Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.

OBJECTIVE: To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA). DESIGN: A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial. RESULTS: In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported. CONCLUSION: Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT00755326).

Implementing Faraday effect measurement constraints into the Grad-Shafranov equilibrium fitting code EFIT.

A new tool for the exploration and diagnosis of the internal magnetic field of plasmas in the DIII-D tokamak in the form of a constraint on the EFIT (Equilibrium Fitting) Grad-Shafranov code based on the Faraday-effect Radial Interferometer-Polarimeter (RIP) diagnostic is presented, including description, verification, and sample application. The physics underlying the diagnostic and its implementation into EFIT are discussed, and the results showing the verification of the model are given, and the model's limitations are discussed. The influence of the diagnostic's input on the resulting equilibrium parameters is characterized. The effect of electron density profile refinement is evaluated and found to be negligible. A sample application of the diagnostic is shown, indicating that the RIP constraint has similar effects on the equilibrium as motional Stark effect constraints do.

[Best evidence summary of prevention strategies for pressure injury in adult hospitalized burn patients].

Objective: To summarize the best evidence of prevention strategies for pressure injury in adult hospitalized burn patients. Methods: A bibliometric approach was used. Systematic searches were carried out to retrieve the published evidence of prevention strategies for pressure injury in adult hospitalized burn patients in the official websites of relevant academic organizations such as International Society for Burn injury, American Burn Association, and Japanese Dermatology Association, National Pressure Injury Advisory Panel, European Pressure Injury Advisory Panel, Pan Pacific Pressure Injury Alliance International Guidelines Website, foreign language databases such as UpToDate, BMJ Best Practice, MedSci, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Web of Science, Embase, and PubMed, and Chinese databases such as China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, and China Clinical Guidelines Library. The literature types include clinical decision-making, evidence summary, guidelines, systematic review, and expert consensus. The search time was till February 21st, 2023. Two researchers independently screened the literature and evaluated the quality, and other researchers extracted and graded the evidence according to the topic. Results: A total of 10 papers were included, including 6 evidence summaries, 3 guidelines, and 1 expert consensus, all with high literature quality. After extracting evidence and classifying, 27 pieces of best evidences were summarized from three aspects, including prevention training and supervision, risk assessment, and prevention measures of pressure injury. Conclusions: A total of 27 pieces of best evidences of prevention strategies for pressure injury in adult hospitalized burn patients were summarized from 3 aspects. Medical workers can follow the best evidence and give personalized prevention strategies according to the specific condition of adult hospitalized burn patients to reduce the incidence of pressure injury.

Electroacupuncture inhibition of hyperalgesia in an inflammatory pain rat model: involvement of distinct spinal serotonin and norepinephrine receptor subtypes.

BACKGROUND: Although acupuncture analgesia is well documented, its mechanisms have not been thoroughly clarified. We previously showed that electroacupuncture (EA) activates supraspinal serotonin- and norepinephrine-containing neurones that project to the spinal cord. This study investigates the involvement of spinal alpha(2)-adrenoceptors (α2-ARs) and 5-hydroxytryptamine (serotonin) receptors (5-HTRs) in EA effects on an inflammatory pain rat model. METHODS: Inflammatory hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08 ml) into the plantar surface of one hind paw and assessed by paw withdrawal latency (PWL) to a noxious thermal stimulus. The selective α2a-AR antagonist BRL-44408, α2b-AR antagonist imiloxan hydrochloride, 5-HT2B receptor (5-HT2BR) antagonist SB204741, 5-HT3R antagonist LY278584, or 5-HT1AR antagonists NAN-190 hydrobromide, or WAY-100635 were intrathecally administered 20 min before EA or sham EA, which was given 2 h post-CFA at acupoint GB30. RESULTS: EA significantly increased PWL compared with sham [7.20 (0.46) vs 5.20 (0.43) s]. Pretreatment with α2a-AR [5.35 (0.45) s] or 5-HT1AR [5.22 (0.38) s] antagonists blocked EA-produced anti-hyperalgesia; α2b-AR, 5-HT2BR, and 5-HT3R antagonist pretreatment did not. Sham plus these antagonists did not significantly change PWL compared with sham plus vehicle, indicating that the antagonists had little effect on PWL. Immunohistochemical staining demonstrated that α2a-ARs are on primary afferents and 5-HT1ARs are localized in N-methyl-d-aspartic acid (NMDA) subunit NR1-containing neurones in the spinal dorsal horn. CONCLUSIONS: The data show that α2a-ARs and 5-HT1ARs are involved in the EA inhibition of inflammatory pain and that the NMDA receptors are involved in EA action.

