Cow placenta extract ameliorates d-galactose-induced liver damage by regulating BAX/CASP3 and p53/p21/p16 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Placenta is a kind of traditional Chinese medicine, known as "Ziheche", which has the function of tonifying qi and blood, nourishing liver and kidney. Placenta extract (PE) has been used for delaying organismal aging and treating various liver diseases. Cow placenta is a rich natural resource with large mass. Its composition is similar to that of human placenta, but it has not been effectively utilized. However, little is known about the effect of CPE on the liver of aging mice. AIM OF THE STUDY: The aim of this study is to explore the protective effect and mechanism of CPE on the liver of d-galactose (D-gal) induced aging mice. MATERIALS AND METHODS: Statistical methods were used to calculate mouse body weight and liver index. Hematoxylin-eosin (H&E) and transmission electron microscopy (TEM) were used to detect the morphological structure of the liver. Automatic biochemical analyzer was used to measure serum biochemical indicators. Three special staining methods were used to observe hepatocytes apoptosis, senescence and proliferation respectively. Relative kits were used to detect oxidative, inflammatory, and aging markers in the liver. Finally, real-time quantitative polymerase chain reaction and western-blot were used to detect aging related signaling pathways. RESULTS: CPE significantly improved the morphological damage and dysfunction of liver, restored the activities of liver enzymes in serum, and alleviated liver oxidative stress and inflammatory response in D-gal induced aging mice. Furthermore, CPE inhibited hepatocyte apoptosis and senescence, and promoted hepatocyte proliferation by regulating BAX/CASP3 and p53/p21/p16 signaling pathways, ultimately reduced the effects of aging on the liver. CONCLUSION: CPE effectively ameliorated the impact of aging on the liver by inhibiting free radical production or scavenging excessive free radicals, and its mechanism is associated to the regulation of apoptosis and proliferation-related factors.

Exploration of the immuno-adjuvant effect and mechanism of Anemoside B4 through network pharmacology and experiment verification.

BACKGROUND: Extensive investigation has been undertaken about the utilization of saponin adjuvants in vaccines intended for veterinary and human applications. AB4 is the main constituent of the traditional Chinese medicine, Pulsatilla chinensis (Bunge) Regel, and has immunomodulatory activity. However, there is a paucity of reports on AB4 as a potential adjuvant. PURPOSE: The objective of this work was to clarify the adjuvant role of AB4 and the molecular mechanisms that underlie its immunomodulatory actions. STUDY DESIGN AND METHODS: The immunomodulatory effects of AB4 were investigated using network pharmacological analyses. These effects were validated by evaluating the developmental status of the immune organs and by using the following techniques: ELISA for the quantification of serum-specific antibodies to determine immune-related cytokine levels; the MTS method for the assessment of proliferative activity of splenic lymphocytes; flow cytometry to analyze lymphocyte and dendritic cell activation status; and western blotting for mechanistic analysis at the protein level. RESULTS: The network pharmacological analysis predicted a total of 52 targets and 12 pathways for AB4 to exert immunomodulatory effects. In a mouse model with immunity to OVA, the introduction of AB4 resulted in the enhancement of immunological organ growth and maturation, elevation of blood antibodies targeting OVA, and amplification of the production of cytokines associated with Th1 and Th2 immune responses. Additionally, the administration of AB4 resulted in a notable augmentation of lymphocyte proliferation and an elevation in the CD4+/CD8+ T lymphocyte ratios. Furthermore, the administration of AB4 enhanced the maturation process of DCs in the draining LNs and increased the production of co-stimulatory factors and MHC II molecules. AB4 induces the upregulation of TLR4 and IKK proteins, as well as the phosphorylation of NF-κB p65 protein within the TLR4/NF-κB signaling cascade, while concurrently suppressing the expression of IκBα protein. CONCLUSION: The specific immunoadjuvant effects of AB4 have been demonstrated to modulate the growth and maturation of immune organs and enhance the secretion and cellular activity of pertinent immune molecules. The utilization of network pharmacology, combined within and in vivo vitro assays, clarified the adjuvant function of AB4, which potentially involves the regulation of the TLR4/NF-κB signaling pathway.

Smilagenin induces expression and epigenetic remodeling of BDNF in alzheimer's disease.

