PIK3R6 Promotes Angiogenesis in Hepatocellular carcinoma by Activating STAT3 Signaling Pathway.

Objective: Abundant angiogenesis in hepatocellular carcinoma (HCC) is critical in its malignant course; however, its mechanism is incompletely understood. Meanwhile, the corresponding roles of PIK3R6 molecules in HCC have not been investigated. This study aims to explore the intrinsic mechanism of PIK3R6 and provide theoretical reference for the treatment of hepatocellular carcinoma. Methods: Differential expressions of PIK in ovarian cancer and normal ones were detected by Western blotting and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Analyze the relationship between the expression of PIK3R6 and patient prognosis through the TCGA database. Subsequently constructed corresponding stable cell lines, combined with transcriptome sequencing and several cell biology experiments, we explored the inner mechanism and clinical significance of PIK3R6. Results: By analyzing multiple cohorts, we found that high PIK3R6 expression in tumor tissues negatively correlates with patient prognosis. PIK3R6 could increase angiogenesis in HCC by boosting the activity of the STAT3 signalling pathway to hasten the malignant progression of the disease, according to corresponding cellular and molecular experimental studies. Then again, immunohistochemistry on a series of tissue chips confirmed the important clinical significance of PIK3R6-STAT3 regulatory axis. Couclusions: This study initially addressed the clinical significance of PIK3R6 and revealed its mechanism for promoting angiogenesis in hepatocellular carcinoma, providing a reliable working foundation for future in-depth research and clinical translation.

Integrated strategy facilitates rapid in-depth chemome characterization of traditional Chinese medicine prescriptions: Shengbai oral liquid as a case.

Chemome characterization is the prerequisite for either therapeutic mechanism clarification or quality control of traditional Chinese medicine prescriptions (TCMPs). Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) currently serves as the most popular analytical tool; however, chemome characterization is still challenged by MS/MS spectral acquisition and post-acquisition data processing. Here, an integrated strategy was proposed for in-depth chemome clarification of Shengbai oral liquid (SBOL). Gas phase ion fractionation with staggered mass ranges was demonstrated to be the superior acquisition method regarding MS2 spectrum coverage in this study, and narrower mass range further advanced coverage. To facilitate information extraction, all ingredient materials were measured in parallel to form an in-house library, where each MS1 -MS2 item generated a square mass-to-charge ratio (m/z) frame to capture the tagged identity and each chemical family produced a pentagon frame for mass defect features to accomplish chemical analogs-targeted quasi-molecular ion extraction. Square m/z frame imprinting captured 355 identities, while mass defect frames extracted 275 compounds. Attributing to comprehensive MS2 spectrum acquisition and efficient data processing, 355 components were captured and tentatively identified, resulting in a clarified chemical composition for SBOL. Therefore, the proposed strategy should be meaningful for the chemome characterization of TCMPs.

Effect and mechanism of tai chi on blood pressure of patients with essential hypertension: a randomized controlled study.

BACKGROUND: Tai chi is a traditional Chinese martial art that is increasingly popular in the world for positive health benefits. The influence and mechanism of tai chi on blood pressure in patients with essential hypertension still have high value for research. METHODS: A total of 99 patients with hypertension were randomly divided into control group and tai chi group. Tai chi intervention lasted for 12 weeks, and the control group maintained normal dietary and exercise habits. The changes of systolic and diastolic blood pressures in patients before and after the intervention were monitored. The serum concentrations of angiotensin II (Ang II) and nitric oxide (NO) were detected. RESULTS: There was no significant difference in baseline parameters between the two groups (P>0.05). Compared with the control group, the decreased systolic and diastolic blood pressure in tai chi group was higher after 12 weeks (P<0.001). At the 12th week, the decreased level of Ang II and the increased level of NO in tai chi group were higher than those in the control group (P<0.001). CONCLUSIONS: Tai chi can improve the blood pressure of patients with hypertension by decreasing the serum Ang II level and increasing the serum NO level.

The Impact of the Declaration of the State of Emergency on the Spread of COVID-19: A Modeling Analysis.

