Cost-effectiveness analysis of Shexiang Baoxin Pill (MUSKARDIA) as the add-on treatment to standard therapy for stable coronary artery disease in China.

BACKGROUND: Recent evidence indicates that Shexiang Baoxin Pill (MUSKARDIA), as an add-on treatment to standard therapy for stable coronary artery disease (CAD), is effective. Nevertheless, the cost-effectiveness of introducing the Shexiang Baoxin Pill (Abbreviation SBP) to the current standard treatment for patients with CAD in China remains unknown. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of introducing SBP into the current standard treatment in China for patients with CAD. METHOD: The effects of two treatment strategies-the SBP group (SBP combined with standard therapy) and the standard therapy group (placebo combined with standard therapy)-were simulated using a long-term Markov model. The simulation subjects might experience non-fatal MI and/or stroke or vascular or non-vascular death events. The study parameters were primarily derived from the MUSKARDIA trial, which was a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial. Furthermore, age-related change, event costs, and event utilities were drawn from publicly available sources. Both costs and health outcomes were discounted at 5.0% per annum. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. Based on the MUSKARDIA trial results, the risk with the events of major adverse cardiovascular events (MACE) was decreased (P < 0.05) in the female subgroup treated with SBP therapy compared with standard therapy. Consequently, a scenario analysis based on subgroups of Chinese females was conducted for this study. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per quality-adjusted life-year (QALY) saved. RESULTS: After 30 years of simulation, the SBP group has added 0.32 QALYs, and the cost has been saved 841.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -2628.13 CNY per QALY. Scenario analyses of Chinese females showed that, after 30 years of simulation, the SBP therapy has been increased by 0.82 QALYs, and the cost has been reduced by 19474.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -26569.51 CNY per QALY. Similar results were obtained in various extensive sensitivity analyses. CONCLUSIONS: This is the first study to evaluate the cost-effectiveness of SBP in the treatment of CAD. In conclusion, SBP as an add-on treatment to standard therapy appears to be a cost-effective strategy for CAD in Chinese patients.

[Morphological and biochemical characterization during seed development of Notopterygium incisum].

This study aimed to examine the morphological, physiological, and biochemical alterations occurring in Notopterygium incisum seeds throughout their developmental stages, with the objective of establishing a theoretical foundation for the cultivation of superior quality seeds. The experimental materials utilized in this study were the seeds of N. incisum at various stages of development following anthesis. Through the employment of morphological observation and plant physiology techniques, the external morphology, nutrients, enzyme activity, and endogenous hormones of the seeds were assessed. The results revealed a transition in seed coat color from light green to brown during the growth and development of N. incisum seeds. Additionally, as the seeds matured, a decrease in water content was observed. Conversely, starch content exhibited a progressive increase, while sucrose content displayed fluctuations. At 7 days after anthesis, the soluble sugar content attained its highest level of 4.52 mg·g~(-1), whereas the soluble protein content reached its maximum of 6.00 mg·g~(-1) at 14 days after anthesis and its minimum of 4.94 mg·g~(-1) at 42 days after anthesis. The activity of superoxide dismutase(SOD) exhibited an initial increase, followed by a decrease, and eventually reached a stable state. Conversely, the activities of catalase(CAT) and peroxidase(POD) demonstrated a decrease initially, followed by an increase, and then another decrease. The levels of the four endogenous hormones, namely gibberellin(GA_3), zeatin riboside(ZR), auxin(IAA), and abscisic acid(ABA), in the seeds displayed significant variations, with IAA and ABA exhibiting considerably higher levels compared to the other hormones. The levels of plant growth-promoting hormones, represented by IAA, generally displayed a pattern of initial increase followed by a subsequent decrease during seed development, while the plant growth-inhibiting hormone ABA showed the opposite trend. The findings indicate that the alterations in nutrient composition, antioxidant enzyme activity, and endogenous hormone levels vary throughout the maturation process of N. incisum seeds. These observations hold relevance for the cultivation of N. incisum seeds.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.

Emergence of an ancient and pathogenic mammarenavirus.

Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαßR-/- mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77-88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).