An effectiveness study comparing acupuncture, physiotherapy, and their combination in poststroke rehabilitation: a multicentered, randomized, controlled clinical trial.

CONTEXT: Stroke is a leading cause of death and disability worldwide, being the third leading cause of death in the United States and the second and third most common causes of death in Chinese cities and rural areas, respectively. Evaluation of different rehabilitative modalities appears necessary to optimize treatment. OBJECTIVES: To compare acupuncture and physiotherapy for effectiveness and reliability in treating hemiplegic patients after stroke. DESIGN: The research team designed a multicentered, three-arm, randomized controlled trial. Power calculations revealed a targeted sample size of 310 participants. SETTING: The study took place at seven in-patient hospitals in China. PARTICIPANTS: The research team screened a total of 310 patients. Of that number, 274 completed the study, 15 did not meet the inclusion/exclusion criteria, and 21 dropped out. Adverse events were rare (less than 1%), mild, and temporary. INTERVENTION: The research team randomly divided participants into three groups that all received conventional care as needed-including psychological counseling, standard nursing care, and daily medical evaluation plus (1) acupuncture, (2) physiotherapy, or (3) acupuncture plus physiotherapy. The participants received treatments once a day, 6 days a week for 4 weeks. OUTCOME MEASURES: The research team evaluated all patients at baseline, after 2 weeks, and after 4 weeks using the Fugl-Meyer Assessment of Physical Performance (FMA), a modified Barthel Index (BI), and the Neurologic Defect Scale (NDS). RESULTS: No significant differences existed between the three groups at baseline. Compared to baseline, participants in all groups improved their FMA, BI, and NDS scores by the end of week 2 (P≤.05) and further improved by the end of week 4 (P≤.05) The study found no statistically significant differences in outcomes between the three groups after treatment (P>.05). CONCLUSION: Acupuncture plus conventional care was similar in effectiveness to physiotherapy treatment plus conventional care for poststroke rehabilitation. The study found no synergistic effects for the combination of acupuncture and physiotherapy in addition to conventional care; that combination of treatments was no more effective than either treatment by itself. The effectiveness and lack of adverse events associated with acupuncture in this study suggest that it may represent an additional treatment option for stroke patients.

Complete blood count during the first trimester predicting spontaneous preterm birth.

OBJECTIVE: This work aimed at assessing the peripheral complete blood count during the first trimester of pregnancy in women with spontaneous preterm birth (sPTB) compared with age-matched controls who are women with healthy pregnancies. PATIENTS AND METHODS: This was a cross-sectional case-control study, with 175 sPTB and 175 age-matched healthy controls, carried out between January 2019 and December 2019. Baseline data and the complete blood count parameters examined during the first trimester of all the participants were recorded. The receiver operator characteristic curve (ROC) was used to evaluate cut-off point and diagnostic characteristics and area under the curve predicting sPTB. RESULTS: White blood count, platelet, lymphocyte, monocyte, and lymphocyte-monocyte ratio values were significantly higher, and platelet-lymphocyte ratio and neutrophil-lymphocyte ratio values were lower in sPTB group than healthy control group in the first trimester of pregnancy. Receiver-operator curve analysis suggested that lymphocyte, white blood count, platelet-lymphocyte ratio, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, monocyte, and platelet in the first trimester of pregnancy had predictive value for sPTB. The greatest predictive was lymphocyte, and the areas under the receiver operator characteristic curve (AUROCs) reached 0.853. CONCLUSIONS: Lymphocyte values during the first trimester of pregnancy were the most predictive spontaneous preterm delivery. Therefore, in the management of the higher risk of preterm delivery, lymphocyte values could be a more cost-effective method during the first trimester of pregnancy because it does not need any kit.