BACKGROUND: Smilagenin (SMI) is a lipid-soluble steroidal sapogenin, extracted from traditional Chinses medicinal herbs Radix Asparagi, which is extracted from the dry root of Asparagus cochinchinensis (Lour.) Merr. We previously found that SMI significantly increased brain-derived neurotrophic factor (BDNF) expression in Aß-intoxicated SH-SY5Y cells. METHODS: In this study, we performed behavioral tests to analyze cognitive function of WT and APP/PS1 mice treated with or without SMI, and found that SMI could significantly improve the learning and memory ability of APP/PS1 mice. Moreover, immunofluorescence and ELISA results showed that SMI pretreatment could effectively reduce the deposition of ß-amyloid plaques in the cortex and hippocampus of APP/PS1 mice (26 mg/kg/day for 60 days) and inhibit the secretion of Aß1-42 in N2a/APPswe cells (10 µM concentration for 24 hours). RESULTS: Mechanistically, SMI enhanced BDNF mRNA expression, elevated the global level of H3AC and H4AC, and increased the expression of P300 in AD models. Furthermore, chromatin immunoprecipitation results showed that SMI could increase the levels of H3AC and H4AC at the promoter of BDNF promoter Ⅱ and Ⅳ, indicating that SMI epigenetically regulates BDNF expression through HAT enhancement. To further verify the critical role of P300 by which SMI upregulated histone acetylation in BDNF, AD mice were treated with SMI and C646 simultaneously. Behavioral experiments showed that the improvement effects of SMI on cognitive impairment were abolished after P300 inhibition in APP/PS1 mice. CONCLUSIONS: Our research for the first time demonstrated that SMI showed neuroprotective effects by increasing the expression of P300 protein, thus upregulating histone acetylation levels in the promoter region of BDNF and promoting its transcription. Our findings provide an important theoretical basis for the treatment of Alzheimer's disease with SMI extracted from Asparagus cochinchinensis (Lour.) Merr.

[Comprehensive review and prospect of acupuncture and moxibustion discipline: a review of Discipline History of Acupuncture and Moxibustion in China].

After reviewing and evaluating the Discipline History of Acupuncture and Moxibustion in China, the authors concludes that this book has the following characteristics: the scientific research focuses on the combination of internal and external history, and the conclusions are rigorous; the narrative style and structure featured by the division of discipline history of ancient times, modern times and current times are quite characteristic and enlightening; the reference materials are detailed and advanced, which showes profound thoughts and concerns about the difficulties and challenges faced by the development of acupuncture and moxibustion discipline and the internal path selection of acupuncture and moxibustion research. In addition, this book discusses the unique importance of the cultural attribute behind acupuncture and moxibustion technology in the process of theoretical research of acupuncture and moxibustion.

Ferrous iron-induced formation of glycyrrhizic acid hydrogels for Staphylococcus aureus-infected wound healing.

Severe skin wound healing is mainly hindered by bacterial infection and uncontrolled inflammatory reaction. As a wound dressing, multifunctional hydrogel is expected to offer the potential possibility for overcoming current barriers in wound therapeutics. Herein, a natural drug molecule (glycyrrhizic acid, GA) and metal ion (Fe2+) were used to achieve the metal coordination-induced gelation. This as-prepared Fe2+-induced GA hydrogel showed excellent injectability, self-healing property, and sustained release behavior at a relatively lower concentration of GA, thereby reducing the high dose-caused cytotoxicity. In addition to acting as an inducer of gelation, Fe2+ promoted the antibacterial performance of hydrogel against Escherichia coli and Staphylococcus aureus through causing lipid peroxidation, membrane damage, and DNA degradation. Moreover, the released GA from hydrogel significantly accelerated cell migration and inhibited the inflammatory reaction by mediation of NF-κB signaling pathway to downregulate levels of important inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells. Using a mouse skin infected model, we revealed that the Fe2+/GA hydrogel applied to the wound resulted in the rapid wound healing. It is believed that the construction of natural drug molecule-derived hydrogel with antibacterial and anti-inflammatory capabilities may shed a new light to serve as a promising dressing for managing the severe skin wounds.