Effect of allyl isothiocyanate on oxidative stress in COPD via the AhR / CYP1A1 and Nrf2 / NQO1 pathways and the underlying mechanism.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death globally. Oxidative stress affects various molecular mechanisms and is the main driving factor of COPD. Ally isothiocyanate (AITC) is an effective component of Semen Sinapis Albae, which has favorable effects for the treatment of COPD, but its mechanism has not been fully elucidated. PURPOSE: This study aimed to elucidate the antioxidant effect of AITC on COPD and its molecular mechanism, and preliminarily determine the role of AhR in the progression of COPD. STUDY DESIGN: The COPD rat model was established by smoking combined with intratracheal instillation of lipopolysaccharide. Different doses of AITC, positive control drug acetylcysteine, AhR inhibitor alpha-naphthoflavone, and agonist beta-naphthoflavone were administered by gavage. Human bronchial epithelial cells induced by cigarette smoke extract (CSE) were used in an in vitro model to explore the molecular mechanisms of AITC. METHODS: The effects of AITC on lung function and oxidative stress in rats were evaluated in vivo using the respiratory function test, white blood cell count, enzyme-linked immunosorbent assay, and histological staining. The changes in protein expression in the lung tissue were detected by immunohistochemistry and Western blotting. RT-PCR, western blotting, and immunofluorescence were used to explore the molecular mechanisms of AITC. Enzyme-linked immunosorbent assay, reactive oxygen species probing, and flow cytometry were used to determine the antioxidant effect of AITC. RESULTS: AITC can improve the lung function of rats with COPD, restore lung tissue structure, improve oxidative stress, reduce inflammation, and inhibit lung cell apoptosis. AITC reversed the upregulation of AhR and CYP1A1 and the down-regulation of Nrf2 and NQO1 in the lung tissues of rats with COPD. CSE stimulation can increase the expressions of AhR and CYP1A1 and decrease the expressions of Nrf2 and NQO1 in 16HBE cells, leading to severe oxidative stress and inflammatory response and, ultimately, apoptosis. AITC inhibited AhR and CYP1A1 expressions, induced Nrf2 and NQO1 expressions, promoted Nrf2 nuclear translocation, and improved CSE-induced toxicological effects. CONCLUSION: AITC may improve lung oxidative stress by inhibiting the AhR / CYP1A1 and activating the Nrf2 / NQO1 pathways, thereby delaying the pathological progression of COPD.

[Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults].

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Improvement of inflammatory response and gastrointestinal function in perioperative of cholelithiasis by Modified Xiao-Cheng-Qi decoction.

BACKGROUND: In the perioperative period of biliary surgery, various factors can induce the release of a large number of inflammatory factors, leading to an imbalance in pro-inflammatory and anti-inflammatory responses and resulting in gastrointestinal (GI) dysfunction. Enhanced Recovery After Surgery protocols in biliary surgery have been shown to reduce the stress response and accelerate postoperative recovery. It is crucial to reduce the inflammatory response and promote the recovery of GI function after biliary surgery, both of which are the basis and key for perioperative care and postoperative recovery. AIM: To better understand the effects of Modified Xiao-Cheng-Qi decoction (MXD) on inflammatory response and GI function in the perioperative management of cholelithiasis and their correlation. METHODS: This was a prospective randomized placebo-controlled trial, in which 162 patients who received biliary tract surgery were randomly assigned to three groups: MXD group, XD group, and placebo-control group. The observed parameters included frequency of bowel sounds, time of first flatus and defecation, time of diet, and amount of activity after surgery. The serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, serum amyloid A protein (SAA), and substance P were measured by the enzyme-linked immunosorbent assay. Then, the spearman correlation coefficient was used to analyze the relationship between the indicators of GI function and inflammation. RESULTS: Compared to the placebo-control, improvements in GI function were observed in the MXD groups including reduced incidence of nausea, vomiting, and bloating; and earlier first exhaust time, first defecation time, and feeding time after surgery (P < 0.05). On the 1st and 2nd d after surgery, IL-6, CRP and SAA levels in MXD group were lower than that in placebo control, but substance P level was higher, compared to the control (P < 0.05). Functional diarrhea occurred in both MXD and XD groups without any other adverse effects, toxic reactions, and allergic reactions. Diarrhea was relieved after the discontinuation of the investigational remedies. Bowel sounds at 12 h after surgery, the occurring time of the first flatus, first defecation, postoperative liquid diet and semi-liquid diet were significantly correlated with levels of IL-6, CRP, SAA and substance P on second day after surgery (P < 0.05). CONCLUSION: Treatment with MXD can relieve inflammatory response and improve GI function after surgery. Moreover, there are significant correlations between them. Furthermore, it does not cause serious adverse reactions.

[Effect of intercropping with Vicia faba on secondary metabolites and rhizosphere soil microbial diversity of Notopterygium incisum].

