyroid transcription factor-1, napsin A, p40, CK5/6 and p63. The residual basal/myoepithelial cells surrounding the in situ carcinoma expressed p40, CK5/6 and p63. TP53 mutation and HER2 gene amplification (3 of 5) were the most frequent genetic alterations in LSDC. All patients who underwent surgical lobectomies were alive without recurrence or metastasis. CONCLUSIONS: LSDC is a highly rare malignant tumour. The distinctive architecture of in situ carcinoma and tumour cells expressing AR can provide diagnostic indications for LSDC.

Overexpression of VEGFA mediated by HIF-1 is associated with higher rate of spread through air spaces in resected lung adenocarcinomas.

BACKGROUND: Spread through air spaces (STAS), a newly identified pattern of invasion in lung adenocarcinomas (LACs), is an unfavorable prognostic factor for patients with LAC, but the molecular characteristics and mechanisms underlying STAS have not been adequately explored. METHODS: In total, 650 pathologically confirmed invasive LAC patients who underwent curative resection between December 2019 and April 2020 were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. A comparative deep sequencing analysis was conducted to explore the molecular characteristics underlying STAS. Vascular endothelial growth factor A (VEGFA) expression was evaluated by immunoblotting and immunohistochemical analysis using fresh tumor tissue and tissue microarray. RESULTS: STAS was more prevalent in patients with a smoking history (p < 0.001), high pathological TNM stage (p < 0.001), lymphovascular invasion (p < 0.001), visceral pleural invasion (p < 0.001) and micropapillary/solid histological subtypes (p < 0.001). STAS-negative patients had better DFS (p < 0.001) and OS (p = 0.003) compared to STAS-positive patients with invasive LACs, especially in the lymph node-negative population (p < 0.001). After RNA-sequencing analysis, hypoxia-inducible factor-1 (HIF-1) signaling was enriched and appeared to be strongly correlated with STAS, and more STAS-positive individuals were detected in the higher VEGFA-expressing group (p = 0.042). CONCLUSIONS: We demonstrated that STAS was an independent prognostic marker of poor clinical outcome, especially in lymph node-negative patients, and that higher VEGFA expression mediated by HIF-1 signaling was associated with an increased STAS rate.

New pyrrolo[3,2-b]pyrroles with AIE characteristics for detection of dichloromethane and chloroform.

Three new pyrrolo[3,2-b]pyrrole derivatives containing methoxyphenyl, pyrene or tetraphenylethylene (TPE) units (compounds 1-3) have been designed, synthesized and fully characterized. The aggregation-induced emission (AIE) properties of compounds 1-3 were tested in different water fraction (fw ) of tetrahydrofuran (THF). The pyrrolo[3,2-b]pyrrole derivative 3 containing TPE units exhibited typical AIE features with an enhanced emission (∼32-fold) in the solid state versus in solution; compounds 1 and 2 exhibited an aggregation-caused quenching effect. In addition, the steric and electronic effects of the peripheral moieties on the emission behavior, both in solution and in the solid state, have been investigated. Moreover, pyrrolo[3,2-b]pyrrole 1 exhibits high sensitivity and selectivity for dichloromethane and chloroform solvents, with the system displaying a new emission peak and fast response time under ultraviolet irradiation.

Intravascular ultrasonography assisted carotid artery stenting for treatment of carotid stenosis: Two case reports.

