A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.

[Effects of mycorrhizal planting on small molecular chemical components of Dendrobium officinale].

This study aimed to provide a scientific basis for the application of the mycorrhizal planting technology of Dendrobium officinale by investigating the effects of mycorrhizal planting on the fingerprints of D. officinale and the content of six chemical components. Seventeen samples of D. officinale under mycorrhizal and conventional planting were collected from four regions, such as Jinhua of Zhejiang. The HPLC fingerprints were established to evaluate the similarity of the samples. The content of six chemical components of the samples was determined by HPLC. There were 15 common peaks in the fingerprints, and five of them were identified by marker compounds, which were naringenin, 4,4'-dihydroxy-3,5-dimethoxybibenzyl, 3,4'-dihydroxy-5-methoxybibenzyl, 3',4-dihydroxy-3,5'-dimethoxybibenzyl(gigantol), and 3,4-dihydroxy-4',5-dimethoxybibenzyl(DDB-2). The similarities of the fingerprints of mycorrhizal and conventional planting samples and the control fingerprint were in the ranges of 0.733-0.936 and 0.834-0.942, respectively. The influences of mycorrhizal planting on fingerprints were related to planting regions, the germplasm of D. officianle, and the amount of fungal agent. The content of six chemical components in the samples varied greatly, and the content of DDB-2 was the highest, ranging from 69.83 to 488.47 µg·g~(-1). The mycorrhizal planting samples from Chongming of Shanghai and Taizhou of Jiangsu showed an increase in the content of 5-6 components, while samples from Zhangzhou of Fujian and Jinhua of Zhejiang showed an increase in the content of 1-2 components. The results showed that mycorrhizal planting technology did not change the chemical profile of small molecular chemical components of D. officinale, but affected the content of chemical components such as bibenzyls, which has a good application prospect.

Combination immunotherapy of PEG-modified preladenant thermosensitive liposomes and PD-1 inhibitor effectively enhances the anti-tumor immune response and therapeutic effects.

Immunotherapy is a promising cancer treatment strategy. In contrast, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors are associated with low response rates and are only useful in a small group of cancer patients. A combination of treatments may be effective for overcoming this clinical issue. Preladenant is an adenosine (ADO) receptor inhibitor that can block the ADO pathway and improve the tumor microenvironment (TME), thereby enhancing the immunotherapeutic effect of PD-1 inhibitors. However, its poor water solubility and low targeting limit its clinical applications. We designed a PEG-modified thermosensitive-liposome (pTSL) loaded with ADO small molecule inhibitor preladenant (P-pTSL) to overcome these problems and enhance the effect of PD-1 inhibitor on breast cancer immunotherapy. The prepared P-pTSL was round and uniformly distributed with a particle size of (138.9 ± 1.22) nm, PDI: 0.134 ± 0.031, and zeta potential (-10.1 ± 1.63) mV; preladenant was released slowly at 37 °C but released fast at 42 °C from P-pTSL, which was 76.52 ± 0.44%. P-pTSL has good long-term and serum stability and excellent tumor-targeting ability in mice. Moreover, the combination with PD-1 inhibitor significantly enhanced the anti-tumor effect, and the improvement of related factors in serum and lymph was more obvious under the condition of 42 °C thermotherapy in vitro.

Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome.

The incidence of frailty gradually increases with age. This condition places a heavy burden on modern society, of which the aging population is increasing. Frailty is one of the most complicated clinical syndromes; thus, it is difficult to uncover its underlying mechanisms. Oxidative stress (OS) is involved in frailty in multiple ways. The association between the gut microbiota (GM) and frailty was recently reported. Herein, we propose that OS is involved in the association between the GM and the occurrence of frailty syndrome. An imbalance between oxidation and antioxidants can eventually lead to frailty, and the GM probably participates in this process through the production of reactive oxygen species. On the other hand, OS can disturb the GM. Such dysbiosis consequently induces or exacerbates tissue damage, leading to the occurrence of frailty syndrome. Finally, we discuss the possibility of improving frailty by intervening in the vicious cycle between the imbalance of OS and dysbiosis.

Ethyl acetate extract of Caesalpinia sappan L. inhibited acute myeloid leukemia via ROS-mediated apoptosis and differentiation.