CaCO3-assistant synthesis of pH/near-infrared light-responsive and injectable sodium alginate hydrogels for melanoma synergistic treatment.

Melanoma is an aggressive tumor located in skin with high rates of recurrence and metastasis. Due to the limited traditional therapies, the development of novel strategies against melanoma is urgently quested. To reduce the side effects of traditional administration ways and amplify the killing effect, an injectable sodium alginate (SA)-based hydrogels were developed, in which CaCO3/polydopamine nanoparticles (CaCO3/PDA NPs) were embedded for the synergistic photothermal/calcium ions interference therapy of melanoma. In the study, the formation conditions and mechanical properties of CaCO3/PDA-SA hydrogels were characterized, and their antitumor efficiency and mechanism against mouse melanoma cells were investigated. Wheninjectedintratumorally, CaCO3/PDA-SA fluid was converted into hydrogel in situ through the interaction of pH-sensitive released Ca2+ and alginate chains, which increased the retention time of photothermal agents (CaCO3/PDA NPs) at tumor sites and thereby was more conducive to produce hyperthermia via photothermal conversion to combat melanoma. Moreover, in acidic tumor microenvironment, the residual CaCO3/PDA NPs in hydrogels continuously decomposed and released Ca2+ to destroy the Ca2+ buffering capacity and evoke the mitochondrial Ca2+-overloading, resulting in the inhibition of adenosine triphosphate production to accelerate cell death. Notably, besides the heat elevation, the near-infrared light (NIR) irradiation would further enhance the release of Ca2+ to promote the Ca2+-involved cell death. Therefore, a pH/NIR-responsive and injectable SA-based hydrogels were successfully established and showed enhanced treatment efficacy of melanoma through the synergism of photothermal therapy and calcium ions interference therapy.

Traditional Chinese Medicine in Treatment of COVID-19 and Viral Disease: Efficacies and Clinical Evidence.

Coronavirus disease 2019 (COVID-19) remains an uncontained, worldwide pandemic. While battling the disease in China, the Chinese government has actively promoted the use of traditional Chinese medicine, and many studies have been conducted to determine the efficacy of traditional Chinese medicine for treating COVID-19. The present review discusses the effectiveness and safety of traditional Chinese medicine in curing COVID-19 and provides clinical evidence from all confirmed cases in China. Applications of traditional Chinese medicine and specific recipes for treating other viral infections, such as those caused by severe acute respiratory syndrome coronavirus and influenza A viruses (including H1N1), are also discussed. Studies have reported that traditional Chinese medicine treatment plays a significant role in improving clinical symptoms. Therefore, further investigation may be of high translational value in revealing novel targeted therapies for COVID-19.

Antioxidant Capacity and Protective Effect of Cow Placenta Extract on D-Galactose-Induced Skin Aging in Mice.

Placental extract has been used for skin care and delaying skin aging. Cow placenta is an abundant resource with a large mass, which has not been harnessed effectively. Cow placenta extract (CPE) has the functions of antioxidation, anti-inflammatory, promoting growth and development, and promoting hair growth. However, little is known about the effect of oral administration of cow placenta extract on skin conditions. Therefore, the present study aimed to investigate the antioxidant capacity of CPE in vitro and in vivo and its protective effect on d-galactose (D-gal) induced skin aging in mice. The results showed that CPE had strong free radical scavenging, reducing and metal chelating activities. CPE can increase the activity of catalase (CAT), glutathione peroxidase (GSH-Px), peroxidase (POD), superoxide dismutase (SOD), and the content of glutathione (GSH), decrease the content of malondialdehyde (MDA). Moreover, CPE can decrease the gene and protein expression of matrix metalloproteinase 1a (MMP-1a) and matrix metalloproteinase 3 (MMP-3) and increase the expression of transforming growth factor-ß (TGF-ß) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of mouse skin. Histopathological analysis showed CPE reduced the collagen damage caused by D-gal, increased collagen synthesis and reduced its degradation to delay skin aging.

Ca:Mg ratio, medium-chain fatty acids, and the gut microbiome.