BACKGROUND: Digital subtraction angiography (DSA), the gold standard of cerebrovascular disease diagnosis, is limited in its diagnostic ability to evaluate arterial diameter. Intravascular ultrasonography (IVUS) has advantages in assessing stenosis and plaque nature and improves the evaluation and effectiveness of carotid artery stenting (CAS). CASE SUMMARY: Case 1: A 65-year-old man presented with a five-year history of bilateral lower limb weakness due to stroke. Physical examination showed decreased strength (5-/5) in both lower limbs. Carotid artery ultrasound, magnetic resonance angiography, and computed tomography angiography (CTA) showed a right proximal internal carotid artery (ICA) stenosis (70%-99%), acute cerebral infarction, and severe right ICA stenosis, respectively. We performed IVUS-assisted CAS to measure the stenosis and detected a low-risk plaque at the site of stenosis prior to stent implantation. Post-stent balloon dilatation was performed and postoperative IVUS demonstrated successful expansion and adherence. CTA six months postoperatively showed no significant increase in in-stent stenosis. Case 2: A 36-year-old man was admitted with a right common carotid artery (CCA) dissection detected by ultrasound. Physical examination showed no positive neurological signs. Carotid ultrasound and CTA showed lumen dilation in the proximal CCA with an intima-like structure and bulging in the proximal segment of the right CCA with strip-like low-density shadow (dissection or carotid web). IVUS-assisted DSA confirmed right CCA dissection. CAS was performed and intraoperative IVUS suggested a large residual false lumen. Post-stent balloon dilatation was performed reducing the false lumen. DSA three months postoperatively indicated good stent expansion with mild stenosis. CONCLUSION: IVUS aids decision-making during CAS by accurately assessing carotid artery wall lesions and plaque nature preoperatively, dissection and stenosis morphology intraoperatively, and visualizing and confirming CAS postoperatively.

Emerging roles of circular RNAs in cancer therapy-induced cardiotoxicity.

Cancer therapy-induced cardiotoxicity (CTIC) is an important cause of death in cancer survivors which often results in the withdrawal or discontinuation of drugs. The underlying mechanisms of CTIC remain unclear. Circular RNAs (circRNAs) are a class of non-coding regulatory RNA molecules which have emerged in recent years. They are generated by back splicing and have powerful biological functions, including transcription and splicing, isolating or building macromolecular scaffolds to interfere with microRNA activity and signaling pathways, and acting as templates for translation. Moreover, circRNAs demonstrate high abundance and significant stability. CircRNAs can be used as novel biomarkers because they often function in a cell-type and tissue-specific manner. CircRNAs have attracted increasing attention in cardiovascular disease research, and recent studies exploring the role of circRNAs in CTIC have had promising results. This review will summarize the current understanding of circRNAs' biogenesis, regulation and function. Their clinical potential as biomarkers, therapeutic agents and drug targets will also be explored.

The IASLC grading system for invasive pulmonary adenocarcinoma: a potential prognosticator for patients receiving neoadjuvant therapy.

Background: Grading system for resected invasive pulmonary adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) was validated as a strong prognostic indicator. Nonetheless, the efficacy of utilizing such grading system in prognostic assessment of patients receiving neoadjuvant therapy still needs elucidating. Methods: A retrospective study was conducted including patients with resected adenocarcinoma following neoadjuvant chemotherapy or targeted therapy from August 2012 to December 2020 in Shanghai Pulmonary Hospital. All the surgical specimens were re-evaluated and graded. The prognostic value of the grading system was further validated. Results: Ultimately, a total of 198 patients were enrolled in this study, and subdivided into three cohorts according to the grading system. There were 13 (6.6%), 37 (18.7%), and 148 (74.7%) patients belonging to Grades 1, 2, and 3, respectively. IASLC grading system demonstrated significant power in prognosis differentiation of the entire cohort [recurrence-free survival (RFS), p < 0.001; overall survival (OS), p < 0.001] and the neoadjuvant chemotherapy and targeted therapy cohorts separately, and was further verified as a significant prognostic indicator for RFS and OS in multivariable Cox analysis. Since the majority of the patients (84.8%) did not achieve major pathologic response (MPR), representing a wide spectrum of survival, the prognostic value of grading system in non-MPR cohort was further evaluated. Similar results were also obtained that IASLC grading system was assessed significant in univariable analysis of RFS (p < 0.001) and univariable analysis of OS (p = 0.001). Conclusions: The prognostic efficacy of pathological evaluation of the residual proportion of pulmonary adenocarcinoma post-neoadjuvant therapy using IASLC grading system was preliminarily verified. Such grading system might assist prognostic evaluation of neoadjuvant cohort other than traditional pathological parameters.

Clinical Significance of Dual-Block Elastic Stain Evaluating Visceral Pleural Invasion in Peripheral Non-Small Cell Lung Cancer.