BACKGROUND: The dried heartwood of Caesalpinia sappan L. is traditionally prescribed in the formula of traditional Chinese medicine (TCM) for the treatment of acute myeloid leukemia (AML), while nothing is yet known of the active fractions and the underlying mechanisms. PURPOSE: This study aims to investigate the effect of the ethyl acetate extract of the dried heartwood of Caesalpinia sappan L. (C-A-E) on induction of apoptosis and promotion of differentiation in vitro and anti-AML activity in vivo. STUDY DESIGN/METHODS: The aqueous extract was sequentially separated with solvents of increasing polarity and the active fraction was determined through the inhibition potency. The inhibition of the active fraction on cell viability, proliferation and colony formation was performed in different AML cells. Induction of apoptosis and the promotion of differentiation were further determined. Then, the level of the reactive oxygen species (ROS) and its potential role were assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice. RESULTS: C-A-E exhibited the highest inhibition on the cell viability of HL-60 cells. Meanwhile, C-A-E significantly suppressed the proliferation and the colony formation ability of HL-60 and Kasumi-1 cells. Moreover, C-A-E significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. C-A-E also reduced the level of mitochondrial membrane potential, promoted the release of cytochrome C, decreased the Bcl-2/Bax ratio, and promoted the cleavage of caspase-9 and -3. In addition, Mdivi-1 (mitochondrial fission blocker) remarkably reduced the apoptosis caused by C-A-E. Meanwhile, C-A-E also induced the expression of Mff and Fis1 and increased the location of Drp1 in mitochondria. Furthermore, C-A-E obviously promoted the differentiation of AML cells characterized by the typic morphological changes, the increased NBT positive cells, as well as the increased CD11b and CD14 levels. Notably, C-A-E significantly enhanced the intracellular ROS level. Moreimportantly, C-A-E-mediated apoptosis and differentiation of HL-60 cells was significantly mitigated by NAC. Additionally, C-A-E also exhibited an obvious anti-AML effect in NOD/SCID mice with the injection of HL-60 cells. CONCLUSIONS: C-A-E exhibited an inhibitory effect on AML cells by inducing mitochondrial apoptosis and promoting differentiation, both of which were highly correlated to the activation of ROS.

A Mobile Phone App-Based Tai Chi Training in Parkinson's Disease: Protocol for a Randomized Controlled Study.

Introduction: With an increasing number of China's aging population, Parkinson's disease (PD) increases year by year. Persons with PD exhibit abnormal balance functions, leading to motor skills difficulties, such as unstable walking or even falling. Therefore, activities of daily living and quality of life are affected. This study aims to explore the effectiveness of Tai Chi training based on the mobile phone app in improving the balance ability of persons with PD. Methods and Analysis: A randomized, single-blind, parallel controlled trial will be conducted in this study. One hundred forty-four persons with PD who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio: (1) control group, (2) basic experimental group (basic app with no Tai Chi training features), and (3) balanced-enhanced experimental group (basic app with Tai Chi training features). Individuals with PD will be evaluated on balance and motor function outcomes. The primary outcome measure is the limits of stability (including the maximum excursion and direction control); the secondary outcome measures include the Unified Parkinson's Disease Rating Scale III (UPDRS-III), Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up & Go (TUG), 6-Minute Walk Test (6MWT), and 39-item Parkinson's Disease Questionnaire (PDQ-39). Each group of patients will go through an assessment at baseline, 17 and 33 weeks. Discussion: This study will evaluate the effectiveness of the mobile phone app Tai Chi training on the balance function of persons with PD. We assume that a challenging Tai Chi project based on a mobile phone app will improve balance in the short and long term. As walking stability progresses, it is expected that daily activities and quality of life improve. These findings will be used to improve the effectiveness of future home management measures for persons with PD. Ethics and Dissemination: This study has been approved by the ethical review committee of the Shanghai University of Sport (approval number: 102772019RT056). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000029135).

Micromotors for Active Delivery of Minerals toward the Treatment of Iron Deficiency Anemia.