Rhizosphere soil microbial community and its diversity are important for the structure and functions of medicinal plant ecosystem. In this study, based on high-throughput sequencing, rhizosphere soil microbial diversity, and yield and quality of rhizome and root of Notopterygium incisum cultivated alone(control, CK) and intercropped with Vicia faba(QH) were analyzed, which is expected to lay a basis for optimization of the cultivation mode and ecological production of N. incisum. RESULTS:: showed that the rhizosphere soil bacteria of N. incisum were dominated by Proteobacteria and Bacteroides, with the relative abundance of 50.38%-51.95% and 16.36%-17.02%, respectively. Soil bacterial community at the phylum level was not significantly different between CK and QH. At the genus level, the relative abundance of MND1(3.54%), Spinstomonas(3.50%), Nitrospira(1.53%), and Rhizobacter(1.05%) was significantly higher and that of Gemmatimonas, Candidatus＿Solibacter, and Bryophytes was lower in QH treatment than in the CK. The plant height, leaf length, leaf width, and petiole length of N. incisum in QH treatment was significantly increased and the underground biomass rose by 71.43% compared with those in the CK. Thus, intercropping with V. faba promoted the aboveground growth of N. incisum and improved the yield of root and rhizome. Moreover, the content of notopterol and isoimperatorin increased by 37.96% and 4.09% in QH treatment, respectively, indicating that the intercropping with V. faba boosted the accumulation of secondary metabolites in N. incisum. Pearson's correlation analysis showed that the soil bacterial community was mainly influenced by the soil factors including the content of soil available nutrients, soil organic matter, pH value, and soil water. The influence was in the order: total potassium>total nitrogen>pH>organic matter>available potassium>soil water content>available nitrogen>available phosphorus. In conclusion, the intercropping with V. faba altered soil microenvironment and also increased the yield and accumulation of secondary metabolites of N. incisum, which is a promising ecological planting model for N. incisum.

Cyclic mechanical strain with high-tensile triggers autophagy in growth plate chondrocytes.

BACKGROUND: Mechanical loading has been widely considered to be essential for growth plate to maintain metabolism and development. Cyclic mechanical strain has been demonstrated to induce autophagy, whereas the relationship between cyclic tensile strain (CTS) and autophagy in growth plate chondrocytes (GPCs) is not clear. The objective of this study was to investigate whether CTS can regulate autophagy in GPCs in vitro and explore the potential mechanisms of this regulation. METHODS: The 2-week-old Sprague-Dawley rat GPCs were subjected to CTS of varying magnitude and duration at a frequency of 2.0 Hz. The mRNA levels of autophagy-related genes were measured by RT-qPCR. The autophagy in GPCs was verified by transmission electron microscopy (TME), immunofluorescence and Western blotting. The fluorescence-activated cell sorting (FACS) was employed to detect the percentage of apoptotic and necrotic cells. RESULTS: In GPCs, CTS significantly increased the mRNA and protein levels of autophagy-related genes, such as LC3, ULK1, ATG5 and BECN1 in a magnitude- and time-dependent manner. There was no significant difference in the proportion of apoptotic and necrotic cells between control group and CTS group. The autophagy inhibitors, 3-methyladenine (3MA) and chloroquine (CQ) reversed the CTS-induced autophagy via promoting the formation of autophagosomes. Cytochalasin D (cytoD), an inhibitor of G-actin polymerization into F-actin, could effectively block the CTS-induced autophagy in GPCs. CONCLUSION: Cyclic mechanical strain with high-tensile triggers autophagy in GPCs, which can be suppressed by 3MA and CQ, and cytoskeletal F-actin microfilaments organization plays a key role in chondrocytes' response to mechanical loading.

The efficacy of platelet rich plasma on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVß3 and Exerts Chondroprotective Effect.

Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the in vitro administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1ß-induced chondrocyte inflammation response. Moreover, PA reduced IL-1ß-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, in vivo experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-κB signaling pathway inhibiting properties of PA on IL-1ß-induced chondrocytes could be reversed when integrin αVß3 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin αVß3. Thus, PA or integrin αVß3 might be a promising agent or molecular target for the treatment of OA.

Effects of allyl isothiocyanate on the expression, function, and its mechanism of ABCA1 and ABCG1 in pulmonary of COPD rats.