Visceral pleural invasion (VPI) is a critical component in the staging of peripheral non-small cell lung carcinoma (NSCLC). We aim to investigate whether dual-block elastic stain increases visceral pleural invasion positivity compared with single-block elastic stain. We further analyze the potential predictors of visceral pleural invasion. 8419 peripheral NSCLC patients (including 6008 patients with tumor size≤3 cm in stage I) were divided into a cohort using one paraffin block (single-block group, n = 5184) and a cohort using dual paraffin blocks (dual-block group, n = 3235) for elastic stain. The VPI-positive rate demonstrated by the dual-block elastic stains group was significantly higher than that of the single-block elastic stain group (17.7% (573/3235) versus 9.1% (474/5184), respectively, P < .001). The presence of visceral pleural invasion in T1 (≤3 cm) patients detected by single- and dual-block elastic stain was 6.3% (235/3730) and 12.0% (273/2278), respectively (P < .001). 5.7% of T1 patients (stage IA) were additionally upstaged to T2a (stage IB) by dual-block elastic stain. However, the incidence of visceral pleural invasion in pT2a patients showed no significant difference between the single-block group and the dual-block group (16.8% vs. 17.1%, P = .916). Lymphovascular invasion, lymph node metastasis, dedifferentiated carcinomas, the presence of spread through airspaces (STAS) and a poorly differentiated adenocarcinomatous growth pattern could be significant predictors of visceral pleural invasion (P < .001). Our results indicate that using dual-block elastic stain identifies more visceral pleural invasion positive T1 NSCLC patients who are upstaged to T2a, and who could benefit from optimal management post-operatively. The application of dual-block elastic stain is an efficient and practical method to detect visceral pleural invasion status.

The Correlation Between Histologic, Immunophenotypic, and Molecular Characteristics of Pulmonary Sarcomatoid Carcinoma Reveals That Sarcomatoid Change Is Potentially Derived From Epithelial Carcinoma Cells Undergoing Epithelial-Mesenchymal Transition.

Pulmonary sarcomatoid carcinoma (PSC) is characterized by biphasic tumors with epithelial and mesenchymal phenotype. Little is known about the correlation between histologic, immunophenotypic features and the genetic profile of PSC. We analyzed the expression of epithelial-mesenchymal transition-related markers, adenocarcinoma (ADC) and squamous cell carcinoma lineage-specific markers of 205 PSC cases. The alteration of 5 targeted genes was detected by amplification-refractory mutation system-polymerase chain reaction. The intensity of cytokeratin staining was stronger in epithelial carcinoma (EC) than that of the sarcomatoid component (SC) of pleomorphic carcinoma, while vimentin was positive in only 16.3% (17/104) of EC of pleomorphic carcinoma. There is no significant difference between thyroid transcription factor 1 (TTF-1) expression in the SC (46.5%, 33/71) of pleomorphic carcinoma with ADC components and pure PSC (44.2%, 42/95) without p40 expression ( P =0.858). Four cases with ALK rearrangement were confirmed to co-express ALK fusion protein in both the SC and EC. The incidence of EGFR/ALK/KRAS mutation was similar between pleomorphic carcinoma with ADC components (40.6%, 26/64) and TTF-1 + pure PSC (38.2%, 13/34) ( P =0.583). However, higher proportions of TTF-1 + /p40 - PSC patients (44.8%, 39/87) had EGFR/ALK/KRAS mutation than those with TTF-1 - /p40 - PSC (16.7%, 4/24) ( P =0.031). The incidence of EGFR mutation was significantly higher in TTF-1-positive (18.4%, 16/87) than TTF-1-negative (2.7%, 2/74) PSC ( P =0.002). No EGFR and ALK abnormality were observed in 24 pleomorphic carcinoma cases with squamous cell carcinoma components or pure PSC with p40 expression. Our study reveals a close correlation between SC and EC components of pleomorphic carcinoma in terms of immunophenotypic and genetic features, which suggests that pleomorphic carcinoma is potentially derived from the sarcomatoid change of EC cells undergoing epithelial-mesenchymal transition.

Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma.