As the most common nutritional disorder, iron deficiency represents a major public health problem with broad impacts on physical and mental development. However, treatment is often compromised by low iron bioavailability and undesired side effects. Here, we report on the development of active mineral delivery vehicles using Mg-based micromotors, which can autonomously propel in gastrointestinal fluids, aiding in the dynamic delivery of minerals. Iron and selenium are combined as a model mineral payload in the micromotor platform. We demonstrate the ability of our mineral-loaded micromotors to replenish iron and selenium stores in an anemic mouse model after 30 days of treatment, normalizing hematological parameters such as red blood count, hemoglobin, and hematocrit. Additionally, the micromotor platform exhibits no toxicity after the treatment regimen. This proof-of-concept study indicates that micromotor-based active delivery of mineral supplements represents an attractive approach toward alleviating nutritional deficiencies.

[Regulation of exogenous calcium on photosynthetic system of honeysuckle under salt stress].

Exogenous calcium can enhance the resistance of certain plants to abiotic stress. However,the role of calcium insaltstressed honeysuckle is unclear. The study is aimed to investigate the effects of exogenous calcium on the biomass,chlorophyll content,gas exchange parameters and chlorophyll fluorescence of honeysuckle under salt stress. The results showed that the calcium-treated honeysuckle had better photochemical properties than the salt-stressed honeysuckle,such as PIABS,PItotal,which represents the overall activity of photosystemⅡ(PSⅡ),and related parameters for characterizing electron transport efficiency φP0,ψE0,φE0,σR,and φR are significantly improved. At the same time,the gas exchange parameters Gs,Ci,Trare also maintained at a high level. In summary,exogenous calcium protects the activity of PSⅡ,promotes the transmission of photosynthetic electrons,and maintains a high Ci,therefore enhances the resistance of honeysuckle under salt stress.

Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism.

To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, inhibitor kappa B kinase ß (IKKß), and nuclear factor (NF)-κB were increased in obese male mice. Diet, exercise, and diet combined with exercise interventions reversed the decreases in serum nesfatin-1, FSH, LH, and T levels; increased hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels; and reduced hypothalamic TNF-α, IL-1ß, IKKß, and NF-κB levels. These changes were accompanied by reduced adiposity, and these effects were more obvious in the diet combined with exercise group. Overall, our findings suggested that the hypogonadotropic hypogonadism associated with obesity may be induced by reduced hypothalamic NUCB2/nesfatin-1 levels, which attenuated the stimulatory effect on GnRH directly or indirectly by suppressing its anti-inflammatory effect in the brain. Diet and/or exercise interventions were able to alleviate the hypogonadotropic hypogonadism associated with obesity, potentially by increasing hypothalamic NUCB2/nesfatin-1 levels.

Comprehensive and Holistic Analysis of HT-29 Colorectal Cancer Cells and Tumor-Bearing Nude Mouse Model: Interactions Among Fractions Derived From the Chinese Medicine Formula Tian Xian Liquid in Effects on Human Colorectal Carcinoma.

The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 mRNA; TXL potently reversed most multidrug resistance via downregulation of MDR-1 protein. In conclusion, the comprehensive and holistic effects of TXL were demonstrated with ( a) mutual accentuation and mutual enhancement, ( b) mutual counteraction and mutual suppression, and ( c) mutual antagonism among the 3 constituent fractions. Moreover, the design of the present study may lead to further development of more tissue-specific effective drugs with minimal side effects for clinical use in combating carcinoma.

[Treatment of Mixed Hemorrhoids by RPH with the Simplified Milligan-Morgan Surgery: a Multi-center, Randomized, Controlled Clinical Trial].

Objective To observe the safety and efficacy of RPH with the simplified. Milligan-Mor- gan(M-M) surgery on mixed hemorrhoids. Methods Totally 1 200 patients with mixed hemorrhoid were assigned to the control group(600 cases) and the treatment group(600 cases) according to randomized, parallel controlled,multi-center trial design. Patients in the control group received PPH with the simplified M-M surgery, and patients in the treatment group received RPH with the simplified M-M surgery. Postop- erative complications, operation time,the postoperative hospitalization days and the efficacy were ob- served. Results Compared with the control group, the numbers of postoperation hemorrhage, postop- erative uroschesis, anal fissure and anorectal stenosis in treatment group were decreased(P <0. 01 , P < 0. 05), operation time and the postoperative hospitalization days were decreased (P <0. 01 , P <0. 05 ), the cure rate for 3 and 12 months after operation were increased (P <0. 01, P <0. 05). Conclusions RPH with the simplified M-M surgery could reduce the incidence of postoperative complications,improve the clinical cure rate and the curative effect in treatment of mixed hemorrhoids.