BACKGROUND & AIMS: Ketogenic medium-chain fatty acids (MCFAs) with profound health benefits are commonly found in dairy products, palm kernel oil and coconut oil. We hypothesize that magnesium (Mg) supplementation leads to enhanced gut microbial production of MCFAs and, in turn, increased circulating MCFAs levels. METHODS: We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants. Six 24-h dietary recalls were performed for all participants at the baseline and during the intervention period. Based on the baseline 24-h dietary recalls, the Mg treatment used a personalized dose of Mg supplementation that would reduce the calcium (Ca): Mg intake ratio to around 2.3. We measured plasma MCFAs, sugars, ketone bodies and tricarboxylic acid cycle (TCA cycle) metabolites using the Metabolon's global Precision Metabolomics™ LC-MS platform. Whole-genome shotgun metagenomics (WGS) sequencing was performed to assess microbiota in stool samples, rectal swabs, and rectal biopsies. RESULTS: Personalized Mg treatment (mean dose 205.58 mg/day with a range from 77.25 to 389.55 mg/day) significantly increased the plasma levels of C7:0, C8:0, and combined C7:0 and C8:0 by 18.45%, 25.28%, and 24.20%, respectively, compared to 14.15%, 10.12%, and 12.62% decreases in the placebo arm. The effects remain significant after adjusting for age, sex, race and baseline level (P = 0.0126, P = 0.0162, and P = 0.0031, respectively) and FDR correction at 0.05 (q = 0.0324 for both C7:0 and C8:0). Mg treatment significantly reduced the plasma level of sucrose compared to the placebo arm (P = 0.0036 for multivariable-adjusted and P = 0.0216 for additional FDR correction model) whereas alterations in daily intakes of sucrose, fructose, glucose, maltose and C8:0 from baseline to the end of trial did not differ between two arms. Mediation analysis showed that combined C7:0 and C8:0 partially mediated the effects of Mg treatment on total and individual ketone bodies (P for indirect effect = 0.0045, 0.0043, and 0.03, respectively). The changes in plasma levels of C7:0 and C8:0 were significantly and positively correlated with the alterations in stool microbiome α diversity (r = 0.51, p = 0.0023 and r = 0.34, p = 0.0497, respectively) as well as in stool abundance for the signatures of MCFAs-related microbiota with acyl-ACP thioesterase gene producing C7:0 (r = 0.46, p = 0.0067) and C8:0 (r = 0.49, p = 0.003), respectively, following Mg treatment. CONCLUSIONS: Optimizing Ca:Mg intake ratios to around 2.3 through 12-week personalized Mg supplementation leads to increased circulating levels of MCFAs (i.e. C7:0 and C8:0), which is attributed to enhanced production from gut microbial fermentation and, maybe, sucrose consumption.

Yolk-shell Fe3O4@Carbon@Platinum-Chlorin e6 nanozyme for MRI-assisted synergistic catalytic-photodynamic-photothermal tumor therapy.

HYPOTHESIS: Tumor treatments based on phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), are promising anticancer strategies. However, their dependence on light also poses several limitations for their application. Therefore, the establishment of a multifunctional nanotheranostic platform based on light therapy is needed to improve applicability of the technology. EXPERIMENTS: We designed yolk-shell magnetic Fe3O4@Carbon@Platinum-Chlorin e6 nanoparticles (MCPtCe6), which may be used for Magnetic resonance imaging (MRI) and synergistic catalytic-photodynamic-photothermal (catalytic-PDT-PTT) tumor therapy. FINDINGS: We designed to compound multiple nanozymes and solve the drawbacks of single nanozyme and give additional functionalization to nanozymes for tumor therapy. Fe3O4 has T2 weighted MRI ability. The designed yolk-shell structure can disperse Fe3O4 in the carbon shell layer, which in turn can act as a carrier for PtNPs and improve the dispersion of both Fe3O4 and Pt. Pt nanoparticles attached to the surface of N-doped carbon spheres enhanced the catalytic ability of the nanozyme to generate reactive oxygen species (ROS). The covalently linked photosensitizer chlorin e6 (Ce6) on the Fe3O4@C@Pt (MCPt) nanozyme is essential for the therapeutic effects of PDT. MCPtCe6 can be specifically activated by the microenvironment through an enzyme-like catalytic process and extend PDT/PTT in acidic and H2O2-rich microenvironments. The results showed that MCPtCe6 had a high photothermal conversion efficiency (η = 28.28%), indicating its feasibility for PTT. Further cellular and animal studies have revealed that catalytic-PDT-PTT therapy can effectively inhibit tumors both in vitro and in vivo.