BACKGROUND: The diversity of histologic composition reflects the inter- and intra-tumor heterogeneity of lung adenocarcinomas (LUADs) macroscopically. Insights into the oncological characteristics and tumor microenvironment (TME) of different histologic subtypes of LUAD at the single-cell level can help identify potential therapeutic vulnerabilities and combinational approaches to improve the survival of LUAD patients. METHODS: Through comparative profiling of cell communities defined by scRNA-seq data, we characterized the TME of LUAD samples of distinct histologic subtypes, with relevant results further confirmed in multiple bulk transcriptomic, proteomic datasets and an independent immunohistochemical validation cohort. RESULTS: We find that the hypoxic and acidic situation is the worst in the TME of solid LUADs compared to other histologic subtypes. Besides, the tumor metabolic preferences vary across histologic subtypes and may correspondingly impinge on the metabolism and function of immune cells. Remarkably, tumor cells from solid LUADs upregulate energy and substance metabolic activities, particularly the folate-mediated one-carbon metabolism and the key gene MTHFD2, which could serve as a potential therapeutic target. Additionally, ubiquitination modifications may also be involved in the progression of histologic patterns. Immunologically, solid LUADs are characterized by a predominance of exhausted T cells and immunosuppressive myeloid cells, where the hypoxic, acidified and nutrient-deprived TME has a non-negligible impact. Discrepancies in stromal cell function, evidenced by varying degrees of stromal remodeling and fibrosis, may also contribute to the specific immune phenotype of solid LUADs. CONCLUSIONS: Overall, our research proposes several potential entry points to improve the immunosuppressive TME of solid LUADs, thereby synergistically potentiating their immunotherapeutic efficacy, and may provide precise therapeutic strategies for LUAD patients of distinct histologic subtype constitution.

DATA-driven shock impact of COVID-19 on the market financial system.

The Corona Virus Disease 2019(COVID-19) has a dramatic effect on my country's market and financial system. Although China has controlled the deterioration of the epidemic, this global epidemic will inevitably have an impact on the global economy including China. In order to study the shock effect of the COVID-19 on the market financial system, this paper builds a data model processing system based on the event analysis method, and analyzes the shock effect from three aspects of supply chain finance, financial securities, and corporate financial systems. Moreover, this paper uses crawler technology to obtain valid data from major websites, analyzes model data with mathematical statistics combined with event models, and outputs the results and compares them with the actual situation. Through data analysis, it can be seen that the model constructed in this paper can effectively reflect the shock effect of the COVID-19 on the market financial system. Finally, the comparison method is used to compare the research results with the actual situation. The results show that the two are basically the same. Therefore, it can be seen that the proposed research method has significant effects and has certain reference value for studying the shock effect of the epidemic on the financial system.

The effects of Danggui-Shaoyao-San on neuronal degeneration and amyloidosis in mouse and its molecular mechanism for the treatment of Alzheimer's disease.

The abnormal deposition of the extracellular amyloid-ß peptide is the typical pathological hallmark of Alzheimer's disease. Strategies to reduce the amyloid-ß deposition effectively alleviate the neuronal degeneration and cognitive deficits of Alzheimer's disease. Danggui-Shaoyao-San has been considered a useful therapeutic agent known for the treatment of Alzheimer's disease. However, the mechanism of Danggui-Shaoyao-San for the treatment of Alzheimer's disease remains unclear. We investigated Danggui-Shaoyao-San's effect on amyloidosis and neuronal degeneration in an APP/PS1 mouse model. We found Danggui-Shaoyao-San alleviated the cognitive deficits in APP/PS1 mice. Additionally, Danggui-Shaoyao-San ameliorated the neuronal degeneration in these mice. Danggui-Shaoyao-San reduced the amyloidosis and amyloid-ß1-42 deposition in APP/PS1 mouse brain and down-regulated the receptor for advanced glycation end products, and up-regulated the level of low-density lipoprotein receptor-related protein-1. However, the protein expression of the ß-amyloid precursor protein, ß-Secretase and presenilin-1 (PS1) in the amyloid-ß production pathway, and the expression of neprilysin and insulin-degrading enzyme in the amyloid-ß degradation pathway were not altered. Our findings collectively suggest that Danggui-Shaoyao-San could ameliorate the amyloidosis and neuronal degeneration of Alzheimer's disease, which may be associated with its up-regulation lipoprotein receptor-related protein-1 and down-regulation of the receptor for advanced glycation end products.