In Silico Ventilation Within the Dose-Volume is Predictive of Lung Function Post-radiation Therapy in Patients with Lung Cancer.

Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = - 0.61). Patients with higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT.

"Skin-like" fabric for personal moisture management.

Personal moisture management fabrics that facilitate sweat transport away from the skin are highly desirable for wearer's comfort and performance. Here, we demonstrate a "skin-like" directional liquid transport fabric, which enables continuous one-way liquid flow through spatially distributed channels acting like "sweating glands" yet repels external liquid contaminants. The water transmission rate can be 15 times greater than that of best commercial breathable fabrics. This exceptional property is achieved by creating gradient wettability channels across a predominantly superhydrophobic substrate. The flow directionality is explained by the Gibbs pinning criterion. The permeability, mechanical property, and abrasion resistance (up to 10,000 cycles) of the fabric were not affected by the treatment. In addition to functional clothing, this concept can be extended for developing materials for oil-water separation, wound dressing, geotechnical engineering, flexible microfluidics, and fuel cell membranes.

Genetic diagnosis of Hailey-Hailey disease in two Chinese families: novel mutations in the ATP2C1 gene.

Hailey-Hailey disease (HHD; OMIM 169600), is an autosomal dominantly inherited disorder characterized by suprabasal cell separation of the epidermis. Mutations in ATP2C1, which encodes the human secretory pathway Ca(2+)/ Mn(2) +/- ATPase protein 1 (hSPCA1), have been identified as the pathogenic gene of HHD without evidence of genetic heterogeneity. In this study, the ATP2C1 gene was screened in two typical Chinese pedigrees with HHD, and two specific novel mutations of the ATP2CL gene were identified. Family 1 had a 16-base deletion mutation c.1068-1083del16 and family 2 had a substitution mutation c.1982T>G (p.Met661Arg). DNA sequencing of the three descendants of the probands revealed that they all had the normal genotype, indicating that there had been no transmission of the mutation.

Chinese Medicine in Cancer Treatment - How is it Practised in the East and the West?

Chinese medicine therapies in cancer treatment are very common in the East. Although it is usually classified as a form of complementary and alternative therapy in the West, Chinese medicine is an independent medical profession in Hong Kong and mainland China. It has a different perspective in understanding health and diseases compared with Western medicine. In oncology practice, whereas Western medicine focuses on direct tumour eradication by surgery, radiation therapy and systemic therapies, Chinese medicine focuses on restoring body balance and enhancing the body's defences (immunity), in addition to some cytotoxic herbal therapies. Most often patients, especially those in the East, receive both treatments. Chinese medicine is also commonly used to reduce side-effects from chemotherapy or radiation therapy, to aid recovery after an operation, to palliate symptoms and to address survivorship issues. However, this raises concerns of drug-herb interactions and toxicity in combination therapies. Commonly used Chinese medicine treatment modalities include acupuncture, moxibustion, diet therapy, prescribed Chinese medicine herbal decoction, single Chinese medicine herbs or supplements and tai chi. Although there is an increasing trend of Chinese medicine use in cancer patients in both the East and the West, the scientific evidence of safety and efficacy is often questioned by oncologists. This article reviews the current evidence in different Chinese medicine therapies in cancer management in both the East and the West.

Using motional Stark splitting of D α emission to constrain MHD equilibrium analysis in DIII-D plasmas.