Natural allelic variation of GmST05 controlling seed size and quality in soybean.

Seed size is one of the most important agronomic traits determining the yield of crops. Cloning the key genes controlling seed size and pyramiding their elite alleles will facilitate yield improvement. To date, few genes controlling seed size have been identified in soybean, a major crop that provides half of the plant oil and one quarter of the plant protein globally. Here, through a genome-wide association study of over 1800 soybean accessions, we determined that natural allelic variation at GmST05 (Seed Thickness 05) predominantly controlled seed thickness and size in soybean germplasm. Further analyses suggested that the two major haplotypes of GmST05 differed significantly at the transcriptional level. Transgenic experiments demonstrated that GmST05 positively regulated seed size and influenced oil and protein contents, possibly by regulating the transcription of GmSWEET10a. Population genetic diversity analysis suggested that allelic variations of GmST05 were selected during geographical differentiation but have not been fixed. In summary, natural variation in GmST05 determines transcription levels and influences seed size and quality in soybean, making it an important gene resource for soybean molecular breeding.

Staphylococcus aureus-targeting peptide/surfactant assemblies for antibacterial therapy.

To address the challenge from microbial resistance, this work developed a surfactant with 18-carbon single hydrocarbon chain and multi-amine head groups (C18N3). After assembling with Staphylococcus aureus-targeting peptide (CARG), the obtained C18N3/CARG assemblies exhibited excellent antimicrobial activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in vitro and in vivo, in which the targeting peptide CARG bonded specifically to Staphylococcus aureus and C18N3 killed bacteria with a mechanism of membrane disruption. Importantly, C18N3 could also work as a ß-lactamase inhibitor to overcome the bacterial resistance to ß-lactam antibiotics through noncompetitive inhibition. The combination of ß-lactam antibiotic and C18N3/CARG assemblies more effectively suppressed methicillin-resistant Staphylococcus aureus in vitro and in vivo relative to equivalent dose of free antibiotic or C18N3. Thus, the antibacterial platform of antibiotic-carrying surfactant assemblies bearing bacteria-targeted peptides, in which C18N3 performed dual function, antibacterial agent and ß-lactamase inhibitor, may help fight against the difficult-to-treat infections.

Supramolecular Core-Shell Nanoassemblies with Tumor Microenvironment-Triggered Size and Structure Switch for Improved Photothermal Therapy.

Photothermal therapy (PTT) is demonstrated to be an effective methodology for cancer treatment. However, the relatively low photothermal conversion efficiency, limited tumor accumulation, and penetration still remain to be challenging issues that hinder the clinical application of PTT. Herein, the core-shell hierarchical nanostructures induced by host-guest interaction between water-soluble pillar[5]arene (WP5) and polyethylene glycol-modified aniline tetramer (TAPEG) are constructed. The pH-responsive performance endows the core-shell nanostructures with size switchable property, with an average diameter of 200 nm in the neutral pH and 60 nm in the acidic microenvironment, which facilitates not only tumor accumulation but also tumor penetration. Moreover, the structure switch of WP5⊃TAPEG under acidic microenvironment and the dual mechanism regulated extending of п conjugate, inclusion in the hydrophobic cavity of WP5 and the dense distribution in the core-shell structured assemblies, dramatically enhance the absorption in the near-infrared-II region and, further, the photothermal conversion efficiency (60.2%). The as-designed intelligent nanoplatform is demonstrated for improved antitumor efficacy via PTT.

Gold nanorod@void@polypyrrole yolk@shell nanostructures: Synchronous regulation of photothermal and drug delivery performance for synergistic cancer therapy.