ISL Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Downregulation of PI3K/AKT/mTOR Pathway in vivo and in vitro.

AIMS: Isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, has previously been reported to have anti-tumor effects in vivo and in vitro. However, the mechanisms whereby ISL exerts its anticancer effects remain poorly understood in hepatocellular carcinoma (HCC). PURPOSE: In the present study, we investigated the anticancer efficacy and associated mechanisms of ISL in HCC MHCC97-H and SMMC7721 cells. RESULTS: We found that ISL inhibited cell viability and proliferation and induced apoptosis in a dose- and time-dependent manner in liver cancer lines. Furthermore, ISL could activate autophagy in HCC cells, and the autophagy inhibitor HCQ enhances ISL-induced apoptosis in HCC cells. Additionally, ISL induced apoptosis and autophagy through inhibition of the PI3K/Akt/mTOR pathway. Most importantly, in a xenograft tumor model in nude mice, data showed that the administration of ISL decreased tumor growth and concurrently promoted the expression of LC3-II and cleaved-caspase-3. Interestingly, we found that ISL inhibits mTOR by docking onto the ATP-binding pocket of mTOR (ie, it competes with ATP). We thus suggest that mTOR is a potential target for ISL inhibition of hepatocellular carcinoma development, which could be of interest for future investigations. CONCLUSION: Taken together, the results reveal that ISL effectively inhibited proliferation and induced apoptosis in HCC through autophagy induction in vivo and in vitro, probably via the PI3K/Akt/mTOR pathway. ISL may be a potential therapeutic agent for hepatocellular carcinoma.

[Acupuncture improves locomotor activity and learning-memory ability by improving hippocampal cellular autophagy in rats with fetal intrauterine distress].

OBJECTIVE: To investigate the effect of acupuncture stimulation of head acupoints "Jin San Zhen" (JIN's Three Acupuncture Needles Therapy) on behavior reactions, hippocampal neuronal autophagy and expression of autophagy associated proteins (Beclin-1 and light chain 3 Ⅱ/Ⅰ [LC 3 Ⅱ/Ⅰ]) in rats with hypoxic-ischemic brain damage (HIBD) due to fetal intrauterine distress, so as to reveal its underlying mechanisms in improving neonatal HIBD. METHODS: Pregnant SD rats were used in the present study. The HIBD model was established by delayed caesarean delivery and bilateral uterine arteries clipping for 10 minutes. The HIBD rats were randomly divided into model group and acupuncture groups (n＝9 rats in each group). The other 9 rats delivered naturally were used as the normal control group. On day 14 after delivery, the neonatal rats in the acupuncture group received acupuncture stimulation of head acupoints ("Nao San Zhen""Nie San Zhen" and "Zhi San Zhen") by twirling each needle leftward and rightward for 10 times, once a day for 14 d. The open field test and Morris water maze test were used to determine the locomotive activity and spatial learning-memory ability, respectively. The ultrastructure and autophagosomes in the hippocampal neurons were observed by transmission electron microscope. The contents and expression levels of Beclin-1 and LC3 Ⅱ/Ⅰ in the hippocampus tissues were detected by flow cytometry and Western blot, separately. RESULTS: Compared with the normal control group, the time to go out of the central region of open field test, and the escape latency and duration of first platform-quadrant-crossing of spatial exploration of Morris water maze tests were significantly increased (P<0.01，P<0.05，P<0.001), and the total distance and number of activities in the central region, and the target quadrant resistance time and number of platform-cros-sing remarkably decreased in the model group (P<0.01, P<0.05), suggesting a decline of both locomotor activity and learning-memory ability after modeling. The expression level (%) of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ proteins were considerably increased in the model group (P<0.01). Following acupuncture interventions, the locomotor activity and spatial learning-memory ability were obviously increased (P<0.05，P<0.01，P<0.001), and the expression of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ were further up-regulated relevant to the model group (P<0.001). Moreover, ultrastructural observation showed serrated change of nuclear membrane and widened perinuclear space, vacuolization in the mitochondria, dilation of endoplasmic reticulum and increase of autophagosomes in the hippocampal neurons in the model group. These situations were relatively milder in the acupuncture group. CONCLUSION: Acupuncture of head acupoints of "JIN San Zhen" may increase locomotor activity and learning-memory abi-lity in rats with HIBD due to fetal intrauterine anoxia, which is closely with its effect in promoting hippocampal neuronal autophagy via up-regulating the expression of Beclin-1 and LC3 Ⅱ/Ⅰ.