BACKGROUND AND AIMS: Allyl isothiocyanate(AITC) has been shown to play an important role in the improved symptoms of chronic obstructive pulmonary disease(COPD) and the inhibition of inflammation, but the role in COPD lipid metabolism disorder and the molecular mechanism remains unclear. We aimed to explore whether and how AITC affects COPD by regulating lipid metabolism and inflammatory response. METHODS: The COPD rat model was established by cigarette smoke exposure. Cigarette smoke extract stimulated 16HBE cells to induce a cell model. The effect of AITC treatment was detected by lung function test, H&E staining, Oil red O staining, immunohistochemistry, ELISA, CCK-8, HPLC, fluorescence efflux test, siRNA, RT-PCR, and Western blotting. Biological analysis was performed to analyze the results. Graphpad Prism 8.0 software was used for statistical analysis. RESULTS: AITC can improve lung function and pathological injury in COPD rats. The levels of IL-1 ß and TNF- α in the AITC treatment group were significantly lower than those in the model group(P < 0.05), and the lipid metabolism was also improved (P < 0.05). AITC reverses CSE-induced down-regulation of LXR α, ABCA1, and ABCG1 expression and function in a time-and concentration-dependent manner (P < 0.05). AITC regulates the cholesterol metabolism disorder induced by CSE in NR8383 cells and attenuates macrophage inflammation (P < 0.05). In addition, after silencing LXR α with siRNA, the effect of AITC was also inhibited. CONCLUSION: These results suggest that AITC improves COPD by promoting RCT process and reducing inflammatory response via activating LXR pathways.

[Pharmacoeconomic evaluation of Suhuang Zhike Capsules using Markov model for inpatients with acute exacerbation of chronic obstructive pulmonary disease].

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.

[Meta-analysis of efficacy and safety of Shexiang Tongxin Dripping Pills combined with conventional therapy of coronary heart disease].

The aim of the research was to evaluate the efficacy and safety associated with Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD). We searched 8 electronic databases up to November 2020, including PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP and SinoMed. Eligible studies were clinical trials of Shexiang Tongxin Dropping Pills combined with conventional therapy used in the treatment of coronary heart disease(CHD). The Meta-analysis was performed using STATA 15 software. A total of 21 RCTs(n=2 186) were shortlisted for the Meta-analysis. The results of efficacy evaluation showed that the total effective rate of Shexiang Tongxin Dropping Pills combined with conventional therapy was higher than that of conventional therapy of coronary heart disease(RR=1.20, 95%CI[1.15, 1.26], Z=8.63, P<0.001). Furthermore, Shexiang Tongxin Dripping Pills combined with conventional therapy had better effect on electrocardiogram efficacy(RR=1.24, 95%CI[1.16, 1.34], Z=5.98, P<0.001) and the number of angina attacks(SMD=-2.30, 95%CI[-3.47,-1.14], Z=3.88, P<0.001), the duration of angina attack(SMD=-2.31, 95%CI[-3.07,-1.55], Z=5.97, P<0.001), with lower levels of LDL-C(SMD=-0.73, 95%CI[-1.32,-0.14], Z=2.42, P=0.016), TC(SMD=-1.16, 95%CI[-1.35,-0.96], Z=11.56, P<0.001) and TG(SMD=-0.87, 95%CI[-1.06,-0.68], Z=8.97, P<0.001), and higher levels of HDL-C(SMD=0.87, 95%CI[0.02, 1.71], Z=2.00, P=0.045). The results of safety evaluation showed that the incidence of adverse reactions of Shexiang Tongxin Dropping Pills combined with conventional therapy was lower than that of conventional therapy of coronary heart disease(RR=0.45, 95%CI[0.22, 0.91], Z=2.23, P=0.026). There were significant differences in the above outcome indexes between the two groups. After the Harbord method test, the total effective rate outcome index has publication bias, but the sensitivity analysis of the cut-and-fill method suggested that the result was stable. In general, limited by the quantity and quality of included literature, more high-quality studies are needed to further verify the conclusions of this study.

[Pharmacoeconomic evaluation of Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment for coronary heart disease by Markov model].

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.

METTL3-mediated m6A methylation of SPHK2 promotes gastric cancer progression by targeting KLF2.

N6-methyladenosine (m6A) RNA methylation is profoundly involved in epigenetic regulation, especially for carcinogenesis and tumor progression. Mounting evidence suggests that methyltransferase METTL3 regulates malignant behaviors of gastric cancer (GC). However, the clinical significance and biological implication of SPHK2 and its related m6A modification in GC remain unclear. In this study, quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry were utilized to detect the expression profiles and prognostic significance of SPHK2 in GC. Here, we showed that increased SPHK2 was signified a poor prognosis of GC patients. Phosphorylation and ubiquitination assays were used to investigate the possible mechanisms of SPHK2-mediated KLF2 expression. SPHK2 can promote the phosphorylation of KLF2, which triggers the ubiquitination and degradation of KLF2 protein in GC. Methylated RNA immunoprecipitation (MeRIP) was performed to uncover the m6A modification of SPHK2 mRNA. METTL3 promotes translation of SPHK2 mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting KLF2 expression. SPHK2/KLF2 regulates the cell proliferation, migration, and invasion induced by METTL3 in GC. Overall, our findings reveal that METTL3-mediated m6A modification of SPHK2 contributes to GC progression, which extends the understanding of the importance m6A methylation in GC and represents a potential target for GC therapy.