Synergistic therapy has been emerging as new trend for effective tumor treatment due to synchronous function and cooperative reinforcement of multi therapeutic modalities. Herein, gold nanorods (GNRs) encapsulated into polypyrrole (PPy) shell with tunable void space (GNRs@Void@PPy) showing yolk@shell nanostructures were innovatively designed. The exploitation of dual near-infrared (NIR) absorptive species offered synergistic enhancement of photothermal performance. In addition, the manipulation of the void space between them provided additional benefits of high drug encapsulation efficiency (92.6%) and, interestingly, tumor microenvironment and NIR irradiation triggered targeted drug releasing. Moreover, the GNRs@Void@PPy exhibited excellent biocompatibility, and optimal curative effect by chemo-photothermal synergistic therapy was achieved through both in vitro and in vivo antitumor activity investigation.

Comparative proteomic profiling of hippocampi in mice treated with Jingui Shenqi Pills and Liuwei Dihuang Pills / 中国中药杂志

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.

Prognostic nutritional index, a novel biomarker which predicts worse prognosis in diffuse large B cell lymphoma.

The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with survival in several types of lymphoma. The purpose of this study was to investigate the prognostic value of PNI in diffuse large B cell lymphoma (DLBCL). With three hundred and ten patients were enrolled, the median level of PNI was 45.90 (range 25.30-139.70). According to the receiver operating characteristic (ROC) curve, 44.85 was determined to be the best cutoff value to divide patients into two different groups. With a median follow-up of 33.3 months (range 3.5-118.5), compared with the high PNI group, the 3-year and adjusted 3-year progression-free survival (PFS) and overall survival (OS) were worse in the low PNI group (all P < 0.050). Multivariate Cox analysis suggested that low PNI was an independent risk factor for PFS (hazard ratio (HR) 2.196, 95 % CI 1.197-4.030, P = 0.011) and showed a tendency to predict inferior OS (HR 1.918, 95 % CI 0.932-3.948, P = 0.077). Furthermore, PNI combined with other significant prognostic factors to build a novel prognostic index, namely NPI, was more accurate than the National Comprehensive Cancer Network international prognostic index (NCCN-IPI) to predict worse PFS and had a similar effect on predicting OS. All these findings suggested that PNI, as a novel available biomarker, was of prognostic significance in DLBCL patients.

[Network Meta-analysis of oral Chinese patent medicine for adjuvant treatment of primary liver cancer].

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.

[Systematic evaluation of Huaier Granules adjuvant treatment of primary liver cancer].

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.

Hypoxia enhances the cytotoxic effect of As4S4 on rat ventricular H9c2 cells through activation of ubiquitin-proteasome system.

BACKGROUND: As4S4 is widely used in Chinese traditional medicine compound. However, based on some recent studies, we found that the cardiotoxicity risk of using As4S4 in ischemic heart disease patients may be increased. To study this potential risk, we compared the effects of As4S4 on rat ventricular H9c2 cell line with or without hypoxic pretreatment, and to elucidate mechanisms of c-Cbl mediated ubiquitination/degradation of integrin ß1. METHODS: The present study was conducted on rat ventricular H9c2 cell line in the absence or presence of hypoxic pretreatment for 6 h followed by As4S4 treatment for 24 h. Following As4S4 treatment, cell viability assay, flow cytometric quantification of apoptotic cells, caspase-3 activity assay and DAPI staining were conducted. Western blotting was carried out to detect expressions of ubiquitination related proteins. In addition, the ubiquitination/degradation of integrin ß1 and the role of c-Cbl in it was evaluated by immunoprecipitation and immunoblot assay. RESULTS: The viability of cells with hypoxic pretreatment followed by As4S4 treatment was decreased significantly, apoptosis rate and the activity of caspase-3 were increased than As4S4 treatment alone. The ubiquitin-proteasome degradation pathway induced by As4S4 was further enhanced by hypoxic pretreatment. The results of IP and immunoblot assay showed hypoxic enhanced down-regulation effect of As4S4 on integrin ß1 probably through c-Cbl activation. CONCLUSIONS: This study demonstrated that the hypoxia enhanced cytotoxicity of As4S4 on H9c2 cells may through increasing the ubiquitin-proteasome degradation of integrin ß1 mediated by the E3 ligase c-Cbl. The results provide an important clue that, in patients with ischemic heart disease, use of As4S4 may be associated with increased cardiotoxicity. We believe that the results worth to be further illuminated by in vivo and clinical research.

Network Meta-analysis of oral Chinese patent medicine for adjuvant treatment of primary liver cancer / 中国中药杂志

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.