Steroidogenic effect of Erxian decoction for relieving menopause via the p-Akt/PKB pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Erxian decoction (EXD), an empirical Chinese medicine formula, is effectively used in the clinical treatment of menopause-related symptoms in China. Previous data from our group show that EXD has steroidogenic effect on natural menopausal Sprague-Dawley-rats (SD-rats) as an animal model of menopause. However, the mechanistic studies on steroidogenic effects of EXD are still inadequate. Hence, the mechanisms of steroidogenic effects of EXD were studied in vitro and in vivo in this study. MATERIALS AND METHODS: Menopause causes a decline of endocrine function and a series of symptoms. In this study, 16-20-month-old female SD rats with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD (4.1g/kg) were assessed by determination of their serum estradiol level. Proteins involved in the steroidogenic pathway including StAR, 17ßHSD, 3ßHSD, aromatase, and activation of phosphorylated Protein Kinase B (p-Akt/PKB), as well as estradiol receptor proteins (ERα & ERß) after EXD treatment were analyzed. Kinase inhibition assay was conducted to confirm the mechanism of steroidogenic effects of EXD in vitro. MCF-7 and BT-483 cells were used to investigate whether EXD stimulated breast cancer cell proliferation. RESULTS: Results revealed a significantly ameliorated serum estradiol level, and a significantly increased expression of ovarian aromatase and PKB in the EXD-treated rats. EXD attenuated 17ß-estradiol stimulated proliferation of breast cancer cells. CONCLUSIONS: The results obtained from immunoblotting and measurements of serum estradiol level of the present investigation revealed that EXD may relieve the menopausal syndrome through an upregulation of ovarian aromatase and p-PKB expression without stimulating the growth of breast cancer cells.

Network pharmacological identification of active compounds and potential actions of Erxian decoction in alleviating menopause-related symptoms.

BACKGROUND: Erxian decoction (EXD) is used to treat menopause-related symptoms in Chinese medicine. This study aims to identify the bioactive compounds and potential actions of EXD by network pharmacological analysis. METHODS: Two databases, the Traditional Chinese Medicine Systems Pharmacology database and TCM Database@Taiwan, were used to retrieve literature of phytochemicals of EXD. STITCH 4.0 and the Comparative Toxicogenomics Database were used to search for compound-protein and compound-gene interactions, respectively. DAVID Bioinformatics Resources 6.7 and Cytoscape 3.01 with Jepetto plugin software were used to perform a network pharmacological analysis of EXD. RESULTS: A total of 721 compounds were identified in EXD, of which 155 exhibited 2,656 compound-protein interactions with 1,963 associated proteins determined by STITCH4.0 database, and of which 210 had 14,893 compound-gene interactions with 8,536 associated genes determined by Comparative Toxicogenomics Database. Sixty three compounds of EXD followed the Lipinski's Rule with OB ≥30% and DL index ≥0.18, of which 20 related to 34 significant pathway- or 12 gene- associated with menopause. CONCLUSIONS: Twenty compounds were identified by network pharmacology as potential effective ingredients of EXD for relieving menopause with acceptable oral bioavailability and druggability.

[Jatropha seed oils extracted by different methods and their effect on killing cercaria of Schistosoma japonicum].

OBJECTIVE: To evaluate the effect of Jatropha seed oils extracted by different methods on killing cercaria of Schistosomajaponicum so as to screen the optimum process and formulations. METHODS: The cercaria directly contacting tests with Jatropha seed oils extracted by 6 different extraction processes were carried out, and the mouse immediate contacting cercaria infection trials with different formulations of Jatropha seed oil and various additives were performed. RESULTS: With 95% ethanol, the ratio of material to liquid being 1:8, and 2 h extraction, the oil extraction rate was 30.7%. The cercaria directly contacting tests showed that 6 kinds of Jatropha seed oil killed all cercaria within 30 min. In the mouse immediate contacting cercaria infection trials, the worm declined rate of Jatropha seed oil liquid was 70.97%, and the worm declined rate of the sample added with benzyl benzoate was 58.87%, and the worm declined rate of the sample added with laurocapram was 77.42%. The worm declined rate of the samples added with benzyl benzoate, dibutyl phthalate and laurocapram was 100%. CONCLUSION: The process with 95% ethanol, the ratio of material to liquid being 1:8, and 2 h extraction is the optimum, and the Jatropha seed oil has a good killing schistosome cercaria effect.