When encountering the outbreak and early spreading of COVID-19, the Government of Japan imposed gradually upgraded restriction policies and declared the state of emergency in April 2020 for the first time. To evaluate the efficacy of the countering strategies in different periods, we constructed a SEIADR (susceptible-exposed-infected-asymptomatic-documented-recovered) model to simulate the cases and determined corresponding spreading coefficients. The effective reproduction number R t was obtained to evaluate the measures controlling the COVID-19 conducted by the Government of Japan during different stages. It was found that the strict containing strategies during the state of emergency period drastically inhibit the COVID-19 trend. R t was decreased to 1.1123 and 0.8911 in stages 4 and 5 (a state of emergency in April and May 2020) from 3.5736, 2.0126, 3.0672 in the previous three stages when the containing strategies were weak. The state of emergency was declared again in view of the second wave of massive infections in January 2021. We estimated the cumulative infected cases and additional days to contain the COVID-19 transmission for the second state of emergency using this model. R t was 1.028 which illustrated that the strategies were less effective than the previous state of emergency. Finally, the overall infected population was predicted using combined isolation and testing intensity; the effectiveness and the expected peak time were evaluated. If using the optimized control strategies in the current stage, the spread of COVID-19 in Japan could be controlled within 30 days. The total confirmed cases should reduce to less than 4.2 × 105 by April 2021. This model study suggested stricter isolating measures may be required to shorten the period of the state of emergency.

Acupuncture for cancer-related hiccups: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hiccups are involuntary contractions of the diaphragm and intercostal muscles, which lead to sudden contractions of the glottis. CAM, such as acupuncture is commonly used and stimulation of the vagus nerve and interference with phrenic nerve conduction are also used to treat hiccups. However, there is little evidence on the effectiveness of acupuncture for cancer-related hiccups. We will plan to conduct a systematic review and meta-analysis of RCTs to evaluate the current evidence on the effects of acupuncture for cancer-related hiccups. METHOD: The following databases will be searched: PubMed, the Cochrane Library, Wanfang Data, China National Knowledge Infrastructure (CNKI), SinoMed, VIP, Medline, Embase, and EI. Randomized controlled trials will be included to evaluate the effect and safety of acupuncture on cancer patients with hiccups. We will set standards for the curative effect on the basis of the standard of cure and improvement for clinical disease diagnoses. The risk of bias will be assessed by the Cochrane risk of bias tool. We will conduct a meta-analysis and sensitivity analysis, as well as a subgroup analysis if high heterogeneity is present, using Revman 5.3. We will use funnel plots to identify potential reporting biases. We will test asymmetry using Egger test. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used to evaluate the quality of evidence. RESULTS: This study will be to assess the effect and safety of acupuncture for cancer-related hiccups. CONCLUSIONS: This study will assess the effect of acupuncture for cancer-related hiccups and provide reliable evidence for the choice of treatments.

Effects of the Kunlun snow chrysanthemum polysaccharides on acetaminophen-induced oxidative stress, inflammation and apoptosis using animal model.

To investigate the preventive effect of Kunlun snow chrysanthemum polysaccharides (KSCP) on acetaminophen (AP) induced liver damage and its possible mechanism. Mice acute liver injury model was established via intraperitoneal injection of AP (300 mg/kg). The biochemical indicators of plasma and liver tissue were tested. The effects of KSCP on the liver index were examined. The liver pathological changes were investigated. The expressions of related protein were detected via Western blotting. In our study, compared with model group, the concentrations and contents of ALT, AST, TNF-α, IL-1ß and MDA were reduced and activities of SOD were increase in H-KSCP (1.2mg/10 g)-pretreated mice (P<0.01). The liver index was significantly reduced in H-KSCP-pretreated mice compared with model group (4.89±0.22 vs 7.4±0.66, P<0.01). Liver cellular swelling, degeneration and necrosis relieved, and pathological injury had been improved. Western blotting results showed that the caspase-3 protein level in H-KSCP group was significantly decreased, expression of Bcl-2 protein and Bcl-2/Bax ratio was increased, whereas which of Bax protein was decreased (P<0.01). KSCP-pretreated at middle and high doses can prevent against the liver injury, its action mechanism may be related to its anti-inflammatory effects and regulation of apoptosis related proteins expression. Overall, our results showed that KSCP may be an effective preventive agent in preventing acute liver injury.