We report tests of an alternate technique for constraining MHD equilibrium analysis in tokamak plasmas using internal magnetic field measurements based on | B | measurements from the motional Stark splitting of Dα spectral lines emitted by a neutral heating beam (MSE-LS). We compare results using MSE-LS with those of the standard equilibrium analysis technique based on line polarization of the Dα emission (MSE-LP). An alternative to MSE-LP is needed in future devices such as ITER where MSE-LP will be difficult due to a plasma-induced coating of the first optical element. The tests utilized data from 10 DIII-D shots with 7 MSE-LS and 14 MSE-LP views covering a range of radii along the outer midplane of the plasma. Seven MSE-LS measurements can contribute significantly to the equilibrium reconstruction of pressure and q profiles using both synthetic and experimental DIII-D MSE-LS data. For example, 7 MSE-LS plus seven MSE-LP measurements give a fit quality that is as good as the same cases with 14 MSE-LP measurements. Analyzing synthetic data for 14 MSE-LS measurements shows significant improvement in fitting quality over the case with 7 MSE-LS locations.

Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats.

BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min at the equivalent of human acupoint GB30 (Huantiao) once every other day between days 14 and 26. For sham control, EA needles were inserted into GB30 without stimulation. Von Frey filaments with bending forces of 2-8 g and 15 g were used to assess mechanical allodynia and hyperalgesia, respectively, on day 13 and once every other day between 14-26 days and then for 2-3 weeks after EA treatment. RESULTS: Compared to sham control, EA significantly alleviated paclitaxel-induced mechanical allodynia and hyperalgesia, as shown by less frequent withdrawal responses to the filaments. The alleviation of allodynia/hyperalgesia lasted up to 3 weeks after the EA treatment. EA significantly inhibited phosphorylation of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) in the spinal cord. KN-93, a selective inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII. 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII. CONCLUSIONS: Electroacupuncture activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia. The data support acupuncture/EA as a complementary therapy for CIP. SIGNIFICANCE: Electroacupuncture (EA) activates spinal 5-HT1A receptors to inhibit p-CaMKII to alleviate paclitaxel-induced pain. Acupuncture/EA may be used as a complementary therapy for CIP.

DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose.

This corrects the article DOI: 10.1038/cdd.2015.26.

Comparison of chemical profiles and effectiveness between Erxian decoction and mixtures of decoctions of its individual herbs: a novel approach for identification of the standard chemicals.

BACKGROUND: Identification of bioactive standard chemicals is a major challenge in the study of the Chinese medicinal formula. In particular, the chemical components may interact differently depending on the preparative methods, therefore affecting the amounts of bioactive components and their pharmacological properties in the medicinal formula. With the use of Erxian decoction (EXD) as a study model-a  well-known Chinese medicinal formula for treating menopausal symptoms, a novel and rapid approach in seeking standard chemicals has been established by differentially comparing the HPLC profiles and the menopause-related biochemical parameters of combined decoction of EXD (EXD-C) and mixtures of the decoctions of its individual herbs (EXD-S). METHODS: The levels of six chemicals, which exerted actions on the HPO axis, have been measured in EXD-C and EXD-S by HPLC. Twelve-month-old female Sprague-Dawley rats were employed and treated with EXD-C and EXD-S. Their endocrine functions after treatment were evaluated by determining the ovarian mRNA levels of aromatase, a key enzyme for estradiol biosynthesis. The effect of the antioxidant regimen was determined by the hepatic superoxide dismutase-1 (SOD), catalase (CAT) and glutathione peroxidase (GPx-1) mRNA levels. RESULTS: The amounts of mangiferine, ferulic acid, jatrorrhizine and palmatine in EXD-S were twofold higher than those in EXD-C. EXD-S was more effective in stimulating ovarian aromatase and the expression of the antioxidant enzymes compared with EXD-C. CONCLUSION: Mangiferine, ferulic acid, jatrorrhizine and palmatine are suitable for use as standard chemicals for quality evaluation of EXD according to our approach. EXD-S could be more effective than EXD-C.