System Xc-: a key regulatory target of ferroptosis in cancer.

Ferroptosis is a type of oxidative stress-dependent regulated necrosis characterized by excessive lipid peroxide accumulation. This novel cell death modality has been implicated in preventing cancer progression. Cancer cells tend to modulate their redox state to prevent excessive peroxidation, eventually facilitating tumor growth. System Xc- (a cystine/glutamate antiporter system) is a promising target in cancer cells for ferroptosis induction. The overexpression of system Xc-, especially its core subunit xCT, has been reported in several tumors, and these high expression levels were closely related to cancer cell proliferation, invasion, metastasis and the tumor microenvironment. xCT might serve as a novel biomarker, and its upregulation almost always indicates drug tolerance and poor survival. Therefore, system Xc- inhibition may enhance chemotherapy sensitivity and optimize patient prognosis. Here, we elaborate on the mediation of ferroptosis by suppressing system Xc- and the relevant underlying molecular mechanism in cancer cells. The spotlight on this approach to cancer treatment is creating a new horizon and pointing to future opportunities.

Epidermal growth factor-like domain multiple 6 (EGFL6) promotes the migration and invasion of gastric cancer cells by inducing epithelial-mesenchymal transition.

Epidermal growth factor-like domain multiple 6 (EGFL6) is implicated in tumor growth, metastasis and angiogenesis, and its ectopic alteration has been detected in aggressive malignancies. However, the pathophysiologic roles and molecular mechanisms of EGFL6 in gastric cancer (GC) remain to be elucidated. In this study, we investigated EGFL6 expression in GC cell lines and tissues using western blotting and immunohistochemistry. We found that EGFL6 was elevated expression in GC cell lines and tissues. The high expression of EGFL6 significantly was correlated with histological grade, depth of invasion, lymph node involvement, distant metastasis and TNM stage in GC and predicted poorer prognosis, and it could act an independent prognostic factor for GC patients. EGFL6 enhanced the proliferation, migration and invasion of GC cells. In addition, we identified the possible molecular mechanisms of EGFL6-involved epithelial-mesenchymal transition (EMT). EGFL6 regulated EMT process and induced metastasis partly through FAK/PI3K/AKT/mTOR, Notch and MAPK signaling pathways. In conclusion, EGFL6 confers an oncogenic function in GC progression and may be proposed as a potential therapeutic target for GC.

Voacafrines A-N, aspidosperma-type monoterpenoid indole alkaloids from Voacanga africana with AChE inhibitory activity.

Fourteen undescribed monoterpenoid indole alkaloids, voacafrines A-N, along with 7 known monoterpenoid indole alkaloids were isolated from the seeds of Voacanga africana Stapf. Among them, voacafrines A-G were aspidosperma-aspidosperma type bisindole alkaloids, while voacafrines H-N were aspidosperma-type monomers. Their structures and absolute configurations were elucidated by a combination of NMR, MS, and ECD analyses. Voacafrines A-C were characterized by an acetonyl moiety at C-5', while voacafrine H possessed a methoxymethyl moiety at C-14 within aspidosperma-type alkaloids. The acetylcholinesterase (AChE) inhibitory activity and cytotoxicity of voacafrines A-N were evaluated. Voacafrines A-C and E-G were bisindole alkaloids that exhibited AChE inhibitory activity with IC50 values of 4.97-33.28 µM, while voacafrines I and J were monomers that showed cytotoxicity against several human cancer cell lines with IC50 values of 4.45-7.49 µM.

Bousmekines A-E, New Alkaloids from Two Bousigonia Species: B.angustifolia and B. mekongensis.

Four new monoterpenoid indole alkaloids, bousmekines A-D (1-4), and one new pyranopyridine alkaloid, bousmekine E (5), were isolated from the twigs and leaves of Bousigonia angustifolia and Bousigonia mekongensis. Their structures including absolute configurations were elucidated by a combination of MS, NMR, ECD calculation, and single-crystal X-ray diffraction analysis. Compound 2 was an eburnea-type MIAs characterized by a rare chlorine atom while 5 possessed a novel pyranopyridine moiety. Their cytotoxicities against several human cancer cell lines were evaluated and compound 1 exhibited significant cytotoxicity with IC50 values of 0.8-7.4 µM.