Immoderate inhibition of estrogen by anastrozole enhances the severity of experimental polyarthritis.

Aromatase inhibitors have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. Meanwhile, more and more breast cancer patients who are treated with aromatase inhibitors as adjuvant therapies often experience arthralgias and musculoskeletal aching, in some cases, have necessitated discontinuation of treatment. We therefore use a rat model of human RA to test the hypothesis that anastrozole, an aromatase inhibitor, could enhance arthritis. The parameters used for analyzing the disease severity included paw volume, radiology, histopathological examination, markers for cytokine profile, immunophenotypic assays, and immune response to type II collagen. Administration of anastrozole significantly increased the severity of arthritis. Anastrozole induced the increased levels of proinflammatory cytokines, IFN-gamma, IL-12, and the decreased levels of IL-4, IL-10 secretion. We further found that anastrozole suppressed the differentiation of naive T cells to Treg cells, and it blocked the balance of IgG2a/IgG1 in peripheral blood. Meanwhile, estradiol concentration was the lowest in the anastrozole group. In a well-established model of postmenopausal RA, anastrozole potently promote the progression of arthritis and the associated development of osteoporosis. This potential problem should alert the oncologists and other health professionals.

[Experimental study on anti-angiogenesis in mice with Lewis lung carcinoma by low-dose of cyclophosphamide combined with ginsenoside Rg3].

OBJECTIVE: To evaluate the anti-angiogenetic effect of the combination of low-dose cyclophosphamide(CTX) and ginsenoside Rg3 in mice with Lewis lung carcinoma, and to observe the anti-tumor effect, toxicity, adverse reaction of the treatment and survival time of the tumor bearing mice. METHODS: Holland C57/ BL6 Lewis lung carcinoma mice were taken as the model and randomly divided into 5 groups, i.e. the low-dose CTX (LDCTX) group, the maximum tolerable dose CTX (MTDCTX) group, the ginsenoside Rg3 (Rg3) group, the low-dose CTX combined with ginsenoside Rg3 group (LDCTX + Rg3), and the model group. Tumor volume, weight of mice, peripheral white blood cell counts and survival time of mice were observed, tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) gene expression were determined during the therapeutic course. RESULTS: In the LDCTX group, tumor grew comparatively slow, no significant decrease in body weight or peripheral white blood cells, and survival time was prolonged. In the LDCTX + Rg3 group, the tumor inhibitory effect was more persistent and steady without any increase of toxicity or adverse reaction. Besides, the survival time of mice was prolonged (P < 0.01). MVD was lower in the LDCTX group than that in the MTDCTX group (P< 0. 05). Compared with the model group, MVD and VEGF expression were lower in the LDCTX and the Rg3 group, and the lowering action was more significant when the two drugs were used in combination (P < 0.05). CONCLUSION: The combination of low-dose CTX and Rg3 has obvious synergetic action of anti-angiogenesis, it shows significant and persistent tumor inhibitory effect, with less toxic and adverse reaction, and could induce longer survival time than treatment of CTX or Rg3 alone.

[Effect on late-stage mammary cancer treated by endocrinotherapy or chemotherapy combined with pingxiao capsule].

OBJECTIVE: To explore the action of pingxiao capsules (PXC) and its significance in the treatment of late stage mammary cancer (LSMC). METHODS: One hundred and forty-two LSMC patients were randomized into four groups: the two single treated groups treated by endocrinotherapy (ET) alone (n = 27) and by chemotherapy alone (n=44) respectively, and the two PXC combined treated groups treated with PXC plus endocrinotherapy (n=27) or chemotherapy (n=44). The remission rate and progression time (TTP) of disease, the survival time and quality of life (QOL) of patients, and the adverse reaction were compared between the single treated groups and the combined treated groups. RESULTS: The median progression time was obviously prolonged, and QOL improved in the combined treated groups than those in the single treated groups (P < 0.05), but no significant difference was found in the remission rate or adverse reaction between them. CONCLUSION: PXC can improve QOL, prolong the progression time in patients of LSMC, and with less adverse reaction. It is worth spreading combination of PXC with chemo- or endocrino-therapy in clinical application for treatment of LSMC patients.