Acupuncture for treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS), a disorder of altered bowel habits associated with abdominal pain or discomfort. The pain, discomfort, and impairment from IBS often lead to healthcare medical consultation (Talley 1997) and workplace absenteeism, and associated economic costs (Leong 2003). A recent randomized controlled trial shows variable results but no clear evidence in support of acupuncture as an effective treatment for IBS (Fireman 2001). OBJECTIVES: The objective of this systematic review is to determine whether acupuncture is more effective than no treatment, more effective than 'sham' (placebo) acupuncture, and as effective as other interventions used to treat irritable bowel syndrome. Adverse events associated with acupuncture were also assessed. SEARCH STRATEGY: The following electronic bibliographic databases were searched irrespective of language, date of publication, and publication status: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, EMBASE, the Chinese Biomedical Database, the Cumulative Index to Nursing and Allied Health (CINAHL), and the Allied and Complementary Medicine Database (AMED). References in relevant reviews and RCTs were screened by hand. The last date for searching for studies was 7 February 2006. SELECTION CRITERIA: Published reports of randomized controlled trials (RCTs) and quasi-randomised trials of acupuncture therapy for IBS. DATA COLLECTION AND ANALYSIS: All eligible records identified were dually evaluated for eligibility and dually abstracted. Methodological quality was assessed using the Jadad scale and the Linde Internal Validity Scale. Data from individual trials were combined for meta-analysis when the interventions were sufficiently similar. Heterogeneity was assessed using the I squared statistic. MAIN RESULTS: Six trials were included. The proportion of responders, as assessed by either the global symptom score or the patient-determined treatment success rate, did not show a significant difference between the acupuncture and the sham acupuncture group with a pooled relative risk of 1.28 (95% CI 0.83 to 1.98; n=109). Acupuncture treatment was also not significantly more effective than sham acupuncture for overall general well-being, individual symptoms (e.g., abdominal pain, defecation difficulties, diarrhea, and bloating), the number of improved patients assessed by blinded clinician, or the EuroQol score. For two of the studies without a sham control, acupuncture was more effective than control treatment for the improvement of symptoms: acupuncture versus herbal medication with a RR of 1.14(95% CI 1.00 to 1.31; n=132); acupuncture plus psychotherapy versus psychotherapy alone with a RR of 1.20 (95% CI 1.03 to 1.39; n=100). When the effect of ear acupuncture treatment was compared to an unclearly specified combination of one or more of the drugs diazepam, perphenazine or domperidone, the difference was not statistically significant with a RR of 1.49(95% CI 0.94 to 2.34; n=48). AUTHORS' CONCLUSIONS: Most of the trials included in this review were of poor quality and were heterogeneous in terms of interventions, controls, and outcomes measured. With the exception of one outcome in common between two trials, data were not combined. Therefore, it is still inconclusive whether acupuncture is more effective than sham acupuncture or other interventions for treating IBS.

Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting.

BACKGROUND: There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms. OBJECTIVES: The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts. SELECTION CRITERIA: Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both. DATA COLLECTION AND ANALYSIS: Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes. MAIN RESULTS: Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. AUTHORS' CONCLUSIONS: This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Comparative Analysis of Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro Using Both Phenotypic and Target-based Approaches: Implication for Treating Menopause.