Bushen Huoxue decoction improves cognitive decline in rats with cerebral hypoperfusion.

Cerebral hypoperfusion is a common feature of vascular dementia and has recently been recognized to contribute to the progression of cognitive decline. The present study aimed to investigate the effects of Bushen Huoxue decoction (BHD), a two­herb Chinese Medicine, on cognitive impairment in a rat model of cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO). The results demonstrated that BHD significantly attenuated learning and spatial memory deficits in the Morris water maze test in a dose­dependent manner. Transmission electron microscopy observation revealed that the reduction of synapse density in hippocampal CA1 and cortex parietal isolated from rats with 2VO was partially restored by BHD treatment. In addition, the expression levels of a number of antioxidants, including superoxide dismutase, catalase (CAT), glutathine and glutathione peroxidase­1 (GPx­1) increased, whereas malondialdehyde decreased in the hippocampi of rats with 2VO following BHD treatment. Polymerase chain reaction and western blot analysis further confirmed that the GPx­1 and CAT expression increased in the BHD treatment group. In conclusion the results suggested that BHD has therapeutic potential to treat vascular dementia, which may be associated with synapse density and anti­oxidant activities in the hippocampus.

Chinese Medicines as an Adjuvant Therapy for Unresectable Hepatocellular Carcinoma during Transarterial Chemoembolization: A Meta-Analysis of Randomized Controlled Trials.

Objective. To conduct a comprehensive PRISMA-compliant systematic review and meta-analysis to evaluate the efficacy and safety of Chinese medicines (CMs) as an adjuvant therapy for unresectable HCC during transarterial chemoembolization (TACE). Methods. Main databases were searched up to October 2012 for randomized controlled trials (RCTs) evaluating the effects of CMs plus TACE on unresectable HCC compared with TACE alone. References of relevant reviews and eligible studies were also assessed. Risk ratios with 95% confidence intervals and mean difference were calculated. Heterogeneity and publication bias were examined. Results. Sixty-seven trials (N = 5,211) were included in the meta-analysis. Sensitivity analysis and random-effects model were performed for assessing significant heterogeneity. CMs plus TACE showed beneficial effects on tumor response, survival at 6, 12, 18, 24, and 36 months, quality of life, and TACE toxicity reduction compared with TACE alone. Conclusion. The results show that the use of CMs may increase the efficacy and reduce the toxicity of TACE in treating patients with unresectable HCC. These findings suggest that CMs could be considered as an adjuvant therapy for unresectable HCC patients during TACE. Larger-scale RCTs using standard methods and long-term follow-up are warranted to confirm these findings.

A randomized, double-blind, controlled trial of a Chinese herbal formula (Er-Xian decoction) for menopausal symptoms in Hong Kong perimenopausal women.

OBJECTIVE: The aim of this study is to investigate the effectiveness and safety of a Chinese herbal formula, Er-Xian decoction (EXD), in the treatment of menopausal symptoms among Hong Kong perimenopausal women. METHODS: A randomized, double-blind, controlled trial was conducted for 12 weeks among 108 Hong Kong perimenopausal women who reported Menopause Rating Scale (MRS) total scores of 28 or higher. Posttreatment follow-up was performed 3 months after the intervention. The primary outcome measure was the frequency and severity of hot flushes. The secondary outcome measures included the MRS, the Menopause-Specific Quality of Life questionnaire, and serum hormone levels. RESULTS: Among 108 participants, 101 participants finished the study. EXD significantly reduced the mean (SD) frequency of hot flushes from 5.8 (5.0) to 2.2 (3.0) in the treatment group and from 5.0 (3.8) to 2.4 (2.5) in the placebo group (P = 0.04). The mean (SD) hot flush score was also reduced from 19.6 (6.6) to 4.9 (7.8) in the treatment group and from 16.6 (5.4) to 7.0 (6.4) in the placebo group (P = 0.02). The superiority of EXD to placebo was also observed with greater improvement in the total scores for the MRS (P = 0.03) and the Menopause-Specific Quality of Life questionnaire (P < 0.01). There were no differences in serum hormone levels between the EXD group and the placebo group. There were no serious adverse events, and the safety indices of whole blood counts, renal function, and liver function were within the normal range before and after treatment. CONCLUSIONS: The Chinese herbal formula EXD is superior to placebo in reducing the frequency and severity of hot flushes and in improving menopausal symptoms in Hong Kong perimenopausal women. It is well tolerated, with no serious adverse events noted during the study period.

Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control.

OBJECTIVES: Experimental studies on the pharmacokinetics of traditional Chinese medicines (TCMs) have achieved great progress in recent years. This review aims to summarize the progress made on intestinal absorption and bioavailability of TCMs, and proposes the application of intestinal absorption assays as new tools for the quality and safety control of these medicines. KEY FINDINGS: Since only the absorbed constituents may produce possible therapeutic effect (except those that directly target the digestive tract), intestinal absorption is of utmost importance for the drug action of TCMs, which are usually taken orally. Meanwhile, complicated drug interactions may occur among the multiple ingredients in a herbal mixture. In this regard, the intestinal permeability assays not only provide useful pharmacokinetic data of TCMs, but have potential applications for quality and safety control. Moreover, knockout animals, 2/4/A1 in-vitro cell model and physiologically-based in-silico models based on the online TCM database can be quite useful for the prediction of absorption and bioavailability of TCMs. SUMMARY: A variety of in-vivo, in-vitro, in-situ and in-silico models for predicting the intestinal absorption and bioavailability can be applied to study the herbal interactions and screen appropriate biomarkers for the quality and safety control of TCMs.

The efficacy of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer: a systematic review and meta-analysis.

Many published studies reflect the growing application of complementary and alternative medicine, particularly Chinese herbal medicine (CHM) use in combination with conventional cancer therapy for advanced non-small cell lung cancer (NSCLC), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with conventional chemotherapy (CT) in the treatment of advanced NSCLC. Publications in 11 electronic databases were extensively searched, and 24 trials were included for analysis. A sum of 2,109 patients was enrolled in these studies, at which 1,064 patients participated in CT combined CHM and 1,039 in CT (six patients dropped out and were not reported the group enrolled). Compared to using CT alone, CHM combined with CT significantly increase one-year survival rate (RR = 1.36, 95% CI = 1.15-1.60, p = 0.0003). Besides, the combined therapy significantly increased immediate tumor response (RR = 1.36, 95% CI = 1.19-1.56, p<1.0E-5) and improved Karnofsky performance score (KPS) (RR = 2.90, 95% CI = 1.62-5.18, p = 0.0003). Combined therapy remarkably reduced the nausea and vomiting at toxicity grade of III-IV (RR = 0.24, 95% CI = 0.12-0.50, p = 0.0001) and prevented the decline of hemoglobin and platelet in patients under CT at toxicity grade of I-IV (RR = 0.64, 95% CI = 0.51-0.80, p<0.0001). Moreover, the herbs that are frequently used in NSCLC patients were identified. This systematic review suggests that CHM as an adjuvant therapy can reduce CT toxicity, prolong survival rate, enhance immediate tumor response, and improve KPS in advanced NSCLC patients. However, due to the lack of large-scale randomized clinical trials in the included studies, further larger scale trials are needed.

Erxian decoction, a traditional chinese herbal formula, inhibits angiogenesis in human umbilical vein endothelial cells.

Our previous study demonstrated that Erxian Decoction (EXD), a traditional Chinese herbal formula, inhibited angiogenesis in zebrafish embryos. To further investigate the anti-angiogenic activity and mechanism of EXD, we evaluated its inhibitory effect on angiogenesis in mammalian endothelial cells in vitro. Cell based assays included proliferation, apoptosis, migration, tube formation and cell cycle analysis. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were carried out to evaluate the molecular targets and signaling pathways of EXD in human umbilical vein endothelial cells (HUVECs). EXD inhibited proliferation, migration and tube formation in HUVECs. EXD also caused HUVEC apoptosis and cell increase in G0/G1 phase in cell cycle analysis. Furthermore, it decreased the mRNA expressions of vascular endothelial growth factor A (VEGF-A), VEGFR-1 and VEGFR-2 in HUVECs. It also inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt activation, suggesting the involvement of these signaling pathways in the anti-angiogenic action of EXD in HUVECs. The anti-angiogenic activity of EXD provides new insights to its clinical application and may lead to potential drug development for treating various cancers, especially in menopausal period in the future.