Betulinic acid induces autophagy-mediated apoptosis through suppression of the PI3K/AKT/mTOR signaling pathway and inhibits hepatocellular carcinoma.

Betulinic acid (BA) is a pentacyclic triterpenoid compound that widely exists in Chinese herbal medicine, and it has remarkable biological activity. However, the involved molecular targets and mechanisms of BA are still ambiguous. Here, we aim to validate the preventive effects and molecular mechanisms of BA against hepatocellular carcinoma via related experiments. We extracted the 2D and 3D structure of BA from the PubChem database. MTT assay and colony formation assay were used to determine the anti-proliferation and cytotoxicity of BA using in vitro cell models. Hoechst 33258 staining was used to investigate the extent of apoptosis after BA treatment. Western blot and immunofluorescence experiments were used to evaluate apoptosis-related and autophagy-related proteins and molecular mechanisms. We demonstrated that BA significantly inhibited cell proliferation in HepG2 and SMMC-7721 hepatocellular carcinoma cells, but with little cytotoxicity effects on l-02 normal liver cells. We further determined that the hepatocellular carcinoma prevention effects of BA were closely correlated with apoptosis and autophagy. Furthermore, our data indicated that BA-induced autophagy has a protective effect against cancer cell proliferation and promotes cell apoptosis. Additionally, apoptosis and autophagy were induced by BA through suppression of the PI3K/AKT/mTOR signaling pathway. Collectively, our study provides experimental evidence that BA inhibits cell proliferation and induces cell apoptosis and autophagy via suppressing the PI3K/AKT/mTOR pathway. Additionally, BA is a safe and effective herbal medicine compound that can be used for the prevention of hepatocellular carcinoma growth, and may be a potential therapeutic strategy against hepatocellular carcinoma.

Astragaloside IV ameliorates motor deficits and dopaminergic neuron degeneration via inhibiting neuroinflammation and oxidative stress in a Parkinson's disease mouse model.

Oxidative stress and neuroinflammation are the key and early events during the pathological process of Parkinson's disease (PD). Thus, therapeutic intervention to regulate oxidative stress and neuroinflammation would be an effective strategy to alleviate the progression of PD. Astragaloside IV, the main active component isolated from Astragalus membranaceus, has been shown to possess anti-inflammatory and anti-oxidant properties in neurodegeneration diseases, however, the molecular mechanisms of Astragaloside IV in the pathology of PD are still unclear. In this study, we explored the mechanisms of Astragaloside IV of PD on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model and lipopolysaccharide (LPS)-induced BV2 microglia cells. Our results showed Astragaloside IV significantly alleviated behavioral impairments and dopaminergic neuron degeneration induced by MPTP. Also, Astragaloside IV inhibited microglia activation and reduced the oxidative stress of MPTP mouse model. In addition, Astragaloside IV significantly inhibited NFκB mediated NLRP3 inflammasome activation and activated Nrf2 both in vivo and in vitro. Furthermore, Astragaloside IV lessened reactive oxygen species (ROS) generation in LPS-induced BV2 microglia cells remarkably. These findings demonstrate that Astragaloside IV protects dopaminergic neuron from neuroinflammation and oxidative stress which are largely dependent upon activation of the Nrf2 pathways and suppression of NFκB/NLRP3 inflammasome signaling pathway. Therefore, Astragaloside IV is a promising neuroprotective agent that should be further developed for neurodegeneration diseases.