Rhizomes of Dioscorea species are traditionally used for relieving menopausal syndromes in Chinese medicine. The estrogen-stimulating bioactive principles have been demonstrated in our previous study. In this study, the estrogen-stimulating effects of proteins isolated from four Dioscorea species [D. alata L. (DA), D. zingiberensis C.H. Wright (DH), D. collettii var. hypoglauca (Palib.) S.J. Pei & C.T. Ting (DH), and D. oppositifolia L. (DO)] have been investigated and compared. Microscopic authentication of four Dioscorea species was performed by using paraffin and powder sections of the rhizomes. The potential bioactive proteins of four Dioscorea species have been rapidly isolated by using a DOI-antibody affinity column chromatography on immobilized antibodies against on estradiol-stimulating protein from DO (DOI), and their bioactivity has been rapidly confirmed and compared by phenotypic (i.e., estradiol-stimulating effect) and target-based (i.e., STAR, aromatase, estrogen receptors) screening approaches. The estrogen-stimulating activity of bioactive proteins from DO is the highest. In addition, bioactive proteins from DO upregulated the estradiol-metabolizing enzymes (aromatase and steroidogenic acute regulatory protein). Meanwhile, bioactive proteins from DA, DH and DO upregulated estrogen receptor ß (ERß). All bioactive proteins did not change the expression of estrogen receptor ß (ERα). The estrogen-stimulating bioactive proteins isolated from DO increased biosynthesis of estradiol and upregulated the protein expression of aromatase, steroidogenic acute regulatory protein, and ERß. The results scientifically support the traditional use of DO in Chinese medicine for relieving menopausal syndrome. Besides, proteins from DA and DZ could also upregulate the translational levels of ERß, and potentially reducing the risk of ovarian cancer, which also support the clinical use of them for treating female aging disorder. Graphical Abstract Comparative Analysis of DOI-like Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro.

GABA(A) receptor facilitation of neurokinin release from primary afferent terminals in the rat spinal cord.

Our goal was to test the following hypotheses: 1) GABA(A) receptors facilitate neurokinin release from primary afferent terminals; 2) they do this by suppressing an inhibitory effect of GABA(B) receptors; 3) the activation of these two receptors is controlled by the firing frequency of primary afferents. We evoked neurokinin release by stimulating the dorsal root attached to spinal cord slices, and measured it using neurokinin 1 receptor (NK1R) internalization. Internalization evoked by root stimulation at 1 Hz (but not at 100 Hz) was increased by the GABA(A) receptor agonists muscimol (effective concentration of drug for 50% of the increase [EC50] 3 microM) and isoguvacine (EC50 4.5 microM). Internalization evoked by root stimulation at 100 Hz was inhibited by the GABA(A) receptor antagonists bicuculline (effective concentration of drug for 50% of the inhibition [IC50] 2 microM) and picrotoxin (IC50 243 nM). Internalization evoked by incubating the root with capsaicin (to selectively recruit nociceptive fibers) was increased by isoguvacine and abolished by picrotoxin. Therefore, GABA(A) receptors facilitate neurokinin release. Isoguvacine-facilitated neurokinin release was inhibited by picrotoxin, low Cl-, low Ca2+, Ca2+ channel blockers and N-methyl-D-aspartate receptor antagonists. Bumetanide, an inhibitor of the Na(+)-K(+)-2Cl- cotransporter, inhibited isoguvacine-facilitated neurokinin release, but this could be attributed to a direct inhibition of GABA(A) receptors. The GABA(B) agonist baclofen inhibited NK1R internalization evoked by 100 Hz root stimulation (IC50 1.5 microM), whereas the GABA(B) receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl) phosphinic acid (CGP-55845) increased NK1R internalization evoked by 1 Hz root stimulation (EC50 21 nM). Importantly, baclofen inhibited isoguvacine-facilitated neurokinin release, and CGP-55845 reversed the inhibition of neurokinin release by bicuculline. In conclusion, 1) GABA(B) receptors located presynaptically in primary afferent terminals inhibit neurokinin release; 2) GABA(A) receptors located in GABAergic interneurons facilitate neurokinin release by suppressing GABA release onto these GABA(B) receptors; 3) high frequency firing of C-fibers stimulates neurokinin release by activating GABA(A) receptors and inhibiting GABA(B) receptors, whereas low frequency firing inhibits neurokinin release by the converse mechanisms.