C-terminus of heat shock protein 60 can activate macrophages by lectin-like oxidized low-density lipoprotein receptor 1.

Immune responses against antigens generally require an efficient activation of antigen-presenting cells (APCs). Currently, the targeting of vaccine antigens to APCs has emerged as a promising strategy for boosting vaccine immunogenicity. Here, we reported that the C-terminus of heat shock protein 60 (HSP60C) can activate mouse peritoneal macrophages to secret a series of cytokines, and phosphorylation of p38 mitogen-activated protein kinase (MAPK) and NF-κB p65 was involved in the pathway. We showed that the activation effect of HSP60C on macrophages was independent of toll-like receptor (TLR) 4 and the TLR-associated myeloide differentiation factor 88 (MyD88). Knockdown of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) reduced the activation of HSP60C-induced macrophage p38 MAPK, NF-κB p65 and cytokine secretion to some extent. Finally, we found that HSP60C up-regulated the expression of LOX-1 on macrophages and ovalbumin (OVA) model antigen fused with HSP60C markedly enhanced OVA-specific IgG responses. Thus, our results unravel a novel LOX-1-dependent pathway by which HSP60C can effectively activate macrophages and APCs targeting based on LOX-1 interaction is a promising approach to improve vaccines.

[Exploration on "three eye-needling" technique of acupuncture].

The "three eye-needling" technique is one of the important component of Jin's three needling therapy, mainly used for the treatment of eye disorders such as optic atrophy, macular pigment degeneration, myopia, hyperopia, strabismus, amblyopia, diplopia, glaucoma, cataract, etc. In the paper, Jin's "three eye-needling" technique is explored, including the keys of manipulation, operation procedure and basic skills. This technique is particularly for "mind regulation", focusing on tranquilizing, observing and concentrating the mind. The precise selection of point is the basic requirement, the technique for fixing, pressing and pricking are the most important link. The needle insertion with one hand is adopted with gentle rotation manipulation. Mind regulation, point selection and specific operation are coordinated with each other to bring the function of "three eye-needling" technique into play and achieve better therapeutic effects.

[Analysis of Clinicopathological Characteristics and Prognosis of 112 Patients with Primary Waldeyer's Ring Lymphoma].

OBJECTIVE: To investigate the clinical and pathological characteristics of patients with primary Waldeyer's ring lymphomas (PWRL), and to analyze its therapeutic efficacy and prognostic factors. METHODS: A total of 112 patients with PWRL confirmed by pathological and immunohistochemical methods between January 2009 and January 2014 were studied. Clinical data were collected and analyzed retrospectively. RESULTS: PWRL accounted for 3.9% of lymphoma over the same period. Median age of patients with PWRL was 51.5 years old. The affected areas were tonsil, nasopharynx, tongue base and oropharynx, which accounted for 63.4% (71/112), 22.3% (25/112), 5.3% (6/112) and 4.5% (5/112) respectively. The most common pathological types of these four areas were diffused large B-cell lymphoma (DLBCL) and extranodal NK/T cell lymphoma (NKTCL) which accounted for 58% and 15.2%. The overall response rate (CR/CRu = 51.4%; PR = 30.8%) in all patients was 82.2%, the estimated 5-year overall survival (OS) rate were 71.6%. The 5-year OS rate were 94.7% in the group used Rituximab. Meanwhile, chemotherapy combined with radiotherapy could improve the outcome of T-cell PWRL patients and the 5-year OS rate were 88.9%. Age, disease stages, pathological types, IPI scores, LDH level, ß2-MG level and the efficacy of initial therapy were prognostic factors with statistical significance. Cox multivariate analysis showed that age of more than 60 years, LDH level, pathological types and the efficacy of the initial therapy were independently associated with OS. CONCLUSION: PWRL has a relatively good prognosis. The pathological types affect the prognosis directly and guide treatment. Combined modality therapy should be chosen for patients with PWRL. Patients with T-cell PWRL should accept chemotherapy combined with radiotherapy, while rituximab may be better for B-cell PWRL. The efficacy of initial therapy is crucial for the outcome of patients. Age and LDH level are also important prognostic factors.